Results and complications of a surgical technique for correction of coxa vara in children with osteopenic bones.
Surgical correction of coxa vara in children with osteopenic bone diseases could be very challenging. In this study, we describe a modified surgical technique for the correction of coxa vara in children with bone fragility. We also report the results and complications of this technique in 16 children (21 coxa vara) with osteopenic bone diseases. Charts, clinic notes, and radiology images of 16 patients (21 hips) who had a proximal femoral osteotomy for the treatment of coxa vara in osteogenesis imperfecta (18 hips) and fibrous dysplasia (3 hips) in our institution between 1996 and 2005 were reviewed. The modified surgery involved an intertrochanteric osteotomy and the use of Kirshner wires and intramedullary rods. Neck-shaft angle, Hilgenreiner-epiphyseal angle, and head-shaft angle were assessed at preoperative, postoperative, and final follow-up. The average age at surgery was 8.3 years (range, 3.3-15.8 years). The average correction of the neck-shaft angle was from 84.6 to 114.4 degrees, and for the Hilgenreiner-epiphyseal angle, it was from 67.7 to 42 degrees at final follow-up. All osteotomies were healed at 3 months postoperatively. The mean follow-up was 4.29 years (range, 1.70-8.12 years). The average improvement in abduction and external rotation of the hips was 14 and 15 degrees, respectively. There were no cases of infection and 2 cases (12%) of implant-related complications. One patient with fibrous dysplasia needed replacement of the intramedullary rod and additional distal femoral osteotomy 1 week postsurgery. In another patient, the intramedullary rod had migrated proximally, which was corrected 5 months postsurgery by advancing the rod distally. Results suggest that this surgical technique provides satisfactory correction of coxa vara in children with osteopenic bone diseases. The described surgical technique used to correct coxa vara is reproducible and safe and has few complications. Furthermore, the size of the implants used allows surgery to be performed in very young children.


Mining dynamic noteworthy functions in software execution sequences.
As the quality of crucial entities can directly affect that of software, their identification and protection become an important premise for effective software development, management, maintenance and testing, which thus contribute to improving the software quality and its attack-defending ability. Most analysis and evaluation on important entities like codes-based static structure analysis are on the destruction of the actual software running. In this paper, from the perspective of software execution process, we proposed an approach to mine dynamic noteworthy functions (DNFM)in software execution sequences. First, according to software decompiling and tracking stack changes, the execution traces composed of a series of function addresses were acquired. Then these traces were modeled as execution sequences and then simplified so as to get simplified sequences (SFS), followed by the extraction of patterns through pattern extraction (PE) algorithm from SFS. After that, evaluating indicators inner-importance and inter-importance were designed to measure the noteworthiness of functions in DNFM algorithm. Finally, these functions were sorted by their noteworthiness. Comparison and contrast were conducted on the experiment results from two traditional complex network-based node mining methods, namely PageRank and DegreeRank. The results show that the DNFM method can mine noteworthy functions in software effectively and precisely.


A comparative evaluation of thoracic and lumbar epidural fentanyl for post thoracotomy pain.
Thirty patients undergoing closed mitral valvotomy were prospectively randomised to receive either thoracic or lumbar epidural catheter. General anaesthesia consisted of morphine sulphate 0.15 mg/kg (single dose given before skin incision), thiopentone sodium 4-6 mg/kg, vecuronium and halothane titrated to stable haemodynamics. In the immediate postoperative period, pain was assessed by VAS (visual analogue scale) and VRS (verbal ranking score) and an epidural fentanyl bolus of 1.5 microg/kg was given followed by an infusion of 0.4 microg/kg/hr. Pain was assessed after 30 min and if pain relief was still inadequate, another fentanyl bolus of 1 microg/kg was administered, followed by an increase in infusion rate to 0.6 microg/kg/hr. If two consecutive pain scores were satisfactory (VAS <4, VRS <1) maintenance dose of fentanyl was decreased by 0.2 microg/kg/hr. Thoracic group received significantly less total dose of fentanyl in 24 hrs period (446.7 +/- 101.70 microg) compared with the lumbar group (705.33 +/- 181.03 microg) (p<0.01). The mean infusion rate was also significantly less in the thoracic group as compared with the lumbar group (0.44 +/- 0.08 microg/kg/hr vs 0.61 +/- 11 microg/kg/hr, p<0.001). The side effects were comparable between both the groups and none of the patients had significant respiratory depression. The data suggest that thoracic epidural fentanyl infusion is superior to lumbar infusion for post thoracotomy pain relief because of smaller dose requirement.


Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression.
Spasticity is one of the most physically debilitating disabilities following stroke and may slow down the potential success of rehabilitation. Glutamate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been shown to play a crucial role in spasticity following cerebral ischemia/reperfusion (I/R) injury. Gua Lou Gui Zhi decoction (GLGZD) is a well-known traditional Chinese formula that has long been used clinically in China to treat muscular spasticity following stroke, epilepsy or spinal cord injury. However, the precise mechanisms behind its neuroprotective and anti-spasticity effects remain poorly understood. In the present study, using a rat model of focal cerebral I/R injury, we evaluated the neuroprotective and anti-spasticity effects of GLGZD and investigated the underlying mechanisms. We found that GLGZD improved neurological deficits and reduced infarct volumes in cerebral I/R-injured rats. In addition, GLGZD reduced cerebral ischemic spasticity since it improved the screen test and Hoffman's reflex (H-reflex) scores. It also reduced glutamate levels in the cerebrospinal fluid and altered the expression of the AMPA receptor subunits. Our data demonstrate that GLGZD exerts neuroprotective and anti-spasticity effects in a cerebral ischemia model via the modulation of glutamate levels and AMPA receptor expression.


Chemoselective protection of alpha-ketoacids by direct annulations with oximes.
Oximes and alpha-ketoacids undergo an unexpectedly facile and chemoselective annulation to afford 2,5-dihydrooxazole 3-oxides. The resulting cyclic nitrones serve as chemically and configurationally stable masked alpha-ketoacids that can be easily elaborated and manipulated. Deprotection is achieved by mild reduction with zinc metal and hydrolysis. This methodology allows for the protection, elaboration, and deprotection of enantiopure peptide derived alpha-ketoacids, which are the key starting materials for the chemoselective ketoacid-hydroxylamine peptide ligation.


[Bilateral claw deformity of the fingers due to fasciitis with eosinophilia (Shulman's syndrome). Apropos of a case].
Shulman's syndrome or fasciitis with eosinophilia is a disease of unknown origin with unclear relations with scleroderma, characterised by thickening of the fascia superficialis associated with blood eosinophilia. This diagnosis should be considered in a patient presenting with a lesion of the anterior surface of the forearms, which have an "armoured" appearance, associated with claw deformity of the wrist, hand and fingers. The diagnosis is based on cutaneo-muscular biopsy and treatment consists of corticosteroids. The clinical course is generally favourable, although recovery is sometimes incomplete. There is generally no visceral or systemic involvement apart from rare cytopenic forms which must be identified.


Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease.
Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ (P < 0.0001) and λ (P = 0.0003) free light chains and the κ : λ ratio (P = 0.0049) are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.


Chirality transfer in the aza-[2,3]-Wittig sigmatropic rearrangement.
The aza-[2,3]-Wittig sigmatropic rearrangements of substrates derived from enantiomerically pure alanine, valine and serine with phenyl and ester anion stabilising groups were investigated for their efficiency in chirality transfer. It was found that a methyl substituent at the stereogenic centre of the rearrangement precursors was inadequate to control the alkene stereoselectivity and enantioselectivity of the rearrangement. Ester stabilised anions of valine and serine derivatives were the most successful with up to 66% yield, 14 : 1 alkene (E)-stereoselection and 88% chirality transfer. A limitation to the steric bulk of the stereogenic centre was noted in that the substituent has to be bulky enough to dictate alkene stereoselection, but not too large to compromise the directing effect of the activating phenyldimethyl silyl substituent on the anion stabilising group. Experimental evidence suggested a possible complimentary coordinating effect of an O-MOM serine substituent, which may assist alkene stereoselectivity and enantioselectivity.


Molecular analysis of IgE H-chain transcripts expressed in vivo by peripheral blood lymphocytes from normal and atopic individuals.
The low levels of IgE produced by PBMC from normal individuals has so far prevented an analysis of their IgE H chain repertoire. Using a nested polymerase chain reaction approach, we were able to detect epsilon transcripts in all normal and allergic individuals we investigated. We further cloned epsilon CDR3/FW4 regions from two normal and two atopic individuals with low serum IgE levels. Sequence analysis of 104 clones identified 26 different epsilon CDR3/FW4 regions and an additional number of clonally related transcripts in the two atopic individuals. Preferential usage of DH genes from the DXP family (33%) and of the JH4b gene (35%) were observed, similar to reported findings for the IgM-producing peripheral blood B cell subset. Using CDR3 specific oligonucleotides, we detected the CDR3/FW4 regions of a particular set of clonally related epsilon transcripts in mu and gamma 4 transcripts of the same individual. This finding demonstrates the in vivo production of IgE together with the two other Ig isotypes (IgM and IgG4) by the progeny of a common B cell precursor, and suggests a possible mechanism for regulating the allergic response. The clonally related epsilon transcripts were found to be only of the secreted form. We give also evidence that the IgE-producing B cells undergo somatic mutation because a number of identical mutations were observed in the FW4 regions of epsilon and mu clonally related transcripts. Some of these mutations were shared with other transcripts from the same and other individuals, supporting the existence of sequence-specific hot spots for the somatic hyper-mutation machinery in the JH gene segments.


