Volvulus of the transverse colon after resection of the sigmoid volvulus: A case report.
Sigmoid volvulus is a common cause of colon obstruction, while volvulus of the transverse colon rarely causes bowel obstruction. The occurrence of transverse colon volvulus after resection of the sigmoid colon volvulus is extremely rare. This report presents a 73-year-old man who presented with abdominal pain and peritonitis. The patient underwent exploratory laparotomy, and sigmoid volvulus and cecum perforation were confirmed. A right hemicolectomy, end-to-side ileotransverse colon anastomosis for the cecal perforation, and sigmoidectomy with end-colostomy (Hartmann's procedure) for the sigmoid volvulus were performed. A month later, the patient returned to the emergency room with abdominal distention and the blockage of colostomy. Abdominal CT revealed a transverse colon volvulus. A transverse and descending colon resection and ileorectal anastomosis were performed. The patient's condition was stable at the time of discharge from the hospital. The management of metachronous colon volvulus should include surgical intervention. If patients are not diagnosed immediately, their condition may deteriorate dramatically because of bowel infarction or peritonitis. It is essential to highlight this case, as many surgeons may not have attended a transverse colon volvulus after sigmoid volvulus, which might lead to high morbidity or mortality. Overall, metachronous colonic volvulus must be considered in the differential diagnosis of bowel obstruction, particularly in patients with significant risk factors.


Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles.
Decisions on the fate of cells and their functions are dictated by the spatiotemporal dynamics of molecular signalling networks. However, techniques to examine the dynamics of these intracellular processes remain limited. Here, we show that magnetic nanoparticles conjugated with key regulatory proteins can artificially control, in time and space, the Ran/RCC1 signalling pathway that regulates the cell cytoskeleton. In the presence of a magnetic field, RanGTP proteins conjugated to superparamagnetic nanoparticles can induce microtubule fibres to assemble into asymmetric arrays of polarized fibres in Xenopus laevis egg extracts. The orientation of the fibres is dictated by the direction of the magnetic force. When we locally concentrated nanoparticles conjugated with the upstream guanine nucleotide exchange factor RCC1, the assembly of microtubule fibres could be induced over a greater range of distances than RanGTP particles. The method shows how bioactive nanoparticles can be used to engineer signalling networks and spatial self-organization inside a cell environment.


Social isolation stress down-regulates cortical early growth response 1 (Egr-1) expression in mice.
Social isolation stress induces behavioral disturbances such as aggression, cognitive impairments, and deficits in prepulse inhibition in mice. Social isolation mice have, therefore, been studied as an animal model of neuropsychiatric disorders such as schizophrenia. Recently, the decrease in early growth response (Egr) gene expression levels were reported in the post-mortem brains of schizophrenia patients. In this study, we investigate the effects of social isolation stress on the expression levels of Egr mRNA and protein in the frontal cortex. Social isolation stress exposure significantly down-regulated the expression of Egr-1 protein and Egr-1 gene transcript in nucleus of cortical neurons in a manner dependent on a social isolation period. This stress had no effect on the expression level of Egr-1 in the striatum or the expression levels of other Egr family members (Egr-2, -3, and -4) in the frontal cortex. These results suggest that the decrease in Egr-1 expression in the frontal cortex may be involved in social isolation stress-induced behavioral abnormalities.


A three dimensional view of stereopsis in dentistry.
Stereopsis and its role in dental practice has been a topic of debate in recent editions of this Journal. These discussions are particularly timely as they come at a point when virtual reality simulators are becoming increasingly popular in the education of tomorrow's dentists. The aim of this article is to discuss the lack of robust empirical evidence to ascertain the relationship (if any) between stereopsis and dentistry and to build a case for the need for further research to build a strong evidence base on the topic.


Cost and Factors Associated With the Hospitalization of Patients Undergoing Heart Transplantation.
The aim of the study was to describe the cost and factors associated with the hospitalization of patients undergoing heart transplantation. A cross-sectional, descriptive study with a quantitative approach developed at an important heart transplant center in southern Brazil. Twenty patients who had undergone transplantation during the period 2007 to 2016 were included in the study. Central tendency measures and values presented as mean ± SD or median and quartiles were calculated. Multiple linear regression was performed to verify the variables that interfered with the cost. The cost of hospitalization of patients undergoing heart transplantation was $522,997.26 in Brazilian reals ($220,002.58 in US dollars). The Brazilian public health system was responsible for paying the hospital bill of all patients. Female sex, patients up to 40 years of age, and length of stay in the hospital units were variables that were related to the highest values for the hospital service. Clinical complications of the patients during the hospitalization period were also factors that were related to the greater length of stay in the hospitalization units, reflecting higher expenses for the health institution. There is a need for health managers to implement strategies that will minimize complications, such as health care-related infections, that can be prevented during hospitalization and to stimulate the allocation of resources in order to improve care and reduce hospital expenses.


Spindle positioning: going against the actin flow.
Successful completion of meiosis in vertebrate oocytes requires the localization and maintenance of the meiotic spindle at the cell cortex. Arp2/3-nucleated actin filaments are now shown to flow away from the cortex overlying the spindle, resulting in cytoplasmic streaming, which maintains the spindle in its asymmetric position.


The membrane systems of the cardiac muscle cell of Euchaeta norvegica Boeck (crustacea, copepoda).
The membrane systems of the cardiac muscle cell of the copepod Euchaeta norvegica Boeck are described. The heart wall, which is between 0.12 and 1.36 micrometer thick, consists of an epicardium and a single layer of muscle cells. Invaginations of the sarcolemma forming transverse tubules have been found at all levels of the sarcomere with the exception of the H-band level. The longitudinal tubules of the same system are closely associated with the sarcoplasmic reticulum to form interior couplings at the A-I level of the sarcomere. Triadic couplings at the Z band level were not seen in E. norvegica, but peripheral couplings were demonstrated. Nex-uses were found in the intercalated discs.


Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema.
A patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was studied with serial diffusion-weighted MRI (DWI) after stroke-like episodes and the apparent diffusion coefficient (ADC) was measured in an infarct-like lesion. In the acute and subacute stages, the affected area gave high signal on DWI and its ADC was much lower than that in a normal control region. In the chronic stage, the ADC became higher than that in normal brain. We therefore suggest that the stroke-like episodes did not cause vasogenic oedema but were related to energy failure and cytotoxic oedema.


Formation of trihalomethanes and haloacetic acids from 2,6-dichloro-1,4-benzoquinone during chlorination: Decomposition kinetics, conversion rates, and pathways.
As a typical aromatic disinfection byproduct (DBP), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) attracts much concern due to the potential toxicity. To further evaluate the role of 2,6-DCBQ as an intermediate DBP in water with or without chlorine, their decomposition characteristics and transformation potential to the regulated DBPs (i.e., trihalomethanes (THMs) and haloacetic acids (HAAs)) were investigated under different chlorine doses, pH values, temperatures, contact times, and bromide levels. The decomposition of 2,6-DCBQ under different conditions all fit apparent first-order kinetics. The hydrolysis rate constants of 2,6-DCBQ significantly increased with pH. The half-live values of 2,6-DCBQ were 108.3-568.7 h at pH 6.0-6.5, and 1.8-31.1 h at pH 7.0-8.5. During the hydrolysis of 2,6-DCBQ, there was no THMs and HAAs generated. During chlorination, 2,6-DCBQ decayed rapidly accompanied by the fast formation of trichloromethane (TCM) and the gradual generation of dichloroacetic acid and trichloroacetic acid. The molar conversion rates of 2,6-DCBQ-to-THMs (i.e., TCM) and 2,6-DCBQ-to-HAAs were 2.9-10.0% and 0.1-2.2% under different conditions. The presence of bromide increased the conversion rates of 2,6-DCBQ-to-THMs and caused the generation of brominated THMs and HAAs. According to the decomposition characteristics of 2,6-DCBQ and the formation trends of THMs and HAAs under different conditions, multiple formation pathways from 2,6-DCBQ to THMs and HAAs were proposed.


Human elastin-like polypeptides as a versatile platform for exploitation of ultrasensitive bilirubin detection by UnaG.
A new, bifunctional recombinant protein was expressed as the fusion product of human elastin-like polypeptide (HELP) and the bilirubin-binding protein UnaG. The engineered product displays both the HELP-specific property of forming a functional hydrogel matrix and the UnaG-specific capacity of emitting green fluorescence upon ligand binding. The new fusion protein has been proven to be effective at detecting bilirubin in complex environments with high background noise. A cell culture model of the stress response, consisting of bilirubin released in the cell culture medium, was set up to assess the bilirubin-sensing properties of the functional matrix obtained by cross-linking the HELP moiety. Our engineered protein allowed us to monitor cell induction by the release of bilirubin in the culture medium on a nanomolar scale. This study shows that elastin-like protein fusion represents a versatile platform for the development of novel and commercially viable analytical and biosensing devices.


Left-handed versus right-handed computer mouse use: effect on upper-extremity posture.
Alternatives to reduce postural constraints have to be sought in order to reduce musculoskeletal complaints related to computer work. This study aimed at documenting the impact of using the mouse on the left side of a standard keyboard (with a right numeric keypad) on upper-extremity posture. A simulated computer task was performed by 27 subjects in a laboratory before and 1 month after ergonomics training. Shoulder flexion and abduction, as well as wrist extension were reduced with left-handed mouse use. Sixteen of the 27 subjects truly converted to using the mouse with the left hand. After a month of using the mouse with the left hand, the time required to perform the same task reduced, the perceived difficulty and discomfort improved, though the time to perform the task was still longer than when using the mouse with the right hand. For work involving both keyboard and mouse use, and without the need of the numeric keypad, it would probably be preferable to use a keyboard without the numeric keypad if the mouse is to be used on the right-hand side. If such keyboards are unavailable, an interesting alternative would be to use the mouse on the left side provided sufficient time is allowed to get accustomed to it.


Two-color two-dimensional electronic spectroscopy using dual acousto-optic pulse shapers for complete amplitude, phase, and polarization control of femtosecond laser pulses.
We demonstrate a dual pulse-shaper setup capable of independent polarization, phase, and amplitude control over each pulse. By using active phase stabilization, we achieve a phase stability of ~λ/314 between the two pulse shapers, making the dual-shaper setup suitable for both two-quantum and one-quantum measurements. The setup is compact and easily switchable between pump-probe and collinear geometries. We further illustrate the functionality of the dual-shaper setup by performing two-color 2D visible spectroscopy on colloidal CdSe quantum dots in pump-probe geometry.


