Predicting defect stability and annealing kinetics in two-dimensional PtSe2using steepest entropy ascent quantum thermodynamics.
The steepest-entropy-ascent quantum thermodynamic (SEAQT) framework was used to calculate the stability of a collection of point defects in 2D PtSe2and predict the kinetics with which defects rearrange during thermal annealing. The framework provides a non-equilibrium, ensemble-based framework with a self-consistent link between mechanics (both quantum and classical) and thermodynamics. It employs an equation of motion derived from the principle of steepest entropy ascent (maximum entropy production) to predict the time evolution of a set of occupation probabilities that define the states of a system undergoing a non-equilibrium process. The system is described by a degenerate energy landscape of eigenvalues, and the entropy is found from the occupation probabilities and the eigenlevel degeneracies. Scanning tunneling microscopy was used to identify the structure and distribution of point defects observed experimentally in a 2D PtSe2film. A catalog of observed defects includes six unique point defects (vacancies and anti-site defects on Pt and Se sublattices) and twenty combinations of multiple point defects in close proximity. The defect energies were estimated with density functional theory, while the degeneracies, or density of states, for the 2D film with all possible combinations or arrangements of cataloged defects was constructed using a non-Markovian Monte-Carlo approach (i.e. the Replica-Exchange-Wang-Landau algorithm (Vogelet al2013Phys. Rev. Lett.110210603)) with a q-state Potts model. The energy landscape and associated degeneracies were determined for a 2D PtSe2film two molecules thick and30×30unit cells in area (total of 5400 atoms). The SEAQT equation of motion was applied to the energy landscape to determine how an arbitrary density and arrangement of the six defect types evolve during annealing. Two annealing processes were modeled: heating from 77 K (-196 ∘C) to 523 K (250 ∘C) and isothermal annealing at 523 K. The SEAQT framework predicted defect configurations, which were consistent with experimental STM images.


Actual tissue temperature during ablation index-guided high-power short-duration ablation versus standard ablation: Implications in terms of the efficacy and safety of atrial fibrillation ablation.
Actual in vivo tissue temperatures and the safety profile during high-power short-duration (HPSD) ablation of atrial fibrillation have not been clarified. We conducted an animal study in which, after a right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We recorded tissue temperatures during a 50 W-HPSD ablation and 30 W-standard ablation targeting an ablation index (AI) of 400 (5-15 g contact force). Maximum tissue temperatures reached with HSPD ablation were significantly higher than that reached with standard ablation (62.7 ± 12.5 vs. 52.7 ± 11.4°C, p = 0.033) and correlated inversely with the distance between the catheter tip and thermocouple, regardless of the power settings (HPSD: r = -0.71; standard: r = -0.64). Achievement of lethal temperatures (≥50°C) was within 7.6 ± 3.6 and 12.1 ± 4.1 s after HPSD and standard ablation, respectively (p = 0.003), and was best predicted at cutoff points of 5.2 and 4.4 mm, respectively. All HPSD ablation lesions were transmural, but 19.2% of the standard ablation lesions were not (p = 0.011). There was no difference between HPSD and standard ablation regarding the esophageal injury rate (30% vs. 33.3%, p > 0.99), with the injury appearing to be related to the short distance from the catheter tip. Actual tissue temperatures reached with AI-guided HPSD ablation appeared to be higher with a greater distance between the catheter tip and target tissue than those with standard ablation. HPSD ablation for <7 s may help prevent collateral tissue injury when ablating within a close distance.


Medical management of thyroid eye disease.
Thyroid eye disease (TED) is the most common cause of orbital disease in adults. The immunologic pathogenesis of TED has been an area of active research and considerable progress has resulted in an expansion of therapeutic options. Although surgical intervention may be required, a majority of TED patients can be managed with medical therapies. Of medical therapies, glucocorticoids remain the agent of choice in the control of TED activity. The objective of this review is to discuss the paradigm and options in medical management of TED.


Electromechanical characterization of cinnamophilin, a natural thromboxane A2 receptor antagonist with anti-arrhythmic activity, in guinea-pig heart.
Cinnamophilin, a thromboxane A(2) receptor antagonist, has been identified as a prominent anti-arrhythmic agent in rat heart. This study aimed to determine its electromechanical and anti-arrhythmic effects in guinea-pig hearts. Microelectrodes were used to study action potentials in ventricular papillary muscles. Fluo-3 fluorimetric ratio and whole-cell voltage-clamp techniques were used to record calcium transients and membrane currents in single ventricular myocytes, respectively. Intracardiac electrocardiograms were obtained and the anti-arrhythmic efficacy was determined from isolated perfused hearts. In papillary muscles, cinnamophilin decreased the maximal rate of upstroke (V(max)) and duration of action potential, and reduced the contractile force. In single ventricular myocytes, cinnamophilin reduced Ca(2+) transient amplitude. Cinnamophilin decreased the L-type Ca(2+) current (I(Ca,L))(IC(50)=7.5 microM) with use-dependency, induced a negative shift of the voltage-dependent inactivation and retarded recovery from inactivation. Cinnamophilin also decreased the Na(+) current (I(Na)) (IC(50)=2.7 microM) and to a lesser extent, the delayed outward (I(K)), inward rectifier (I(K1)), and ATP-sensitive (I(K,ATP)) K(+) currents. In isolated perfused hearts, cinnamophilin prolonged the AV nodal conduction interval and Wenckebach cycle length and the refractory periods of the AV node, His-Purkinje system and ventricle, while shortening the ventricular repolarization time. Additionally, cinnamophilin reduced the occurrence of reperfusion-induced ventricular fibrillation. These results suggest that the promising anti-arrhythmic effect and the changes in the electromechanical function induced by cinnamophilin in guinea-pig heart can be chiefly accounted for by inhibition of I(Ca,L) and I(Na).


Control of plasmonic nanoantennas by reversible metal-insulator transition.
We demonstrate dynamic reversible switching of VO2 insulator-to-metal transition (IMT) locally on the scale of 15 nm or less and control of nanoantennas, observed for the first time in the near-field. Using polarization-selective near-field imaging techniques, we simultaneously monitor the IMT in VO2 and the change of plasmons on gold infrared nanoantennas. Structured nanodomains of the metallic VO2 locally and reversibly transform infrared plasmonic dipole nanoantennas to monopole nanoantennas. Fundamentally, the IMT in VO2 can be triggered on femtosecond timescale to allow ultrafast nanoscale control of optical phenomena. These unique features open up promising novel applications in active nanophotonics.