Treatment of lateral ankle instability patient-specific remnant approach.
Lateral ankle instability is one of the most common problems seen in the orthopaedic setting. Proper diagnosis is essential in order to provide the ideal treatment for these patients. All patients are subjected to nonoperative management in the form of functional rehabilitation. For those, however, who did not respond well to therapy, surgical treatment is then recommended. There are several surgical techniques available which have been meticulously studied and discussed in previous articles. The focus of this paper is on the author's perspective on choosing the surgical technique based on the quality of the anterior talofibular ligament and calcaneofibular ligament remnants. All patients are subjected to a diagnostic arthroscopy, where the remnant is assessed. The procedure then of doing an all-arthroscopic, open Modified Brostrom or anatomic reconstruction is then chosen based on this initial assessment.


Impact of laser excitation intensity on deep UV fluorescence detection in microchip electrophoresis.
A high intensity 266 nm continuous wave (cw-) laser developed for material processing was utilised as an excitation source for sensitive native fluorescence detection of unlabelled compounds in MCE. This 120 mW laser was attached via an optical fibre into a commercial epifluorescence microscope. With this MCE set-up we evaluated the impact of laser power on the S/N of aromatic compounds as well as of proteins. Compared with a previous work which used a 4 mW pulsed laser for excitation, improved S/N for small aromatics and to a lesser extent for proteins could be attained. The LOD of the system was determined down to 24 ng/mL for serotonin (113 nM), 24 ng/mL for propranolol (81 nM), 80 ng/mL for tryptophan (392 nM) and 80 ng/mL for an aromatic diol (475 nM). Sensitive protein detection was obtained at concentrations of 5 microg/mL for lysocyme, trypsinogen and chymotrypsinogen (340, 208 and 195 nM, respectively). Finally, a comparison of the cw- with a pulsed 266 nm laser, operating at the same average power, showed a higher attainable sensitivity of the cw-laser. This can be attributed to fluorescence saturation and photobleaching effects of the pulsed laser at high pulse energies.


Characterization of molecular markers for specific and sensitive detection of Botrytis cinerea Pers.: Fr. in strawberry (Fragariaxananassa Duch.) using PCR.
Random amplified polymorphic DNA (RAPD) assays were applied on 34 fungal strains isolated from strawberry and other host plants, in order to detect polymorphism to consequently identify and isolate molecular markers specific to Botrytis cinerea. Among the 26 10-mer primers tested, one primer mainly amplified a 750-bp product present in all the B. cinerea strains and absent in the other species and genera examined. This product was cloned and sequenced in order to design a specific 20-mer primer pair, which was tested on the 34 fungal isolates by polymerase chain reaction (PCR). A single 0.7-kb band was amplified in all the 13 strains of B. cinerea isolated from different host plants. Moreover, a 0.6-kb band was amplified in both Botrytis fabae strains. No band was observed for the nine other Botrytis species and 12 fungal genera isolated from strawberry plants. A comparison between the 0.7-kb B. cinerea sequence and the 0.6-kb B. fabae sequence revealed 98% homology and one 122-bp deletion for B. fabae, including an EcoRI site. Hybridization of Southern blots with RAPD and EcoRI-digested DNA confirmed the specificity of the marker. The limit of detection of B. cinerea genomic DNA was approximately 0.2 pg. The PCR procedure was able to amplify the 0.7-kb B. cinerea fragment form mixed samples of DNA as low as 2 pg B. cinerea genomic DNA and 1 microg plant DNA. Thus this PCR-based detection procedure is a powerful tool for diagnosis of B. cinerea in symptomless strawberry plants, and should allow infection and latency sites to be localized in order to improve knowledge of the epidemiology of the pathogen under field conditions.


Stealth surgery: Subcutaneous endoscopic excision of benign lesions of head, neck and trunk in children.
Subcutaneous endoscopic excision of benign lesions of the head, neck and trunk is a new dimension in paediatric minimally invasive surgery. This study is a case series where cases are operated endoscopically with minimal scars. This is a prospective study where in 13 patients who underwent Stealth surgery were enrolled in this study. Factors such as intraoperative time, blood loss, intraoperative complications, postoperative recovery and appearance and placing of minimal scars at inconspicuous sites were taken into consideration. All patients underwent successful surgery without converting to open surgery. Out of 13 patients, five were torticollis, four were suprasternal dermoid, one had chest wall swelling, one had swelling of arm, one had back lipoma and one had forehead lipoma. The mean operation time was 50 min (range 32-70). All patients were followed up regularly postoperatively. All patients were operated as daycare, less postoperative pain, no evident scars, lower complications related to scars. Subcutaneous endoscopic surgery addresses concerns related to scarring by replacing large visible incisions with smaller incisions placed in inconspicuous locations. This is a safe and effective procedure of early recovery.


Safecast: successful citizen-science for radiation measurement and communication after Fukushima.
The Fukushima Daichi Nuclear Power Plant disaster, which began on 11 March 2011, provided a crucial opportunity to evaluate the state of preparation on the part the powerplant operator (TEPCO), relevant Japanese government agencies, and international oversight bodies, to gather necessary information on radiation risks quickly and to share it with those tasked with emergency response as well as with the general public. The inadequacy of this preparation and the chaotic nature of inter-agency and inter-governmental communication has been well noted in several official reports on the disaster. In response, Safecast, an international, volunteer-based organization devoted to monitoring and openly sharing information on environmental radiation and other pollutants, was initiated on 12 March 2011, one day following the start of the accident. Since then the group has implemented participatory, open-source, citizen-science-centered radiation mapping solutions developed through a process of collaborative open innovation. The information Safecast provided has proven useful to experts, to policy makers, and to the public. This paper briefly describes the methodology and toolsets Safecast has developed and deployed, as well as organizational and social aspects, and summarizes key results obtained to date. In addition, it discusses appropriate criteria for evaluating the success of citizen-science efforts like Safecast, and places it in context with other non-governmental radiation monitoring efforts.


Concurrent Adult-Onset Diffuse β-Cell Nesidioblastosis and Pancreatic Neuroendocrine Tumor: A Case Report and Review of the Literature.
Nesidioblastosis is an uncommon cause of organic persistent hyperinsulinemic hypoglycemia in adults. We report a case of adult-onset diffuse β-cell nesidioblastosis in a 49-year-old woman who was status-post Roux-en-Y gastric bypass and distal pancreatectomy for a well-differentiated pancreatic neuroendocrine tumor. While the neuroendocrine tumor was suspected to be an insulinoma, persistent hypoglycemia postoperatively suggested either incomplete resection or a second pancreatic neoplasm. Completion pancreatectomy revealed islet β-cell hyperplasia and nuclear pleomorphism consistent with β-cell nesidioblastosis. The patient's blood glucose levels normalized after completion pancreatectomy. While β-cell nesidioblastosis and insulinomas can coexist in the same patient, pathologists should be aware of β-cell nesidioblastosis as a potential cause for hyperinsulinemic hypoglycemia and should exclude it in patients who have not shown definitive clinical response after surgical excision of a pancreatic neuroendocrine tumor.


tRNA's and priming of RNA-directed DNA synthesis in mouse mammary tumor virus.
The low-molecular-weight RNAs of mouse mammary tumor virus (MuMTV) were examined by two-dimensional acrylamide gel electrophoresis. Unlike other retroviruses, MuMTV was found to contain only two major fractions of tRNA. These have been fully characterized and shown to correspond to the published sequences for tRNA1+2Lys and tRNA3Lys. By determining which of these tRNA's was most tightly associated with the MuMTV genome and which of them acquired label from [alpha-32P]deoxynucleoside triphosphates in limited DNA synthesis reactions, we identified tRNA3Lys as the primer for MuMTV reverse transcription in vitro. tRNA3Lys does not share any unusual sequence feature with the other previously characterized retrovirus primers, tRNATrp and tRNAPro.


[Solid-phase extraction coupled with high-field proton nuclear magnetic resonance spectroscopy: application to the analysis of brodimoprim metabolites in rat urine].
The use of coupled solid-phase extraction and high-field proton nuclear magnetic resonance spectroscopy (SPE-1HNMR) for the detection and identification of the urinary metabolites of brodimoprim is described. Urine was obtained from Wistar rats following a dose of 200 mg.kg-1 of brodimoprim. Analysis was performed on partially purified extracts obtained by solid-phase extraction onto C-18 bonded silica gel. As each spectrum was often given by a mixture of more than two kinds of metabolites, stepwise identification of the individual metabolites was achieved by sorting out signal sets having invariant proportionality. Five kinds of metabolites of the drug were found by the analysis.


Screening and isolation for anti-hepatofibrotic components from medicinal mushrooms using TGF-(β1-induced live fibrosis in hepatic stellate cells.
Liver fibrosis is a wound-healing response to chronic liver injury that could lead to liver failure, but treatment remains ineffective. In this study, we investigated anti-hepatic fibrosis activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia from six commercially available medicinal mushrooms in submerged culture, namely Antrodia camphorata, Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. Their anti-fibrotic activities were evaluated via inhibition against accumulation of TGF-β1-induced collagen deposition in CFSC-8B cells. Hex, Chl, and MeOH extracts of A. camphorata and Hex extract of A. mellea significantly decreased collagen production. Bioactivity-guided fractionation led to the identification of seven compounds using UPLC-Q-TOF-MS from the Hex Fr.2 of A. camphorata. At the molecular level, Hex Fr.2 of A. camphorata suppressed α-SMA, Collagen I, Collagen III, and Fibronectin expression induced by TGF-β1 in CFSC-8B cells as indicated by qRT-PCR analysis. They also inhibited α-SMA and Collagen I protein expression according to western blot analyses. Mechanistically, Hex Fr.2 of A. camphorata negatively regulates TGF-β1/Smad2/3 signaling. Our studies demonstrate that A. camphorata has in vitro anti-hepatofibrotic activity and that there is great potential for the discovery of new drugs for the treatment of liver fibrosis by screening more medicinal mushrooms.


Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years.
Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers. In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status. Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria. Assessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.


Sterol Regulation of Development and 20-Hydroxyecdysone Biosynthetic and Signaling Genes in Drosophila melanogaster.
Ecdysteroids are crucial in regulating the growth and development of insects. In the fruit fly Drosophila melanogaster, both C27 and C28 ecdysteroids have been identified. While the biosynthetic pathway of the C27 ecdysteroid 20-hydroxyecdysone (20E) from cholesterol is relatively well understood, the biosynthetic pathway of C28 ecdysteroids from C28 or C29 dietary sterols remains unknown. In this study, we found that different dietary sterols (including the C27 sterols cholesterol and 7-dehydrocholesterol, the C28 sterols brassicasterol, campesterol, and ergosterol, and the C29 sterols β-sitosterol, α-spinasterol, and stigmasterol) differentially affected the expression of 20E biosynthetic genes to varying degrees, but similarly activated 20E primary response gene expression in D. melanogaster Kc cells. We also found that a single dietary sterol was sufficient to support D. melanogaster growth and development. Furthermore, the expression levels of some 20E biosynthetic genes were significantly altered, whereas the expression of 20E signaling primary response genes remained unaffected when flies were reared on lipid-depleted diets supplemented with single sterol types. Overall, our study provided preliminary clues to suggest that the same enzymatic system responsible for the classical C27 ecdysteroid 20E biosynthetic pathway also participated in the conversion of C28 and C29 dietary sterols into C28 ecdysteroids.


Stressful experiences in relation to depth of sedation in mechanically ventilated patients.
In mechanically ventilated patients, sedatives and analgesics are commonly used to ensure comfort, but there is no documented knowledge about the impact of depth of sedation on patients' perception of discomfort. The aim of this study was, therefore, to investigate the relationship between stressful experiences and intensive care sedation, including the depth of sedation. During 18 months, 313 intubated mechanically ventilated adults admitted to two general intensive care units (ICU) for more than 24 h were included. Patients (n = 250) were interviewed on the general ward 5 days after ICU discharge using the ICU Stressful Experiences Questionnaire. Patient data including sedation scores as measured by the Motor Activity Assessment Scale (MAAS) were collected from hospital records after the interview. Of the 206 patients with memories of the intensive care, 82% remembered at least one experience as quite a bit or extremely bothersome. Multivariate analyses showed that higher proportion of MAAS score 3 (indicating more periods of wakefulness), longer ICU stay and being admitted emergent were factors associated with remembering stressful experiences of the ICU as more bothersome. The findings indicate that the depth of sedation has an impact on patients' perception of stressful experiences and that light sedation compared with heavy seems to increase the risk of perceiving experiences in the ICU as more bothersome. In reducing discomfort, depth of sedation and patient comfort should be assessed regularly, non-pharmacological interventions taken into account and the use of sedatives and analgesics adapted to the individual requirements of the patient.


Self-healing of CdSe nanocrystals: first-principles calculations.
Ab initio calculations of the structural, electronic, and optical properties of CdSe nanoparticles are presented. The atomic structures of the clusters are relaxed both in vacuum and in the presence of surfactant ligands. In both cases, we predict significant geometrical rearrangements of the nanoparticle surface while the wurtzite core is maintained. These reconstructions lead to the opening of an optical gap without the aid of passivating ligands, thus "self-healing" the surface electronic structure. Our calculations also predict the existence of a midgap state responsible for recently observed subband emission.


Genetic constraints on adaptation: a theoretical primer for the genomics era.
Genetic constraints are features of inheritance systems that slow or prohibit adaptation. Several population genetic mechanisms of constraint have received sustained attention within the field since they were first articulated in the early 20th century. This attention is now reflected in a rich, and still growing, theoretical literature on the genetic limits to adaptive change. In turn, empirical research on constraints has seen a rapid expansion over the last two decades in response to changing interests of evolutionary biologists, along with new technologies, expanding data sets, and creative analytical approaches that blend mathematical modeling with genomics. Indeed, one of the most notable and exciting features of recent progress in genetic constraints is the close connection between theoretical and empirical research. In this review, we discuss five major population genetic contexts of genetic constraint: genetic dominance, pleiotropy, fitness trade-offs between types of individuals of a population, sign epistasis, and genetic linkage between loci. For each, we outline historical antecedents of the theory, specific contexts where constraints manifest, and their quantitative consequences for adaptation. From each of these theoretical foundations, we discuss recent empirical approaches for identifying and characterizing genetic constraints, each grounded and motivated by this theory, and outline promising areas for future work.


A comparative clinical study of three different dosages of intramuscular midazolam-medetomidine-ketamine immobilization in cats.
A low dose of midazolam-medetomidine-ketamine (MMK) combination was evaluated in three increasing dosages. Each of the 18 cats was randomly allocated for several times to one of four groups. Five minutes after premedication with intramuscular (IM) 0.04 mg/kg atropine, group A (n = 43), B (n = 40) and C (n = 28) all were anaesthetized with 0.5 mg/kg midazolam, combined with 10, 20 or 30 microg/kg medetomidine, and 1.0, 2.0 or 3.0 mg/kg ketamine, respectively, IM in one syringe. Group D (n = 11) received the established combination of 50 microg/kg medetomidine and 10.0 mg/kg ketamine for comparison. Because this study was in cooperation with a project on dental prophylaxis, cats had to be immobilized for approximately 1 h. Therefore, anaesthesia was prolonged with propofol to effect, if necessary. Duration of MMK anaesthesia was between 30 +/- 15, 45 +/- 19 and 68 +/- 28 min in groups A, B and C respectively. A significant decrease of respiratory rate was observed with increasing dosage, but venous carbon dioxide (pCO(2)) and pH values in combination with arterial oxygen saturation (SpO(2)) values were not alarming. The diastolic blood pressure particularly showed an increase. MMK combination A showed the best cardiovascular results, but it cannot be recommended due to disadvantages like a long induction time sometimes accompanied by excitations and the short duration of surgical immobilization. Dosage C in contrast had fewer side effects but less favourable cardiovascular results and a longer recovery period. However, either dosage B or C was suitable as a repeatable IM immobilization method for non-invasive procedures in healthy cats.


Tunable near-infrared optical properties of three-layered metal nanoshells.
The extinction spectra of a three-layered metal nanoshell, which consists of a particle with a dielectric core, a middle Ag (Au) layer, and an outer Au (Ag) shell, have been investigated by means of the Mie theory. With a decrease in the outer shell thickness or the middle layer thickness, the wavelengths of the localized surface plasmon resonance (LSPR) for SiO(2)-Ag-Au (SiO(2)-Au-Ag) nanoshells show distinct redshifts and the full widths at half maximum (FWHMs) for the dipole peaks in the extinction spectra decrease first and then increase. We have further investigated the influence of the embedding medium on the LSPRs for SiO(2)-Ag-Au and SiO(2)-Au-Ag nanoshells and found that the resonance wavelengths of the particles show redshift and the FWHM of the dipole peak increases with increasing the dielectric constant of the embedding medium. The calculated results indicate that the LSPR of the three-layered gold-silver nanoshells can be controlled to the near-infrared region by changing the geometry, which has practical biomedical application.


Rating the raters: evaluating the predictions from a life expectancy rating service.
There is a growing market for the resale of life insurance policies to third party investors. A key factor in the valuation of a policy is how long the insured is likely to live. Various commercial rating services offer to provide estimates of individuals' likely longevity, but the reliability of their estimates has rarely been correctly evaluated. The question is how to compare the estimates provided for a large group of policy-holders with the observed "truth data"--the actual mortality experience observed during follow-up. Various approaches to this have been used in practice, some of them quite wrong. The correct method does not seem to be practiced or widely known in the life settlement industry. It is based on a comparison of observed and expected deaths computed on the basis of person-years of exposure rather than of individual persons. The method is explained in detail here and illustrated with the results from a large portfolio of policies.


Residual Kidney Function: Implications in the Era of Personalized Medicine.
The association of residual kidney function (RKF) with improved outcomes in peritoneal dialysis and hemodialysis patients is now widely recognized. RKF provides substantial volume and solute clearance even after dialysis initiation. In particular, RKF provides clearance of nonurea solutes, many of which are potential uremic toxins and not effectively removed by conventional hemodialysis. The presence of RKF provides a distinct advantage to incident dialysis patients and is an opportunity for nephrologists to individualize dialysis treatments tailored to their patients' unique solute, volume, and quality of life needs. The benefits of RKF present the opportunity to personalize the management of uremia.


Evidence-based medicine: Unilateral cleft lip and nose repair.
After reading this article, the participant should be able to: 1. Describe the anatomical malformations found in unilateral cleft lip deformity. 2. Discuss current methods of measuring the deformity and subsequent outcomes. 3. Discuss preoperative assessments, workup, and the use of early interventions before definitive cheiloplasty (e.g., preoperative orthopedics, lip adhesion). 4. Discuss the different techniques used for cheiloplasty and nasal repair. 5. Discuss the use of postoperative splints, taping, or molding. 6. Discuss the outcomes and evidence of cleft lip repairs and identify areas for future research. The Maintenance of Certification module series is designed to help clinicians structure their individualized course of study to specific areas appropriate to their clinical practice. This article was prepared to accompany practice-based assessment of preoperative evaluation, anesthesia, surgical treatment plan, perioperative management, and outcomes. In this format, the clinician is invited to compare his or her methods of patient assessment and treatment, outcomes, and complications, with authoritative, information-based references. This information base is then used for self-assessment and benchmarking in parts II and IV of the Maintenance of Certification process of the American Board of Plastic Surgery. This article is not intended to be an exhaustive treatise on the subject. Rather, it is designed to serve as a reference point for further in-depth study by review of the reference articles presented.


