Molecular spinning top: visualizing the dynamics of M3N@C80 with variable temperature single crystal X-ray diffraction.
Variable temperature X-ray diffraction studies on two single crystals containing M3N@C80, i.e., Ho2LuN@C80·NiOEP·2(C6H6) and Lu3N@C80·NiOEP·2(C6H6), (NiOEP = Nickel octaethylporphyrin) unravelled the temperature dependent rotation of the M3N cluster and C80 cage on the static NiOEP molecule.


[Computerized oculomotor training in dyslexia: A randomized, crossover clinical trial in pediatric population].
Several studies have reported abnormal oculomotor capacities leading to reading/writing difficulties among dyslexic children. However, no randomized clinical trial has been conducted to determine whether oculomotor training improves reading/writing skills of these children. The present study aims to evaluate the efficacy of computer-based oculomotor training among dyslexic children. Crossover randomized trial with enrollment from January 12, 2015 to July 24, 2015, and follow-up to February 4, 2016. Eleven children (aged 7 to 12 years old) with dyslexia were included in a French psychiatric unit. The computer-based oculomotor training consisted of exercises focused on control of saccadic movements (reflexes and voluntary saccades), vergences and visual attention and memory. At baseline, 3 and 6 months, participants were assessed on reading and writing skills as well as phonological skills, visuo-attentional skills and verbal memory using the French batterie analytique du langage écrit (BALE). Saccadic and antisaccadic ocular movements (latencies and gains) were recorded using a specific device. Several Anova models were performed to test whether oculomotor training improves reading, writing and phonological, verbal memory and visuo-attentional skills. Our analyses were considered exploratory (alpha at 5%). No effect of oculomotor training was found on reading skills. However, oculomotor training was associated with a short-term effect (after 3 months of training) on several tests measuring phonological skills (syllabic suppression; P-value=0.022), visuo-attentional skills (search of anarchic verbal cues; P-value=0.035) and verbal memory (digit span backward; P-value=0.022) and with a long-term effect (3 months after the end of the 3 months of training) on a measure of writing skills (regular words; P-value=0.019). Finally, training was associated with an increase of saccadic latencies indicating an increase of visuo-attentional skills (P-value=0.026). Our results suggested that computer-based oculomotor training might be effective on writing skills and several cognitive skills among dyslexic children, but future clinical trials are needed to confirm our results.


A technique for the correction of bifid scrotum in patients with hypospadias.
A technique to correct a bifid scrotum in patients with severe hypospadias is described. The operation is used as a second stage procedure to 1) repair the bifid scrotum, 2) add length to the penis and 3) correct the tendency for the erect penis to point into the scrotum, eventually interfering with intromission. The procedure, which advances the penis superiorly, detaches the urethra from the prominent median raphe to correct the bifid scrotum, It has been used successfully in 3 patients.


Acute skin phototoxicity in hairless mice following exposure to crude shale oil or natural petroleum oil.
The acute skin phototoxicity in hairless mice resulting from applications of crude shale oil or natural petroleum oil and exposure to near ultraviolet light has been investigated. In addition, the absorption and excitation-emission spectra of these oils have been described. While the application of crude shale oil alone was shown to elicit acute skin damage, the combination of the crude shale oil and near ultraviolet light induced skin damage much more severe than that produced by either agent alone. In contrast, the application of the natural petroleum oil and near ultraviolet light was less toxic than that of the crude shale oil in the absence of light. These results suggest that a potential health hazard exists from contact with shale oil compounds and exposure to near ultraviolet light from either the sun or artificial sources.


Fat malabsorption--advances in our understanding.
The intestinal absorption of triglyceride constitutes a multistep process with active involvement of the pancreatobiliary system, the intestine and lymphatics. It is only through the integrated function of these organs that dietary triglyceride can be efficiently absorbed and delivered to the peripheral blood for subsequent metabolism. In this review we discuss each aspect of triglyceride absorption and chylomicron formation and illustrate how various diseases may interfere with the process resulting in fat malabsorption. In addition, the role of the intestine as a major synthetic source of lipoprotein constituents for circulating lipoproteins is discussed.


Application of histochemistry to a living organ: polyglucose histochemically synthesized in the paraboloid of the chick accessory cone in vivo by phosphorylase and branching glycosyltransferase.
Histochemical application in a living animal was tested on the paraboloid of the accessory cone of the chick retina. After the anterior part of the eye had been cut with a Graefe's knife under ether anesthesia, the posterior part was filled with the medium for phosphorylase under exposure to light. The specimens were embedded for routine electron microscopy and the paraboloid of the accessory cone was observed by electron microscopy. Polyglucose particles were synthesized from glucose-l-phosphate in the paraboloid by the activities of phosphorylase and branching glycosyl transferase and found to be in the cytoplasmic matrices. These particles were larger in size and better stainable with lead citrate than those found in the paraboloid of the retina incubated in the medium in vitro by the conventional histochemical method. Overproduction of polyglucose particles was not found in the paraboloid of the retina incubated in the medium in vivo. These findings suggest that polyglucose particles synthesized in vivo have a close resemblance to native glycogen particles and that glycogen metabolism is regulated by the living cell. Glycolysis may not be related to the membranous structures. Therefore, application of enzyme histochemical techniques to the living organ can demonstrate more accurate morphological aspects of metabolism in the cell.


Diffusion-weighted imaging findings on MRI as the sole radiographic findings in a child with proven herpes simplex encephalitis.
We present a case of herpes simplex encephalitis in an 8-year-old girl, in whom hyperintensity was detected on diffusion-weighted imaging (DWI) while conventional MRI sequences were normal 1 week after the onset of neurological symptoms. This case is rare in that a child beyond the neonatal period with focal herpes simplex encephalitis had an abnormal DWI sequence as the only MRI finding.


Taxonomy of coagulase-negative staphylococci: a comparison of two widely used classification schemes.
In a comparative study 351 strains of Micrococcus subgroups 1-3 (Baird-Parker, 1963, 1965, 1974) were classified according to the Kloos and Schleifer scheme (1975b). The results showed that Micrococcus subgroups 1, 2 and 3 are heterogeneous groups in the Kloos and Schleifer scheme. Strains belonging to Micrococcus subgroups 1 and 2 were mostly classified by the Kloos and Schleifer criteria as Staphylococcus hominis, Micrococcus subgroup 3 strains from the skin as S. cohnii, while Micrococcus subgroup 3 strains from urinary infections were classified mainly as S. saprophyticus. The correlation of novobiocin resistant S. saprophyticus biotype III (Baird-Parker, 1974) with S. saprophyticus (Kloos and Schleifer, 1975a, 1975b) when isolated from urine, was 80%. Although the Kloos and Schleifer scheme provides more information about biochemical characters, doubts are expressed about the validity of some of the species so delineated.


Cross-cultural adaptation and validation of the Motivation in Stroke Patients for Rehabilitation Scale in Chinese hospitalized older adults with stroke.
To translate, cross-culturally adapt, and validate the Motivation in Stroke Patients for Rehabilitation Scale (MORE) questionnaire in Chinese hospitalized older adults with stroke. The Chinese version of the MORE was produced following Brislin's guidelines. The psychometric properties of the MORE were evaluated among 420 eligible patients. The Cronbach's alpha coefficient of the Chinese version of the MORE scale was 0.983, and the content validity index (S-CVI) was 0.94, with good reliability. Exploratory factor analysis showed a single-factor structure that explained 78.01% of the total variance, and the confirmatory factor analysis model had a good fit index (X2/df=2.97; NFI =0.93; CFI=0.96; TFI=0.95; IFI=0.96). The MORE presented acceptable validity and reliability and could be used in Chinese hospitalized older adults with stroke.


Optimization of northern analysis by vacuum-blotting, RNA-transfer visualization, and ultraviolet fixation.
We have optimized Northern analysis at several steps. Overnight electrophoresis was replaced by short gel runs and overnight capillary transfer by rapid vacuum-blotting adapted to Northern analysis. Short uv irradiation was used as a substitute for the usual RNA fixation by baking. Direct staining of RNA before electrophoresis made it possible to check RNA integrity and to evaluate the quality of the size separation immediately after electrophoresis. In this system, RNA transfer onto the membrane support could also be quickly assessed after the blotting step. The net result of all modifications was a doubling of the autoradiography signal compared with that obtained by modern Northern protocols. At the same time, the duration of the procedure was shortened drastically, allowing an autoradiography signal to be obtained within 24 h.


Release of adenosine-induced immunosuppression: Comprehensive characterization of dual A2A/A2B receptor antagonist.
Immunosuppression is one of the main mechanisms facilitating tumor expansion. It may be driven by immune checkpoint protein expression, anti-inflammatory cytokine secretion or enhanced metabolic enzyme production, leading to the subsequent build-up of metabolites such as adenosine. Under physiological conditions, adenosine prevents the development of tissue damage resulting from a prolonged immune response; the same mechanism might be employed by tumor tissue to promote immunosuppression. Immune cells expressing A2A and A2B adenosine receptors present in an adenosine-rich environment have suppressed effector functions, such as cytotoxicity, proinflammatory cytokine release, antigen presentation and others, making them inert to cancer cells. This study was designed to investigate the dual antagonist potential of SEL330-639 to abolish adenosine-driven immunosuppression. SEL330-639 has slow dissociation kinetics. It inhibits cAMP production in human CD4+ cells, CD8+ cells and moDCs, which leads to diminished CREB phosphorylation and restoration of antitumor cytokine production (IL-2, TNFα, IL-12) in multiple primary human immune cells. The aforementioned results were additionally validated by gene expression analysis and functional assays in which NK cell line cytotoxicity was recovered by SEL330-639. Adenosine-driven immunosuppression is believed to preclude the effectiveness of immune checkpoint inhibitor therapies. Hence, there is an urgent need to develop new immuno-oncological strategies. Here, we comprehensively characterize SEL330-639, a novel dual A2A/A2B receptor antagonist effective in both lymphoid and myeloid cell populations with nanomolar potency. Due to its tight binding to the A2A and A2B receptors, this binding is sustained even at high adenosine concentrations mimicking the upper limit of the range of adenosine levels observed in the tumor microenvironment.