Evaluation of the effect of Islamic fasting on lung volumes and capacities in the healthy persons.
To evaluate the changes in pulmonary volumes during and after Islamic fasting. It is a cohort study conducted on 117 healthy subjects selected on a random basis from employees, professors and students of Iran University of Medical Sciences, Tehran, Iran, between December 1999 and January 2000. All of them underwent spirometry 10 days prior to Ramadan, 2 times during Ramadan, and one time 10 days post-Ramadan. In first visit, in addition to spirometry they underwent medical examination to make sure they are healthy. All of their spirometries and background information were collected. Repeated measurements analysis of variance method was used to compare the measurements. Approximately 69% of subjects were male and the mean age was 23.9 years. Mean fasting time was 27.8 days. The mean difference in forced expiratory volume in 1 second (FEV1%) was significant between the 4 visits (p=0.01). The mean FEV1% increased both during fasting and after Ramadan (p=0.017). The mean vital capacity and peak expiratory flow rate values increased during Ramadan significantly (p=0.043, p<0.001). Although the mean maximum mid-expiratory flow decreased in the beginning of Ramadan and significantly increased subsequently (p=0.02), MEF50% (p=0.004) and MEF75% (p=0.047) increased in the beginning of Ramadan and decreased subsequently. As a whole, fasting increases lung volumes and might improve pulmonary function. This finding seems to be relevant to the changes in weight during Ramadan.


Vertical-Injection AlGaInP LEDs with n-AlGaInP Nanopillars Fabricated by Self-Assembled ITO-Based Nanodots.
The light output power of AlGaInP-based vertical-injection light-emitting diodes (VI-LEDs) can be enhanced significantly using n-AlGaInP nanopillars. n-AlGaInP nanopillars, ~200 nm in diameter, were produced using SiO2 nanopillars as an etching mask, which were fabricated from self-assembled tin-doped indium oxide (ITO)-based nanodots formed by the wet etching of as-deposited ITO films. The AlGaInP-based VI-LEDs with the n-AlGaInP nanopillars provided 25 % light output power enhancement compared to VI-LEDs with a surface-roughened n-AlGaInP because of the reduced total internal reflection by the nanopillars at the n-AlGaInP/air interface with a large refractive index difference of 1.9.


A one-stage surgical approach to ectopic ureterocele.
Whenever a ureterectomy for treatment of ectopic ureterocele is appropriate total extravesical excision avoiding a ureteral stump is the preferred approach to avoid a pyoureter or alternating diverticulum and possible surgical complications from an intravesical procedure in small infants and children with large and distorting ectopic ureteroceles.


Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey.
This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 ± 10.4 % vs. 90.3 ± 6.6 %, p = 0.0013; antibiotics documented 87.9 ± 9.0 % vs. 95.6 ± 5.1 %, p < 0.0001; and duration or review date documented 31.9 ± 15.4 % vs. 67.7 ± 15.2 %, p < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.


Interaction of platelet-activating factor with endothelial and vascular smooth muscle cells in coculture.
Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]) is a vasoactive ether lipid produced by activated blood cells. To examine the molecular traffic and sites of metabolism of PAF released in the vascular wall, we used a coculture system in which endothelial cells are grown on micropore filters suspended over confluent cultures of vascular smooth muscle cells. The endothelial cells took up PAF 5-7 times more readily from the apical than from the basolateral surface, converting it to 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (2-acyl-PAF) and other minor metabolites. Intact endothelial monolayers effectively shielded the underlying smooth muscle cells from PAF present in the apical fluid; after a 30-min incubation with [3H]-PAF, only 1% of the radioactivity was transferred to the interstitial fluid. By contrast, PAF readily entered the interstitial fluid when the endothelial monolayers were injured by exposure to xanthine and xanthine oxidase. PAF did not significantly increase the permeability of endothelial monolayers to albumin. Smooth muscle cells took up and metabolized interstitial PAF more quickly and more completely than did endothelial cells; 65% was converted to 2-acyl-PAF in 15 min by the smooth muscle cells. PAF enhanced the proliferative effect of PDGF on smooth muscle cells, as assessed by [3H]-thymidine incorporation. These findings suggest that endothelial cells form a barrier to PAF released at the luminal surface, but PAF released in the vascular intima interacts primarily with smooth muscle cells, possibly stimulating proliferation in these cells.


Electrophysiological and behavioral measures of phonological processing of auditory nonsense V-CV-VCV stimuli.
An event-related potential, the Phonological Mapping Negativity (PMN), has been reported to reflect recognition of phonological mismatches in speech stimuli. The purpose of the present study was to explore how the PMN response to the auditory nonsense syllable reflects phonological processing in isolation without the letter prime or lexical/semantic context. Sixty-four nonsense syllable stimuli were composed for each of three stimulus conditions: phonological match (PM), phonological mismatch with similar sound (PMMS), and phonological mismatch with different sound (PMMD), making a total of 192 stimuli. The PMN was measured from fourteen normal-hearing listeners. Electroencephalogram (EEG) activity was recorded while subjects were listening to the stimuli and responding behaviorally. Subjects were asked to determine what vowel-consonant-vowel (VCV) (e.g. /apa/) would be formed from the combination of the preceding vowel (V) (e.g. /a/) and consonant-vowel (CV) (e.g. /pa/), and press a 'correct' or 'incorrect' response button as soon as they decided whether the target VCV stimulus matched their expectation. In this way, along with the PMN, behavioral response accuracy and reaction times were obtained. The results were as follows: (1) PMN amplitude was not different by stimulus condition, (2) PMN amplitude was larger over frontal and central than posterior regions, but not different between the left versus right hemisphere, (3) PMN was detected in the absence of N400, and (4) behavioral responses were more accurate and faster in PMMD than PM and PMMS. Results indicate that the PMN can reflect phonological processing of auditory nonsense syllables in isolation. The scalp distribution of PMN is most dominant in the fronto-central regions without lateralization. Lastly, behavioral response accuracy and reaction times appear to be influenced by the extent of the task difficulty or processing demand rather than by the extent of phonological violation.


Deep learning-based segmentation of lithium-ion battery microstructures enhanced by artificially generated electrodes.
Accurate 3D representations of lithium-ion battery electrodes, in which the active particles, binder and pore phases are distinguished and labeled, can assist in understanding and ultimately improving battery performance. Here, we demonstrate a methodology for using deep-learning tools to achieve reliable segmentations of volumetric images of electrodes on which standard segmentation approaches fail due to insufficient contrast. We implement the 3D U-Net architecture for segmentation, and, to overcome the limitations of training data obtained experimentally through imaging, we show how synthetic learning data, consisting of realistic artificial electrode structures and their tomographic reconstructions, can be generated and used to enhance network performance. We apply our method to segment x-ray tomographic microscopy images of graphite-silicon composite electrodes and show it is accurate across standard metrics. We then apply it to obtain a statistically meaningful analysis of the microstructural evolution of the carbon-black and binder domain during battery operation.