Safety evaluation of a strategy to restart elective orthopaedic surgery during the de-escalation phase of the COVID-19 pandemic.
To evaluate safety outcomes and patient satisfaction of the re-introduction of elective orthopaedic surgery on 'green' (non-COVID-19) sites during the COVID-19 pandemic. A strategy consisting of phased relaxation of clinical comorbidity criteria was developed. Patients from the orthopaedic waiting list were selected according to these criteria and observed recommended preoperative isolation protocols. Surgery was performed at green sites (two local private hospitals) under the COVID-19 NHS contract. The first 100 consecutive patients that met the Phase 1 criteria and underwent surgery were included. In hospital and postoperative complications with specific enquiry as to development of COVID-19 symptoms or need and outcome for COVID-19 testing at 14 days and six weeks was recorded. Patient satisfaction was surveyed at 14 days postoperatively. There were 54 females and 46 males (mean age 44 years, mean body mass index (BMI) 25.6 kg/m2). In all, 56 patients underwent major orthopaedic procedures. There were no exclusions. One patient had a postoperative positive SARS-CoV-2 RT-PCR test but had no typical symptoms of COVID-19 infection and no clinical sequelae. 99% of patients were satisfied with the process and 98% would recommend undergoing elective orthopaedic surgery in the study period. In an environment with appropriate infrastructure, patient selection, isolation, screening, and testing, elective orthopaedic surgery is safe during the COVID-19 pandemic, and associated with high patient satisfaction. Further follow-up is required to establish that safety is maintained as the clinical restrictions are eased with the phased approach described.Cite this article: Bone Joint Open 2020;1-8:450-456.


Anesthetic and airway management during laser treatment for retinopathy of prematurity: a survey of US ophthalmologists and neonatologists.
Ophthalmologists and neonatologists were surveyed to assess current practices for anesthetic and airway management techniques used during laser treatment for retinopathy of prematurity. Of the 351 practitioners who completed the survey, most perform fewer than 10 treatments annually. Intravenous sedation, rather than general anesthesia, is used by 60% of respondents. Routine intubation is used by 58%, whereas 36% monitor infants at their current level of respiratory support.


Long-Term Bone Scintigraphy Results After Intravenous Zoledronate in Paget's Disease of Bone.
Zoledronate produces long-term normalization of biochemical markers in Paget's disease but whether this implies the absence of active disease is unknown. We have determined whether bone scintigraphy, a more sensitive index of disease activity, is also normalized ≥5 years after treatment with zoledronate. A consecutive case series of 11 individuals with Paget's disease treated with zoledronate 5 mg ≥5 years previously is reported. Eight patients received a single zoledronate infusion and were assessed 55-120 months later. Bone scintigraphy showed no evidence of active disease in four of these patients, and there was minimal residual disease activity in the other four. Three other patients required second infusions because of evidence of ongoing disease activity. In two of these, scintigraphy was normal ~90 months after their second infusions. In the third, further follow-up is not available. Procollagen-I N-terminal propeptide and total alkaline phosphatase were normal in all subjects at the time of bone scintigraphy. This case series confirms the high rate of response of Paget's disease to zoledronate, demonstrates the much greater sensitivity of scintigraphy compared with biochemical markers in detecting ongoing disease activity, and indicates that about one-third may be scintigraphically "cured" after one infusion; one-third have scintigraphically trivial disease activity subsequently, and the balance may require a second infusion. Scintigraphic "cure" is achievable after second infusions. Scintigraphy has an important place in the long-term management of Paget's patients following zoledronate, and should guide follow-up decisions in those with normal biochemical markers.


Age-dependent expression of immune-privilege and proliferation-related molecules on porcine Sertoli cells.
The immunoprotective nature of the testes has prompted numerous investigations into their supportive roles during allogeneic or xenogeneic cellular grafts. However, the optimal developmental stage of these cells in terms of maximum efficacy for cellular grafts has not been elucidated. In this study, the time-dependent expressions of immune-privilege- and proliferation-related molecules in Sertoli cells were determined. To investigate the time course of the expression of proteins related to immune privilege and proliferation, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) were performed using testes of 18 Yorkshire pigs from birth to 20 weeks of age. We included fas ligand (FasL), transforming growth factor beta1 (TGF-beta1) and clusterin as the immune-protective molecules, and follicle stimulating hormone receptor (FSHR), p27Kip1, GATA-4 and Wilm's tumor antigen (WT1) as Sertoli cell proliferation markers. RT-PCR was used to complement histological assessment. The expression of FasL in Sertoli cells gradually increased with age, whereas TGF-beta1 showed the reverse pattern, and clusterin expression showed no age-related difference. p27Kip1 showed a gradual increase in its expression from week 12, but GATA-4 showed earlier postnatal expression from birth to week 12. WT1 expression gradually increased from week 16. We confirmed the age-dependent expression of immune-privilege- and proliferation-related molecules in porcine Sertoli cells. These data may be useful for determining the optimal time for harvesting Sertoli cells with respect to maximal immunoprotection and proliferative activity.


Preventative interventions by dental care professionals in Africa on oral human papillomavirus, gonorrheal, chlamydial, syphilitic and trichomonas infections: A scoping review.
Oral human papillomavirus (HPV), gonorrheal, chlamydial, syphilitic and trichomonas infections are very common sexually transmitted diseases (STDs) in Africa. However, no known study has reviewed the available evidence concerning the preventative interventions by dental care professionals (DCPs) in Africa on oral STDs; hence, this scoping review was conducted to evaluate the research landscape of this topic area in Africa. The scoping review methodology and documentation were informed by the Arksey and O'Malley's guideline, the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for conducting Scoping Reviews (PRISMA-ScR) checklist, and the AMSTAR-2 guideline. Ten electronic research databases were searched to retrieve literatures relevant to the scoping review question. The retrieved literature were deduplicated and screened for eligibility based on the review's selection criteria. Data charting, collation and summarization were intended to be done in this review, but it could not be done because no relevant literature was found eligible for inclusion into this scoping review. A total of 523 literature were retrieved. After deduplication of the retrieved literatures, the residual literatures (n = 353) were screened for eligibility for inclusion into the review, of which no eligible article was found. Hence, this scoping review was an empty review. This empty scoping review demonstrates that DCPs in Africa do not engage in research-based oral STD prevention. Therefore, the implementation of research-based preventative interventions, by DCPs, on oral STDs should be encouraged in Africa.


Superconductivity in undoped BaFe2As2 by tetrahedral geometry design.
Fe-based superconductors exhibit a diverse interplay between charge, orbital, and magnetic ordering. Variations in atomic geometry affect electron hopping between Fe atoms and the Fermi surface topology, influencing magnetic frustration and the pairing strength through changes of orbital overlap and occupancies. Here, we experimentally demonstrate a systematic approach to realize superconductivity without chemical doping in BaFe2As2, employing geometric design within an epitaxial heterostructure. We control both tetragonality and orthorhombicity in BaFe2As2 through superlattice engineering, which we experimentally find to induce superconductivity when the As-Fe-As bond angle approaches that in a regular tetrahedron. This approach to superlattice design could lead to insights into low-dimensional superconductivity in Fe-based superconductors.


Cocaine and the porcine coronary microcirculation: effects of chronic cocaine exposure and hypercholesterolemia.
To examine the acute effect of cocaine on the coronary microcirculation and whether chronic cocaine administration with or without a concomitant high-cholesterol diet affects beta-adrenoceptor and endothelial functions in the coronary microcirculation. Prospective experimental study. Laboratory and animal research facility. Yorkshire pigs. Pigs were fed a high (2%)-cholesterol diet or a regular diet for 3 months. Animals in both groups received cocaine chronically (7 mg/kg/day, IM). Control animals were fed a regular diet. Responses of the porcine coronary arterioles (90 to 190 microns in diameter) were examined in vitro in a pressurized (40 mmHg) no-flow state using a video-imaging apparatus. Acute application of cocaine caused a significant contraction with a mean maximal diameter decrease of 14% +/- 5%, which was markedly reduced by muscarinic blockade but not significantly affected by alpha 1-adrenergic blockade. Lidocaine or procainamide had no vasoconstrictor effect. Chronic exposure of animals to cocaine diminished contractile responses to cocaine and reduced relaxation responses to the nonselective beta-adrenergic receptor agonist isoproterenol. Phenylephrine caused a minimal (< 4%) contraction of vessels in all groups. Chronic cocaine administration with concomitant high-cholesterol feeding attenuated endothelium-dependent relaxations to serotonin, whereas endothelium-dependent relaxations to bradykinin were unaffected. Endothelium-independent relaxations to sodium nitroprusside were similar in all groups. These results suggest that cocaine can exert a direct vasoconstrictor effect on the porcine coronary microcirculation via a muscarinic mechanism. Chronic exposure to cocaine significantly decreases beta-adrenoceptor-mediated relaxation and blunts endothelium-dependent relaxation to a small degree.


Subjective and model-estimated reward prediction: association with the feedback-related negativity (FRN) and reward prediction error in a reinforcement learning task.
In this study, we examined whether the feedback-related negativity (FRN) is associated with both subjective and objective (model-estimated) reward prediction errors (RPE) per trial in a reinforcement learning task in healthy adults (n=25). The level of RPE was assessed by 1) subjective ratings per trial and by 2) a computational model of reinforcement learning. As results, model-estimated RPE was highly correlated with subjective RPE (r=.82), and the grand-averaged ERP waves based on the trials with high and low model-estimated RPE showed the significant difference only in the time period of the FRN component (p<.05). Regardless of the time course of learning, FRN was associated with both subjective and model-estimated RPEs within subject (r=.47, p<.001; r=.40, p<.05) and between subjects (r=.33, p<.05; r=.41, p<.005) only in the Learnable condition where the internal reward prediction varied enough with a behavior-reward contingency.