Loss of high-temperature requirement protein A2 protease activity induces mitonuclear imbalance via differential regulation of mitochondrial biogenesis in sarcopenia.
Cellular homeostasis requires tight coordination between nucleus and mitochondria, organelles that each possesses their own genomes. Disrupted mitonuclear communication has been found to be implicated in many aging processes. However, little is known about mitonuclear signaling regulator in sarcopenia which is a major contributor to the risk of poor health-related quality of life, disability, and premature death in older people. High-temperature requirement protein A2 (HtrA2/Omi) is a mitochondrial protease and plays an important role in mitochondrial proteostasis. HtrA2mnd2(-/-) mice harboring protease-deficient HtrA2/Omi Ser276Cys missense mutants exhibit premature aging phenotype. Additionally, HtrA2/Omi has been established as a signaling regulator in nervous system and tumors. We therefore asked whether HtrA2/Omi participates in mitonuclear signaling regulation in muscle degeneration. Using motor functional, histological, and molecular biological methods, we characterized the phenotype of HtrA2mnd2(-/-) muscle. Furthermore, we isolated the gastrocnemius muscle of HtrA2mnd2(-/-) mice and determined expression of genes in mitochondrial unfolded protein response (UPRmt ), mitohormesis, electron transport chain (ETC), and mitochondrial biogenesis. Here, we showed that HtrA2/Omi protease deficiency induced denervation-independent skeletal muscle degeneration with sarcopenia phenotypes. Despite mitochondrial hypofunction, upregulation of UPRmt and mitohormesis-related genes and elevated total reactive oxygen species (ROS) production were not observed in HtrA2mnd2(-/-) mice, contrary to previous assumptions that loss of protease activity of HtrA2/Omi would lead to mitochondrial dysfunction as a result of proteostasis disturbance and ROS burst. Instead, we showed that HtrA2/Omi protease deficiency results in different changes between the expression of nuclear DNA- and mitochondrial DNA-encoded ETC subunits, which is in consistent with their transcription factors, nuclear respiratory factors 1 and 2, and coactivator peroxisome proliferator-activated receptor γ coactivator 1α. These results reveal that loss of HtrA2/Omi protease activity induces mitonuclear imbalance via differential regulation of mitochondrial biogenesis in sarcopenia. The novel mechanistic insights may be of importance in developing new therapeutic strategies for sarcopenia.


The role of p95HER2 in trastuzumab resistance in breast cancer.
Trastuzumab, the HER2 oncogene targeting drug, shows remarkable clinical efficacy in HER2-amplified breast cancer patients. Despite of robust activity, some of the patients with HER2-positive breast cancers do not get the benefit due to trastuzumab resistance. Overexpression of p95HER2 is one of the molecular mechanisms of trastuzumab resistance. The purpose of this study was to investigate whether p95HER2 overexpressing breast cancers were resistant to trastuzumab. p95HER2 (truncated HER2) and HER2 were determined by real-time polymerase chain reaction (RT-PCR) analysis. HER2 protein expression and HER2 gene amplification were also determined by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). Archival material from 80 formalin-fixed paraffin-embedded (FFPE) breast cancer tumor tissues was used for the study. None of the cases had metastases at the initial diagnosis. HER2-positive cases were treated with trastuzumab with/without chemotherapy. Of 80 breast cancer cases 39 (48.7%) were HER2-positive and had trastuzumab treatment. Of these 39 cases 11 (28.2%) were trastuzumab-resistant and 28 (71.8%) were not, 17 (43.6%) were recurrent cases and 22 (56.4%) were not. Three patients died during follow-up. p95HER2 mean ratio was 11.01±19.73 in 11 cases which were trastuzumab-resistant, while p95HER2 mean ratio was 1.99±1.37 in 28 cases without trastuzumab resistance. If p95HER2 ratio was low, there was no trastuzumab resistance. However, when p95HER2 ratio was high, there was trastuzumab resistance (p=0.210, Mann-Whitney U test). p95HER2 was correlated with trastuzumab resistance, but it was not an independent factor of trastuzumab resistance. We claim that p95HER2 is sensitive but not specific for the prediction of trastuzumab resistance.


CHILDREN'S LANGUAGE: WORD-PHRASE RELATIONSHIP.
Unsystematic observations indicated that small children who could reverse the order of certain two-unit utterances had difficulty reversing utterances that formed common English sequences. Findings of this study indicate that the following factors are sources of difficulty in reversing pairs: (i) inability to separate English sequences into word units, and (ii) semantic absurdity of reversed pairs.


Walk-in health centres are a politician's folly.
This article is a personal opinion by a GP on one of the latest additions to primary care, the nurse-led walk-in centre. The author argues that they are unnecessary for a host of reasons, not least because they duplicate the work already done by GP practices, but without the personal knowledge of patients, and divert funding from other areas of primary care.


Gas-phase behavior of noncovalent transmembrane segment complexes.
Specific helix oligomerization between transmembrane segments (TMSs) is often promoted by motifs like GxxxG. Disruption of this motif in the transmembrane segments of vesicular stomatitis virus G-protein and of glycophorin A results in a reduced dimerization level studied by in vivo systems like ToxR. This paper reports the influence of sequence motifs like GxxxG in solution and the gas phase.The transmembrane segments may behave differently in the gas and liquid phase, because of the absence of surrounding solvent molecules in the gas phase. Comparison of experiments depending on peptide properties performed in the gas and liquid phase discloses that the peptides retain 'some memory' of their liquid-phase structure in the gas phase. A direct correlation has been found between helicity in solution as determined by circular dichroism and dimerization in the gas phase monitored by electrospray mass spectrometry. These results show that a proper folding in solution is required for oligomerization.On the other hand, sequence-specific oligomerization depending on the GxxxG motif was not observed with the mass spectrometric detection. Further on, neither concentration-dependent complex studies nor studies regarding complex stability in the gas phase - via collision-induced dissociation (CID) - led to sequence-specific differences.Finally, the findings show that in mass spectrometric measurements noncovalent interactions of studied TMSs is rather more dependent on the secondary structure and proper folding than on their primary structure.


Political post-mortems and morbid anatomy in seventeenth-century England.
Michel Foucault argued that the development of morbid anatomy, which he located in late eighteenth-century France, led to a great increase in the power of doctors over patients. The use of autopsy findings to confirm the cause of death and to provide information for systematic pathology had a prior history, however. When introduced into England, in the seventeenth century, the practice was already well established in Europe, notably in connection with the enbalming of the French kings. Several highly controversial autopsies, conducted on royalty and politicians, publicized the procedure and helped to make it socially acceptable. English anatomists were then able to draw on the results of autopsies conducted on their patients to correlate normal anatomy with the post-mortem signs. Most patients did not feel threatened by this procedure because it was undertaken privately and with consent, as a final act of clinical care. English physicians abandoned autopsies to the surgeons towards the end of the century in pursuit of a more genteel style of self-presentation. The connection between power and morbid anatomy seems to arise not from the practice of autopsy itself but from the impersonal authority of late eighteenth-century hospital doctors over poor patients.


Prevalence of Malaria and Associated Factors among Malaria-Suspected Patients Attending Hamusit Health Center, Northwest Ethiopia: A Cross-Sectional Study.
Malaria is one of the major public health problems in developing countries like Ethiopia. Despite efforts to reduce the mortality and morbidity, the disease is still a prominent health problem in Ethiopia. This study, therefore, was undertaken to assess the prevalence of malaria and associated factors among symptomatic patients in Northwest Ethiopia. A facility based cross-sectional study was conducted from February to March 2020 among 210 febrile patients attending Hamusit Health Center, Northwest Ethiopia. A structured questionnaire was used to collect data on sociodemographic characteristics and factors perceived to be associated with Plasmodium infection. Questionnaire data was collected through face to face interview. Thin and thick blood films were prepared from capillary blood buffy coat samples. Data were analyzed using Statistical Package for Social Sciences Software version 20. Out of 210 malaria-suspected participants, 61 (29.0%) were confirmed to be infected by Plasmodium species. Plasmodium falciparum and P. vivax monoinfections were detected in 41 (19.5%) and 10 (4.8%) participants, respectively. Mixed infection was detected in 10 (4.8%) participants. Female participants (AOR = 2.261; 95% CI: 1.118-4.571; P = 0.023) and those having family members with history of malaria (AOR =2.261; 95% CI: 1.264-5.340; P = 0.009) had higher odds of acquiring Plasmodium infection as compared to their counterparts. Using insecticide-treated bed net and draining stagnant water were the most commonly mentioned malaria prevention measures reported by 71.9% and 8.1% of the respondents, respectively. Malaria contributes significantly for febrile illnesses in the study area. Therefore, community mobilization should be strengthen in order to improve implementation of malaria control activities and, hence, reducing the prevalence.