Rapid determination of radium-224/226 in seawater sample by alpha spectrometry.
A new radiochemical separation method has been developed for rapid determination of alpha-emitting radium isotopes in seawater samples. This method can be applied for the measurement of 226Ra in seawater samples when 224Ra is used as tracer for chemical recovery correction. Likewise, 226Ra can also be added as tracer for the determination of 224Ra in seawater sample. In the method, radium is first pre-concentrated with hydrous titanium oxide (HTiO) and is purified by combined anion/cation exchange column chromatographic separation. The radium in the eluate is then co-precipitated with HTiO, dissolved in 9 M H2SO4, and followed through a BaSO4 micro-precipitation step to prepare a thin-layer counting source to determine the activities of 224Ra/226Ra by alpha spectrometry. Replicate spike and blank samples were measured to evaluate the performance of the procedure. The minimum detectable activity concentration was determined to be 0.5 mBq·L-1 for 226Ra and 0.4 mBq·L-1 for 224Ra in 1 L of seawater sample with a counting time of 48 h. The method is a promising candidate for rapid measurement for alpha-emitting Ra isotopes in a large population of environment water samples.


Fluid-like cathode enhances valuable biomass production from brewery wastewater in purple phototrophic bacteria.
The climate crisis requires rethinking wastewater treatment to recover resources, such as nutrients and energy. In this scenario, purple phototrophic bacteria (PPB), the most versatile microorganisms on earth, are a promising alternative to transform the wastewater treatment plant concept into a biorefinery model by producing valuable protein-enriched biomass. PPB are capable of interacting with electrodes, exchanging electrons with electrically conductive materials. In this work, we have explored for mobile-bed (either stirred or fluidized) cathodes to maximize biomass production. For this purpose, stirred-electrode reactors were operated with low-reduced (3.5 e-/C) and high-reduced (5.9 e-/C) wastewater under cathodic polarization (-0.4 V and -0.8 V vs. Ag/AgCl). We observed that cathodic polarization and IR irradiation can play a key role in microbial and phenotypic selection, promoting (at -0.4 V) or minimizing (at -0.8 V) the presence of PPB. Then, we further study how cathodic polarization modulates PPB biomass production providing a fluid-like electrode as part of a so-called photo microbial electrochemical fluidized-bed reactor (photoME-FBR). Our results revealed the impact of reduction status of carbon source in wastewater to select the PPB photoheterotrophic community and how electrodes drive microbial population shifts depending on the reduction status of such carbon source.


A Pellino-2 variant is associated with constitutive NLRP3 inflammasome activation in a family with ocular pterygium-digital keloid dysplasia.
Ocular pterygium-digital keloid dysplasia (OPDKD) is a rare hereditary disease characterized by corneal ingrowth of vascularized conjunctival tissue early in life. Later, patients develop keloids on fingers and toes but are otherwise healthy. In a recently described family with OPDKD, we report the presence of a de novo c.770C > T, p.(Thr257Ile) variant in PELI2 in the affected individual. PELI2 encodes for the E3 ubiquitin ligase Pellino-2. In transgenic U87MG cells overexpressing Pellino-2 with the p.(Thr257Ile) amino acid substitution, constitutive activation of the NLRP3 inflammasome was observed. However, the Thr257Ile variant did not affect Pellino-2 intracellular localization, its binding to known interaction partners, nor its stability. Our findings indicate that constitutive autoactivation of the NLRP3 inflammasome contributes to the development of PELI2-associated OPDKD.


Mechanics of ventilation with positive end-expiratory pressure.
The effect of graded increments in positive end-expiratory pressure (PEEP) on arterial oxygen partial pressure (PaO2) and shunt fraction (Qs/QT), oxygen delivery, and respiratory mechanics and work required to ventilate 8 critically ill patients is reported. The work required to ventilate the patients increases markedly with the application and progressive increase in the level of PEEP. However, improvement in lung mechanics lowers the net work of ventilating the lungs. At 20 cm H2O PEEP, the mean value for the work of ventilation in this group of patients is twice the mean value without PEEP. The increase in work of ventilation with PEEP is critical in the use of PEEP when patients are breathing spontaneously with or without intermittent mandatory ventilation.


Mobilization of gastric histamine during repeated administration of a proton potassium adenosine triphosphatase inhibitor in intact and antrectomized rats.
Intact and antrectomized female rats were treated with the potent proton pump inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin concentration and urinary excretion of N-terminal big gastrin increased until day 14 and persisted at a high level in intact rats treated with E3810, but did not increase in antrectomized rats. Urinary excretion of histamine increased progressively and reached 7 times the control value following 4 weeks of treatment with E3810 in intact rats, but not in antrectomized rats. At the termination of the treatment, the endocrine cell density in the oxyntic mucosa of intact rats had increased by 85% with increased histamine content and elevated histidine decarboxylase activity, while antrectomized rats showed a low histamine level and low histidine decarboxylase activity. Administration of gastrin-17 I (10 micrograms/kg weight, sc) itself caused a significant increase in urinary excretion of histamine, which was inhibited by the specific gastrin receptor antagonist, L-365,260. These results suggests that the massive urinary excretion of histamine caused by the treatment with E3810 reflects gastrin-induced mobilization of gastric histamine and that neither E3810 itself nor E3810-induced luminal pH elevation has direct effects on mobilization of oxyntic mucosal histamine.


Smart Vest: wearable multi-parameter remote physiological monitoring system.
The wearable physiological monitoring system is a washable shirt, which uses an array of sensors connected to a central processing unit with firmware for continuously monitoring physiological signals. The data collected can be correlated to produce an overall picture of the wearer's health. In this paper, we discuss the wearable physiological monitoring system called 'Smart Vest'. The Smart Vest consists of a comfortable to wear vest with sensors integrated for monitoring physiological parameters, wearable data acquisition and processing hardware and remote monitoring station. The wearable data acquisition system is designed using microcontroller and interfaced with wireless communication and global positioning system (GPS) modules. The physiological signals monitored are electrocardiogram (ECG), photoplethysmogram (PPG), body temperature, blood pressure, galvanic skin response (GSR) and heart rate. The acquired physiological signals are sampled at 250samples/s, digitized at 12-bit resolution and transmitted wireless to a remote physiological monitoring station along with the geo-location of the wearer. The paper describes a prototype Smart Vest system used for remote monitoring of physiological parameters and the clinical validation of the data are also presented.


Short and regiospecific synthesis of echinamine A--the pigment of sea urchin Scaphechinus mirabilis.
New convenient two-step synthesis of natural pigment echinamine A by the condensation of 2,3-dichloro-6-ethyl-7-hydroxy-1,4-naphthoquinone with sodium nitrite and subsequent reduction of intermediate 7-ethyl-2,5,6,8-tetrahydroxy-3-nitro-1,4-naphthoquinone has been developed.


Radon in the environment and in dwellings in a uranium mining area in eastern India: an overview.
Radon has been extensively studied in the Singhbhum Thrust Belt (STB) of eastern India where mining and processing of uranium ore has been in progress for over four decades. Emanation from the soil is the main natural source of environmental radon. Releases from mine and emanations from waste rocks and tailings are the technological sources. Rn studies in the environment, dwellings and ground waters in STB are reviewed in this paper.


Open space swimming test to index antidepressant activity.
Depression is characterized by a lack of "motivation" rather than a lack of "physical space" to move around. This study was designed to evaluate predictivity of an open space swimming test for antidepressant activity of various antidepressants in rats. Without drug treatment, rats showed a significant reduction in the distance moved (increased immobility) over successive trials in an open space water pool. Three major classes of antidepressants and a selective serotonin reuptake inhibitor (SSRI) were tested. Repeated treatment (10 mg/kg x 3 per day) of imipramine, a prototypical tricyclic antidepressant, iproniazid, a monoamine oxidase inhibitor, mianserin, an atypical antidepressant, and alaproclate, an SSRI, all significantly reduced the immobility. These results suggest that the open space swimming test is highly predictive of antidepressant action and is more sensitive to the drug treatments. The measurement is more objective than that of the forced swimming test and does not involve judging and scoring the animals' movement or lack of movement by investigators. The demonstrated effectiveness of three major types of antidepressants and an SSRI suggests that the effects on the test are not restricted to a particular underlying molecular mechanism of action. Thus, this swimming test shows promising potential as a screen for novel antidepressants and, perhaps, for revealing some of the underlying pathophysiology of depression.


Complete nucleic acid sequence of Penaeus stylirostris densovirus (PstDNV) from India.
Infectious hypodermal and hematopoietic necrosis virus (IHHNV) of shrimp, recently been classified as Penaeus stylirostris densovirus (PstDNV). The complete nucleic acid sequence of PstDNV from India was obtained by cloning and sequencing of different DNA fragment of the virus. The genome organisation of PstDNV revealed that there were three major coding domains: a left ORF (NS1) of 2001 bp, a mid ORF (NS2) of 1092 bp and a right ORF (VP) of 990 bp. The complete genome and amino acid sequences of three proteins viz., NS1, NS2 and VP were compared with the genomes of the virus reported from Hawaii, China and Mexico and with partial sequence available from isolates from different regions. The phylogenetic analysis of shrimp, insect and vertebrate parvovirus sequences showed that the Indian PstDNV isolate is phylogenetically more closely related to one of the three isolates from Taiwan (AY355307), and two isolates (AY362547 and AY102034) from Thailand.


Continent cutaneous urinary diversion is still a valid alternative after cystectomy for bladder carcinoma.
We compared patient opinions concerning reservoir/bladder function as well as quality of life (QOL) after cystectomy for bladder carcinoma and continent cutaneous urinary diversion or orthotopic bladder reconstruction. Fifteen patients with Kock reservoirs (11 females, 4 males) and 11 men with orthotopic bladders answered the European Organization for Research and Treatment of Cancer quality-of-life questionnaire-C30 as well as specially constructed questions concerning reservoir/bladder function. The glomerular filtration rate (GFR) was determined using Cr-EDTA or iohexol clearance. Functioning and global health/QOL scales did not differ between the two groups of operated patients or between diverted patients and gender- and age-matched groups from the general population. The majority of the patients were satisfied/very satisfied with their diversion but more patients were troubled by leakage in the orthotopic bladder group than in the Kock reservoir group. The GFR was similar in the two groups. Continent cutaneous urinary diversion is associated with fewer leakage problems than orthotopic bladder reconstruction after cystectomy for bladder carcinoma.