Effects of spatial configuration on contrast detection.
We studied spatial integration at low contrasts by testing the detection thresholds of multi-Gabor element displays, examining configuration parameters such as orientation uniformity, contour smoothness, continuity, spacing and relative phase. We find that detectability depends on stimulus geometry and is constrained by collinearity and proximity spatial relationships. For textures, thresholds decrease with local orientation uniformity. For a 'coherent' contour (e.g. smooth and continuous), thresholds decrease linearly with increased number of elements, on a log-log scale, with a slope of -1/4 (sensitivity S proportional to N1/4). However, for a 'non-coherent' contour (e.g. jagged or with spacing > 5 lambda) thresholds are only slightly affected by the number of patches. Similar behavior is observed for supra-threshold stimuli embedded in band-pass noise. These results suggest that contrast integration is primarily based on local mechanisms and constrained by contour properties. These local mechanisms are possibly mediated by lateral interactions in the primary visual cortex.


Surgery for hallux valgus. The expectations of patients and surgeons.
Two-hundred patients who had undergone surgery for hallux valgus were interviewed in an attempt to study the different variables which may have contributed to the success of their surgery. These data were compared to the results obtained by using clinically applied scores. To obtain data on surgeons' expectations, 186 members of two national orthopaedic foot societies were interviewed in order to quantify the importance and value of these variables in prognosis. The main interest of the patients is a painless great toe which, when wearing conventional shoes, gives no problems. They also wish to have their bursitis and bunion treated in order to regain their ability to walk as much as they wish. Surgeons are not only specially interested in pain and shoe problems but also in restoring an adequate range of motion in the metatarsophalangeal joint (MTP), removal of the bunion and the treatment of tender callosities. We found that the correction of footwear problems, alleviation of pain and restoration of adequate walking are the most important factors influencing the outcome of surgery. It was surprising that these expectations are only partly revealed by using clinical foot scores.


Toxicity assessment of anaerobic digestion intermediates and antibiotics in pharmaceutical wastewater by luminescent bacterium.
In order to evaluate the effect of anaerobic digestion intermediates and antibiotics in pharmaceutical wastewaters on anaerobic digestion process, their acute toxicities were tested using the 15 min median inhibitory concentration (IC(50)) at pH 7.00 ± 0.05. The results showed that the IC(50) of ethanol, acetate, propionate and butyrate were 19.40, 20.71, 10.47 and 12.17 g L(-1) respectively, which suggested the toxicity descended in the order of propionate, butyrate, ethanol and acetate. The IC(50) of aureomycin, polymyxin and chloromycetin were 12.06, 6.24 and 429.90 mg L(-1) respectively, which indicated the toxicity descended in the order of polymyxin, aureomycin and chloromycetin. Using equitoxic ratio mixing method, the joint toxicities of five groups referred by A (four anaerobic digestion intermediates), B (four anaerobic digestion intermediates and aureomycin), C (four anaerobic digestion intermediates and polymyxin), D (four anaerobic digestion intermediates and chloromycetin) and E (four anaerobic digestion intermediates, aureomycin, polymyxin and chloromycetin) were investigated respectively. Their interactions were additive (A), synergistic (B), additive (C), synergistic (D) and synergistic (E). The investigation would lay a basis for the optimization of anaerobic biotechnology for pharmaceutical wastewater treatment.


Natural killer cell activity in the rat. Analysis of effector cell morphology and effects of interferon on natural killer cell function in the athymic (nude) rat.
Athymic (nude) rats were found to have increased levels of natural killer (NK) activity, 3- to 5-fold higher than in euthymic rats. Studies were performed to determine the nature of the NK cells in these animals and the basis for their increased cytotoxic reactivity. Large granular lymphocytes (LGL), which were previously shown to be the NK cells in euthymic rats, were increased 2- to 7-fold in the peripheral blood and spleen of nude rats. The LGL, enriched by centrifugation on discontinuous Percoll density gradients, were shown to have augmented NK activity similar to that seen with LGL-enriched fractions from euthymic rats. These results indicate that the NK cells in euthymic and athymic rats are morphologically and functionally similar, and that the higher NK activity in nude rats appears to be mainly attributable to an increased proportion of effector cells. In a single-cell cytotoxicity assay, interferon pretreatment of LGL was shown to increase: (a) the percentage of LGL which form conjugates with target cells; (b) the percentage of conjugate-forming cells which kill; and (c) the kinetics of lysis. Different effects were seen depending on the target cell tested.


Prognostic Value of Computed Tomography: Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers.
Previous reports suggest that body composition parameters can be used to predict outcomes for patients with gastrointestinal (GI) cancers. However, evidence for an association with long-term survival is conflicting, with much of the data derived from patients with advanced disease. This study examined the effect of body composition on survival in primary operable GI cancer. Patients with resectable adenocarcinoma of the GI tract (esophagus, stomach, colon, rectum) between 2006 and 2014 were identified from a prospective database. Computed tomography (CT) scans were analyzed using a transverse section at L3 to calculate sex-specific body composition indices for skeletal muscle, visceral fat, and subcutaneous fat. Kaplan-Meier and log-rank analysis were used to compare unadjusted survival. Multivariate survival analyses were performed using a proportional hazards model. The study enrolled 447 patients (191 woman and 256 men) with esophagogastric (OG) (n = 108) and colorectal (CR) (n = 339) cancer. Body composition did not predict survival for the OG cancer patients. Among the CR cancer patients, survival was shorter for those with sarcopenia (p = 0.017) or low levels of subcutaneous fat (p = 0.005). Older age (p = 0.046) and neutrophilia (p = 0.013) were associated with sarcopenia in patients with CR. Tumor stage (p = 0.033), neutrophil count (p = 0.011), and hypoalbuminemia (p = 0.023) were associated with sarcopenia in OG cancer patients. In the multivariate analysis, no single measure of body composition was an independent predictor of reduced survival. Sarcopenia and reduced subcutaneous adiposity are associated with reduced survival for patients with primary operable CR cancer. However, in this study, no parameter of body composition was an independent prognostic marker when considered with age, tumor stage, and systemic inflammation.


Eosinophilic cholecystitis caused by Ascaris lumbricoides.
Eosinophilic cholecystitis is caused by the accumulation of eosinophils in the gallbladder wall and diagnosis is usually made based on histopahologic studies. The purpose of this paper is to comment on a case report published in World J Gastroenterol 2007 July; 13 (27): 3760-3762, about eosinophilic cholecystitis along with pericarditis without histopathological studies, which are considered necessary for its diagnosis.


The upside of downsizing: asymmetric trifunctional organocatalysts as small enzyme mimics for cooperative enhancement of both rate and enantioselectivity with regulation.
Small molecule organic catalysts (organocatalysts) are widely used in asymmetric catalysis and synthesis. Compared to their enzymatic and transition-metal counterparts, organocatalysts have advantages in catalytic scope and efficiency but are more limited in proficiency. Chiral trifunctional organocatalysts, in which multiple catalytic motifs act cooperatively on a chiral scaffold, are an emerging class of organocatalysts with improved proficiency. Cooperativity design that enables both enantioselectivity and rate enhancement is essential to developing future generations of organocatalysts in biomimetic asymmetric catalysis.