Scaling law analysis of electrohydrodynamics and dielectrophoresis for isomotive dielectrophoresis microfluidic devices.
Isomotive dielectrophoresis (isoDEP) is a unique DEP geometrical configuration where the gradient of the field-squared ( ∇Erms2 ) is constant. IsoDEP analyzes polarizable particles based on their magnitude and direction of translation. Particle translation is a function of the polarizability of both the particles and suspending medium, the particles' size and shape, and the frequency of the electric field. However, other electrokinetics act on the particles simultaneously, including electrothermal hydrodynamics. Hence, to maximize the DEP force relative to over electrokinetic forces, design parameters such as microchannel geometry, fabrication materials, and applied electric field must be properly tuned. In this work, scaling law analyses were developed to derive design rules, relative to particle diameter, to reduce unwanted electrothermal hydrodynamics relative to DEP-induced particle translation. For a particle suspended in 10 mS/m media, if the channel width and height are below ten particle diameters, the electrothermal-driven flow is reduced by ∼500 times compared to a channel that is 250 particles diameters in width and height. Replacing glass with silicon as the device's underlying substrate for an insulative-based isoDEP reduces the electrothermal induced flow approximately 20 times less.


Anxiety Sensitivity and Arousal Symptom Implicit Association Task Performance: An Event-Related Potential Study of Cognitive Processing of Anxiety-Relevant Stimuli.
Anxiety sensitivity (AS), or the fear of anxious arousal, is a transdiagnostic risk factor. Despite the proliferation of self-report research showing AS is related to anxiety, cognitive processes underlying AS are poorly understood. Specifically, AS may reflect processes related to early attentional orientation and response monitoring (reflecting automatic processes), or later engagement and assigning emotional salience towards stimuli (reflecting conscious processes). To elucidate cognitive processes underlying AS, event-related potential (ERP) components were elicited in the current study during a novel implicit association task (IAT) in which participants paired self (versus other) words with anxious arousal (versus calm) words. Analyses were then conducted in a sample of community adults (N = 67; M age 39.43, SD = 15.33, 61.2% female) to investigate the association between AS and ERP markers indicative of cognitive processing derived during the IAT. AS was not related to performance on the arousal-IAT and that ERP components did not differ by IAT condition. AS predicted overall late positive potential (LPP) amplitude, particularly in the me/anxiety condition. Elevated IAT scores (reflecting greater ease pairing self-words with anxiety-words) predicted greater P300 amplitude in the me/anxiety condition. The sample was relatively small, and bottom-up processes were not assessed. These findings are inconsistent with the claim that AS is related to top-down cognitive processes driving self-arousal automatic associations. Instead, AS may relate to cognitive processes regulating emotional engagement with stimuli. Further investigations of cognitive processes underlying AS are needed to inform novel interventions targeting AS.


Advances and Ongoing Controversies in Patent Foramen Ovale Closure and Cryptogenic Stroke.
Up to a third of strokes are cryptogenic. The prevalence of patent foramen ovale (PFO) in patients with cryptogenic stroke is higher than in individuals with stroke of known origin. It has been proposed that some cryptogenic strokes can be caused by paradoxic embolism across a PFO. The treatment of PFO includes medical treatment with antithrombotic agents and percutaneous PFO closure. There is limited evidence to support PFO closure in unselected cases of cryptogenic stroke. However, large randomized clinical trials confirmed the superiority of transcatheter PFO closure compared with medical treatment in young patients with cryptogenic stroke.


Direct voltammetry and electrocatalytic properties of catalase incorporated in polyacrylamide hydrogel films.
The direct voltammetry and electrocatalytic properties of catalase (Cat) in polyacrylamide (PAM) hydrogel films cast on pyrolytic graphite (PG) electrodes were investigated. Cat-PAM film electrodes showed a pair of well-defined and nearly reversible cyclic voltammetry peaks for Cat Fe(III)/Fe(II) redox couples at approximately -0.46 V vs. SCE in pH 7.0 buffers. The electron transfer between catalase and PG electrodes was greatly facilitated in the microenvironment of PAM films. The apparent heterogeneous electron transfer rate constant (k(s)) and formal potential (E degrees ') were estimated by fitting square wave voltammograms with non-linear regression analysis. The formal potential of Cat Fe(III)/Fe(II) couples in PAM films had a linear relationship with pH between pH 4.0 and 9.0 with a slope of -56 mV pH(-1), suggesting that one proton is coupled with single-electron transfer for each heme group of catalase in the electrode reaction. UV-Vis absorption spectroscopy demonstrated that catalase retained a near native conformation in PAM films at medium pH. The embedded catalase in PAM films showed the electrocatalytic activity toward dioxygen and hydrogen peroxide. Possible mechanism of catalytic reduction of H(2)O(2) at Cat-PAM film electrodes was proposed.


Flight and dispersal of periodical cicadas.
Periodical cicadas (Magicicada spp.) rarely flew distances greater than 50 m across an open field or along a forest edge. Most cicadas caught after flying 50 m or more were females and all of these females had mated. Flights were most common when adults were 2 to 3 weeks old. Among insects in general, most dispersing individuals are barely post-teneral or extremely young. Cicadas are discussed as an exception to this generality. Both sexes of cicadas are attracted by the male song to chorusing centers for mating (Alexander and Moore 1958). Trees which were chorusing centers had more eggnests than those which were not, suggesting a lack of postmating dispersal from the chorusing trees.


Treatment pattern and clinical outcomes in portopulmonary hypertension: A database study in Japan.
Portopulmonary hypertension (PoPH) is a complication associated with portal hypertension. Since the epidemiological study in Japan was limited, this study aimed to investigate the characteristics, treatment patterns, and prognosis of PoPH patients in real-world data. The characteristics and treatment patterns of PoPH (n = 386) and portal hypertension without pulmonary arterial hypertension (portal hypertension w/o PAH) (n = 96 463) were analyzed based on the Medical Data Vision (MDV) dataset from April 2008 to September 2020. Survival-time analyses of emergency hospitalization and mortality were also conducted between matched pair cohorts of PoPH (n = 210) and portal hypertension w/o PAH (n = 840). Among 386 PoPH patients, the Child-Pugh classification of PoPH group comprised patients with Class A (59 [15.3%]), B (109 [28.2%]), and C (42 [10.9%]), and missing (176 [45.6%]). Regarding the feature of PoPH group, the proportion of primary biliary cholangitis (PBC) (13.7%) and splenomegaly (9.8%) was higher compared with portal hypertension w/o PAH group. The survival time of all-cause hospitalization in PoPH group was shorter than portal hypertension w/o PAH group in matched pair cohort (P < 0.001 by log-rank test). Of PoPH patients, the frequency of PAH-specific medicine usage within 90 days was monotherapy of 79 patients (20.5%), combination therapy of 64 patients (16.6%), and PAH-specific medicine usage of 243 patients (63.0%). This was the first study demonstrating that high proportion of PBC and splenomegaly and a greater risk of hospitalization were observed in PoPH patients based on the analysis using administrative claim database.


Occurrence of platelet-activating factor in rabbit spermatozoa.
Spermatozoa obtained from rabbit ejaculate were analyzed for the presence of platelet-activating factor [PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC)] by using standard HPLC and TLC procedures. Fractions corresponding to synthetic PAF (AGEPC) revealed PAF-like activity amounting to 0.35 +/- 0.06 pmol/10(8) cells (mean +/- SE) as determined by bioassays based on the release of [3H]serotonin from washed rabbit platelets. This activity was lost upon base-catalyzed methanolysis, but was restored to the original level after reacetylation. Analysis of the phosphatidylcholine (PC) fraction by GC-MS subsequent to base-catalyzed methanolysis showed that 1-O-alkyl-2-acylphosphocholine comprises about 12% of the PC fraction with alkyl chain lengths of 16:0 (88%) and 18:0 (12%).


Detection and quantitation of 17F formation during the cyclotron production of 13N.
The positron emitter 17F has been identified for the first time as a radioactive contaminant formed during 13N production. It was determined that 17F made up 18% of the short-lived radioactivity previously thought to be exclusively 15O. Mathematical deconvolution of decay curve data was employed as a complement to radioanalytical techniques. The nuclidic composition of the effluents from the proton bombardment of (a) water, (b) dilute ethanol and (c) 13C powder/water slurry was determined and compared with previous literature values.


Generation of MoClo Standard Parts Using Golden Gate Cloning.
Availability of efficient DNA assembly methods is a basic requirement for synthetic biology. A variety of modular cloning systems have been developed, based on Golden Gate cloning for DNA assembly, to enable users to assemble multigene constructs from libraries of standard parts using a series of successive one-pot assembly reactions. Standard parts contain the DNA sequence coding for a genetic element of interest such as a promoter , coding sequence or terminator . Standard parts for the modular cloning system MoClo must be flanked by two BsaI restriction sites and should not contain internal sequences for two type IIS restriction sites, BsaI and BpiI, and optionally for a third type IIS enzyme, BsmBI. We provide here a detailed protocol for cloning of basic parts. This protocol requires the following steps (1) defining the type of basic part that needs to be cloned, (2) designing primers for amplification, (3) performing PCR amplification, (4) cloning of the fragments using Golden Gate cloning, and finally (5) sequencing of the part. For large basic parts, it is preferable to first clone subparts as intermediate level -1 constructs. These subparts are sequenced individually and are then further assembled to make the final level 0 module.


Competitive electrochemical immunoassay for detection of β-amyloid (1-42) and total β-amyloid peptides using p-aminophenol redox cycling.
β-Amyloid (1-42) peptide (Aβ(1-42)) is believed to be important for diagnosis and prognosis of Alzheimer's disease (AD) serving as a reliable molecular biomarker. However, the levels of Aβ(1-42) may differ by gender and age; thus, assay of Aβ(1-42) only might be unable to discriminate between AD and health or other types of dementia. In this work, we reported a sensitive and selective electrochemical method for detection of both Aβ(1-42) and total Aβ using p-aminophenol (p-AP) redox cycling on antibody-modified gold electrodes. Specifically, the conjugates performed between streptavidin-conjugated alkaline phosphatase (SA-ALP) and biotinylated Aβ peptides were captured by the antibody-modified electrodes, which induced the production of electrochemically active p-AP from the p-aminophenyl phosphate (p-APP) substrate. In the presence of tris(2-carboxyethyl)phosphine (TCEP), p-AP could be cycled after its electro-oxidization on the electrode, enabling the increase of the anodic current. Because native Aβ competed with the conjugates to bind the anchored antibody, the signal decreased with the increase of native Aβ concentration. A detection limit of 5 pM was achieved. To demonstrate the viability of the method for analysis of Aβ(1-42) and total Aβ in real sample, artificial cerebrospinal fluid (aCSF) containing Aβ(1-40), Aβ(1-42) and Aβ(1-16) was tested. We believe that the simultaneous detection of Aβ(1-42) and total Aβ would be valuable for the early diagnosis of AD.