A life cycle for Borrelia spirochetes?
Subsequent to Schaudinn and Hoffman's visualization of Treponema pallidum in 1905, many distinguished syphilologists proposed that spirochetes have a life cycle. What is the "essence" of a life cycle? Simply put, life cycles are diverse arrays of life forms, which emerge in an ordered sequence; which are "connected" to one another across primary and secondary hosts, and constitute a cycle with "circular" relationship between hosts. Fecal-oral life cycles and blood-to-blood life cycles are exemplary of host parasite relationships in this realm. The "blood-to-blood" begins and ends with an insect taking a blood "meal". In this operatic scenario, a "blood-less" insect functions simultaneously as a hypodermic needle and as an incubator for some of the infectious components. The initial phase is inside the body fluid compartment of an insect. The second phase is in the blood or body fluid of a warm-blooded mammal. Third, is the phase inside the cell of a mammalian host. And a final portion of the "life" marked by "death" of the parasitized mammalian cells and the release of infectious parasites which return to the "warm" blood where the "cold blooded" vector again takes a blood meal. The cycle then begins again. In each phase of a blood to blood life cycle, the infectious agent changes its shape. Blood phase "profiles" look different from "tissue phase" profiles. Some of the tissue phase profiles may be "invisible". Borrelia spirochetes offer an excellent example of a life cycle, by virtue of the insect vector to mammalian "piece", the blood and intracellular residence "pieces" and the morphologic diversity "piece". Stereotypes of what a spirochete "should " look like, have actually produced a state of "perseveration" in spirochetal pathobiology. We have been "stuck" like a broken record, on the corkscrew form, and have failed to see the rest of the life cycle. Cystic, granular, and cell wall deficient spirochetal profiles, which were well known in the 19th and 20th centuries by such titans as Schaudinn, Hoffman, Noguchi, Delamater, Steiner, and Mattman, have been repudiated by professional microbiologists, and by pathologists who practice and who confer the status of 21st century truths in microbiology matters. Proper microscopic study, as is required by Dr. Robert Koch's second postulate, for establishing links between microbes and disease, presupposes that the microscopist be aware of the complete array of morphologic repertoires of the alleged pathogen. (Morphologies, which are herein introduced.).


Rate and Predictors of 30-day Readmission Following Diabetic Ketoacidosis in Type 1 Diabetes Mellitus: A US Analysis.
Diabetic ketoacidosis (DKA) is a serious endocrine emergency, associated with morbidity and mortality. Readmissions play a significant but sometimes preventable role in healthcare cost burden on the US. This study aimed to describe rates and characteristics of nonelective 30-day readmission among adult patients with diabetes mellitus type 1 (T1DM) hospitalized for DKA and also identify predictors of readmission. The study analyzed the 2018 Nationwide Readmission Database. DKA hospitalizations in patients with T1DM were classified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. We utilized chi-squared tests to compare baseline characteristics between readmissions and index hospitalizations. Multivariable Cox regression was employed to identify independent predictors of readmission. Following this, we developed a 30-day readmission risk scoring system based on independent predictors. The 30-day all-cause readmission rate for DKA was 19.4%. A majority of patients (64.8%) had DKA as the principal diagnosis on readmission. Readmitted patients had a significantly higher mean age (35.3 vs 34.9 years, P = .018) and a higher proportion of females (52.8 vs 49.6%, P < .001) than the index admission. Readmission following DKA was associated with higher odds of inpatient mortality (0.69 vs 0.24%, OR 2.84, 95% CI 1.99-4.06, P < .001). Independent predictors of 30-day all-cause readmission included female sex, index hospitalizations with Charlson Comorbidity Index (CCI) score of 3 or greater, and being discharged against medical advice (AMA). The readmission rate for DKA in T1DM patients is high, and most patients have DKA as the principal diagnosis on readmission. A CCI equal to or greater than 3, hypertension, female sex, and being discharged AMA were significant predictors of readmission.


High-throughput screening of a collection of known pharmacologically active small compounds for inhibitors of Salmonella invasion and intracellular replication.
The aim of this study was to screen a chemical library consisting of over 1200 pharmacologically active, already approved off-patent compounds, to determine whether any of the compounds reduced or eliminated the invasion or intracellular replication phenotypes of Salmonella enterica serovar Typhimurium (S. Typhimurium). LacZ reporter and tissue culture-based infection assays were used to screen for compounds that significantly reduced expression of key virulence genes, and were required for the invasion or intracellular replication phenotypes of S. Typhimurium in host cells. The search lead to the discovery of four compounds that reduced invasion by between 90-100%, and two compounds that reduced intracellular replication by between 65-93% at concentrations of either 2, 10 or 50 μg ml-1 , relative to an untreated control strain. We identified six compounds that significantly reduced expression of S. Typhimurium virulence genes resulting in decreased in vitro virulence. The emergence of multidrug-resistant strains of Salmonella poses a considerable and growing worldwide threat to human and animal health. The screening of off-patent chemical libraries represents a potential discovery route for novel antimicrobials.


Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila.
Spinocerebellar ataxia type 5 (SCA5) is an autosomal dominant neurodegenerative disorder caused by mutations in the SPBTN2 gene encoding beta-III-spectrin. To investigate the molecular basis of SCA5, we established a series of transgenic Drosophila models that express human beta-III-spectrin or fly beta-spectrin proteins containing SCA5 mutations. Expression of the SCA5 mutant spectrin in the eye causes a progressive neurodegenerative phenotype, and expression in larval neurons results in posterior paralysis, reduced synaptic terminal growth, and axonal transport deficits. These phenotypes are genetically enhanced by both dynein and dynactin loss-of-function mutations. In summary, we demonstrate that SCA5 mutant spectrin causes adult-onset neurodegeneration in the fly eye and disrupts fundamental intracellular transport processes that are likely to contribute to this progressive neurodegenerative disease.


Arterial supply of the acetabulum in the fetus: application to periacetabular surgery in childhood.
The need to perform triple osteotomies of the pelvis passing very close to the articular surface leads to the isolation of bony fragments whose vascularisation may be precarious. To assess the risks of such surgery, we undertook an anatomic study of the vascularisation of the acetabulum in the fetus. 53 specimens were injected to study the vessels to the acetabulum and their distribution within the osteocartilaginous specimen. The acetabular a., a branch of the obturator a., gives a central pedicle distributed to the acetabular fossa, the triradiate cartilage and ending in the three primary bony components. The superior gluteal, inferior gluteal, internal pudendal and obturator aa. form a periacetabular vascular circle. The abundant vascularity of the acetabulum makes massive necrosis improbable in the child. However, there is a zone of precarious anastomosis at the anterior portion of the acetabulum.


The levels of pain experienced with lower limb fractures.
This paper gives an overview of a small study of practice in Coventry and Warwickshire Hospital. The study set out to discover how long male patients experienced unrelieved pain following admission to hospital with fractures to their lower limbs.


Spatiotemporal prediction of vancomycin-resistant Enterococcus colonisation.
Vancomycin-resistant enterococci (VRE) is the cause of severe patient health and monetary burdens. Antibiotic use is a confounding effect to predict VRE in patients, but the antibiotic use of patients who may have frequented the same ward as the patient in question is often neglected. This study investigates how patient movements between hospital wards and their antibiotic use can explain the colonisation of patients with VRE. Intrahospital patient movements, antibiotic use and PCR screening data were used from a hospital in the Netherlands. The PageRank algorithm was used to calculate two daily centrality measures based on the spatiotemporal graph to summarise the flow of patients and antibiotics at the ward level. A decision tree model was used to determine a simple set of rules to estimate the daily probability of patient VRE colonisation for each hospital ward. The model performance was improved using a random forest model and compared using 30% test sample. Centrality covariates summarising the flow of patients and their antibiotic use between hospital wards can be used to predict the daily colonisation of VRE at the hospital ward level. The decision tree model produced a simple set of rules that can be used to determine the daily probability of patient VRE colonisation for each hospital ward. An acceptable area under the ROC curve (AUC) of 0.755 was achieved using the decision tree model and an excellent AUC of 0.883 by the random forest model on the test set. These results confirms that the random forest model performs better than a single decision tree for all levels of model sensitivity and specificity on data not used to estimate the models. This study showed how the movements of patients inside hospitals and their use of antibiotics could predict the colonisation of patients with VRE at the ward level. Two daily centrality measures were proposed to summarise the flow of patients and antibiotics at the ward level. An early warning system for VRE can be developed to test and further develop infection prevention plans and outbreak strategies using these results.


Viscoelastic properties of isolated collagen fibrils.
Understanding the viscoelastic behavior of collagenous tissues with complex hierarchical structures requires knowledge of the properties at each structural level. Whole tissues have been studied extensively, but less is known about the mechanical behavior at the submicron, fibrillar level. Using a microelectromechanical systems platform, in vitro coupled creep and stress relaxation tests were performed on collagen fibrils isolated from the sea cucumber dermis. Stress-strain-time data indicate that isolated fibrils exhibit viscoelastic behavior that could be fitted using the Maxwell-Weichert model. The fibrils showed an elastic modulus of 123 ± 46 MPa. The time-dependent behavior was well fit using the two-time-constant Maxwell-Weichert model with a fast time response of 7 ± 2 s and a slow time response of 102 ± 5 s. The fibrillar relaxation time was smaller than literature values for tissue-level relaxation time, suggesting that tissue relaxation is dominated by noncollagenous components (e.g., proteoglycans). Each specimen was tested three times, and the only statistically significant difference found was that the elastic modulus is larger in the first test than in the subsequent two tests, indicating that viscous properties of collagen fibrils are not sensitive to the history of previous tests.


[Study of elongation complexes for T7 RNA polymerase].
Complexes of bacteriophage T7 RNA polymerase with a DNA template for transcription elongation were visualized by atomic force microscopy. Images for complexes of T7 RNA polymerase with terminal fragments of DNA template were obtained for single molecules. Complexes of a single DNA template molecule with several T7 RNA polymerase molecules corresponding to stages of initiation, elongation and termination of transcription were visualized under the elimination of unspecific DNA-protein binding. Immobilized on the amino mica RNA transcripts form rod-like condensed structures. Detailes of specific and unspecific complex formation for the T7 RNA polymerase-DNA system during initiation and transcription elongation are discussed.