Racial differences in survival for early stage (T1) penile cancer: Analysis from the SEER database.
Penile cancer accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors are potentially curable with local therapy. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. From 2004 to 2016 all men with T1, N0, M0 penile cancer in the SEER-18 database were included. Kaplan-Meier analysis and multivariable Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CSS). A total of 4,406 men were identified with penile cancer; 1,941 men had T1 disease. The Kaplan-Meier (KM) analysis showed those with primary site surgery had better 5-year CSS compared to those without primary site surgery (P <.0001) and a significant difference in CSS based on race (P= 0.0078). On multivariable analysis, Hispanic individuals had worse CSS (HR 1.92; P = 0.0057) compared to the White men. Black men were also found to have a poor CSS however this was not statistically significant (HR 1.53, P = 0.118). Men with penile cancer who had either penectomy (HR 0.45; P = 0.006) or penile preservation surgery (HR 0.25; P< 0.001) had improved CSS. Racial disparities in CSS exist among men with in early-stage penile cancer. KM analysis showed significant differences in CSS by race and in those receiving primary site surgery. On multivariable analysis, the CSS is worse in Hispanic compared to White men. There is a trend towards worse CSS in Black men however this was not statistically significant.


Prevention and Treatment of Hyponatremia in Patients with Subarachnoid Hemorrhage: A Systematic Review.
Current guidelines for the management of hyponatremia in patients with subarachnoid hemorrhage (SAH) are not based on a systematic assessment of the literature. We evaluated published studies on the efficacy and safety of current preventative and treatment strategies for hyponatremia in patients with SAH. We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and PubMed for relevant studies. Primary outcomes of interest included neurologic functional outcomes, symptomatic vasospasm, and others. Secondary outcomes included measures of sodium and volume status. We included 5 out of 117 identified studies: 1 before-and-after observational trial (using fludrocortisone) and 4 randomized controlled trials (2 using fludrocortisone; 2 using hydrocortisone). All 5 trials had a high risk of bias in at least 1 domain. We could not perform a meta-analysis of functional outcomes; however, individual studies did not demonstrate statistically significant differences. Mineralocorticoid use did not statistically significantly reduce the incidence of symptomatic vasospasm (relative risk, 0.60; 95% confidence interval, 0.35-1.03; I2 = 0%). The studies did not report other primary outcomes. In the 4 RCTs, mineralocorticoid use reduced natriuresis and volume contraction. Current evidence does not demonstrate a benefit of preventative treatment with mineralocorticoids in clinically important outcomes, although a difference cannot be ruled out due to imprecision. Larger well-designed trials are needed to establish the impact of mineralocorticoids and fluid and sodium supplementation strategies on clinically relevant outcomes in the prevention and treatment of hyponatremia in patients with SAH.


Gut microbial genetic variation modulates host lifespan, sleep, and motor performance.
Recent studies have shown that gut microorganisms can modulate host lifespan and activities, including sleep quality and motor performance. However, the role of gut microbial genetic variation in regulating host phenotypes remains unclear. In this study, we investigated the links between gut microbial genetic variation and host phenotypes using Saccharomyces cerevisiae and Drosophila melanogaster as research models. Our result suggested a novel role for peroxisome-related genes in yeast in regulating host lifespan and activities by modulating gut oxidative stress. Specifically, we found that deficiency in catalase A (CTA1) in yeast reduced both the sleep duration and lifespan of fruit flies significantly. Furthermore, our research also expanded our understanding of the relationship between sleep and longevity. Using a large sample size and excluding individual genetic background differences, we found that lifespan is associated with sleep duration, but not sleep fragmentation or motor performance. Overall, our study provides novel insights into the role of gut microbial genetic variation in regulating host phenotypes and offers potential new avenues for improving health and longevity.


Suggestion for a subdivision of processed meat products on the Danish market based on their content of carcinogenic compounds.
Carcinogenic effects in humans are ascribed to processed meat by organisations such as International Agency for Research on Cancer, World Cancer Research Fund and American Institute for Cancer Research. However, the term 'processed meat' covers a heterogenic group of products whose content of potential hazards differ considerably. To improve estimates of associations between processed meat intake and cancer risk we investigated ways to divide processed meat into subgroups that more precisely reflects its carcinogenic characteristics. We collected ingredient lists and declarations of salt content for >1000 processed meat products on the Danish market and combined the information with knowledge related to processing parameters. Some compounds that could affect the products' carcinogenic characteristics, alone or in combination, were evaluated and compared for 12 types of processed meat products, and we suggest subgrouping of processed meat with similar level of carcinogenic potential, which could improve the understanding of the cancer risk associated with processed meat intake in scientific human studies.


T1rho MRI of Alzheimer's disease.
Alzheimer's disease (AD) is the most common form of dementia in the elderly. Classic symptoms of the disease include memory loss and confusion associated with the hallmark neuro-pathologic lesions of neurofibrillary tangles (NFT) and senile plaques (SP) and their sequelae, gray matter atrophy. Volumetric assessment methods measure tissue atrophy, which typically follows early biochemical changes. An alternate MRI contrast mechanism to visualize the early pathological changes is T1rho (or "T-1-rho"), the spin lattice relaxation time constant in the rotating frame, which determines the decay of the transverse magnetization in the presence of a "spin-lock" radio-frequency field. Macromolecular changes (in plaques and tangles) that accompany early AD are expected to alter bulk water T1rho relaxation times. In this work, we measure T1rho MRI on patients with clinically diagnosed AD, MCI and in age-matched cognitively normal control subjects in order to compare T1rho values with changes in brain volume in the same regions of the brain and demonstrate that T1rho can potentially constitute an important biomarker of AD.


A Missed Celiac Artery Aneurysm Leading to Rupture: A Case Report.
Abdominal pain is a common complaint seen in the emergency department (ED). We report a case of celiac artery aneurysm (CAA) in a male patient presenting with abdominal pain to the ED on two separate occasions, approximately 24 hours apart. On the initial visit the patient was discharged with undifferentiated abdominal pain after computed tomography imaging and laboratory investigations. On the repeat visit he was found to have a rapidly expanding CAA with rupture. He became unstable requiring intubation, blood transfusions, and emergent transfer to a tertiary care center for surgical management where, unfortunately, he died hours after failed operative management. Although rare, abdominal pain caused by CAAs can rapidly progress to rupture and have a high mortality.