Anisomycin induces COX-2 mRNA expression through p38(MAPK) and CREB independent of small GTPases in intestinal epithelial cells.
Cyclooxygenase (COX)-2 expression in intestinal epithelial cells is associated with colorectal carcinogenesis. COX-2 expression is induced by numerous growth factors and gastrointestinal hormones through multiple protein kinase cascades. Here, the role of mitogen activated protein kinases (MAPKs) and small GTPases in COX-2 expression was investigated. Anisomycin and sorbitol induced COX-2 expression in non-transformed, intestinal epithelial IEC-18 cells. Both anisomycin and sorbitol activated p38(MAPK) followed by phosphorylation of CREB. SB202190 and PD169316 but neither PD98059 nor U0126 blocked COX-2 expression and CREB phosphorylation by anisomycin or sorbitol. Clostridium difficile toxin B inhibition of small GTPases did not affect anisomycin-induced COX-2 mRNA expression or phosphorylation of p38MAPK and CREB but did inhibit sorbitol-dependent COX-2 expression and phosphorylation of p38MAPK and CREB. Angiotensin (Ang) II-dependent induction of COX-2 mRNA and induced phosphorylation of p38MAPK and CREB were inhibited by toxin B. Reduction of CREB protein in cells transfected with CREB siRNAs inhibited anisomycin-induced COX-2 expression. These results indicate that activation of p38MAPK signaling is sufficient for COX-2 expression in IEC-18 cells. Ang II and sorbitol require small GTPase activity for COX-2 expression via p38MAPK while anisomycin-induced COX-2 expression by p38MAPK does not require small GTPases. This places small GTPase activity down-stream of the AT1 receptor and hyperosmotic stress and up-stream of p38MAPK and CREB.


Impact of estimated glucose disposal rate for identifying prevalent ischemic heart disease: findings from a cross-sectional study.
Insulin resistance is one of the major mechanisms for cardiovascular events. Estimated glucose disposal rate(eGDR) has been demonstrated as a simple, accurate, and cost-effective estimator of insulin resistance. Our study aims to evaluate the correlation between eGDR and the prevalent IHD and assess the incremental value of eGDR for identifying prevalent IHD in the rural general population. Our study enrolled 10,895 participants from a cross-sectional survey of a metabolic management program. The survey was conducted in the rural areas of southeastern China between October 2019 and April 2020. eGDR = 21.158 - (0.09 * waist circumference) - (3.407 * hypertension) - (0.551 * HbA1c). The prevalence of IHD was 4.20%. After adjusting for demographic, anthropometric, laboratory, and medical history covariates, each SD increase of eGDR brought a 25.9% risk reduction for prevalent IHD. After dividing eGDR into groups, the top group had a 58.9% risk reduction than the bottom group. Furthermore, smooth curve fitting demonstrated that the correlation between eGDR and prevalent IHD was linear in the whole range of eGDR. Additionally, AUC suggested that eGDR could significantly improve the identification of prevalent IHD by adding it to cardiovascular risk factors (0.703 vs. 0.711, P for comparison = 0.041). Finally, the category-free net reclassification index and integrated discrimination index also implicated the improvement from eGDR to identify prevalent IHD. Our data demonstrated a significant, negative, and linear correlation between eGDR and prevalent IHD. Our findings could suggest the potential usefulness of eGDR to improve the identification of prevalent IHD in the rural general population.


Identification of a novel heterozygous missense mutation of SEMA3E (c.1327G>A; p. Ala443Thr) in a labor induced fetus with CHARGE syndrome.
CHARGE syndrome is a complex multisystem genetic disease. We aimed to find the potential gene mutation in the labor induced fetus with CHARGE syndrome. Genomic DNA was extracted from the fetal thigh muscle tissue and the peripheral blood of his parents. The resulting exomes were sequenced using whole exome sequencing (WES) followed by the selection of the candidate causative mutation genes. The deleteriousness of the identified variants was predicted. Analysis of multiple alignment of protein sequences and protein conserved domains was performed by online software. Finally, Sanger sequencing was applied for validation of the identified variants in the WES. After sequencing and bioinformatics filtering, a heterozygous missense mutation of SEMA3E (c.1327G>A; p. Ala443Thr) was found in the fetus, while the mutation was absent in his parents. Genotyping results showed that the mutation cosegregated fully with definite CHARGE phenotypes between the fetus and his parents. This change was located in the Sema superfamily and highly conserved across different species. Sanger validation result was consistent with the WES analysis. Our investigations suggested that the heterozygous missense mutation of SEMA3E (c.1327G>A; p. Ala443Thr) may be a potential causal variant in the fetus with CHARGE syndrome.


Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo.
Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of ACLF. In this study, 23 compounds with 6,386 drug targets were obtained from Wenyang Jiedu Huayu (WYJDHY), and 8,096 genes were identified as ACLF disease targets, among which 3,132 were overlapping co-targets. Expression profile analysis identified 105 DEGs among the co-targets, which were associated with biological activities such as lymphocyte activation, immune response regulation, and pathways such as Th17 cell differentiation and NF-κB signaling. After PPI analysis and network construction, atractylenolide I (AT-1) has been identified as the hub active ingredient of the WYJDHY formula. LPS stimulation inhibited rat hepatocytes' BRL 3A cell viability, promoted cell apoptosis, increased the levels of ALT, AST, IL-6, and VCAM-1 within the culture medium, and activated NF-κB signaling, whereas AT-1 treatment significantly attenuated LPS-induced toxicity on BRL 3A cells. Furthermore, the NF-κB signaling inhibitor PDTC exerted effects on LPS-stimulated BRL 3A cells similar to those of AT-1, and the combination of PDTC and AT-1 further attenuated LPS-induced toxicity on BRL 3A cells. In vivo, AT-1 alone or with PDTC improved the symptoms and local inflammation in ACLF model rats. In conclusion, 23 active ingredients of six herbs in the WYJDHY formula were retrieved, and 105 co-targets were differentially expressed in ACLF. AT-1 exerts protective effects on LPS-stimulated hepatocytes and ACLF rats, possibly by inhibiting the NF-κB pathway.


Anisakid nematodes (Nematoda: Anisakidae) from the marine fishes Plectropomus laevis Lacépède (Serranidae) and Sphyraena qenie Klunzinger (Sphyraenidae) off New Caledonia, including two new species of Hysterothylacium Ward & Magath, 1917.
Based on light and scanning electron microscopical studies, two new species of Hysterothylacium Ward & Magath, 1917 (Nematoda: Anisakidae) are described from the digestive tract of perciform fishes off New Caledonia: H. alatum n. sp. from Plectropomus laevis (Lacépède) (Serranidae) and H. sphyraenae n. sp. from Sphyraena qenie Klunzinger (Sphyraenidae). The former species (H. alatum) is mainly characterised by its large body (male 42.05 mm, gravid females 51.18-87.38 mm long), the shape of the dorsal lip, conspicuously broad cervical alae, a short caecum and a long ventricular appendix, the length of the spicules (925 µm), the number (25 pairs) and distribution of the genital papillae and the tail tip bearing numerous minute cuticular protuberances. The other species (H. sphyraenae) is mainly characterised by the presence of narrow lateral alae, a short caecum and a long ventricular appendix, the length (762-830 µm) and shape of the spicules, the number (37-38 pairs) and arrangement of the genital papillae, and by the tail tip which lacks any distinct cuticular projections visible under the light microscope. In addition, and unidentifiable at the species level, conspicuously large (45.71-66.10 mm long) larvae of Contracaecum Railliet & Henry, 1912, were found in the body cavity of P. laevis, which serves as a paratenic host for this parasite.


Laws' masks descriptors applied to bone texture analysis: an innovative and discriminant tool in osteoporosis.
The objective of this study was to explore Laws' masks analysis to describe structural variations of trabecular bone due to osteoporosis on high-resolution digital radiographs and to check its dependence on the spatial resolution. Laws' masks are well established as one of the best methods for texture analysis in image processing and are used in various applications, but not in bone tissue characterisation. This method is based on masks that aim to filter the images. From each mask, five classical statistical parameters can be calculated. The study was performed on 182 healthy postmenopausal women with no fractures and 114 age-matched women with fractures [26 hip fractures (HFs), 29 vertebrae fractures (VFs), 29 wrist fractures (WFs) and 30 other fractures (OFs)]. For all subjects radiographs were obtained of the calcaneus with a new high-resolution X-ray device with direct digitisation (BMA, D3A, France). The lumbar spine, femoral neck, and total hip bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. In terms of reproducibility, the best results were obtained with the TRE5E5 mask, especially for three parameters: "mean", "standard deviation" and "entropy" with, respectively, in vivo mid-term root mean square average coefficient of variation (RMSCV)%= 1.79, 4.24 and 2.05. The "mean" and "entropy" parameters had a better reproducibility but "standard deviation" showed a better discriminant power. Thus, for univariate analysis, the difference between subjects with fractures and controls was significant (P<10(-3)) and significant for each fracture group independently (P<10(-4) for HF, P=0.025 for VF and P< 10(-3) for OF). After multivariate analysis with adjustment for age and total hip BMD, the difference concerning the "standard deviation" parameter remained statistically significant between the control group and the HF and VF groups (P<5 x 10(-5), and P=0.04, respectively). No significant correlation between these Laws' masks parameters and BMD was obtained. In addition, this study showed the dependence of Laws' masks parameters on image resolution, which confirms the necessity to perform Laws' textural measurement on high-resolution images. The reproducibility and discriminant power of the Laws' masks analysis has been demonstrated on bone images; thus, this method constitutes a promising routine technique for the determination of osteoporosis fracture risk from radiographs.