Isolation of Brucella melitensis from aborting ruminants in Jordan.
Thirty-four isolates (16.5 per cent) of Brucella melitensis were cultured from 206 samples from aborted, still-born or weak full-term animals and vaginal swabs from aborted animals. Twenty-six of 31 isolates from sheep were B. melitensis biovar 3. Two isolates were biovar 1 and one of these was the vaccine strain Rev 1. The three remaining isolates were from vaginal swabs and were not biotyped since B. melitensis biovar 3 had been isolated from the aborted fetuses. One of two isolates from cattle and one isolate from a goat were biovar 1. The remaining cattle isolate was biovar 3.


Natural history of spinal cord metastasis from brain glioblastomas.
Spinal cord metastasis arising from an intracranial glioblastoma is a rare and late event during the natural course of the disease. These pathological entities remain poorly characterized. This study aimed to identify and investigate the timeline, clinical and imaging findings, and prognostic factors of spinal cord metastasis from a glioblastoma. Consecutive histopathological cases of spinal cord metastasis from glioblastomas in adults entered in the French nationwide database between January 2004 and 2016 were screened. Overall, 14 adult patients with a brain glioblastoma (median age 55.2 years) and harboring a spinal cord metastasis were included. The median overall survival as 16.0 months (range, 9.8-22.2). The median spinal cord Metastasis Free Survival (time interval between the glioblastoma diagnosis and the spinal cord metastasis diagnosis) was 13.6 months (range, 0.0-27.9). The occurrence of a spinal cord metastasis diagnosis greatly impacted neurological status: 57.2% of patients were not ambulatory, which contributed to dramatically decreased Karnofsky Performance Status (KPS) scores (12/14, 85.7% with a KPS score ≤ 70). The median overall survival following spinal cord metastasis was 3.3 months (range, 1.3-5.3). Patients with a cerebral ventricle effraction during the initial brain surgery had a shorter spinal cord Metastasis Free Survival (6.6 vs 18.3 months, p = 0.023). Out of the 14 patients, eleven (78.6%) had a brain IDH-wildtype glioblastoma. Spinal cord metastasis from a brain IDH-wildtype glioblastoma has a poor prognosis. Spinal MRI can be proposed during the follow-up of glioblastoma patients especially those who have benefited from cerebral surgical resection with opening of the cerebral ventricles.


Brief Report: The Broad Autism Phenotype in Swedish Parents of Children With and Without Autism Spectrum Conditions.
The broad autism phenotype (BAP) is a set of characteristics often observed in typically developing people with a genetic load for autism, such as parents of autistic children. The Broad Autism Phenotypic Questionnaire (BAPQ) is a 36-item questionnaire developed to identify the BAP in first-degree relatives of autistic people. We translated the BAPQ into Swedish and examined its psychometric properties in a Swedish sample consisting of 45 parents of children with ASC and 74 parents of non-autistic children. We found support for the original 3-factor structure (aloof, pragmatic language and rigid), good internal consistency and convergent validity with the Autism Quotient. Thus, the Swedish BAPQ exhibits acceptable psychometric properties and may be useful for assessing the BAP in non-clinical populations.


The effect of orthotic devices on freeway space.
After any orthotic device placement, there are three possible outcomes to the freeway space. The freeway space is either decreased, unchanged, or increased. The objective of this study was to determine what effect the placement of an orthotic device has on freeway space. Freeway space was measured in a group of 26 subjects immediately after placement of an orthotic device. In a second group of 26 subjects, freeway space was measured at least one week after placement of their orthotic devices. The freeway space was measured along the closing trajectory path during function. The number recorded was based on the actual measurement of the freeway space using a computer measuring device. Both sets of data were analyzed without taking into account other factors which may have influenced the freeway space. A Mann Whitney U test showed no significant differences between the two groups (Z = 0.027, P = 0.978 ). This study concluded that the thickness of an orthotic device does not necessarily increase or decrease freeway space.


Fungal infection in a patient with multiple sclerosis.
Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, whose causes are still unknown. We have proposed that MS, as well as some ophthalmologic diseases, are associated with fungal infection. In the present study, we closely monitored a patient with MS over a three-year period. Antibodies against different Candida spp. were detected in peripheral blood serum, although the titer of these antibodies fluctuated. The presence of fungal macromolecules, such as proteins, polysaccharides, and DNA, was also tested. In several sera samples, antigens related to C. famata were evidenced by the slot-blot test using a rabbit polyclonal antibody against these species, while high levels of β-1,3 glucan were detected with the commercial Fungitell assay. Despite the variations by sample, we concluded that all fungal macromolecules, that is, proteins, polysaccharides, and DNA, were present in blood from the MS patient which was analyzed. Several fungal species were identified using polymerase chain reaction (PCR) followed by sequencing. Antibodies against Candida spp. as well as C. famata-related antigens were also detected in cerebrospinal fluid (CSF). Our findings provide support for the notion that disseminated mycosis is present in this patient.


Effects of iron surface pretreatment on kinetics of aqueous nitrate reduction.
Using hydrogen gas at 400 degrees C to activate iron surface was proposed to remove nitrate (40 mg NL(-1)) in a HEPES buffer solution at pH value between 6.5 and 7.5. Compared with the nonpretreated iron, the first-order reaction rate constant (kobs) was increased 4.7 times by pretreated iron, and the lag of the early period disappeared. Normalized to iron surface area concentration, the specific rate constant (kSA) was increased approximately by a factor of 6 using hydrogen reduction (0.0020 min(-1)m(-2)L for nonpretreated iron and 0.0128 min(-1)m(-2)L for pretreated iron). The reactivity of aged iron covered by a complex mixture of iron oxides (soaking in nitrate solution for 60 days) were restored by hydrogen gas at 400 degrees C. Scanning electron microscopy (SEM) and temperature-programmed reduction (TPR) exhibited visibly cleaner without pitting and cracking and less oxygen fraction on pretreated iron surface relative to nonpretreated iron. Activation energies (Ea) of nitrate reduction over the temperature range of 10-45 degrees C were 46.0 kJ mol(-1) for nonpretreated iron, and 32.0 kJ mol(-1) for pretreated iron, indicating chemical reaction control, rather than diffusion. The results indicated that this enhancement was attributed to the increase in active site concentration on iron surface by hydrogen reduction.


Identification of hepatitis C virus 1b-derived peptides recognized by both cellular and humoral immune systems in HCV1b(+) HLA-A24(+) patients.
Despite scientific advances, the therapeutic options for hepatitis C virus (HCV) are limited by poor response rates. HCV1b is particularly resistant to standard interferon therapy. The inhibition of the progression of chronic hepatitis and liver cirrhosis and the prevention of the occurrence and recurrence of hepatocellular carcinoma (HCC) are important and thus, there is a need for new therapeutic modalities for HCV1b infection. We, therefore, investigated highly immunogenic peptides and report in this study three novel candidate peptides (at positions 711-720 in envelope 2 protein, 885-893 in non-structural protein 2 and 1716-1724 in non-structural protein 4B) among 35 peptides of conserved regions of HCV1b proteins containing HLA-A24 binding motifs tested. Namely, HCV(711-720), HCV(885-893) and HCV(1716-1724) induced HLA-A24-restricted and peptide-specific cytotoxic T lymphocytes (CTLs) activity in peripheral blood mononuclear cells (PBMCs) from 7, 6 and 5 of 12 patients and also were recognized by plasma of 8, 5 and 7 of 12 HCV1b(+) patients, respectively. These results may provide new insight into the development of a peptide-based specific immunotherapy for HCV1b(+) HLA-A24(+) patients.


Interaction of bottom-up and top-down neural mechanisms in spatial multi-talker speech perception.
How the human auditory cortex represents spatially separated simultaneous talkers and how talkers' locations and voices modulate the neural representations of attended and unattended speech are unclear. Here, we measured the neural responses from electrodes implanted in neurosurgical patients as they performed single-talker and multi-talker speech perception tasks. We found that spatial separation between talkers caused a preferential encoding of the contralateral speech in Heschl's gyrus (HG), planum temporale (PT), and superior temporal gyrus (STG). Location and spectrotemporal features were encoded in different aspects of the neural response. Specifically, the talker's location changed the mean response level, whereas the talker's spectrotemporal features altered the variation of response around response's baseline. These components were differentially modulated by the attended talker's voice or location, which improved the population decoding of attended speech features. Attentional modulation due to the talker's voice only appeared in the auditory areas with longer latencies, but attentional modulation due to location was present throughout. Our results show that spatial multi-talker speech perception relies upon a separable pre-attentive neural representation, which could be further tuned by top-down attention to the location and voice of the talker.


Effects of catecholamines on eicosanoid synthesis with special reference to prostanoid/leukotriene ratio.
Catecholamines (adrenaline, dopamine, and noradrenaline) stimulate prostanoid synthesis by acting as "cosubstrates." On the other hand, many inhibitors of leukotriene synthesis, such as nordihydroguaiaretic acid and caffeic acid, have a catecholic structure. Catecholamines have opposite effects on prostanoid and leukotriene synthesis in human polymorphonuclear leukocytes and whole blood. Basic phenols (catechol, hydroquinone, and phenol) also increase the prostanoid/leukotriene ratio in polymorphonuclear leukocytes. These actions correlate to their antioxidant capacities and oxidation potentials, and they are not mediated via adrenergic receptors. There is only limited knowledge about the effects of natural catecholamines on the prostanoid/leukotriene ratio in vitro and in vivo. Indirect data suggest that catecholamines could increase prostanoid production in physiological or pathological situations, such as heavy physical exercise, myocardial infarction, and surgical stress. This interaction may also be of clinical importance in asthma, gastric ulcer, and psoriasis, where decreased prostanoid/leukotriene ratios have been reported.


Prognostic impact of the glypican family of heparan sulfate proteoglycans on the survival of breast cancer patients.
Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancer patients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancer patients. We used a public database including both gene expression data and survival information for 3951 breast cancer patients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines. We found that high GPC3 levels were associated with a better prognosis in overall breast cancer patients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival. Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancer patients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.