Polyhydroxybutyrate (PHB) production from sugar cane molasses and tap water without sterilization using novel strain, Priestia sp. YH4.
The production cost of biodegradable polymer like polyhydroxybutyrate (PHB) is still higher than that of petroleum-based plastics. A potential solution for reducing its production cost is using a cheap carbon source and avoiding a process of sterilization. In this study, a novel PHB-producing microbial strain, Priestia sp. YH4 was screened from the marine environment using sugarcane molasses as the carbon source without sterilization. Culture conditions, such as carbon, NaCl, temperature, pH, inoculum size, and cultivation time, were optimized for obtaining the highest PHB production by YH4 resulting in 5.94 g/L of dry cell weight (DCW) and 61.7 % of PHB content in the 5 mL culture. In addition, it showed similar PHB production between the cultures with or without sterilization in Marine Broth media. When cultured using only tap water, sugarcane molasses, and NaCl in a 5 L fermenter, 24.8 g/L DCW was produced at 41 h yielding 13.9 g/L PHB. Finally, DSC (Differential Scanning Calorimetry) and GPC (Gel Permeation Chromatography) were used to analyze thermal properties and molecular weights resulting in Tm = 167.2 °C, Tc = 67.3 °C, Mw = 2.85 × 105, Mn = 1.05 × 105, and PDI = 2.7, respectively. Therefore, we showed the feasibility of more economical process for PHB production by finding novel strain, utilizing molasses with minimal media components and avoiding sterilization.


Editorial for Special Issue: Highly Efficient Energy Harvesting Based on Nanomaterials.
Energy-harvesting systems generate electricity or produce fuels such as hydrogen from various energy sources such as thermal energy, kinetic energy, and renewable energy [...].


Protocol to acquire time series data on adverse reactions following vaccination using a smartphone or web-based platform.
Data collection on adverse reactions in recipients after vaccination is vital to evaluate potential health issues, but health observation diaries are onerous for participants. Here, we present a protocol to collect time series information using a smartphone or web-based platform, thus eliminating the need for paperwork and data submission. We describe steps for setting up the platform using the Model-View-Controller web framework, uploading lists of recipients, sending notifications, and managing respondent data. For complete details on the use and execution of this protocol, please refer to Ikeda et al. (2022).1.


Single-molecule study of DNA unlinking by eukaryotic and prokaryotic type-II topoisomerases.
Type-II topoisomerases are responsible for untangling DNA during replication by removing supercoiled and interlinked DNA structures. Using a single-molecule micromanipulation setup, we follow the real-time decatenation of two mechanically braided DNA molecules by Drosophila melanogaster topoisomerase (Topo) II and Escherichia coli Topo IV. Although Topo II relaxes left-handed (L) and right-handed (R-) braids similarly at a rate of approximately 2.9 s-1, Topo IV has a marked preference for L-braids, which it relaxes completely and processively at a rate of approximately 2.4 s-1. However, Topo IV can unlink R-braids at about half that rate when they supercoil to form L-plectonemes. These results imply that the preferred substrate for unlinking by Topo IV has the symmetry of an L-crossing and shed new light on the decatenation of daughter strands during DNA replication, which are usually assumed to be linked in an R-braid.


Tumor-Associated Macrophages and Ovarian Cancer: Implications for Therapy.
The tumor microenvironment (TME) has been implicated to play an important role in the progression of ovarian cancer. One of the most important components of the TME is tumor associated macrophages (TAMs). Phenotypically, macrophages are broadly categorized as M1 pro-inflammatory or M2 anti-inflammatory, based on the cytokines and chemokines that they secrete. The tumor microenvironment is associated with macrophages of an M2 phenotype which suppress the surrounding immune environment, assist tumor cells in evading immune targeting, and support tumor growth and metastasis. Contrarily, M1 macrophages help mount an immune response against tumors, and are associated with a more favorable prognosis in solid tumors. One of the characteristic indicators of a poor prognosis in ovarian cancer is the overrepresentation of M2-type TAMs. As such, therapeutic modalities targeting TME and TAMs are of increasing interest. Pharmacological approaches to eliminate TAMs, include decreasing macrophage survival and recruitment and increasing phagocytosis, have been underwhelming. Clinical strategies targeting these macrophage subtypes via repolarization to an M1 antitumoral state deserve increasing attention, and may serve as a new modality for immunotherapy.


Early differentiation of the human retina. A neurohistological study.
A series of retinas from 30 human embryos, ranging in total length from 10 to 40 mm (i.e., to the end of gestation month 2), were successfully stained by the Golgi method and then examined and compared with routinely stained specimens from pertinent stages. Two more series impregnated with other silver methods were used as controls. In the results we try to clarify some difficult points in the literature on the subject.


A clinicopathological scoring system to select breast cancer patients for sentinel node biopsy.
Selecting patients for sentinel node biopsy, based on grade and size of the primary tumour, often results in the need for a second operation of axillary clearance since intra-operative pathological assessment of sentinel node is in its evolution at present. It may be possible to refine the clinical criteria to select patients for the type of axillary surgery. By using a score based on clinicopathological predictors of axillary lymph node involvement, we hypothesise that it may be possible to identify patients at high or low risk of nodal involvement. This information can be used to assist patients to make informed decision regarding risks and benefits of sentinel node biopsy or axillary clearance. A score was devised based on the clinicopathological variables of 113 patients to assess the likelihood of lymph node positivity. This score was validated on an independent data set of 89 patients who underwent sentinel node biopsy and axillary surgery. Based on the score, patients were divided into two groups, high score and low score groups. For the low score group, lymph node positivity was 18% for the original score and 24% for the validation score. Lymph node positivity rate was 67% for the high score group for the original series and 65% for the validation series of patients. A clinicopathological scoring system can assist in selecting patients with breast cancer for sentinel node biopsy.


Transcriptional regulation of aquaporin-3 in human retinal pigment epithelial cells.
The expression of aquaporin (AQP) water channels may influence the development of retinal edema. We investigated the transcriptional regulation of AQP3 in cultured human retinal pigment epithelial (RPE) cells. As shown by RT-PCR and immunocytochemistry, cultured RPE cells express AQP3 mRNA and protein. The AQP3 mRNA level in RPE cells was elevated under the following conditions: chemical hypoxia induced by CoCl(2), hyperosmolarity induced by 100 mM NaCl, and upon stimulation of the cultures with PDGF, arachidonic acid, prostaglandin E(2), and blood serum, respectively. Chemical hypoxia increased AQP3 gene expression through MEK/ERK and JNK activation. The hyperosmolarity-, PDGF-, and serum-induced upregulation of AQP3 was prevented by inhibition of the phospholipase A(2), but not by inhibition of the cyclooxygenase. Triamcinolone acetonide prevented the upregulation of AQP3 induced by arachidonic acid and prostaglandin E(2), but not by the other factors tested. It is concluded that AQP3 is transcriptionally activated in RPE cells by various pathogenic factors involved in the development of retinal edema in situ. Activation of phospholipase A(2) is a critical factor which induces AQP3 in RPE cells.