Molecular Detection and Genotyping of Toxoplasma gondii in Edward's Long-Tailed Rats (Leopoldamys edwardsi).
Toxoplasma gondii is an important zoonotic parasite infecting humans and various animals with a worldwide distribution. However, limited information is available on T. gondii infection in wild rats. The present study aimed to examine the prevalence and characterize the genotypes of T. gondii in wild rats in two regions of China. Brain tissues were collected from 111 Edward's long-tailed rats (Leopoldamys edwardsi) and 117 Bower's white-toothed rats (Berylmys bowersi) between November 2017 and January 2018. Genomic DNA was extracted and amplified by PCR targeting the T. gondii B1 gene. B1 gene-positive samples were genotyped at 10 genetic markers (SAG1, SAG2 [5', 3'] and [alternative], SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using multilocus nested polymerase chain reaction/restriction fragment length polymorphism. Six (5.41%, 6/111) Edward's long-tailed rats from Chongqing Municipality were positive for T. gondii B1 gene, whereas no T. gondii infection was detected in Bower's white-toothed rats (n = 117) from Guangdong province. T. gondii prevalence in female and male rats was 1.77% (2/113) and 3.48 (4/115), respectively. Four of the six positive DNA samples were completely genotyped at 10 genetic loci and were identified as ToxoDB#20. The present study revealed the occurrence of T. gondii infection in Edward's long-tailed rats. These findings raised public health concerning about T. gondii infection in wild rats. These results provide reference data for understanding the distribution of T. gondii genotypes in wild rats in China.


Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1.
Latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) mediates the episomal replication of the KSHV genome, as well as transcriptional regulation, in latently infected cells. Interaction of LANA-1 with cellular chromatin is required for both these functions. An N-terminal heterochromatin-binding site in LANA-1 is essential for the replication and maintenance of latent episomes, as well as transcriptional regulation. We have recently described a C-terminal domain in LANA-1 that modulates the interaction with cellular interphase chromatin or elements of the nuclear matrix. Here, we used a series of LANA-1 deletion mutants to investigate the relationship between the different functions of LANA-1 and its interaction with the host chromatin-binding protein Brd2/RING3. Our findings suggest that the C-terminal chromatin-binding domain in LANA-1 is required for multiple LANA-1 functions, including the ability to bind to and replicate viral episomal DNA, to modulate transcription, and to interact with Brd2/RING3. Similar to the recently described tethering of bovine papillomavirus E2 protein to host chromatin via Brd4/MCAP, Brd2/RING3, another member of the Brd family of chromatin-binding proteins, therefore interacts with a chromatin-binding region of another viral latent nuclear protein and could play a role in its multiple functions.


Localization of expression of KNAT3, a class 2 knotted1-like gene.
KNAT3 is a class 2 kn1-like gene in Arabidopsis thaliana. The RNA expression patterns of KNAT3 were characterized through the use of promoter-GUS fusion analysis and in situ hybridization. KNAT3 is expressed in several tissues and at several times during development. There are three main expression patterns: (1) during early organ development in young leaves, buds and pedicels; (2) at and near the junction between two organs at specific times during development, including the hypocotyl-root boundary in young seedlings, the anther-filament junction in mature flowers, and the ovule-funiculus and peduncle-silique boundaries in elongating siliques; and (3) in maturing tissues such as the style of elongating siliques, the petioles of maturing leaves, and most of the root. The varied expression patterns may indicate that KNAT3 plays several different roles in plants, depending on when and where it is expressed. Previous work on KNAT3 (Serikawa et al., 1996) indicated that expression of its RNA is regulated by light. Promoter-GUS seedlings were grown under different light conditions (continuous white, red and far-red light) to examine more closely the light regulation of the KNAT3 promoter. Continuous white light resulted in stronger overall GUS staining in the same patterns seen in seedlings grown under long-day conditions (cotyledons, upper hypocotyl and roots). Continuous red light resulted in reduced GUS expression in those same tissues. Continuous far-red light led to seedlings showing stronger staining in the hypocotyl and cotyledons than red light-grown plants but no staining in the roots. Thus, the KNAT3 promoter responds differently to red and far-red light.


Three in One: In Vitro and In Vivo Evaluation of Anticancer Activity of a Theranostic Agent that Combines Magnetic Resonance Imaging, Optical Bioimaging, and Photodynamic Therapy Capabilities.
Cancer treatment is a crucial area of research and development, as current chemotherapeutic treatments can have severe side effects or poor outcomes. In the constant search for new strategies that are localized and minimally invasive and produce minimal side effects, photodynamic therapy (PDT) is an exciting therapeutic modality that has been gaining attention. The use of theranostics, which combine diagnostic and therapeutic capabilities, can further improve treatment monitoring through image guidance. This study explores the potential of a theranostic agent consisting of four Gd(III) DTTA complexes (DTTA: diethylenetriamine-N,N,N″,N″-tetraacetate) grafted to a meso-tetraphenylporphyrin core for PDT, fluorescence, and magnetic resonance imaging (MRI). The agent was first tested in vitro on both nonmalignant TIB-75 and MRC-5 and tumoral CT26 and HT-29 cell lines and subsequently evaluated in vivo in a preclinical colorectal tumor model. Advanced MRI and optical imaging techniques were employed with engineered quantitative in vivo molecular imaging based on dynamic acquisition sequences to track the biodistribution of agents in the body. With 3D quantitative volume computed by MRI and tumoral cell function assessed by bioluminescence imaging, we could demonstrate a significant impact of the molecular agent on tumor growth following light application. Further exhaustive histological analysis confirmed these promising results, making this theranostic agent a potential drug candidate for cancer.


Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes.
Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug. In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00 μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48 h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H2O2 for isolated lymphocytes) were also maintained. While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48 h, 25 μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25 μg/mL, 48 h). It significantly decreased the MI in all the concentrations at 24 h (except 0.78 μg/mL) and in the highest three concentrations at 48 h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index. Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes.


Should internal mammary chain (IMC) sentinel node biopsy be performed? Outcome in 90 consecutive non-biopsied patients with a positive IMC scintigraphy.
Although the status of the regional lymph nodes is an important determinant of prognosis in breast cancer, harvesting sentinel nodes (SN) detected in the internal mammary chain (IMC) is still controversial. To determine in how many patients a positive IMC-SN might change the systemic or locoregional adjuvant therapy, with a possible benefit in outcome. During 6 1/2 years data of T1-2 breast cancer patients, having an SN procedure, were prospectively collected. Our policy was not to explore the IMC even if it was the only localization of an SN. In 86 of 571 patients lymphoscintigraphy showed an IMC-SN. In 64 of these, the axillary SN was negative and only 25 of these patients did not have an indication for adjuvant systemic treatment based on their tumor characteristics. In the literature, IMC metastases are found in 0-10% of axillary negative patients. Routine IMC-SN biopsies would have resulted in an indication for adjuvant systemic therapy in 2-3 of our patients. Four parasternal recurrences were found during a median follow-up of 51 months. Harvesting IMC-SNs is a procedure of which only a limited number of patients have therapeutical benefit. Even with a thorough selection of patients, the extra morbidity of the procedure should be weighed against the potential benefit for the patient.


Plasma dynamics and vacuum pair creation using the Dirac-Heisenberg-Wigner formalism.
We derive a system of coupled partial differential equations for the equal-time Wigner function in an arbitrary strong electromagnetic field using the Dirac-Heisenberg-Wigner formalism. In the electrostatic limit, we present a system of four coupled partial differential equations, which are completed by Ampères law. This electrostatic system is further studied for two different cases. In the first case, we consider linearized wave propagation in a plasma accounting for the nonzero vacuum expectation values. We then derive the dispersion relation and compare it with well-known limiting cases. In the second case, we consider Schwinger pair production using the local density approximation to allow for analytical treatment. The dependence of the pair production rate on the perpendicular momentum is investigated and it turns out that the spread of the produced pairs along with perpendicular momentum depends on the strength of the applied electric field.


Apparent power-law distributions in animal movements can arise from intraspecific interactions.
Lévy flights have gained prominence for analysis of animal movement. In a Lévy flight, step-lengths are drawn from a heavy-tailed distribution such as a power law (PL), and a large number of empirical demonstrations have been published. Others, however, have suggested that animal movement is ill fit by PL distributions or contend a state-switching process better explains apparent Lévy flight movement patterns. We used a mix of direct behavioural observations and GPS tracking to understand step-length patterns in females of two related butterflies. We initially found movement in one species (Euphydryas editha taylori) was best fit by a bounded PL, evidence of a Lévy flight, while the other (Euphydryas phaeton) was best fit by an exponential distribution. Subsequent analyses introduced additional candidate models and used behavioural observations to sort steps based on intraspecific interactions (interactions were rare in E. phaeton but common in E. e. taylori). These analyses showed a mixed-exponential is favoured over the bounded PL for E. e. taylori and that when step-lengths were sorted into states based on the influence of harassing conspecific males, both states were best fit by simple exponential distributions. The direct behavioural observations allowed us to infer the underlying behavioural mechanism is a state-switching process driven by intraspecific interactions rather than a Lévy flight.


Isolation of chemically well-defined semipreparative liquid chromatography fractions from complex mixtures of proanthocyanidin oligomers and polymers.
In this study, a semipreparative liquid chromatography method was developed for the isolation of chemically well-defined proanthocyanidin (PA) oligomer and polymer fractions. The aim was to achieve better separation than traditionally achieved for the PAs with other chromatographic methods. The method was tested with eleven PA rich Sephadex LH-20 fractions, which originated from eleven different plant species. The resulting semipreparative fractions were analyzed by both triple quadrupole and high-resolution mass spectrometry assisted by ultrahigh-performance liquid chromatography (UPLC) separation. The results showed remarkable differences in the procyanidin to prodelphinidin ratio, mean degree of polymerization, and specific oligomeric and polymeric content. However, some of these features indicated consistent patterns between species as the function of UPLC retention time. The developed method enables the production of tens of well-defined fractions of PA oligomers and polymers from the unresolved chromatographic PA hump. Accordingly, this allows researchers to explore the most bioactive parts of the complex PA humps of any plant species, which have not been possible earlier.