Changing the electron donor improves azoreductase dye degrading activity at neutral pH.
The oxygen-insensitive azoreductase AzoRo originating from Rhodococcus opacus 1CP was found to be most active at low pH (ca. 4) and high temperature (ca. 50°C). AzoRo is not an efficient biocatalyst when used at low pH due to stability problems. To overcome this issue, we discovered that AzoRo accepts an alternative electron donor, 1-benzyl-1,4-dihydronicotinamide (BNAH), which allows fast turnover at neutral pH. In order to screen this nicotinamide coenzyme mimic as a source of electrons, AzoRo-catalysed reactions were run under neutral conditions, under which typically slow rates are observed with NADH. For the reduction of 1 azo bond by azoreductases 2mol nicotinamide coenzyme are needed. AzoRo displayed Methyl Red (MR) reduction activities with NADH and NADPH of 5.49±0.14Umg-1 and 4.96±0.25Umg-1, respectively, whereas with BNAH it displayed 17.01±0.74Umg-1 (following BNAH oxidation) and 7.16±0.06Umg-1 (following MR reduction). Binding of BNAH to AzoRo was determined with a Km of 18.75±2.45μM (BNAH oxidation) and 12.45±0.47μM (MR reduction). In order to show applicability of this system an upscaled reaction was performed using 78.6μg of purified AzoRo to convert 2.96μmol of MR (total reaction volume: 40ml) within a 1h reaction.


Hematite decorated with nanodot-like cobalt (oxy)hydroxides for boosted photoelectrochemical water oxidation.
Photoelectrochemical (PEC) water splitting has been considered as an alternative process to produce green hydrogen. However, the energy conversion efficiency of PEC systems was still limited by the inefficient photoanode. Cocatalysts decoration is regarded as an efficient strategy for improving PEC performance of photoanode. In this work, nanodot-like cobalt (oxy)hydroxides was rationally decorated on hematite to fabricate CoOOH/Fe2O3 photoanode. The resulted CoOOH/Fe2O3 exhibits a high photocurrent density of 1.92 mA cm-2 at 1.23 V vs. RHE, which is 2.6 times than that of bare Fe2O3. In addition, the onset potential displays a cathodic shift of ca. 110 mV, indicating that CoOOH can efficiently accelerate water oxidation kinetics over Fe2O3. The comprehensive PEC and electrochemical characterizations reveal that CoOOH could not only provide abundant accessible Co active sites for water oxidation, but also could passivate the surface states of Fe2O3, thus increase the carrier density and decrease the interfacial resistance. As a result, the PEC water oxidation performance over Fe2O3 was significantly boosted. This work supports that the roles of CoOOH cocatalyst is generic and such CoOOH could be used for other semiconductor-based photoanodes for outstanding PEC water splitting performance.


Mandatory Nodal Evaluation During Resection of Clinical T1a Non-Small Cell Lung Cancers.
Recommendations for intraoperative lymph node evaluation are uniform regardless of whether a primary tumor is clinical T1a or T2a according to TNM 8th edition for stage I non-small cell lung cancer (NSCLC). We quantified nodal disease risk in patients with T1a disease (≤1 cm). The National Cancer Database was queried for clinical T1a N0 M0 primary NSCLCs ≤1 cm undergoing lobectomy with mediastinal nodal evaluation from 2004-2014. Nodal disease risk was analyzed as a function of demographics and tumor characteristics. Among 2157 cases, 6.7% had occult nodal disease: 5.1% occult N1 and 1.6% N2. Adenocarcinoma (7.5%), large cell carcinoma (25%), and poor differentiation (11.8%) or undifferentiated/anaplastic (25.0%) had high rates of combined pN1 and N2 disease (P < .001). In univariable analysis, odds of pathologic N1, N2, or N1/N2 nodal disease with respect to N0 was greatest for large cell carcinoma (ref. adenocarcinoma odds ratio [OR] 4.31, 3.62, 4.12 respectively; all P < .05), and anaplastic grade (OR 10.71, 13.09, 11.55). Bronchoalveolar adenocarcinomas had the lowest odds (OR 0.41, 0.11, 0.32) and squamous cell carcinoma had lower odds for N2 (OR 0.29, all P < .05). In multivariable analysis only bronchoalveolar adenocarcinomas had lower odds of pathologic N2 and N1/N2 disease with respect to N0. Worsening grade remained significant for pathologic N1 and N1/N2 disease (both P < .05). A significant rate (6.7%) of occult nodal disease is present in primary NSCLCs ≤1 cm. Risk increases with certain histology and worsening grade. We recommend mandatory systematic hilar and mediastinal nodal evaluation for T1a NSCLC tumors for accurate staging and adjuvant therapy.


Utility of nonfluoroscopic three-dimensional electroanatomical mapping in accessory pathways with prior unsuccessful ablation attempts.
Three-dimensional electroanatomic mapping was performed to guide radiofrequency catheter ablation in 17 patients with accessory pathways (APs) who had undergone 2.0 +/- 0.9 previous unsuccessful conventional procedures. In 14 patients, activation mapping was directed at the atrial insertion of the bypass during tachycardia (6 patients) or right ventricular pacing (7 patients) or by mapping atrial stimulus-delta-wave intervals. The ventricular insertion of the bypass was mapped and targeted for ablation in the remaining 3 patients. Successful AP ablation was obtained in all but 1 patient (94%) after a mean of 8 +/- 7 radiofrequency pulses, without recurrences during a mean follow-up of 16 +/- 15 months. On the basis of mapping results and successful ablation outcomes, the most likely causes of previous failed ablation attempts were anatomic or mapping reasons (13 patients), catheter manipulation-related problems (2 patients), and miscellaneous reasons (1 patient).


Enhanced Strategies for Antibiotic Removal from Swine Wastewater in Anaerobic Digestion.
There is a need for techniques that ensure antibiotic removal in anaerobic digesters for robust methane production. In this article, we discuss recent strategies for enhanced antibiotic removal from swine wastewater and offer insights on anaerobic digestion (AD) process design for improved antibiotic removal.


Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean patients.
We sought to determine whether transporter associated with antigen processing (TAP) gene polymorphism is associated with susceptibility to systemic sclerosis (SSc). TAP1 and TAP2 gene polymorphisms were analyzed in 61 Korean patients with SSc and 100 ethnically matched healthy Koreans by polymerase chain reaction-restriction fragment length polymorphism. Human leukocyte antigen (HLA)-DRB1 genotyping data of the patients from our previous study was used for the assessment of independent role of TAP genes to SSc susceptibility. Patients were stratified according to anti-topoisomerase I (anti-topo I) antibody status and clinical subsets of diffuse and limited cutaneous SSc (dcSSc and lcSSc). TAP1 and TAP2 gene polymorphisms were associated with different subsets of SSc: TAP1*A/A genotype with anti-topo I-positive dcSSc (p = 0.01, p corrected = 0.04), TAP2*A1/C genotype with anti-topo I-positive lcSSc (p < 0.05), TAP2*Bky2 and *C alleles with anti-topo I-negative dcSSc (both p < 0.05), and TAP2*B/E genotype with anti-topo I-negative lcSSc (p = 0.004). Although TAP gene associations were generally weak, some associations (TAP2*A1/C, TAP2*C, and TAP2*B/E) with different subsets of SSc were independent of HLA-DR associations, revealing even stronger associations (TAP2*A1/C and TAP2*C) among individuals not possessing the risk HLA-DR alleles. These results suggest the possible role of TAP gene polymorphisms in the genetic susceptibility to SSc.


Increased urinary albumin leakage is related to injuries of glomerular glycocalyx and podocytes, and associated with tubular dysfunction in preeclampsia.
The pathogenesis of preeclampsia (PE) is known to be endothelial cell damage; however, the existence of dysfunction in glomerular endothelial glycocalyx, podocytes and tubules remains unclear. The glomerular endothelial glycocalyx, basement membrane, podocytes, and tubules are permeability barriers against albumin excretion. This study aimed to assess the relationship between urinary albumin leakage and injuries of the glomerular endothelial glycocalyx, podocytes, and tubules in patients with PE. A total of 81 women with uncomplicated pregnancies (control, n = 22), PE (PE, n = 36), or gestational hypertension (GH) (GH, n = 23) were enrolled. We assessed urinary albumin and serum hyaluronan for glycocalyx injuries, podocalyxin for podocytes injuries, and urinary N-acetyl-β-d-glucosaminidase (NAG) and liver-type fatty acid-binding protein (l-FABP) for renal tubular dysfunctions. The serum hyaluronan and the urinary podocalyxin levels were higher in the PE and GH groups. The urinary NAG and l-FABP levels were higher in the PE group. Urinary NAG and l-FABP levels positively correlated with urinary albumin excretion. Our findings suggest that increased urinary albumin leakage is related to injuries of the glycocalyx and podocytes, and associated with tubular dysfunction in pregnant women with PE. The clinical trial described in this paper was registered at the UMIN Clinical Trials Registry under registration number UMIN000047875. URL of registration: https://centre6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054437.


Co-hydrothermal carbonization of swine manure and cellulose: Influence of mutual interaction of intermediates on properties of the products.
Co-hydrothermal carbonization (HTC) of livestock manure and biomass might improve the fuel properties of the hydrochar due to the high reactivity of the biomass-derived intermediates with the abundant oxygen-containing functionalities. However, the complicated compositions make it difficult to explicit the specific roles of the individual components of biomass played in the co-HTC process. In this study, cellulose was used for co-HTC with swine manure to investigate the influence on the properties of the hydrochar. The yield of hydrochar obtained from co-HTC reduced gradually with the cellulose proportion increased, and the solid yield was lower than the theoretical value. This was because the cellulose-derived intermediates favored the stability of the fragments from hydrolysis of swine manure. The increased temperature resulted in the reduction of the hydrochar yield whereas the prolonged time enhanced the formation of solid product. The interaction of the co-HTC intermediates facilitated the formation of O-containing species, thus making the solid more oxygen- and hydrogen-rich with a higher volatility. In addition, the co-HTC affected the evolution of functionalities like -OH and CO during the thermal treatment of the hydrochar and altered its morphology by stuffing the pores from swine manure-derived solid with the microspheres from HTC of cellulose. The interaction of the varied intermediates also impacted the formation of amines, ketones, carboxylic acids, esters, aromatics and the polymeric products in distinct ways.