The glomerular distribution of type IV collagen and laminin in human membranous glomerulonephritis.
The glomerular distribution of type IV collagen and laminin, the major collagenous and noncollagenous components of the glomerular basement membrane, was studied by immunofluorescence microscopy in idiopathic and lupus membranous glomerulonephritis. Affinity-purified antibodies against type IV collagen reacted preferentially with the inner aspect and irregularly with the adjacent outer area of the thickened basement membrane. In contrast, laminin was detected along the inner aspect of the glomerular basement membrane, in subepithelial basement membrane protrusions ("spikes"), and in the newly formed basement membrane layer above the immune deposits. We conclude that type IV collagen and laminin do not codistribute in the newly formed matrix. This aberrant antigenic distribution may reflect a loss of coordinate biosynthesis or degradation of these matrix components by visceral epithelial cells.


[Sex hormones in female patients with systemic lupus erythematosus].
To explore the levels of sex hormones in female patients with systemic lupus erythematosus (SLE) and its role in the genesis of SLE. The serum levels of estradiol, estriol, testosterone, progesterone, and prolactin were determined by electro-chemiluminescence immunoassay in 98 female patients with SLE and compared with those of 38 healthy women. The serum levels of estradiol, estriol, progesterone, and prolactin were significantly higher than those in the healthy women (P <0.05). The serum levels of estradiol, progesterone, and prolactin in patients with SLE in 25 to 34 year old group were higher than the other age groups and the control group (P < 0.05), and the serum levels of estradiol and prolactin in patients with active phase of SLE were significantly higher than those in patients with stable phase of SLE (P <0.05). The levels of sex hormones have a close corretation with the genesis and development of SLE.


Doxycycline Malaria Prophylaxis Impact on Risk of Travelers' Diarrhea among International Travelers.
International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD prevention. With increasing resistance and recommendations against antibiotic chemoprophylaxis, doxycycline fell out of use. We evaluated TD incidence and risk factors in a prospective cohort of travelers, specifically in regard to malaria prophylaxis. Travelers' diarrhea was defined as ≥ 3 loose stools in 24 hours or two loose stools in 24 hours associated with other gastrointestinal symptoms. The Poisson regression model with robust error variance was used to estimate the RR of TD. Three thousand two hundred twenty-seven trips were enrolled: 62.1% of participants were male, with a median age of 39 years (interquartile range [IQR] 27,59) and a median travel duration of 19 days (IQR 12,49); 17.4% developed TD; 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America; and 20% took doxycycline for malaria chemoprophylaxis, 50% took other antimalarials, and 30% took none. Decreased RR of TD was associated with doxycycline (RR 0.62 [0.47-0.82], P < 0.01) and military travel (RR 0.57 [0.47-0.70], P < 0.01). Increased risk of TD was associated with female gender (RR 1.28 [1.09-1.50], P < 0.01), hotel accommodations (RR 1.30 [1.10-1.53], P < 0.01), travel to tropical South America (RR 1.34 [1.09-1.64], P < 0.01), and duration of travel (RR 1.00 [1.00-1.01], P < 0.01). The use of doxycycline for malaria prophylaxis is associated with lower TD risk, suggesting increasing bacterial enteropathogen susceptibility similar to previous observations. Doxycycline selection for antimalarial chemoprophylaxis may provide additional traveler benefit in infection prevention.


On writing medical history.
Writing medical history papers can be professionally and personally rewarding, but a little overwhelming for novices. This paper offers step-by-step guidelines for the entire process, including developing appropriate topics, finding and using appropriate sources, and writing the paper. Specific reference sources are recommended.


Adaptive edge localisation approach for quantitative coronary analysis.
Lack of reliability, user dissatisfaction and errors in determining coronary vessel wall characteristics are challenging issues in quantitative coronary analysis (QCA). A new approach is proposed for QCA that tackles these issues. The proposed approach extracts the coronary vessel edges by applying dynamic programming techniques that use human-based decision criteria, adaptive edge detection and feature-based cost minimisation. This approach uses image gradient, image intensity, boundary continuity and adaptive thresholding to gain maximum quality assurance. The validation of this approach was conducted through modelled phantoms and real X-ray angiograms. The results show that the accuracies obtained were 0.0116mm and 0.06mm, respectively, and the precisions were 0.0263mm, and 0.04mm, respectively. The proposed approach is reliable, reproducible and user friendly and provides high precision compared with recently published results. Furthermore, the significance of the proposed approach and its limitations are also discussed.


Comparative of machine learning classification strategies for electron energy loss spectroscopy: Support vector machines and artificial neural networks.
Machine Learning (ML) strategies applied to Scanning and conventional Transmission Electron Microscopy have become a valuable tool for analyzing the large volumes of data generated by various S/TEM techniques. In this work, we focus on Electron Energy Loss Spectroscopy (EELS) and study two ML techniques for classifying spectra in detail: Support Vector Machines (SVM) and Artificial Neural Networks (ANN). Firstly, we systematically analyze the optimal configurations and architectures for ANN classifiers using random search and the tree-structured Parzen estimator methods. Secondly, a new kernel strategy is introduced for the soft-margin SVMs, the cosine kernel, which offers a significant advantage over the previously studied kernels and other ML classification strategies. This kernel allows us to bypass the normalization of EEL spectra, achieving accurate classification. This result is highly relevant for the EELS community since we also assess the impact of common normalization techniques on our spectra using Uniform Manifold Approximation and Projection (UMAP), revealing a strong bias introduced in the spectra once normalized. In order to evaluate and study both classification strategies, we focus on determining the oxidation state of transition metals through their EEL spectra, examining which feature is more suitable for oxidation state classification: the oxygen K peak or the transition metal white lines. Subsequently, we compare the resistance to energy loss shifts for both classifiers and present a strategy to improve their resistance. The results of this study suggest the use of soft-margin SVMs for simpler EELS classification tasks with a limited number of spectra, as they provide performance comparable to ANNs while requiring lower computational resources and reduced training times. Conversely, ANNs are better suited for handling complex classification problems with extensive training data.


Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction.
The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. Nine horses with inducible and reversible RAO. Randomized, crossover trial. Horses were challenged with moldy hay to induce airway obstruction. Horses were treated with nebulized albuterol or levalbuterol chosen randomly. Pulmonary function testing (PFT) was measured before and for up to 3 hours after bronchodilatation challenge. Maximum change in transpulmonary pressure (DPmax ) was measured to assess the dose effect and duration of action of each drug. After a 24 hours washout period, the bronchodilatation challenge was repeated with the second bronchodilator. The duration of effect was 60 minutes for albuterol and 120 minutes for levalbuterol. The dose of bronchodilator EDmax was not significantly different between albuterol and levalbuterol (EDmax = 125.0 [125-125 μg] and EDmax = 188 [125-188 μg] respectively; P = .068). The magnitude of bronchodilatation was not significantly different between the 2 treatments (61.1 and 59.9% decrease in DPmax for albuterol and levalbuterol respectively; P = .86). Levalbuterol is as effective a bronchodilator as albuterol; although levalbuterol lasts twice as long as albuterol, its duration of action is still too short to make it practical for RAO treatment.


Development of a rat model for orthotopic liver transplantation for hepatocellular carcinoma.
Surgical resection is of limited benefit in hepatocellular carcinoma accompanied by severe liver cirrhosis or multicentric hepatic cancer. The long-term survival of patients with advanced hepatocellular carcinoma after transplantation is quite poor. We have studied the characteristics, natural course, and cause of diethylnitrosamine-induced liver cancer in rats and have shown it to be a good model of liver cancer in human beings. Therefore we performed orthotopic liver transplantation (OLT) in rats with diethylnitrosamine-induced liver cancer to study the patterns of recurrence. Diethylnitrosamine 100 parts per million in drinking water was administered daily for 4 months to male inbred LEW rats. A laparotomy was performed 120 or 134 days after commencing the oral diethylnitrosamine to confirm the induction of cancer confined grossly to the liver. The livers were resected, and orthotopic transplantation with livers of normal LEW rats was performed. By day 150 all the rats in the non-OLT group died of intraabdominal hemorrhage caused by spontaneous rupture of liver cancer (mean survival time +/- SD, 138.2 +/- 5.3 days; n = 14). However, the OLT (day 120) group recovered their body weight comparatively early after transplantation and survived a maximum of 218 days until death from recurrence (203.8 +/- 21.3 days; n = 4). A significant extension in survival time was observed (p < 0.01). In autopsies performed at the time of death, metastatic liver cancer was observed in the transplanted livers with two showing metastases to the lung. The cause of death was cancer in all the rats. However, the OLT (day 134) group all died of major complications of severe pneumonia and disseminated intravascular coagulation within 2 weeks of OLT (141.3 +/- 5.0 days; n = 4). After liver transplantation to rats with hepatocellular cancer confined to the liver, recurrence was observed at a comparatively early stage in all transplant recipients. Although a significant prolongation of survival was noted, they all died of cancer. The timing of transplantation is also an important factor. This experimental liver transplantation model of progressive rat liver cancer will be useful in the study of primary liver cancer in human beings.


Temporal DeltaB0 and relaxation in the rat heart.
Field maps of the induced main magnetic field offset (DeltaB(0)) were measured in the rat heart at various points in the cardiac cycle for the purpose of identifying their effects on relaxation measurements. The mean DeltaB(0) of the left ventricle averaged across rats was found to be 0.11 +/- 0.35 ppm and 0.19 +/- 0.39 ppm at the onset of systole and diastole, respectively. The root mean square (RMS) variation in resonant frequency of the left ventricle averaged across rats was found to be 0.09 +/- 0.05 ppm and 0.06 +/- 0.04 ppm during systole and diastole, respectively. Temporal variations in DeltaB(0) could substantially affect quantitative MRI measurements. To assess this, transverse relaxation rates (R(2) and R(2)(*)) were measured at different points in the cardiac cycle, and the effects of DeltaB(0) were estimated using measured field map data. For a given region of the left ventricle, DeltaB(0) induced a mean error across rats of < or =3.9% for R(2) and < or =9.6% for R(2)(*). For R(2)(*) measurements, the static component of the field inhomogeneity was found to be responsible for most of the error induced.


Optimization of expression and properties of the recombinant acetohydroxyacid synthase of Thermotoga maritima.
The data provide additional support of the characterization of the biophysical and biochemical properties of the enzyme acetohydroxyacid synthase from the hyperthermophilic bacterium Thermotoga maritima (Eram et al., 2015) [1]. The genes encoding the enzyme subunits have been cloned and expressed in the mesophilic host Escherichia coli. Detailed data include information about the optimization of the expression conditions, biophysical properties of the enzyme and reconstitution of the holoenzyme from individually expressed and purified subunits.


Lipid nanoparticle-assisted miR29a delivery based on core-shell nanofibers improves tendon healing by cross-regulation of the immune response and matrix remodeling.
Inferior healing and peritendinous adhesions are the major clinical problems following Achilles tendon injury, leading to impaired motor function and an increased risk of re-rupture. These complications are presumed to be inextricably linked to inflammation and fibroscar formation. Here, microRNA29a is identified as a promising therapeutic target for tendon injury through the cross-regulation of the immune response and matrix remodeling. MiR29a-LNPs were successfully prepared by microfluidic technology. They are then loaded into the core-shell nanofibers to achieve local delivery in the injured tendon, where the shell layer is composed of PELA for anti-adhesion. Our studies reveal that miR29a regulates collagen synthesis and NF-κB activation in tenocytes, and promotes macrophage polarization by inhibiting the inflammasome pathway. In vivo studies of the Achilles tendon-rupture model indicate the best repair in the miR29a group, as evidenced by superior collagen composition and alignment, higher mechanical strength, and better functional recovery. In conclusion, a functionalized anti-adhesive membrane that promotes nascent tendon matrix remodeling and improves the regenerative immune microenvironment is developed for the treatment of tendon injury.


SPG7 mutations explain a significant proportion of French Canadian spastic ataxia cases.
Hereditary cerebellar ataxias and hereditary spastic paraplegias are clinically and genetically heterogeneous and often overlapping neurological disorders. Mutations in SPG7 cause the autosomal recessive spastic paraplegia type 7 (SPG7), but recent studies indicate that they are also one of the most common causes of recessive cerebellar ataxia. In Quebec, a significant number of patients affected with cerebellar ataxia and spasticity remain without a molecular diagnosis. We performed whole-exome sequencing in three French Canadian (FC) patients affected with spastic ataxia and uncovered compound heterozygous variants in SPG7 in all three. Sanger sequencing of SPG7 exons and exon/intron boundaries was used to screen additional patients. In total, we identified recessive variants in SPG7 in 22 FC patients belonging to 12 families (38.7% of the families screened), including two novel variants. The p.(Ala510Val) variant was the most common in our cohort. Cerebellar features, including ataxia, were more pronounced than spasticity in this cohort. These results strongly suggest that variants affecting the function of SPG7 are the fourth most common form of recessive ataxia in FC patients. Thus, we propose that SPG7 mutations explain a significant proportion of FC spastic ataxia cases and that this gene should be considered in unresolved patients.