From autophagy to mitophagy: the roles of P62 in neurodegenerative diseases.
P62, also called sequestosome1 (SQSTM1), is the selective cargo receptor for autophagy to degenerate misfolded proteins. It has also been found to assist and connect parkin in pink1/parkin mitophagy pathway. Previous studies showed that p62 was in association with neurodegenerative diseases, and one of the diseases pathogenesis is P62 induced autophagy and mitophagy dysfunction. Autophagy is an important process to eliminate misfolded proteins. Intracellular aggregation including α-synuclein, Huntingtin, tau protein and ß-amyloid (Aß) protein are the misfolded proteins found in PD, HD and AD, respectively. P62 induced autophagy failure significantly accelerates misfolded protein aggregation. Mitophagy is the special autophagy, functions as the selective scavenger towards the impaired mitochondria. Mitochondrial dysfunction was confirmed greatly contribute to the occurrence of neurodegenerative diseases. Through assistance and connection with parkin, P62 is vital for regulating mitophagy, thus, aberrant P62 could influence the balance of mitophagy, and further disturb mitochondrial quality control. Therefore, accumulation of misfolded proteins leads to the aberrant P62 expression, aberrant P62 influence the balance of mitophagy, forming a vicious circle afterwards. In this review, we summarize the observations on the function of P62 relevant to autophagy and mitophagy in neurodegenerative diseases, hoping to give some clear and objective opinions to further study.


Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of IL1B, IL6, and IL8 by gingival epithelial cells.
Porphyromonas gingivalis alters cytokine expression in gingival epithelial cells, stimulating inflammatory responses that may lead to periodontal disease. This study explored the effect of Lactobacillus acidophilus on the specific expressions of the interleukins (ILs) IL1B, IL6, and IL8 induced by the pathogen. Human gingival epithelial cells were co-cultured with P. gingivalis, L. acidophilus, or L. acidophilus + P. gingivalis; the control group consisted of the cells alone. Protein and gene expression levels of the ILs were detected using ELISA and qRT-PCR, respectively. The supernatant from the P. gingivalis group held significantly higher protein and mRNA levels of IL1B, IL6, and IL8, compared to the control group. In the mixed bacterial group (L. acidophilus + P. gingivalis), the levels of all three ILs decreased with increasing concentrations of L. acidophilus and were significantly different from the P. gingivalis group. This suggests that in gingival cells, L. acidophilus offsets the P. gingivalis-induced secretion of these ILs in a dose-dependent manner.


The relation of post-traumatic stress symptoms to depression and pain in patients with accident-related chronic pain.
Symptoms of post-traumatic stress disorder (PTSD) are a common comorbidity in patients with a history of accident-related chronic pain and depression. However, little is known regarding the influence of PTSD in contributing to the affective distress, pain experience, and disability associated with chronic pain in this population. This study used structural equation modeling to examine 3 models that assess these relations in a sample of chronic pain patients with accident-related pain. Subjects were assessed for pain experience, depressive symptoms, anxiety, PTSD symptoms, pain disability, and relevant demographic variables. Pearson correlations indicated that symptoms of depression were significantly related to more severe pain, disability, and PTSD symptoms. PTSD symptoms were significantly associated with higher disability. The model of best fit indicated that after controlling for the influence of anxiety on the dependent measures, PTSD symptoms have a direct influence on severity of depressive symptoms, whereas depressive symptoms have a direct influence on pain intensity and an indirect impact on pain intensity by way of their effect on disability. These data point to the importance of unresolved PTSD symptoms in contributing to the level of depression, pain, and disability exhibited by chronic pain patients and highlight the need to consider directed and primary treatment of PTSD in pain rehabilitation programs. This study highlights the impact of symptoms of PTSD on levels of depression, disability, and pain in patients with pain secondary to physical injury. Our results suggest that pain rehabilitation programs provide directed interventions for PTSD symptoms among this population to improve pain treatment outcomes.


Oral cadmium chloride intoxication in mice: effects of dose on tissue damage, intestinal absorption and relative organ distribution.
The acute toxicity of soluble cadmium salts has almost exclusively been studied experimentally after parenteral exposures, where acute mortality is caused by hepatic necrosis. This report describes an alternative experimental model using oral exposure. A single oral toxic dose of CdCl2 to mice induced toxic gastroenteritis; subsequent hepatic and renal lesions were also observed. Whole-body gamma-counting after a single oral toxic 109CdCl2 dose to mice showed a dose-dependent delay of the fecal excretion of non-absorbed cadmium. This delay was absent when a low, non-toxic dose was administered. This effect is most likely due to decreased peristalsis and, at higher doses, intestinal atony due to oral cadmium toxicity. After fecal elimination of non-absorbed cadmium, the residual body burden of cadmium expressed as percent of initial dose reflects the fractional intestinal cadmium absorption due to slow reexcretion of absorbed cadmium. The fractional absorption increased with increasing doses of cadmium. The relative cadmium deposition in brain, testes and intestines decreased with increasing dose, whereas the relative liver deposition increased with dose. The delayed fecal elimination and increased fractional absorption of cadmium may significantly contribute to the development of both local and systemic toxicity in oral cadmium intoxication.


Metabolic programming in the immediate postnatal period.
In recent decades, there has been a dramatic increase in the incidence of obesity in all age groups of the population in the USA. In addition to genetics and life style changes, the important role of metabolic programming effects in the etiology of the obesity epidemic is being increasingly recognized. Although the role of a compromised intrauterine environment in fetal metabolic programming is well documented to contribute to the development of adult-onset diseases, vulnerability in the immediate postnatal period to similar conditions has also been shown. Metabolic programming effects induced by altered nutritional experiences in the immediate postnatal period can give rise to long-term consequences in the context of the current obesity epidemic.


A study of the kinetics of chlorpromazine sulfoxide by a specific radioimmunoassay after a single oral dose of chlorpromazine in healthy volunteers.
Antibody specific for chlorpromazine sulfoxide (CPZSO) was produced in rabbits immunized with a hapten-bovine serum albumin conjugate, which was prepared by linking the 10-alkyl side chain of CPZSO to the protein molecule via a 2-carbon bridge. A simple radioimmunoassay was developed which can measure less then 20 pg of CPZSO in plasma. The assay has adequate specificity so that isolation of CPZSO is unnecessary. It was used together with a previously developed chlorpromazine (CPZ) radioimmunoassay to determine the concentrations of CPZ and CPZSO in plasma samples from five healthy volunteers after they had received a single 50-mg oral dose of CPZ. The plasma level data reported here support the previous findings that a significant portion of CPZ is metabolized to CPZSO during presystemic absorption. There are, however, differences to those previously reported in the plasma concentration ratios of CPZSO to CPZ. The possible reasons for these differences are discussed.


Disturbance and predation in an assemblage of herbivorous Diptera and algae on rocky shores.
Speculation about the effects of disturbance in marine benthic communities is often based on competition theory. Disturbances are thought to "provision" numerically depleted or competitively inferior species with resources associated with open substrate. However, disturbances that remove entire assemblages of sessile species also alter trophic structure, and thereby, influence the outcome of predator/prey relations. Aspects of community structure may be determined by patterns of disturbance and predation.The influence of disturbance and predation on the distribution and seasonality of blooms of ephemeral algae and associated Diptera was investigated with field experiments at several rocky beaches in central California. Blooms of ephemeral algae developed on high intertidal rock faces that were subject to severe seasonal disturbances caused by shifting sediment. These were subsequently colonized by the herbivorous larvae of several Diptera species for predictable periods each year. Other areas, without blooms, were not so disturbed.Experiments were done to determine if seasonal blooms were caused by seasonal disturbances that remove predators which otherwise might prevent the establishment of the Diptera/algae assemblage. The predators were crabs and limpets which eat both algae and larvae while foraging. Blooms of algae and larvae did not develop when limpets were transplanted to disturbed areas in periods between disturbances. Adjacent control areas did support blooms. Transplanted limpets did not survive periods of burial. When both limpets and crabs were excluded from treatment plots in undisturbed areas, blooms developed where they would not otherwise have occurred; controls remaied unchanged. Crabs and limpets differed in their effects on this assemblage. Crabs recruited quickly to the site of a bloom, but did not crop algal cover as closely, nor decrease larval density as much as the slowly recruiting limpets.The results suggest that disturbances favor blooms of some species by reducing predation. Severe localized disturbances increased the variability of the upper shore community by creating a patchwork of differing predator/prey abundances.


CD8 Treg-Mediated Suppression of Naive CD4+ T Cell Differentiation into Follicular Helper T Cells.
The regulatory CD8+ T (CD8+ Treg) cells play an important role in immune tolerance and have been implicated in several human autoimmune diseases. In this context, follicular helper T (TFH) cells contribute by controlling the antibody production. In mice, CD8+ Treg cells control the number and function of TFH cells however the role of human CD8+ Treg cells on the differentiation of naive CD4+ T cells into TFH cells has not been studied. Here, we evaluated the ability of human CD183+ CD8+ Treg cells to suppress TFH cell differentiation in vitro. Activated CD183+CCR7+CD45RA-CD8+ Treg and CD183+CD25highICOS+CD8+ Treg cells were sorted and cocultured with naïve CD4+ T cells under TFH differentiation condition. The differentiation of TFH cells was evaluated by flow cytometry. Our results showed that activated CD183+CD8+ Treg cells upregulated the expression of Forkhead box P3 transcription factor, inducible T-cell co-stimulator (ICOS), and CD25 compared to CD183-CD8+ T cells. The CD183+CD25highICOS+CD8+ Treg cells suppressed TFH cell differentiation and CD4+ T cell proliferation in vitro which was not observed when CD183+CCR7+CD45RA-CD8+ Treg were cocultured with naïve CD4+ T cells under TFH cell differentiation condition. These results suggest that CD25highICOS+CD183+CD8+ Treg cells may regulate autoimmune and inflammatory responses mediated by TFH cells.