Effect of grain size and heavy metals on As immobilization by marble particles.
The effect of grain size and the interaction of heavy metals on As sorption by marble waste with different particle sizes was investigated. Acidic solutions containing only arsenic and a mixture of arsenic, lead, zinc, and cadmium were put in contact with the marble waste. The amount of metal(loid)s that were immobilized was calculated using the difference between the concentration in the acidic solution and in the liquid phase of the suspensions. Approximately 420 μg As m(-2) was sorbed onto the marble grains, both nonspecifically and specifically, where ≥ 80 % of the total arsenic in the acidic solution remained soluble, which suggests that this amendment is not effective to immobilize arsenic. However, in mixed contamination, relatively stable Pb-Ca arsenates were formed on the surface of the marble particles, and the soluble arsenic was reduced by 95 %, which indicates that marble particles can effectively immobilize arsenic and lead when both appear together.


Development and validation of a predictive model algorithm to identify anaphylaxis in adults with type 2 diabetes in U.S. administrative claims data.
To use medical record adjudication and predictive modeling methods to develop and validate an algorithm to identify anaphylaxis among adults with type 2 diabetes (T2D) in administrative claims. A conventional screening algorithm that prioritized sensitivity to identify potential anaphylaxis cases was developed and consisted of diagnosis codes for anaphylaxis or relevant signs and symptoms. This algorithm was applied to adults with T2D in the HealthCore Integrated Research Database (HIRD) from 2016 to 2018. Clinical experts adjudicated anaphylaxis case status from redacted medical records. We used confirmed case status as an outcome for predictive models developed using lasso regression with 10-fold cross-validation to identify predictors and estimate the probability of confirmed anaphylaxis. Clinical adjudicators reviewed medical records with sufficient information from 272 adults identified by the anaphylaxis screening algorithm, which had an estimated Positive Predictive Value (PPV) of 65% (95% confidence interval [CI]: 60%-71%). The predictive model algorithm had a c-statistic of 0.95. The model's probability threshold of 0.60 excluded 89% (84/94) of false positives identified by the screening algorithm, with a PPV of 94% (95% CI: 91%-98%). The model excluded very few true positives (15 of 178), and identified 92% (95% CI: 87%-96%) of the cases selected by the screening algorithm. Predictive modeling techniques yielded an accurate algorithm with high PPV and sensitivity for identifying anaphylaxis in administrative claims. This algorithm could be considered in future safety studies using similar claims data to reduce potential outcome misclassification.


Telangiectatic soft tissue sarcoma and chronic expanding haematoma: a comparative review of MRI features.
Soft tissue sarcomas containing a dominant component of haemorrhage are known to be aggressive tumours associated with a poor prognosis. Importantly, the clinical behaviour and imaging characteristics of extensively haemorrhagic soft tissue sarcomas (also termed telangiectatic soft tissue sarcomas) can resemble those of benign haematomas, particularly those that continue to expand over a prolonged period, so-called chronic expanding haematomas (CEH). The following review evaluates the current literature to identify the clinical, imaging and pathological characteristics of telangiectatic soft tissue sarcomas and to determine features that may help distinguish them from CEH. Ultimately, we suggest that lesions with sizeable regions of internal haemorrhage should be regarded with a high degree of suspicion for underlying malignancy and require referral to a tertiary sarcoma centre, where a carefully planned approach to biopsy and follow-up is needed to avoid errors in diagnosis.


LncRNA XIST Promotes Pancreatic Cancer Proliferation Through miR-133a/EGFR.
According to recent studies, long non-coding RNA X-inactive specific transcript (XIST) is involved in the development and progression of many malignant tumors including pancreatic cancer. We validated the detailed role of XIST in human pancreatic cancer (PC) cell lines and PC tissues so as to determine its exact function and the mechanism by which it affected PC proliferation. In our research, lncRNA-XIST was specifically upregulated in PC tissues and cell lines, and high XIST expression in PC was related to poorer prognosis (larger tumor size, perineural invasion, lymph node micrometastases, and shorter overall survival). XIST augmented PC cell proliferation. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes. In the present study, XIST and miR-133a reciprocally inhibited each other in PC cells. Exogenous miR-133a expression significantly inhibited PC cell proliferation. Moreover, as exhibited by luciferase reporter gene assays, miR-133a bound to XIST and the 3'UTR of EGFR by direct targeting. In PC tissues, miR-133a expression was down-regulated and EGFR expression was up-regulated; miR-133a was inversely correlated with EGFR and XIST, respectively; XIST was positively correlated with EGFR. Taken together, these findings will shed light on the role and mechanism of XIST/miR-133a/EGFR in regulating PC cells proliferation. XIST may serve as a potential therapeutic target in PC in the future. J. Cell. Biochem. 118: 3349-3358, 2017. © 2017 Wiley Periodicals, Inc.


A quantitative approach to resource effectiveness assessment: Application in the Urmia Lake Basin.
This paper aims to present a new quantitative systematic approach to evaluate the effectiveness of utilizing and allocating resources based on the concept of "Work" in physics. This method is examined in the Urmia Lake Basin (ULB), shrinking of which has threatened the life of about five million inhabitants and ecosystem biodiversity. In the proposed approach, the role of three types of financial, human, and environmental resources in the development process is evaluated quantitatively, and they have been compared in two periods before and after the severe reduction of the lake water volume. Results show that although financial resources have increased by 1.9 times in the second period, the effectiveness of the development process has decreased. Therefore, the resources have not been utilized properly in a direction compatible with sustainable development strategies. Additionally, the improperly-spent financial resources on the development projects especially in the second period have had a more destructive role than the human and environmental resources in the ULB crisis.


Assessment of the role of aptitude in the acquisition of advanced laparoscopic surgical skill sets: results from a virtual reality-based laparoscopic colectomy training programme.
The surgeons of the future will need to have advanced laparoscopic skills. The current challenge in surgical education is to teach these skills and to identify factors that may have a positive influence on training curriculums. The primary aim of this study was to determine if fundamental aptitude impacts on ability to perform a laparoscopic colectomy. A practical laparoscopic colectomy course was held by the National Surgical Training Centre at the Royal College of Surgeons in Ireland. The course consisted of didactics, warm-up and the performance of a laparoscopic sigmoid colectomy on thesimulator. Objective metrics such as time and motion analysis were recorded. Each candidate had their psychomotor and visual spatial aptitude assessed. The colectomy trays were assessed by blinded experts post procedure for errors. Ten trainee surgeons that were novices with respect to advanced laparoscopic procedures attended the course. A significant correlation was found between psychomotor and visual spatial aptitude and performance on both the warm-up session and laparoscopic colectomy (r > 0.7, p < 0.05). Performance on the warm-up session correlated with performance of the laparoscopic colectomy (r = 0.8, p = 0.04). There was also a significant correlation between the number of tray errors and time taken to perform the laparoscopic colectomy (r = 0.83, p = 0.001). The results have demonstrated that there is a relationship between aptitude and ability to perform both basic laparoscopic tasks and laparoscopic colectomy on a simulator. The findings suggest that there may be a role for the consideration of an individual's inherent baseline ability when trying to design and optimise technical teaching curricula for advanced laparoscopic procedures.


An open-labelled study of the safety, acute metabolic activity and pharmacokinetic profile of a short-term course of recombinant human growth hormone in healthy volunteers.
The safety and short-term biological effects of recombinant human GH (Genotropin, KmbiVitrum AB, Stockholm, Sweden), given i.m. (8 IU/d) for 4 consecutive days to 10 healthy male volunteers, have been evaluated. No adverse reactions were detected by clinical investigation. Haematological parameters, clinical chemistry and the acute phase inflammatory profile showed no negative effects of the drug. The well-known metabolic effects of GH were seen as an increase in free fatty acids and in the somatomedin level (IGF-1). No antibodies to GH or periplasmic Escherichia coli peptides developed during the first month after treatment. The peak plasma level of hGH (62 +/- 20 mU/l) occurred between 3.0 and 3.5 h. This study shows that recombinant hGH induces no toxic or other adverse reactions and that the acute metabolic effects and the pharmacokinetic profiles are comparable to those reported after injections of GH extracted from pituitary glands.


Discovery of a novel IKK-β inhibitor by ligand-based virtual screening techniques.
Various inflammatory stimuli that activate the nuclear factor kappa B (NF-κB) signaling pathway converge on a serine/threonine kinase that displays a key role in the activation of NF-κB: the I kappa B kinase β (IKK-β). Therefore, IKK-β is considered an interesting target for combating inflammation and cancer. In our study, we developed a ligand-based pharmacophore model for IKK-β inhibitors. This model was employed to virtually screen commercial databases, giving a focused hit list of candidates. Subsequently, we scored by molecular shape to rank and further prioritized virtual hits by three-dimensional shape-based alignment. One out of ten acquired and biologically tested compounds showed inhibitory activity in the low micromolar range on IKK-β enzymatic activity in vitro and on NF-κB transactivation in intact cells. Compound 8 (2-(1-adamantyl)ethyl 4-[(2,5-dihydroxyphenyl)methylamino]benzoate) represents a novel chemical class of IKK-β inhibitors and shows that the presented model is a valid approach for identification and development of new IKK-β ligands.


Evaluation of the different sleep-disordered breathing patterns of the compressed tracheal sound.
Suitability of the compressed tracheal sound signal for screening different sleep-disordered breathing patterns was evaluated. The previous results suggest that the plain pattern in the compressed sound signal represents mostly normal, unobstructed breathing, the thick pattern consists of periodic apneas/hypopneas and during the thin pattern, flow limitation in the nasal cannula signal is abundant. Twenty-seven patients underwent a polysomnography with a tracheal sound and oesophageal pressure monitoring. The tracheal sound data was compressed and scored visually into three different breathing patterns. The percentage of oesophageal pressure values under -8cm H2O, the minimum pressure value and the average duration of the breathing cycles were extracted from 10-min episodes of those plain, thick and thin patterns. In addition, the spectral contents of the tracheal sound during the different breathing patterns were evaluated. The percentage of time when the oesophageal pressure negativity increased was highest during the thin pattern and lowest during the plain pattern. In addition, the thin pattern presented most high frequency components in the 1001-2000Hz frequency band of the tracheal sound. The results confirmed our previous findings that both the thick and thin patterns seem to consist of obstructed breathing, whereas during the plain pattern the breathing is normal, unobstructed. Most screening methods for sleep-disordered breathing reveal only periodic apneas/hypopneas, but with the compressed sound signal the sustained partial obstruction can be estimated as well.