Lifestyles and the risk of depression in the "Seguimiento Universidad de Navarra" cohort.
Lifestyles are involved in the pathogenesis of depression and many of these factors can be modified for the potential prevention of depression. Our aim was to assess the association between a healthy-lifestyle score, that includes some less-studied lifestyle indicators, and the risk of depression. We followed 14,908 participants initially free of any history of depression in the "Seguimiento Universidad de Navarra" (SUN) cohort. Information was collected biennially from 1999 to December 2016. We calculated a healthy-lifestyle score (0-10 points), previously associated with cardioprotection, by giving one point to each of the following components: never smoking, physical activity (> 20 METs-h/week), Mediterranean diet adherence (≥ 4 points), healthy body mass index (≤ 22 kg/m2), moderate alcohol consumption (women 0.1-5 g/d; men 0.1-10 g/d of ethanol), avoidance of binge drinking (never more than 5 alcoholic drinks in a row), low television exposure (≤ 2 h/d), short afternoon nap (≤ 30 min/day), time spent with friends (>1 h/d) and working at least 40 h/week. During a median follow-up of 10.4 years, we observed 774 new cases of major depression among participants initially free of depression. The highest category (8-10 factors) showed a significant inverse association with a 32% relative risk reduction for depression compared to the lowest category (0-3 factors) (multivariable-adjusted hazard ratio: 0.68; 95% CI:0.49-0.95) (p for trend = 0.010). Adopting a healthy-lifestyle was associated with a lower risk of incident depression in the SUN cohort. This index, including ten simple healthy lifestyle habits, may be useful for a more integrative approach to depression prevention.


Carcinoma in situ of the gallbladder. A clinicopathologic study of 18 cases.
Eighteen cases of carcinoma in situ of the gallbladder collected over a 7-year period at the General Hospital of Mexico City are reported. All patients were females whose ages ranged from 26 to 83 years with a mean of 55. Their symptoms and signs were related to the presence of stones. Grossly, the in situ carcinomas could not be differentiated from chronic cholecystitis. In only one case was the diagnosis suspected on macroscopic examination. Thirteen lesions were located either in the fundus or body of the gallbladder. Histologically there were two types of in situ carcinoma--papillary (two cases) and nonpapillary (16 cases). Hyperplasia of the antral-type glands was associated with 12 cases and cholecystitis follicularis with four. The atypical changes began on the surface epithelium and extended into the epithelial invaginations and later into the antral-type glands. Four carcinomas in situ exhibited limited invasion into the underlying lamina propria or inner part of the muscle layer. In the 15 cases that were examined, immunoperoxidase stains revealed cytoplasmic staining for carcinoembryonic antigen (CEA). All patients we were able to follow (those who had only carcinoma in situ) are symptom-free after cholecystectomy. One of the four patients with microinvasion died 7 years after cholecystectomy with clinical evidence of liver metastasis.


Clearinghouse: a teleradiology platform emphasizing security of data and communication.
The Clearinghouse application platform is a web based solution for secure digital exchange of radiological images and other clinical documents among authorized researchers and physicians. It implements a sophisticated security and role model to protect privacy and to minimize the risk of eavesdropping of patient data. The Clearinghouse serves as a centralized platform for distributed, distantly located medical research and health care. It is based on Open-Source software, thus ensuring continued support, maintenance, security and last but not least continuity of the platform. The use of the Clearinghouse minimizes turnaround times by superseding comparably slow and insecure conventional communication methods otherwise used for the exchange of radiological images and clinical documents, such as standard mail and courier services. Furthermore, it alleviates the integration of distantly located expert knowledge into diagnostic routines, culminating in an increased health care quality regardless of location of patients or physicians.


Airway inflammation in chronic obstructive pulmonary disease (COPD): a true paradox.
Chronic obstructive pulmonary disease (COPD) is primarily an airway condition, which mainly affects cigarette smokers and presents with shortness of breath that is progressive and poorly reversible. In COPD research, there has been a long held belief that airway disease progression is due to inflammation. Although this may be true in the airway lumen with innate immunity activated by the effect of smoke or secondary to infection, the accurate picture of inflammatory cells in the airway wall, where the pathophysiological COPD remodeling occurs, is uncertain and debatable. Areas covered: The current review provides a comprehensive literature survey of the changes in the main inflammatory cells in human COPD patients and focuses on contrarian views that affect the prevailing dogma on inflammation. The review also delves into the role of oxidative stress and inflammasomes in modulating the immune response in COPD. Further, the effects of inflammation in affecting the epithelium, fibroblasts, and airway remodeling are discussed. Expert commentary: Inflammation as a driving force for airway wall damage and remodelling in early COPD is at the very least 'oversimplified' and is likely to be misleading. This has serious implications for rational thinking about the illness, including pathogenesis and designing therapy.


Arabidopsis thaliana GYRB3 does not encode a DNA gyrase subunit.
DNA topoisomerases are enzymes that control the topology of DNA in all cells. DNA gyrase is unique among the topoisomerases in that it is the only enzyme that can actively supercoil DNA using the free energy of ATP hydrolysis. Until recently gyrase was thought to be unique to bacteria, but has now been discovered in plants. The genome of the model plant, Arabidopsis thaliana, is predicted to encode four gyrase subunits: AtGyrA, AtGyrB1, AtGyrB2 and AtGyrB3. We found, contrary to previous data, that AtGyrB3 is not essential to the survival of A. thaliana. Bioinformatic analysis suggests AtGyrB3 is considerably shorter than other gyrase B subunits, lacking part of the ATPase domain and other key motifs found in all type II topoisomerases; but it does contain a putative DNA-binding domain. Partially purified AtGyrB3 cannot bind E. coli GyrA or support supercoiling. AtGyrB3 cannot complement an E. coli gyrB temperature-sensitive strain, whereas AtGyrB2 can. Yeast two-hybrid analysis suggests that AtGyrB3 cannot bind to AtGyrA or form a dimer. These data strongly suggest that AtGyrB3 is not a gyrase subunit but has another unknown function. One possibility is that it is a nuclear protein with a role in meiosis in pollen.


Efficacy of the Fun For Wellness Online Intervention to Promote Multidimensional Well-Being: a Randomized Controlled Trial.
Subjective well-being refers to people's level of satisfaction with life as a whole and with multiple dimensions within it. Interventions that promote subjective well-being are important because there is evidence that physical health, mental health, substance use, and health care costs may be related to subjective well-being. Fun For Wellness (FFW) is a new online universal intervention designed to promote growth in multiple dimensions of subjective well-being. The purpose of this study was to provide an initial evaluation of the efficacy of FFW to increase subjective well-being in multiple dimensions in a universal sample. The study design was a prospective, double-blind, parallel group randomized controlled trial. Data were collected at baseline and 30 and 60 days-post baseline. A total of 479 adult employees at a major university in the southeast of the USA were enrolled. Recruitment, eligibility verification, and data collection were conducted online. Measures of interpersonal, community, occupational, physical, psychological, economic (i.e., I COPPE), and overall subjective well-being were constructed based on responses to the I COPPE Scale. A two-class linear regression model with complier average causal effect estimation was imposed for each dimension of subjective well-being. Participants who complied with the FFW intervention had significantly higher subjective well-being, as compared to potential compliers in the Usual Care group, in the following dimensions: interpersonal at 60 days, community at 30 and 60 days, psychological at 60 days, and economic at 30 and 60 days. Results from this study provide some initial evidence for both the efficacy of, and possible revisions to, the FFW intervention.


Extrahepatic biliary obstruction versus intrahepatic disorder. Differentiation with hepatobiliary scintigraphy and ultrasonography.
In 43 patients with various hepatobiliary disorders, we compared retrospectively the sensitivity and specificity of hepatobiliary scintigraphy and ultrasonography in diagnosing extrahepatic biliary obstruction. Hepatic uptake of radioactivity from the circulation was assessed by early scintiscan at 2 min, and the clearance ratio was combined with transit time in the interpretation of hepatobiliary scintiscans. The transit time was defined as the time taken by detectable radioactivity to appear in the extrahepatic biliary tree or small intestine, whichever occurred sooner. The sensitivity and specificity were 92% and 97%, respectively. However, the specificity dropped to 74% when biliary-bowel transit time, i.e., time taken for detectable radioactivity to appear in small intestine only, was used instead of transit time in the interpretation of the scintiscans. The sensitivity and specificity of ultrasonography were 55% and 94%, respectively. We conclude that hepatobiliary scintiscan is more sensitive than ultrasonography and is reliable for diagnosing extrahepatic biliary obstruction when it is done and interpreted by the method described here.


High-concentration ethylene-vinyl alcohol copolymer and endovascular treatment of experimental aneurysms: feasibility of embolization without protection devices at the neck.
Coiling of intracranial aneurysms is both safe and effective but may be followed by recurrences. The purpose of this study was to assess the feasibility of endovascular treatment of aneurysms with high-concentration ethylene-vinyl alcohol copolymer (HCEVOH), without the use of protection devices at the neck. Wide-necked bifurcation aneurysms with a high propensity for recurrences were constructed in 22 dogs. HCEVOH embolization was performed with a dedicated high-pressure microcatheter in 12 animals. Angiographic results at 3 and 12 weeks and pathologic results at 12 weeks were compared with those of a separate group of 10 animals treated with platinum coils. We used a qualitative scoring system to grade angiographic results, neointima formation, and recanalization at the neck. Intraaneurysmal HCEVOH injections could be performed without carotid emboli and without a protection device in 11 of 12 animals. Fragments detached upon traction of the microcatheters at the end of the procedure on two occasions. Immediate and late angiographic results were not significantly different between the two groups (P =.807), with a tendency for angiographic recurrences at 3 months (angiographic scores were significantly worse in both groups at 12 weeks as compared with T0 [P <.02]). A complete occlusion, including the neck, even at the cost of protrusion of material at the level of the branches, is necessary to decrease risks of recurrences. Neointima formation at the surface of the embolic agent was complete at the neck of aneurysms treated with HCEVOH. The neointimal score was significantly improved with HCEVOH as compared with coil embolization (P =.03). HCEVOH embolization of aneurysms without neck protection is feasible. It does not, however, eliminate recurrences in an experimental wide-necked aneurysm model.


Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.
To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.


Generation, Characteristics and Clinical Trials of Ex Vivo Generated Tolerogenic Dendritic Cells.
Dendritic cells (DCs) play a key role not only in the initiation of primary immune responses, but also in the development and maintenance of immune tolerance. Numerous protocols have been developed to generate tolerogenic DCs (tolDCs) ex vivo, and the therapeutic efficacy of ex vivo-generated tolDCs has been demonstrated in autoimmune disease animal models. Based on successes in small animal models, several clinical trials have been completed or are on-going in patients with autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and Crohn's disease. Here we describe the methods used to generate tolDCs ex vivo, and the common features shared by tolDCs. In addition, we overview five completed clinical trials with reported outcomes and summarize the tolDC-based clinical trials that are currently registered with the U.S. National Institutes of Health. Although the number of tolDC-based clinical trials is much smaller than the hundreds of clinical trials using immunogenic DCs, tolDC-based treatment of autoimmune diseases is becoming a reality, and could serve as an innovative cellular therapy in the future.


Meeting report: NCI think tanks in cancer biology.
Over the past year and a half, the Division of Cancer Biology of NCI has been assessing the state of cancer biology, with the goal of developing a research agenda for the near future that would accelerate progress in cancer research. Our goal was to identify emerging concepts and promising opportunities for investigation across nine scientific areas with unusual promise for rapid progress. A series of meetings called Think Tanks was convened, each involving a panel of 15-25 experts. In all, over 160 leaders in cancer research and related fields discussed the current state of science in their disciplines, projected its trajectory and recommended what NCI could or should do to facilitate progress. In addition to emphasizing the importance of continued support for investigator-initiated research, the Think Tanks permitted identification of a number of overarching themes. Critical among them was the need to support the development of integrative cancer biology and to encourage studies of the tumor microenvironment by establishing an infrastructure for interactive research. There was also consensus about the importance of comparative studies of normal and tumor states, and development of mechanisms for supporting collaborative, interdisciplinary research and training.


Single-use accessories and endoscopes in the era of sustainability and climate change-A balancing act.
Gastrointestinal (GI) endoscopy is among the highest waste generator in healthcare facilities. The major reasons include production of large-volume non-renewable waste, use of single-use devices, and reprocessing or decontamination processes. Single-use endoscopic accessories have gradually replaced reusable devices over last two decades contributing to the rising impact of GI endoscopy on ecosystem. Several reports of infection outbreaks with reusable duodenoscopes raised concerns regarding the efficacy and adherence to standard disinfection protocols. Even the enhanced reprocessing techniques like double high-level disinfection have not been found to be the perfect ways for decontamination of duodenoscopes and therefore, paved the way for the development of single-use duodenoscopes. However, the use of single-use endoscopes is likely to amplify the net waste generated and carbon footprint of any endoscopy unit. Moreover, single-use devices challenge one of the major pillars of sustainability, that is, "reuse." In the era of climate change, a balanced approach is required taking into consideration patient safety as well as financial and environmental implications. The possible solutions to provide optimum care while addressing the impact on climate include selective use of disposable duodenoscopes and careful selection of accessories during a case. Other options include use of disposable endcaps and development of effective high-level disinfection techniques. The collaboration between the healthcare professionals and the manufacturers is paramount for the development of environmental friendly devices with low carbon footprint.


Evaluating bone mass and bone quality in patients with breast cancer.
Bone remodeling is a process by which bone renews itself focally in distinct areas on cancellous (ie, trabecular) bone and/or in the Haversian systems of cortical (or compact) bone. Normal bone turnover involves the ordered metabolism of bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Estrogen exerts a multitude of actions on bone tissues and is integral to bone health, and estrogen deprivation leads to accelerated bone loss. Bone strength reflects the integration of bone density and bone quality. Methods to assess bone strength fall into 3 categories: radiologic (ie, bone mineral density [BMD]), biochemical (ie, markers of bone turnover), and histologic (ie, bone biopsies for histomorphometry). The beneficial effect of aromatase inhibitors (AIs) and inactivators on breast cancer depends on reducing levels of circulating estrogens in the peripheral blood. There appears to be variability in the effects of AIs on bone in experimental animals, and this variability may not be the same in humans. In general, bone loss is an expected side effect of the AIs. For postmenopausal women receiving adjuvant anastrozole or other AIs, a BMD measurement using dual-energy x-ray absorptiometry is recommended, to be repeated every 1-2 years. Regular physical exercise is advised together with added calcium 1500 mg and vitamin D 800 U daily. If the T-score reaches a level of >2.5, or if it is between -1.5 and -2.5 in the presence of a fragility fracture or vertebral compression fracture, or if height loss > 2 cm occurs or BMD decreases > 3% in 1 year at the lumbar spine or > 5% at the femoral neck, bisphosphonate therapy should be considered.


Design, synthesis, fungicidal property and QSAR studies of novel β-carbolines containing urea, benzoylthiourea and benzoylurea for the control of rice sheath blight.
Rice sheath blight is a globally important rice disease. Unfortunately, this critical disease has not been effectively controlled, and the intensive and continuous use of the same fungicide might increase the risk of resistance development in the pathogen. To discover new active agents against rice sheath blight, in this study, three series of β-carboline urea, benzoylurea and benzoylthiourea derivatives were designed, synthesized and evaluated for in vitro and in vivo fungicidal activity against Rhizoctonia solani. All these compounds (EC50 : 0.131-1.227 mmol L-1 ) exhibited better fungicidal activity than harmine itself (EC50 : 2.453 mmol L-1 ). Significantly, compound 17c (EC50 : 0.131 mmol L-1 ) displayed the best efficacy in vitro and superior fungicidal activity compared with validamycin A (EC50 : 0.397 mmol L-1 ). Moreover, the in vivo bioassay also indicated that compound 17c could be effective for the control of rice sheath blight. Based on the bioassay result and quantitative structure-activity relationship (QSAR) information, structure modification in β-carboline warrants further investigation and its benzoylurea derivative 17c, which showed the best fungicidal activities, could emerge as a potential fungicide against rice sheath blight. © 2018 Society of Chemical Industry.


Ecological Transitions in Grouping Benefits Explain the Paradox of Environmental Quality and Sociality.
Both benign and harsh environments promote the evolution of sociality. This paradox-societies occur in environments of such contrasting quality-may be explained by the different types of benefits that individuals receive from grouping: resource defense benefits that derive from group-defended critical resources versus collective action benefits that result from social cooperation among group members. Here, we investigate cooperative behavior in the burying beetle Nicrophorus nepalensis along an elevational gradient where environmental quality (climate and competition) varies with altitude. We show that climate (temperature) and competition (both intra- and interspecific) independently and synergistically influence sociality via different grouping benefits that vary along the gradient. At low elevations where interspecific competition for resources is intense, groups gain from the collective action benefit of increased interspecific competitive ability. In contrast, pairs have higher fitness at intermediate elevations where intraspecific competition for resources is greatest because resource defense is the key grouping benefit. However, groups and pairs have similar fitness at high elevations, suggesting that there is no grouping benefit in such physiologically challenging environments. Our results demonstrate that sociality is favored for different reasons under a range of environmental conditions, perhaps explaining why animal societies occur in environments of such contrasting quality.


Genomics of Hereditary Colorectal Cancer: Lessons Learnt from 25 Years of the Singapore Polyposis Registry.
The Singapore Polyposis Registry (SPR) was established in 1989 in Singapore General Hospital (SGH). The aims were to provide a central registry service to facilitate identification, surveillance and management of families and individuals at high risk of colorectal cancer. This is a review of published literature in the department. The registry currently has 253 families with several genetic conditions-93 familial adenomatous polyposis (FAP) families, 138 Amsterdam-criteria positive presumed Lynch syndrome (LS) families, 12 families with Peutz Jeghers syndrome, 2 families with Cowden's syndrome, and 8 families with hereditary mixed polyposis syndrome (HMPS). There are also 169 families with a strong family history of colorectal cancer but no abnormal genes yet identified. In FAP, a diagnostic tool developed has allowed a 94% local APC germline detection rate in FAP families. Knowledge obtained studying the phenotype of FAP patients has allowed better choice of surgery between ileal pouch anal anastomosis (IPAA) against an ileal-rectal anastomosis (IRA). In LS, our review has noted a highly heterogenous mutational spectrum and novel variants made up 46.7% (28/60) of all variants identified in this cohort. This may suggest that our Southeast Asian ethnic groups have distinct mutational variants from Western populations. Pathogenic mutations were only confined to MLH1 and MSH2, and identified in 28.8% of families. The impact of predictive gene testing for hereditary cancer risk in clinical practice has allowed evolution of care. Risk-reducing surgery and aggressive surveillance allows reduction in morbidity and mortality of patients. The SPR will continue to grow and improve outcomes in hereditary colorectal cancer patients and families.