Air quality and the risk of out-of-hospital cardiac arrest in Singapore (PAROS): a time series analysis.
Previous studies have reported positive associations between out-of-hospital cardiac arrest (OHCA) and air pollutant concentrations, but there are inconsistencies across studies. We aimed to investigate the association between pollutant concentrations and the risk of OHCA in Singapore. We did a time series analysis of all cases of OHCA in Singapore reported between July 1, 2010, and Dec 31, 2018, to the Pan-Asian Resuscitation Outcomes Study (PAROS), a prospective, population-based registry. Using multivariable fractional polynomial modelling, we investigated the immediate (day 0) and lagged (up to 5 days after exposure) association between 10 μg/m3 increases in concentrations of particulate matter with a diameter of 2·5 μm or smaller (PM2·5), particulate matter with a diameter of 10 μm or smaller (PM10), ozone (O3), nitrogen dioxide (NO2), and sulphur dioxide (SO2) and 1 mg/m3 increase in carbon monoxide (CO) and relative risk (RR) of OHCA. We extracted data for 18 131 cases of OHCA. The median age of this cohort of cases was 65 years (IQR 56-80), 6484 (35·8%) were female, 11 647 (64·2%) were male, 12 270 (67·7%) were Chinese, 2873 (15·8%) were Malay, and 2010 (11·1%) were Indian. Every 10 μg/m3 increase in PM2·5 was associated with increased risk of OHCA (RR 1·022 [95% 1·002-1·043]) over the next 2 days, which decreased over the subsequent 3 days (3-5 days after exposure; 0·976 [0·955-0·998]). For PM10, O3, NO2, and SO2, we did not observe any associations between increased concentration and risk of OHCA on day 0 or cumulative risk over time (ie, at 0-1 days, 0-2 days, 0-3 days, 0-4 days, 0-5 days, and 3-5 days after exposure). For CO, we observed a cumulative decreased risk of OHCA across 0-5 days after exposure (0·876 [0·770-0·997]) and at days 3-5 after exposure (0·810 [0·690-0·949]). We observed effect modification of the association between increasing PM2·5 concentration and OHCA 0-2 days after exposure by cardiac arrest rhythm (non-shockable 1·027 [1·004-1·050] vs shockable 1·002 [0·956-1·051]) and location of OHCA (at home: 1·033 [1·008-1·057] vs not at home 0·955 [0·957-1·035]). In hypothetical modelling, the number of OHCA events associated with PM2·5 could be reduced by 8% with a 1 μg/m3 decrease in PM2·5 concentrations and by 30% with a 3 μg/m3 decrease in PM2·5 concentrations. Increases in PM2·5 concentration were associated with an initial increased risk of OHCA and a subsequent reduced risk from 3-5 days after exposure, suggesting a short-term harvesting effect. A decrease in PM2·5 concentrations could reduce population demand for emergency health services. National Medical Research Council, Singapore, under the Clinician Scientist Award, Singapore and the Singapore Translational Research Investigator Award (MOH-000982-01).


The Effects of Silicon and Different Types of Acid Rain on Root Growth and Physiology Activity of Oryza Sativa L. Seedlings.
The effect of silicon (Si) and different types of acid rain (AR) on rice seedling roots was elucidated. The results showed different types of AR had different effects. Nitrate AR at pH 3.0 could promote the growth of rice roots, increased the dry weight, improved root phenotype, boosted H2O2 contents and increased peroxidase, catalase and ascorbate peroxidase activities. Sulfate AR at pH 3.0 could significantly inhibit the growth of rice roots, decreased the dry weight, root phenotype, increased H2O2 content and autioxidant enzyme activities. Sulfate-nitrate AR at pH 3.0 spraying had no significant effect on rice roots. Under different types of AR stress, the addition of exogenous Si could significantly promote the growth of rice seedling roots. This results indicated that the effects of rice root caused by AR might be due to not only the types of AR but also the content of Si in soil.


Interactions of cobicistat and ritonavir in patients with HIV and its clinical consequences.
The prescription of antiretroviral treatment (ART) that contains pharmacokinetic enhancers such as ritonavir and cobicistat is frequent. The objective of this stdy was to analyze the potential interactions of ART that include these molecules in their formulation with the patient's home medication, as well as the clinical management of those potentially serious. Prospective study conducted in the pharmacy care clinic of a third level hospital between January and December of 2018. Those HIV+patients with an ART containing cobicistat or ritonavir were included in the study. Potential interactions between ART and concomitant medication were analysed in three databases (Micromedex®, Drugs.com and Liverpool), the interventions carried out were detailed, and adverse drug reactions analysed. 968 patients were included with a total of 2,148 prescriptions (274 different medications). A total of 86 interventions were performed regarding potential interactions in patients. The most frequent were substitutions of corticoid treatments, treatment suspensions and closer monitoring of treatments. A total of possible adverse drug reactions were analysed. The degree of agreement in the severity classification of the interactions for cobicistat and ritonavir was good among the three databases. It was remarkable Micromedex® as the most complete because it has more registered medications. The interactions between ART with pharmacokinetic enhancers in its composition and concomitant medication is frequent and requires a significant variety of interventions. The check of interactions in different databases is recommended since they can cause adverse drug reactions.


Endothelial cell counts after Descemet's stripping automated endothelial keratoplasty versus penetrating keratoplasty in Asian eyes.
The purpose of this study was to compare endothelial cell counts after Descemet's stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty in Asian eyes. This was a retrospective study of patients from our prospective Singapore Corneal Transplant Study cohort who received corneal transplantation in 2006-2008. We compared eyes that underwent DSAEK or penetrating keratoplasty for Fuchs' endothelial dystrophy or pseudophakic and aphakic bullous keratopathy. Clinical data, and donor and recipient characteristics were recorded. Of 241 patients who met our inclusion criteria, 68 underwent DSAEK and 173 underwent penetrating keratoplasty. The main outcome measure was endothelial cell loss at 1 year. Secondary outcome measures were graft survival and visual outcomes at 1-year follow-up. There were no significant differences in baseline characteristics of patients between the treatment groups. Percent endothelial cell loss at 1-year follow-up was greater in penetrating keratoplasty eyes (40.9% ± 2.9%) compared with DSAEK eyes (22.4% ± 2.3%; P < 0.001). DSAEK-treated eyes had significantly superior uncorrected visual acuity (mean difference = 0.42 ± 0.0059; P < 0.001) and best spectacle-corrected visual acuity (mean difference = 0.14 ± 0.032; P < 0.001) as compared with penetrating keratoplasty-treated eyes. Penetrating keratoplasty-treated eyes had worse astigmatism as compared with DSAEK-treated eyes (-3.0 ± 2.1 versus -1.7 ± 0.8; P < 0.001). Graft survival at 1 year was comparable in both groups, ie, 66/68 (97.0%) DSAEK-treated eyes versus 158/173 (92.0%) of penetrating keratoplasty-treated eyes had clear grafts (P = 0.479). We report lower percent endothelial cell loss comparing DSAEK and penetrating keratoplasty at 1-year follow-up in Asian eyes, with comparable graft survival rates in both groups.


Blockade of nociceptive sensory afferent activity of the rat knee joint by the bradykinin B2 receptor antagonist fasitibant.
The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia. Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test. BK (100 μM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 μM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 μg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug. Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.


Reporter ion-based mass spectrometry approaches for the detection of non-enzymatic protein modifications in biological samples.
Development of mass spectrometry techniques to detect protein oxidation, which contributes to signalling and inflammation, is important. Label-free approaches have the advantage of reduced sample manipulation, but are challenging in complex samples owing to undirected analysis of large data sets using statistical search engines. To identify oxidised proteins in biological samples, we previously developed a targeted approach involving precursor ion scanning for diagnostic MS(3) ions from oxidised residues. Here, we tested this approach for other oxidations, and compared it with an alternative approach involving the use of extracted ion chromatograms (XICs) generated from high-resolution MSMS data using very narrow mass windows. This accurate mass XIC data methodology was effective at identifying nitrotyrosine, chlorotyrosine, and oxidative deamination of lysine, and for tyrosine oxidations highlighted more modified peptide species than precursor ion scanning or statistical database searches. Although some false positive peaks still occurred in the XICs, these could be identified by comparative assessment of the peak intensities. The method has the advantage that a number of different modifications can be analysed simultaneously in a single LC-MSMS run.This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. The use of accurate mass extracted product ion chromatograms to detect oxidised peptides could improve the identification of oxidatively damaged proteins in inflammatory conditions.


Comparison of the transport characteristics of ceftibuten in rat renal and intestinal brush-border membranes.
The transport characteristics of ceftibuten, a dianionic cephem antibiotic, in rat renal and intestinal brush-border membranes were compared. Ceftibuten transport was mediated by two transport systems in the renal brush-border membrane and by one transport system in the intestinal brush-border membrane. The apparent kinetic parameters for the uptake of ceftibuten by the renal brush-border membrane vesicles, respectively, were: Km1, Km2 values of 26 and 1946 microM and Vmax1, Vmax2 values of 105 and 1400 pmol/mg protein per 30 s. The apparent kinetic parameters for the uptake by the intestinal brush-border membrane vesicles were: Km of 425 microM and Vmax of 1701 pmol/mg protein per 30 s. In the renal brush-border membrane, L-Ala-L-Pro was partially competitive and competitive inhibitor for the uptake by the high and low affinity systems, respectively. However, L-Ala-L-Pro was a non-competitive inhibitor for the uptake by the intestinal brush-border membrane vesicles. L-Carnosine was a specific and competitive inhibitor for the high affinity system in the renal brush-border membrane, while it had no effect on the low affinity system of the kidney or on the transport system of the intestine. It was concluded that the transport characteristics of ceftibuten in the renal and intestinal brush-border membranes are similar in some aspects but they are not identical.


The pre-Bötzinger complex and phase-spanning neurons in the adult rat.
To characterise respiratory neurons in the pre-Bötzinger complex of adult rats, extracellular recordings were made from 302 respiratory neurons in the ventral respiratory group of sodium pentobarbitone anaesthetised adult rats. Neurons were located 0 to 1.6 mm caudal to the facial nucleus, and ventral to the nucleus ambiguus. The pre-Bötzinger complex comprised expiratory neurons (22%, 22/100), inspiratory neurons (37%, 37/100) and phase-spanning neurons (41%, 41/100). In contrast, 80% (125/157) of Bötzinger neurons were expiratory, and 80% (36/45) of rostral ventral respiratory group neurons were inspiratory. Rostrocaudally, the pre-Bötzinger complex extended about 400 microns, starting at the caudal pole of the nucleus ambiguus compact formation. The pre-Bötzinger complex was also characterised by a predominance of propriobulbar neurons (81%, 13/16). Furthermore, 68% (33/48) of expiratory-inspiratory neurons found were located within the pre-Bötzinger complex. The variety of neuronal subtypes in the pre-Bötzinger complex, including many firing during the expiratory-inspiratory transition is consistent with the hypothesis that this nucleus plays a key role in respiratory rhythm generation in the adult rat.