Arsenic induced apoptosis in rat liver following repeated 60 days exposure.
Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 microM) concentration. The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis.


Team-Based Coaching Intervention to Improve Contrast-Associated Acute Kidney Injury: A Cluster-Randomized Trial.
Up to 14% of patients in the United States undergoing cardiac catheterization each year experience AKI. Consistent use of risk minimization preventive strategies may improve outcomes. We hypothesized that team-based coaching in a Virtual Learning Collaborative (Collaborative) would reduce postprocedural AKI compared with Technical Assistance (Assistance), both with and without Automated Surveillance Reporting (Surveillance). The IMPROVE AKI trial was a 2×2 factorial cluster-randomized trial across 20 Veterans Affairs medical centers (VAMCs). Participating VAMCs received Assistance, Assistance with Surveillance, Collaborative, or Collaborative with Surveillance for 18 months to implement AKI prevention strategies. The Assistance and Collaborative approaches promoted hydration and limited NPO and contrast dye dosing. We fit logistic regression models for AKI with site-level random effects accounting for the clustering of patients within medical centers with a prespecified interest in exploring differences across the four intervention arms. Among VAMCs' 4517 patients, 510 experienced AKI (235 AKI events among 1314 patients with preexisting CKD). AKI events in each intervention cluster were 110 (13%) in Assistance, 122 (11%) in Assistance with Surveillance, 190 (13%) in Collaborative, and 88 (8%) in Collaborative with Surveillance. Compared with sites receiving Assistance alone, case-mix-adjusted differences in AKI event proportions were -3% (95% confidence interval [CI], -4 to -3) for Assistance with Surveillance, -3% (95% CI, -3 to -2) for Collaborative, and -5% (95% CI, -6 to -5) for Collaborative with Surveillance. The Collaborative with Surveillance intervention cluster had a substantial 46% reduction in AKI compared with Assistance alone (adjusted odds ratio=0.54; 0.40-0.74). This implementation trial estimates that the combination of Collaborative with Surveillance reduced the odds of AKI by 46% at VAMCs and is suggestive of a reduction among patients with CKD. IMPROVE AKI Cluster-Randomized Trial (IMPROVE-AKI), NCT03556293.


Corrigendum: Altered composition of the oral microbiota in depression among cigarette smokers: A pilot study.
[This corrects the article DOI: 10.3389/fpsyt.2022.902433.].


[The function of the human posterior vertical canal and the extent of central compensation in unilateral dissection of the vestibular nerve].
The vestibular nerve innervates the semicircular canals through two branches. The first branch innervates the anterior vertical and the horizontal canals and the second branch innervates the posterior vertical canal. In transtemporal neurectomy the dissection of the vestibular nerve was sometimes only in the upper part. In these cases the fibres to the posterior vertical canal are still intact. In Düsseldorf 41 patients were treated by transtemporal neurectomy from 1970 until 1977. Five of these patients show an incomplete dissection of the vestibular nerve. They had a normal endolymph circulation with afferent nerve fibres only from the posterior vertical canal. These patients were examined by caloric and rotatory stimulation in different head positions. Vertical and horizontal eye movements were simultaneously recorded. The stimulation of the posterior vertical canal shows a rotatory eye movement. The results were compared with the second Ewald law.


Predicting pain after Cesarean delivery: pressure algometry, temporal summation, three-item questionnaire.
Approximately one in five women will experience severe postoperative pain after Cesarean delivery (CD). Previously, a bedside three-item questionnaire (3-IQ) has shown to predict women experiencing higher evoked pain intensity after CD, with an area under the receiver operator characteristics (ROC) curve of 0.72. We hypothesized that the addition of psychophysical pain tests to the existing 3-IQ would improve the ability to predict severe pain in women undergoing elective CD under spinal anesthesia METHODS: This was a prospective cohort study on women undergoing elective CD under spinal anesthesia. Women were assessed preoperatively using the 3-IQ, pressure algometry (PA) and mechanical temporal summation (TS) response. All women received standard perioperative care, including a multimodal analgesia regimen that included intrathecal fentanyl and morphine. A 0-100 mm visual analogue scale (VAS) was used to assess the severity of pain at rest (VASr) and on movement (VASm) at 24 and 48 hr after surgery. Patient satisfaction and opioid consumption were also recorded. We performed ROC curve analyses to assess whether we could improve the ability to predict our primary outcome of severe pain on movement at 24 hr (VASm24 ≥ 70). We studied 195 women. Median [interquartile range] VASm24 was 53 [32-72] and 28% of patients experienced a VASm24 ≥ 70. The ability to predict a VASm24 ≥ 70 assessed by the area under the ROC curve was 0.64 using the 3-IQ and 0.67 using the 3-IQ combined with TS and PA. The addition of PA and TS to the 3-IQ model resulted in a predictive model that performed similarly to the 3-IQ model alone. Further research is warranted in this area to better predict women at risk of severe pain post CD.


Dissociation of urethral and anal sphincter activity in neurogenic bladder dysfunction.
In 53 patients with suspected neurogenic bladder dysfunction carbon dioxide cystometry was done in combination with urethral and anal sphincter electromyography. Complete dissociation between the reflex activity of the 2 sphincters was found in 25 per cent of the patients and only 58 per cent of the patients had identical reflex activity. It is concluded that anal sphincter electromyography is highly unreliable in the diagnosis of urethral sphincter dysfunction.


Evaluation of short-term efficacy of extraspinal cementoplasty for bone metastasis: A monocenter study of 31 patients.
To study the effect on pain of per-cutaneous cementoplasty for painful extraspinal bone metastasis. 43 patients with extraspinal bone metastasis were included between April 2006 and October 2014 in this retrospective monocenter study. The primary endpoint was pain level measured on a 0-10 numeric rating scale at week 1 after cementoplasty as compared with pre-cementoplasty. Secondary endpoints were long-term pain level and impact on quality of life and disability. Mean pain score was 4.2 (SD ±3.6) before cementoplasty and 1.09 (SD ±2.4) at week 1 (p = 0.005) (n = 31 patients). At 22 months after cementoplasty, quality of life and disability improved (according to the patient global assessment) for 47.6% and 52.2% of patients (n = 21patients). We did not find a predictor of good response. Cement leakage was the most common adverse event. Percutaneous cementoplasty of extraspinal bone metastasis is a rapidly efficient treatment with few adverse events. Its efficacy persists over time, with a benefit for disability and quality of life. Although this technique is only palliative, it should be considered in this situation.


Color Doppler twinkling artifact in a calcified liver mass.
Twinkling artifact in color Doppler imaging is related both to the presence of a strongly reflective structure and to the scanner's settings. This artifact has been described in association with calculi and various foreign bodies, but to our knowledge it has not been reported in a hepatic mass. If a calcified hepatic mass is examined with color Doppler Mapping without using spectral Doppler analysis, misinterpreted as real blood flow and lead to the erroneous of hypervascular mass.


Clinical implications of experiments on alteration of the labyrinthine fluid pressures.
Hearing is affected by changes in hydrostatic pressure of the perilymph, but very high pressures are required to produce a significant loss. Among the observed findings in cats are a rapidly reversible decrease in the sensitivity of the cochlear microphonic that is greater for low frequencies, harmonic distortion and reduction of dynamic range as measured by the input-output function for the cochlear microphonic, and a change in the summating potential from negative to positive. These changes are attributed to a temporary reduction in the size of the cochlear duct due to a shift of water molecules out of the cochlear duct into the blood until the resulting increase in osmotic pressure balances the increase in hydrostatic pressure. Consequently, the organ of Corti is biased "upward" away from the scala tympani. Increasing the hydrostatic pressure of the endolymph produces a "downward" biasing of the organ of Corti and has an opposite effect upon the summating potential. Presumably this is what happens in Meniere's disease. Because of the presence of the perilymphatic canaliculi, the locus of the hydrostatic pressure effect is assumed to be in the region of the reticular lamina. A theory has been developed to explain why cochlear function is very sensitive to relative differences between the hydrostatic pressures of the perilymph and the endolymph but is resistant to large variations in the absolute magnitudes of those pressures. Some of the clinical implications of this theory are discussed.


Prevalence of heavy episodic drinking and alcohol use disorder diagnosis among US college students: Results from the national Healthy Minds Study.
Alcohol use is a common, recognized problem on college campuses. This study examined alcohol use in a national sample of US college students across 78 campuses. Using four waves of data from the Healthy Minds Study (2015-2019), we explored variations by student demographics in prevalence of recent: alcohol consumption, heavy episodic drinking (HED, 4/5 + drinks in one sitting), frequent HED (3 + HED events), and lifetime alcohol use disorder (AUD) diagnosis. Stratified analyses and logistic regression with response propensity weights were used. Two-thirds of students consumed alcohol and roughly-one-third engaged in HED in the past 2 weeks. Alcohol use was more common among students who: identified as cis women/men, bisexual or gay/lesbian/queer, white non-Hispanic, lived in Greek housing or off-campus, were not first generation, or those not rating religion as important. Prevalence of HED among recent drinkers was high (56.7%) but varied by gender identity, race-ethnicity, living situation, and religiosity. In addition, higher HED prevalence was reported among: international, undergraduate, and underage (under 21) students. There was little variation in HED by sexual orientation identity or first generation status among recent drinkers. In a sub-sample of students engaging in frequent HED, AUD diagnosis was uncommon (1.4%) and less likely among students identifying as: cis women/men, heterosexual, racial-ethnic minorities (particularly Asian/Asian American or Pacific Islander), international, religious, or living in Greek housing. Alcohol use continues to be a part of college life, while screening and treatment remains rare. There are opportunities for improved programming and outreach acknowledging college student diversity.