Benefits of Permanent His Bundle Pacing Combined With Atrioventricular Node Ablation in Atrial Fibrillation Patients With Heart Failure With Both Preserved and Reduced Left Ventricular Ejection Fraction.
Clinical benefits from His bundle pacing (HBP) in heart failure patients with preserved and reduced left ventricular ejection fraction are still inconclusive. This study evaluated clinical outcomes of permanent HBP in atrial fibrillation patients with narrow QRS who underwent atrioventricular node ablation for heart failure symptoms despite rate control by medication. The study enrolled 52 consecutive heart failure patients who underwent attempted atrioventricular node ablation and HBP for symptomatic atrial fibrillation. Echocardiographic left ventricular ejection fraction and left ventricular end-diastolic dimension, New York Heart Association classification and use of diuretics for heart failure were assessed during follow-up visits after permanent HBP. Of 52 patients, 42 patients (80.8%) received permanent HBP and atrioventricular node ablation with a median 20-month follow-up. There was no significant change between native and paced QRS duration (107.1±25.8 versus 105.3±23.9 milliseconds, P=0.07). Left ventricular end-diastolic dimension decreased from the baseline (P<0.001), and left ventricular ejection fraction increased from baseline (P<0.001) in patients with a greater improvement in heart failure with reduced ejection fraction patients (N=20) than in heart failure with preserved ejection fraction patients (N=22). New York Heart Association classification improved from a baseline 2.9±0.6 to 1.4±0.4 after HBP in heart failure with reduced ejection fraction patients and from a baseline 2.7±0.6 to 1.4±0.5 after HBP in heart failure with preserved ejection fraction patients. After 1 year of HBP, the numbers of patients who used diuretics for heart failure decreased significantly (P<0.001) when compared to the baseline diuretics use. Permanent HBP post-atrioventricular node ablation significantly improved echocardiographic measurements and New York Heart Association classification and reduced diuretics use for heart failure management in atrial fibrillation patients with narrow QRS who suffered from heart failure with preserved or reduced ejection fraction.


Thyroid hormone induction of ornithine decarboxylase in ischemic acute renal failure.
Thyroid hormone is an important interventional agent shown to be beneficial in a variety of models of acute renal failure (ARF). While its usefulness is clear, its mechanism of action remains unknown. Although there are a multitude of thyroid-inducible proteins and enzymes, the one singled out in these studies as of potential mechanistic significance in the protective effect of thyroid in ARF is ornithine decarboxylase (ODC). This enzyme catalyzes the entry step in the biosynthesis of polyamines, which possess several potential roles in fostering renal repair and recovery. Ischemic ARF was induced in rats by renal arterial clamp and functional assessment was made by inulin clearance 24 h after injury. Both T4 (10 micrograms/100 g) and T3 (1 and 10 micrograms/100 g) resulted in significant improvement in inulin clearance when compared to ischemia alone, while reverse T3 was without effect. The activity of ODC was reduced 70% at 24 h in the kidney cortex but T3 restored the level to near control. Pretreatment of rats with difluoromethylornithine (DFMO), and irreversible inhibitor of ODC, resulted in nearly complete inhibition of this enzyme in the cortex and medulla, and blocked the increase in activity induced by T3. From the functional standpoint, DMFO did not worsen the severity of ischemic ARF but completely blocked the protective effect of T3. These data strongly suggest roles for ODC stimulation and, presumably, the consequent augmentation of polyamine biosynthesis, in the mechanism by which thyroid hormone enhances recovery from ARF.


From outside to inside to outside: Comments on intrapsychic representations and interpersonal interactions.
The external world is represented intrapsychically in a specific way. Following the age of an infant, for example, the structure, quality, and the degree of symbolization will be different. The term representation in science is filled with different contents. In psychoanalysis, we see a development from Sigmund Freud's "(Sach- or Wort-)Vorstellungen" to internal objects, then to self-object representations and finally-following newer results of the concept of intersubjectivity and especially under the influence of infant mental- and interactional research-to self-object interaction representations. Some aspects of this development are presented more in detail. Knowing that on one hand, interaction in external reality is structured by the self-object interaction representations of each interacting partner and that on the other hand, what happens during the interactions in external reality modifies the representational world of all the interactive persons (i.e., their inner reality), one can observe constant movements from inside to outside (e.g., transference, action) and from outside to inside of the individual (e.g., perception, stimulation, containment, modification). Clinical implications for the actual way of understanding are manifold, but are here only very shortly delineated.


Can Maternal Prenatal Self-Reported and Physiological Distress Predict Postnatal Caregiving Practices?
Maternal prenatal distress is associated with child outcomes, including health, neurocognitive, and socio-emotional development. Knowledge on underlying mechanisms is limited, yet relevant for prevention and intervention. This study investigated whether maternal prenatal distress predicts specific caregiving practices that are known for their effects on child outcomes. Caregiving practices studied were maternal caregiving quality and the initiation and course of breastfeeding and room-sharing. We hypothesized that more maternal prenatal distress would be associated with altered caregiving practices. Participants were 174 healthy mother-child dyads. During the 37th week of pregnancy maternal self-reported distress was assessed using questionnaires, and physiological stress by collecting saliva cortisol. Maternal caregiving quality was observed in postnatal week 5 during infant bathing. Weekly diaries on breastfeeding and daily diaries on room-sharing were completed during the first 6 postnatal months. In a regression analysis, no associations between maternal prenatal distress and caregiving quality were found. Multilevel analyses indicated that maternal prenatal evening cortisol was positively related to the initiation of breastfeeding and room-sharing. Replications are warranted, but these results suggest that breastfeeding and room-sharing initiation may be part of a mechanism underlying links between maternal prenatal physiological stress and child outcomes. As other prenatal cortisol markers and self-reported distress were not found to be related to the caregiving practices, it is likely that alternative mechanisms (co-)exist in explaining links between maternal prenatal distress and child outcomes. Future replication research including child outcomes and (other) potential mechanisms will inform prevention and intervention programs fostering healthy pregnancies and child development.


Deciphering the evolution of Deception Island's magmatic system.
Deception Island (South Shetland Islands) is one of the most active volcanoes in Antarctica, with more than 20 explosive eruptive events registered over the past two centuries. Recent eruptions (1967, 1969, and 1970) and the volcanic unrest episodes that happened in 1992, 1999, and 2014-2015 demonstrate that the occurrence of future volcanic activity is a valid and pressing concern for scientists, technical and logistic personnel, and tourists, that are visiting or working on or near the island. We present a unifying evolutionary model of the magmatic system beneath Deception Island by integrating new petrologic and geochemical results with an exhaustive database of previous studies in the region. Our results reveal the existence of a complex plumbing system composed of several shallow magma chambers (≤10 km depth) fed by magmas raised directly from the mantle, or from a magma accumulation zone located at the crust-mantle boundary (15-20 km depth). Understanding the current state of the island's magmatic system, and its potential evolution in the future, is fundamental to increase the effectiveness of interpreting monitoring data during volcanic unrest periods and hence, for future eruption forecasting.


A jackhammer in the gullet: high amplitude oesophageal contractions as a cause of atypical chest pain.
Chest pain is a common cause for referral to emergency departments. A proportion of these patients have non-cardiac chest pains with normal investigations. Such patients should be considered for oesophageal studies as these may reveal an underlying dysmotility disorder. We report the case of a 51-year-old man who presented with chest pain and underwent oesophageal studies. He was diagnosed with acid reflux and high amplitude oesophageal contractions, otherwise known as a jackhammer oesophagus. Treatment was successful with omeprazole and glyceryl trinitrate relieving his symptoms.


Adverse drug events complicate antifungal therapy for pulmonary aspergilloma.
Aspergillus species are an important cause of fungal infections in immuncompromised patients and also cause a variety of saprophytic conditions such as pulmonary aspergilloma. Surgical resection alone may be warranted for the treatment of pulmonary aspergilloma; in cases where medical therapy is necessary, the triazole antifungal agents itraconazole, voriconazole, and, presumably, posaconazole are thought to provide therapeutic benefit. The high potential for drug-drug interactions with the "azole" antifungal drugs, as well as the possibility for adverse events, while perhaps uncommon, can be problematic. This case describes a 68-year-old patient who developed a pulmonary aspergilloma in the air space of the location of a previous left-upper lobectomy performed five years earlier to treat lung cancer. The patient was initiated on voriconazole, but subsequently developed agitation and hallucinations. The patient was switched to itraconazole and subsequently developed worsening of congestive heart failure. Another switch was made to posaconazole. After an adjustment of his medication regimen for potential drug-drug interactions, the patient was discharged on posaconazole for three to six months, with regular follow-up of liver transaminase monitoring.


Internalization of metformin is necessary for its action on potentiating the insulin-induced Xenopus laevis oocyte maturation.
In this study, metformin (N, N1 dimethylbiguanide) was found to potentiate insulin-induced Xenopus laevis oocyte maturation, a phenomenon of transition from late G2 to M phase of the cell cycle. These cells also accumulated exogenous metformin (130 +/- 6.5 nmol/oocyte). Metformin covalently-coupled to Sepharose 4B beads failed to potentiate the insulin-induced oocyte maturation which suggests that these cells did not take up metformin from the extracellular medium. Addition of metformin alone to Xenopus laevis oocytes did not induce the maturation process, though these cells took up exogenous metformin. Micro-injection of metformin (120 nmol/oocyte) to oocytes accelerated the insulin-induced maturation, but it was lower than in cells which were incubated with free metformin together with insulin. Interestingly, insulin had no effect on metformin uptake by the oocytes. Methylglyoxal-bis(guanylhydrazone), MGBG, an apparent analogue of metformin, induced oocyte maturation. Addition of metformin, either free or Sepharose-bound, did not influence the MGBG-induced 60% maturation of Xenopus laevis oocytes. These results suggest that the internalization of metformin is necessary for its action and its effects are specific on insulin activity.