[Construction and Exploration of Model for Training Excellent Nursing Professionals].
The cultivation of excellent nursing professionals is an important guarantee of competent human resources essential to the implementation of the national strategy of Healthy China initiative. In the face of the health needs of the whole life cycle and the nursing development driven by emerging technologies, the training of excellence nursing professionals is confronted with new requirements and challenges. In order to cope with the new demands at home and abroad for the training of high-quality nursing staffs, meet the needs for health services that are based on precision, the whole population, the whole life cycle, and individualized care in the new era, and cultivate outstanding nursing staffs with clinical critical thinking skills, nursing decision-making skills, innovative research and practice ability, whole life cycle nursing knowledge and skills, and the ability to keep pace with the times, we wrote this paper to help clarify the needs and challenges of training excellent nursing staffs in China. Herein, taking "precision nursing of health and disease in the whole life cycle" as the core and utilizing the personnel training principle of emphasizing foundation, strengthening ability, improving quality, and promoting personality, we elaborated on the construction of the training model of excellent nursing staffs and suggested that efforts should be made in the following areas, setting up training objectives with a scientific orientation, setting up in a targeted way the knowledge system and the curriculum system, organizing the teaching mode reform into different types and implement them accordingly, making innovations in instructional methodology, and building up high-level teaching faculties. We explored for a path for training excellent nursing talents, a path that has Chinese characteristics and that can be further developed in a sustainable way, which will lay the foundation for attaining the strategic goal of Healthy China initiative.


Hypergalactosaemia in a patient with portal-hepatic venous and hepatic arterio-venous shunts detected by neonatal screening.
Hypergalactosaemia was discovered in a newborn girl during routine metabolic screening. Hereditary enzyme deficiency was ruled out. She had multiple hepatic haemangiomas with portal-hepatic venous and hepatic arterio-venous shunts. Since she showed signs of high-output heart failure due to the arterio-venous shunt, hepatic artery embolization was performed at age 3 months. A galactose tolerance test was performed before and after embolization and when the haemangioma no longer appeared on ultrasonography. Even after embolization, the level of blood galactose was abnormally elevated in the galactose tolerance test, but the blood galactose was eliminated more rapidly than before embolization. When the hepatic haemangioma was no longer detected by ultrasonography, the peak galactose level decreased. We surmise that the hypergalactosaemia was due to these shunts. In cases of hypergalactosaemia of unknown cause; liver haemangioma with portal-hepatic venous shunting should be considered as a possible cause. If a hepatic arterio-venous shunt also exists, this may contribute to the effect of the portosystemic shunting.


Frequency of postmortem ethanol formation in blood, urine and vitreous humor - Improving diagnostic accuracy with the use of ethylsulphate and putrefactive alcohols.
This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or positive putrefactive alcohols (PA's) in either medium. Furthermore, it aimed to evaluate the interpretational value of calculated ethanol ratios in relation to EtS and PA results. Blood ethanol positive forensic cases were included; one dataset consisting of 2504 cases with EtS analysed in blood and another dataset with 8001 cases where PA's were analysed. PA's were found in 24.4% of cases. EtS was negative in 15.3%, 9.4% and 7.4% of cases that were positive for ethanol in blood, urine and vitreous humor, respectively. In EtS negative cases, the concentrations of ethanol in blood, urine and vitreous humor were lower than 0.20 g/kg in 51.3%, 67.4% and 77.8%, respectively. It was 1.0 g/kg or higher in blood in 4.2% of cases. More EtS negative and PA positive cases were seen in central compared to peripheral blood. Ethanol ratios between urine or vitreous humor and blood were significantly lower in both EtS negative and PA positive cases, but large variations were observed. EtS and PA analysis improve the diagnostic accuracy of ethanol in postmortem cases. Postmortem ethanol formation in vitreous humor and urine were both more frequent than expected and we recommend the analysis of ethanol primarily in peripheral blood if available.


In vivo assessment of myocardial blood flow in rat heart using magnetic resonance imaging: effect of anesthesia.
To assess the influence of isoflurane and pentobarbital anesthesia and the carrier gases on myocardial blood flow (MBF) in the rat heart in vivo. MBF was quantified in vivo using arterial spin-labeling (ASL) magnetic resonance imaging (MRI). Left ventricular (LV) function was estimated during the same experiment using cine-MRI. Thirty-four male Wistar-Kyoto rats were divided in four groups, one anesthetized with isoflurane in oxygen:nitrous oxide mix (ISO), the three others with intraperitoneal pentobarbital, and breathing either room air (PB), oxygen:nitrous oxide (PB + N(2)O), or oxygen:nitrogen (PB + N(2)). MBF was significantly higher in the ISO and PB + N(2)O groups vs. PB and in ISO vs. PB + N(2), with the following respective MBF values: ISO, 5.9 +/- 1.1; PB, 4.0 +/- 0.8; PB + N(2)O, 5.1 +/- 1.4; and PB + N(2), 4.6 +/- 0.8 mL/g/minute, mean +/- SD. Ejection fractions were reduced by 10% in PB and PB + N(2)O rats vs. ISO rats. Cardiac output (CO) and index (CI) were 25 to 30% lower in all rats anesthetized with pentobarbital than with isoflurane. Isoflurane and nitrous oxide induce a higher MBF than pentobarbital. Isoflurane also induces a higher ejection fraction in healthy rats.


Severe flare-up in a prostate cancer patient treated with luteinizing hormone-releasing hormone analogue depot.
A 65-year-old man with advanced prostate cancer was treated with a luteinizing hormone-releasing hormone (LH-RH) analogue. Four days after the initial injection of 3.6 mg of goserelin acetate, severe dyspnea developed due to worsening pleuritis carcinomatosa, which was considered as a flare-up. Chest drainage was required to save his life. Therefore, we emphasize the importance of treatment to prevent tumor flare during LH-RH analogue therapy.


Comparison of a direct and an indirect approach for the functional assessment of insistence on sameness in a child with autism spectrum disorder and a typically developing child.
To compare indirect and direct functional assessment of insistence on sameness associated with autism spectrum disorder (ASD) and typical development. Parents rated the function of insistence on sameness for a 6-year-old boy with ASD (Peter) and a typically developing 4-year-old boy (Nathan) using the Motivation Assessment Scale (MAS). Ratings were compared to the results of a direct assessment. The results of the assessment procedures were mainly consistent for Peter and suggested that his tendency to insist on sameness was maintained by sensory consequences. The finding of an attention function for Nathan in the play-based assessment was consistent with previous functional assessment studies surrounding typically developing children, but in contrast to the MAS. While the play-based assessment may be more suitable for assessing the high rate insistence on sameness observed in individuals with ASD, the MAS may be more suitable for low rate insistence on sameness.


Getting everyone to the table: exploring everyday and everynight work to consider 'latent social threats' through interprofessional tabletop simulation.
In this methodological intersection article, we describe how we developed a new variation of the established tabletop simulation modality, inspired by institutional ethnography (IE)-informed principles. We aimed to design and conduct pilot implementations of this innovative tabletop simulation modality, which focused uniquely on everyday and everynight work, along with the factors that govern that work. In so doing, we aimed to develop a modality and preliminary findings that researchers and educators can use to simulate healthcare practices across longer episodes of care (i.e., time scales of hours or an entire day) and to detect the 'latent social threats' that can emerge during interprofessional clinical care.An interprofessional team designed tabletop simulation scenarios of interprofessional challenges during transfers of care on a labour and delivery (L&D) unit. Within each scenario, participants provided real-time explanations for their work and associated drivers, both independently and as a team. Thus, we combined 'think-aloud' and simulation principles to design tabletop simulation scenarios to elicit healthcare professionals' descriptions of how they collaborate in their work on the L&D unit. We completed a total of five tabletop simulations with eight participants (obstetricians, N = 2; midwives, N = 2; nurses, N = 5).The conversations stimulated by the tabletop simulation scenarios and debriefs allowed us to generate a preliminary understanding of the texts that govern and organize clinicians' everyday work processes. We generated data about longitudinal, multi-hour work processes in a condensed timeline, with opportunities to pause and probe, and with reduced focus on individual practitioner's competence.We believe our innovative tabletop simulation approach allowed us to examine clinical work in ways no other simulation permits. Participants described how the scenarios opened a productive dialogue between professional groups and suggested this simulation-based approach might contribute to enhanced interprofessional understanding and cultural change. We suggest that others can adapt our low-resource approach to understand clinicians' everyday work and to map how this work is governed by documents, like policies, with the end goal of facilitating system change and managing latent social threats.


Prognostic implications of serum microRNA-21 in colorectal cancer.
MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in carcinogenesis through postranscriptional gene regulatory activity. Few studies have focused on the detection of miR-21 in serum rather than in tissue. The current study aimed to measure serum miR-21 expression levels and to evaluate their association with the outcome of colorectal cancer (CRC). Blood samples were collected from 102 CRC patients undergoing surgery with curative intent. The expression levels of miR-21 were measured using a quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results were analysed to assess the relationship between serum miR-21 levels and patient survival. A univariate analysis revealed that lower expression levels of serum miR-21 were associated with higher local recurrence (P = 0.025) and mortality (P = 0.029). A logistic regression analysis demonstrated that the relative overexpression of miR-21 (expression > 1) was associated with a 51% reduction in the risk of recurrence. A Cox regression analysis identified miR-21 expression as an independent predictor of survival (P = 0.048); a relative increase in miR-21 expression (>1) was associated with a 50% reduction in the risk of mortality. The expression level of serum miR-21 correlates with the recurrence and mortality of CRC patients. Our results suggest that circulating serum miR-21 is a promising prognostic tumour marker, and they highlight the potential clinical utility of miR-21 expression as a prognostic marker for CRC prognosis.