Effect of weight loss on menstrual function in adolescents with polycystic ovary syndrome.
To compare the effects of a hypocaloric low-fat diet with those of a very low carbohydrate diet on body mass index (BMI), waist circumference (WC), and menstrual function in overweight adolescent females with polycystic ovary syndrome (PCOS). Randomized pilot trial of two diets in a prospective, 12-week study. A hospital-based, academic adolescent medicine division. 24 females, age 12-22 years (mean 15.8 ± 2.2), with PCOS and a BMI above the 85(th) percentile for age (mean 35.7 ± 6.0 kg/m(2)). Nutrition counseling was given biweekly, and dietary compliance, menstrual history, and weight were recorded. WC was measured at the beginning and end of the study. Changes in weight, BMI, WC, and improvement in menstrual function over the course of the study period. 16 participants completed the study. 12 completers menstruated during the study period, 8 with regularity. The number of periods over 3 months increased from 0.6 ± 0.6 pre-treatment to 1.6 ± 1.3 post-treatment (P = 0.003). Overall, weight loss averaged 6.5% (P < 0.0001) and the WC decreased by an average of 5.7 ± 7.7 cm (P = 0.01). Those who lost weight were 3.4 times more likely to have improved menstrual function (P = 0.001). There were no statistically significant differences between the two groups. Weight loss is feasible in adolescents with PCOS and results in significant improvements in BMI, WC, and menstrual function. Weight management may be preferable as first-line treatment in adolescents, because it targets both the menstrual dysfunction and risk factors for long-term morbidity associated with PCOS.


Familial alcoholism: evidence from 237 alcoholics.
When male alcoholics with and without a positive family history were compared, differences were found in age of onset, age of presentation, severity of alcoholism, and severity of self-reported antisocial behaviour. No such differences were found for women. The implications of these findings for the concept of 'familial alcoholism' are discussed.


Strategies for the identification of arginine ADP-ribosylation sites.
Mono-ADP-ribosylation of arginine is a protein modification in eukaryotic cells regulating protein activity and thereby influencing signal transduction and metabolism. Due to the complexity of the modification and the fragmentation pattern in MS/MS CID experiments, the identification of ADP-ribosylation sites in complex mixtures is difficult. Here we describe a two-step strategy, in the first step enriching and identifying potentially ADP-ribosylated proteins and in the second step identifying the sites of modification by a combination of LC/MS-, LC/MS(E) (MS at elevated fragmentation energy)- and LC/MS/MS experiments. Using this technique we could identify two ADP-ribosylation sites in TNFα digested with trypsin, protease V8 and both proteases and thereby demonstrate the specific ADP-ribosylation of TNFα. In complex samples the detection of ADP-ribosylated peptides requires further enrichment of the modified peptides. We tested various materials routinely used for the isolation of phosphopeptides. IMAC as well as TiO(2) chromatography were successfully applied for the selective enrichment of ADP-ribosylated model peptides.


Reducing Barriers to Autism Screening in Community Primary Care: A Pragmatic Trial Using Web-Based Screening.
To determine whether an intervention addressing both logistical and knowledge barriers to early screening for autism spectrum disorder (ASD) increases evidence-based screening during 18-month well-child visits and primary care providers' (PCPs') perceived self-efficacy in caring for children with ASD. Forty-six PCPs from 10 diverse practices across four counties in Washington State participated. PCPs attended a 2-hour training workshop on early recognition and care for toddlers with ASD and use of a REDCap-based version of the Modified Checklist for Autism in Toddlers-Revised with Follow-up (webM-CHAT-R/F) that provided automated presentation and scoring of follow-up questions. Data were collected at baseline and 6 months following each county's training window. PCPs' screening methods and rates and perceived self-efficacy regarding ASD care were measured by self-report and webM-CHAT-R/F use was measured via REDCap records. At follow-up, 8 of the 10 practices were using the webM-CHAT-R/F routinely at 18-month visits. The proportion of PCPs reporting routine M-CHAT screening increased from 82% at baseline to 98% at follow-up (16% increase, 95% confidence interval [CI] 3%-28%; McNemar exact P = .02). The proportion using the M-CHAT-R/F follow-up interview questions increased from 33% to 82% (49% increase, 95% CI 30%-68%, exact McNemar test, P < .001). Significant increases in self-efficacy were found for all seven areas assessed (Ps ≤ .008). This brief intervention increased PCPs' self-reported valid use of the M-CHAT-R/F at 18 months and their self-efficacy regarding ASD care. Combining educational information with a web-based ASD screen incorporating the M-CHAT-R/F follow-up questions may increase universal ASD screening with improved fidelity.


Silk fibroin H-fibroin/poly(ε-caprolactone) core-shell nanofibers with enhanced mechanical property and long-term drug release.
The scaffold materials with good mechanical and structural properties, controlled drug release performance, biocompatibility and biodegradability are important tenet in tissue engineering. In this work, the functional core-shell nanofibers with poly(ε-caprolactone) (PCL) as shell and silk fibroin heavy chain (H-fibroin) as core were constructed by emulsion electrospinning. The transmission electron microscopy confirmed that the nanofiber with core-shell structure were successfully prepared. The constructed nanofiber materials were characterized by the several characterization methods. The results showed that ethanol treatment could induce the formation of β-sheet of H-fibroin in composite nanofibers, thus improving the mechanical properties of PCL/H-fibroin nanofiber scaffold. In addition, we evaluated the potential of PCL/H-fibroin nanofiber membrane as a biological scaffold. It was found that PCL/H-fibroin nanofiber scaffold was more conducive to cell adhesion and proliferation with the increment of H-fibroin. Finally, in vitro drug release presented that PCL/H-fibroin core-shell nanofibers could effectively reduce the prophase burst of drug molecules and show the sustained drug release. The PCL/H-fibroin nanofiber scaffolds constructed in this work have good mechanical properties, biocompatibility, and display good potential in biomedical applications, such as drug carriers, tissue engineering and wound dressings, etc.


Regression of CD30-positive large cell transformation arising on patch lesion of early mycosis fungoides.
CD30-positive large cell transformation that occurs in early mycosis fungoides potentially possesses characteristics of spontaneous regression as with CD30-positive lymphoproliferative disorders. Such transformation may not relate to poor prognosis.


Gene involved in transcriptional activation of the hrp regulatory gene hrpG in Xanthomonas oryzae pv. oryzae.
A novel regulatory gene, trh, which is involved in hrp gene expression, is identified in the plant pathogen Xanthomonas oryzae pv. oryzae. In the trh mutant, expression of HrpG, which is a key regulator for hrp gene expression, is reduced both under the in vitro hrp-inducing condition and in planta.


Indications and results of skin flaps in painful digital neuroma.
Of the many procedures for treating painful neuromas, resection and proximal translocation are the most usual techniques, but these can decrease distal sensibility increasing deafferentation pain. In cases of intricate pain (nociception plus deafferentation), certain types of flaps allow the treatment of both components of the pain. We have used 30 such flaps in 28 patients: local flaps (exchange, advancement or lasso island flaps) and distant flaps (free "custom-made" toe flaps). The results of the different techniques provides 86.6% excellent or good results.


Major myofibrillar changes in early onset myopathy due to de novo heterozygous missense mutation in lamin A/C gene.
Mutations in the lamin A/C gene (LMNA) have been associated with neuromuscular diseases and more complex syndromes, involving bone and adipose tissue. We report on a case of early onset myopathy due to a heterozygous LMNA mutation in exon 9, characterized by the presence of a marked number of cytoplasmic bodies with extensive myofibrillar abnormalities and Z-disk disruption in skeletal muscle. This case suggests there is a need to increase the list of genes to be screened in patients with myofibrillar myopathy.


Deleting "fear" from "fear extinction": Estimating the individual extinction rate via non-aversive conditioning.
Individual differences in extinction learning have attracted ample attention of researchers and are under investigation as a marker for the onset of anxiety disorders and treatment response. Unfortunately, the common paradigm for obtaining the extinction rate, which entails aversive stimulus pairings, is subject to practical limitations. Therefore, the present study assessed whether the use of an aversive stimulus is actually needed to get a good estimate of the extinction rate. A total of 161 undergraduate students completed a conditioning task with both an aversive and a non-aversive stimulus. Using latent class growth analysis (LCGA), distinct trajectories, representing normal and stunted extinction learning, were identified for both these stimulus types. Participants' membership in these classes largely overlapped for aversive and non-aversive stimulus pairings and respective extinction indices were significantly correlated. Thereby, findings suggest that the use of a non-aversive stimulus could suffice for successfully capturing individual differences in extinction learning. However, future studies are needed to confirm that conditioning with a non-aversive stimulus may serve to predict clinically relevant outcomes.


An active inference perspective on the negative symptoms of schizophrenia.
Predictive coding has played a transformative role in the study of psychosis, casting delusions and hallucinations as statistical inference in a system with abnormal precision. However, the negative symptoms of schizophrenia, such as affective blunting, avolition, and asociality, remain poorly understood. We propose a computational framework for emotional expression based on active inference-namely that affective behaviours such as smiling are driven by predictions about the social consequences of smiling. Similarly to how delusions and hallucinations can be explained by predictive uncertainty in sensory circuits, negative symptoms naturally arise from uncertainty in social prediction circuits. This perspective draws on computational principles to explain blunted facial expressiveness and apathy-anhedonia in schizophrenia. Its phenomenological consequences also shed light on the content of paranoid delusions and indistinctness of self-other boundaries. Close links are highlighted between social prediction, facial affect mirroring, and the fledgling study of interoception. Advances in automated analysis of facial expressions and acoustic speech patterns will allow empirical testing of these computational models of the negative symptoms of schizophrenia.


Interventional pulmonologist perspective: treatment of malignant pleural effusion.
The management of known malignant pleural effusions focuses around the initial thoracentesis and subsequent objective and subjective findings. A completely reexpanded lung after fluid removal and with symptomatic improvement predicts successful pleurodesis. Pleurodesis method depends on center expertise as well as patient preference. Medical thoracoscopy does not require the operating room setting and is performed on the spontaneously breathing patient with similar success rate to surgical thoracoscopy in the appropriately selected patients. However, it is not widely available. Talc insufflation is preferred for even distribution of sprayed particles to pleural surfaces. Most often, patients can be discharged home within 24 to 48 hours after continuous chest tube suction. Indwelling pleural catheter has become popular given the ease of insertion and patient centered home drainage. Coordinated care with good patient and family education and support is paramount to maximizing the beneficial potential of the catheter. Complications are minimal, and catheters are easily removed if patients can no longer benefit from drainage, or if pleurodesis has occurred. In the setting of trapped lung as a result of visceral pleura encasement from tumor, indwelling catheter can still be useful if the patient improves with thoracentesis. However, if no subjective improvement is seen after thoracentesis for trapped lung, then no procedure is recommended and other modes of palliation should be sought.