Quality of Life and Health Care Utilization in the CIRCA-DOSE Study.
This study evaluated the impact of contact force-guided radiofrequency ablation versus cryoballoon ablation on quality of life and health care utilization. Traditional outcome parameters, such as arrhythmia-free survival, are insufficient to evaluate the clinical impact of atrial fibrillation (AF), as it fails to the capture patient- and health system-level differences in treatment approaches. The CIRCA-DOSE (Cryoballoon Vs. Contact-Force Atrial Fibrillation Ablation) study randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency or cryoballoon ablation. Health-related quality-of-life (HRQOL) was assessed at baseline, and at 6 and 12 months post-ablation using a disease-specific and generic HRQOL instruments. Health care utilization (hospitalization, emergency department visits, and cardioversion) and antiarrhythmic drug use for the 12 months preceding ablation was compared with the 12 months following ablation. Disease-specific and generic HRQOL was moderately to severely impaired at baseline and improved significantly at 6 and 12 months of follow-up (median improvement in AFEQT [Atrial Fibrillation Effect on QualiTy of Life] score 32.4 [interquartile range: 17.7 to 48.9]). When compared with the 12 months pre-ablation, the proportion and absolute number of cardioversions decreased significantly (41.1% vs. 10.1% of patients, 137 vs. 35 events; p < 0.0001). Similar significant reductions in emergency department visits (66.7% vs. 25.1% of patients, 224 vs. 87 events; p < 0.0001), and hospitalizations (25.5% vs. 14.5% of patients, 86 vs. 50 events; p < 0.001) were observed. There were no significant differences between randomized groups. In this multicenter randomized trial, catheter ablation with advanced-generation technologies resulted in a significant improvement in HRQOL and a significant reduction in health care utilization in the year following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation [CIRCA-DOSE]; NCT01913522).


Deoxynivalenol and 3-acetyldeoxynivalenol and Fusarium species in winter triticale.
Fusarium species infecting heads of Triticale and mycotoxins presence in infected kernels and chaff were studied during two seasons. The most important species observed on infected heads were in 1986F. avenaceum (39%),F. nivale (21%),F. culmorum (20%),F. graminearum (14%), and others (6%). In 1987 after long and snowy winterF. nivale dominated (64%), followed byF. avenaceum (24%),F. culmorum (6%), andF. graminearum (5%).The mycotoxins deoxynivalenol (DON) and 3-acetyl DON were present in all 11 subsamples of kernels from heads infected byF. culmorum and/orF. Graminearum (1.6-16.4 mg and 0.7-2.4mg/kg, respectively). Chaff from the same subsamples contained 9.9-33.2mg/kg of DON and 5.2-16.0mg/kg of 3-AcDON. Kernels with visibleFusarium-damage contained 2.4-31.2 mg/kg of DON and 1.2-6.0 mg/kg of 3-AcDON. Remaining part of kernels without symptoms of visibleFusarium-damage contained only DON in an amount of 0.9-5.9 mg/kg.


Enzyme-linked immunosorbent assay (ELISA) for detecting antisperm antibodies in mice with testicular autoimmunity.
We developed an ELISA for measuring antisperm antibodies in the mouse by using serum samples obtained from mice immunized with murine testicular antigens in complete Freund's adjuvant (CFA) as well as from mice rendered vasectomized. Sperm antigens used were syngeneic epididymal spermatozoa and two types of soluble, murine testicular antigens prepared in our laboratory. This study deals with a) the sequential changes of antisperm antibody levels following immunization; b) determination of immunoglobulin classes of these antibodies; c) a correlation between the absorbance values and the endpoint titers of antisperm antibodies; and d) comparison of endpoint titers of antisperm antibodies detected by ELISA with those by immunoperoxidase staining method in immune and nonimmune sera. It is suggested that serum dilution as high as 1/800 or more is required for detecting antibody titers of immune sera, because nonimmune mouse sera reveal a definite, although low, level of absorbance value at a serum dilution of 1/400 or less.


Prenatal Diagnosis and Perinatal Outcomes of Congenital Megalourethra: A Multicenter Cohort Study and Systematic Review of the Literature.
The purpose of this study was to evaluate the prenatal findings and postnatal outcomes in fetuses with congenital megalourethra. This retrospective study reviewed our experience and the literature between 1989 and 2014. Prenatal findings were evaluated and compared with postnatal findings, including neonatal mortality and abnormal renal function (need for dialysis or renal transplantation). Fifty fetuses with congenital megalourethra were analyzed, including 6 cases diagnosed in our centers. Most cases (n = 43 [86.0%]) were diagnosed in the second trimester. Only 1 case was diagnosed in the first trimester, whereas 6 cases (12.0%) were diagnosed in the third trimester. Thirty-five fetuses (70.0%) survived. Bilateral hydroureters were associated with perinatal death (P= .024). Among the survivors, 41.9% of the neonates had renal impairment. The following factors were associated with postnatal renal impairment: presence of severe oligohydramnios/anhydramnios (P = .033), bilateral hydronephrosis (P = .008), and earlier gestational age at delivery (P = .022). In fetal megalourethra, bilateral hydroureters, bilateral hydronephrosis, and severe oligohydramnios/anhydramnios are associated with neonatal mortality and renal impairment.


Robotic vNOTES Techniques for Hysterectomy in a Patient with a 16-week Sized Uterus and a Body Mass Index of 70.
To demonstrate the surgical techniques for robotic vNOTES hysterectomy with bilateral salpingo-oophorectomy (BSO) in a World Health Organization class 3 obesity patient (body mass index = 70) as well as large fibroid uterus (16 weeks sized). Stepwise demonstration with narrated video footage. An academic tertiary care hospital. Our patient is a 50-year-old G0 with postmenopausal vaginal bleeding with an enlarged uterus; her endometrial biopsy showed complex endometrial hyperplasia with atypia. The surgical exposure for extremely obese patients with a concomitantly large uterus can be very challenging transabdominally due to the patient being unable to tolerate the Trendelenburg position and abdominal gas pressure [1-5]. Therefore, transvaginal NOTES can be an alternative option for these types of challenging patients. However, although there are clear benefits of vNOTES surgery in obese patients, we still need to be thoughtful and deliberate in handling this kind of surgery [6]. Several key success factors that aid in the completion of the surgery include 1. Appropriate patient positioning (Trenguard Position) as tolerated. 2. Initial vaginal section of hysterectomy. 3. Successful port placement. 4. Trendelenburg, as far as tolerated. 5. Harnessing the robotic camera for anterior colpotomy. 6. Utilizing alternative surgical exposure techniques: air seal for maintaining gas pressure for optimizing exposure, lap pad for thermal isolation, and maintaining the uterus for safe exposure during BSO. 7. After identification of the bilateral ureters, the broad, round, and uterine ovarian ligaments were transected with vessel sealer (less thermal spread), and the cystectomy was completed. (Supplemental Video 1) 8. BSO was completed. 9. In-bag uterine tissue extraction. 10. Vaginal cuff closure with V-Loc barbed suture. Robotic-assisted NOTES hysterectomy with BSO is feasible and safe in extremely obese patients with large uterus. The combination of all these strategies could aid in the feasibility and safety of patients with these challenging pathology and morbidity.


Antenatal mgnesium sulfate and ritodrine increased potassium levels in preterm infants: A cohort study.
Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.


Impact of the Opioid Epidemic on Drug Testing.
This review provides a description of how the opioid epidemic has impacted drug testing. Four major service areas of drug testing were considered, including emergency response, routine clinical care, routine forensics, and death investigations. Several factors that the opioid epidemic has impacted in drug testing are discussed, including specimens, breadth of compounds recommended for testing, time to result required for specific applications, analytical approaches, interpretive support requirements, and examples of published practice guidelines. Both clinical and forensic laboratories have adapted practices and developed new testing approaches to respond to the opioid epidemic. Such changes are likely to continue evolving in parallel with changes in both prescription and nonprescription opioid availability and use patterns, as well as emerging populations that are affected by the "waves" of the opioid epidemic.


Emergency transarterial embolization followed by staged hepatectomy versus emergency hepatectomy for ruptured hepatocellular carcinoma: a single-center, propensity score matched analysis.
To compare the feasibility and efficacy of emergency transarterial embolization (TAE) followed by staged hepatectomy (SH) with emergency hepatectomy (EH) for ruptured hepatocellular carcinoma (HCC). Between January 2012 and December 2017, 102 patients with HCC rupture received EH or emergency TAE followed by SH in our center. Patients were followed until April 2019. Propensity score matching (PSM) analysis was used at a 1:2 ratio, resulting in 20 patients in the SH group and 40 patients in the EH group. We retrospectively compared the operative variables, recurrence status, disease-free survival (DFS), and overall survival (OS) of patients between the two matched groups. Compared with the matched EH group, the SH group showed significantly decreased perioperative blood loss or blood transfusion, shortened intraoperative duration of clamping and postoperative hospital stay (P < 0.05), while achieving comparable long-term OS (SH group: 39.0 months vs. EH group: 38.1 months, P = 0.342). There was no significant difference in the peritoneal metastasis rate (SH group: 20.0% vs. EH group: 25.6%, P = 0.874), recurrence rate (SH group: 65.0% vs. EH group: 71.8%, P = 0.333) or DFS (SH group: 9.4 months vs. EH group: 7.7 months, P = 0.602) between the two matched groups. For resectable ruptured HCC, emergency TAE of rupture which followed by SH, could bring patients about intraoperative and postoperative benefits when compared to EH. Moreover, this combination treatment will not increase the rate of peritoneal metastasis or recurrence, and might achieve favorable survival benefits for patients.


Djungarian hamsters exhibit temperature-dependent dietary fat choice in long days.
Previous studies have shown that whole-animal thermal responses of ectotherms and heterotherms (e.g., hibernators), both of which experience a wide range of body temperatures, are related to the saturation level of somatic lipids, which in turn can be influenced by the ratio of saturated and unsaturated fatty acids in the diet. This study demonstrates that Djungarian hamsters held in long days display ambient temperature-dependent choice of dietary fats, increasing their preference for saturated fats when ambient temperature increases (to 27 degrees C) and later reversing this preference when ambient temperature is returned to its original value (8 degrees C). Changes in percent contribution of the unsaturated and saturated diets in response to temperature were accomplished almost solely by changes in the amount of unsaturated diet consumed. Temperature-dependent fatty acid choice occurs at a stage in the annual cycle when Djungarian hamsters do not enter spontaneous daily torpor and therefore experience only small changes in core body temperature. These results suggest that temperature-dependent fatty acid choice may occur in a wide range of animals, including nonheterothermic endotherms.