A four node axillary sampling trial on breast cancer patients.
The surgical management of axillary lymph nodes in early breast cancer remains controversial, although several maneuvers have been developed such as axillary node clearance (ANC), four node axillary sampling (4NAS), and sentinel node biopsy. A total of 237 cases of primary breast cancer at stages I and II were studied prospectively to elucidate the correlation between 4NAS and ANC. All calculated values by 4NAS showed high sensitivity, specificity, and overall accuracy as follows in this study: 92.9%, 100% and 98.5% for stage I, and 93.8%, 100% and 98.3% for stage II. Likewise, the false negative (FN) rates were 7.1% for stage I, 6.3% for stage II, 6.7% for T1, 6.4% for T2, 7.4% for N0, 0% for N1, and 6.5% for all cases. These rates were very low, although 7.4% for N0 and 0% for N1 were quite clearly different. This implies that all FN cases were N0, and were caused by micrometastases with normal consistency and size. 4NAS may be as accurate a procedure as ANC in assessing axillary nodal stage.


Investigation of the interaction of VIP binding sites with VIP and PACAP in human brain.
We have compared the binding of [125I]vasoactive intestinal polypeptide (VIP) to human brain membranes with that of [125I]PACAP27. [125I]VIP was displaced by PACAP27, VIP and two synthetic peptides, peptide-1 (N-terminal PACAP27/C-terminal VIP) and peptide-2 (N-terminal VIP/C-terminal PACAP27), but the IC50 of PACAP27 and peptide-1 were 10-20 times lower than those of VIP and peptide-2. [125I]PACAP27 was readily displaced by PACAP27 and peptide-1, with an IC50 of less than 1 nM, but poorly by VIP and peptide-2. Chemical cross-linking revealed that both labels were bound to polypeptides of Mr 66,000 and Mr 50,000. The results indicate that in human brain membranes both binding sites have a higher affinity to the N-terminal sequence of PACAP27, and VIP binding sites prefer PACAP27 to VIP itself.


[Sleep disorders and sleep-related breathing disorders].
Normal sleep consists of 4-5 sleep cycles including light-, deep- and rapid eye-movement sleep. Restoration of physical and psychological function are the main effects of sleep. In most cases, disturbances of normal sleep become clinically evident as problems of initiating and maintaining sleep and/or as increased daytime sleepiness. Approximately 10% of adults suffer from pronounced insomnia, a similar percentage from markedly increased daytime sleepiness. Sleep disorders cause high socio-economic costs due to increased accident risk, cardiovascular sequelae and sick leave. Most of the 88 distinct diagnoses summarized in the international classification of sleep disorders can be differentiated and managed according to patients history. In patients with severe daytime sleepiness - sleep disordered breathing being the most frequent cause - the diagnostic evaluation and treatment in the sleep laboratory is required. Effective therapeutic strategies are available for many sleep disorders. According to the underlying disorder, treatment includes a variety of measures like life style changes, differentiated medical treatment and the use of nasally applied positive pressure in patients suffering from sleep disordered breathing.


Dual-hairpin ligation amplification enabled ultra-sensitive and selective ATP detection for cancer monitor.
Abnormal concentration of ATP is related to many diseases such as Parkinson's disease, hypoglycaemia, inflammation and cancer. However, most of the reported strategies exhibit moderate sensitivity with ∼nM level detection limit and few of them can distinguish ATP from its analogues, such as GTP, CTP, UTP and adenosine. Herein, we report an ultra-sensitive and selective ATP detection strategy that combines dual hairpin ligation-induced isothermal amplification (DHLA) with ATP-dependent enzymatic reaction. A good linear relationship between Cq value and ATP concentration in the range from 16 fM to 160 nM is acquired. Meanwhile, the strategy can distinguish ATP from its analogues with high selectivity. Furthermore, our proposed strategy has been successfully utilized to detect ATP from colon cell line and cell culture media with great potential applications in cell metabolism and cancer diagnosis.


Catheter-related sepsis during home parenteral nutrition.
Catheter-related sepsis (CRS) in patients receiving home parenteral nutrition (HPN) is the most frequent complication, with an annual incidence rate of 0.30-0.50 in investigative/approved centres. CRS is responsible for patient deaths in 2.5% of cases which represent 50% of HPN-related deaths. A detailed and strictly applied protocol is the basis of prevention; therefore a low rate of CRS can be used as a marker of quality of care. Skin and hub cultures are used to rule out CRS since their predictive negative value assessed against (semi) quantitative cultures of cannulae were reported to be almost 100%. In the absence of catheter removal, clinical assessment plus quantitative blood cultures with a threshold ratio of 4:1 in central and peripheral blood is a reasonable basis of established CRS. Removal of the infected external cannula is necessary and immediate in cases of tunnel infection, virulent bacteria (e.g. Candida, Staph aureus or pseudomonas species) and for all occurrences of CRS on implantable chambers since conventional treatment fails to sterilise such devices. Thus standard antibiotic treatment may be effective in the absence of tunnel sepsis in the majority of CRS cases due to non-virulent bacteria (mainly Staph coagulase negative species). In these cases of CRS, our experience suggests that the antibiotic-lock technique offers definite advantages over conventional systemic antibiotic treatment, since external catheters were sterilised without recurrent sepsis in more than 85% of cases.


Sequence analysis of small cryptic plasmids isolated from Selenomonas ruminantium S20.
Two small cryptic plasmids designated pONE429 and pONE430 were isolated from a rumen bacterium, Selenomonas ruminantium S20. The complete sequence of pONE429 was 2100 bp and contained one open reading frame (ORF) of 201 amino acids. The sequence of pONE430 had 1527 bp and one ORF of 171 amino acids with the similarity of replication protein (Rep protein) of pOM1, pSN2, and pIM13 isolated from Butyrivibrio fibrisolvens, Staphylococcus aureus, and Bacillus subtilis, respectively. In these plasmids, the upstream nucleotide sequence of Rep protein had the conserved nucleotides which could be double-strand origin (DSO) of rolling circle replication (RCR) mechanism. The plasmids of pONE429, pONE430, pJJMI, pJDB21, and pS23 were isolated from S. ruminantium strains and had similar regions that were located within a <450-bp nucleotide. These similar regions may be the location that was recognized by the host strain, S. ruminantium.


Increase in intracellular calcium induced by the polycation-coated latex bead, a stimulus that causes postsynaptic-type differentiation in cultured Xenopus muscle cells.
The polycation-coated latex bead is a potent stimulus for the induction of postsynaptic-type differentiation in cultured Xenopus myotomal muscle cells. Specializations characteristic of the neuromuscular junction, such as clusters of acetylcholine receptors and other postsynaptic-specific proteins, develop at the bead-muscle contact. Previous studies have shown that a deprivation of extracellular calcium inhibits the effect of the beads in causing the development of these specializations. This suggests that an increase in intracellular Ca2+ is a necessary condition for the development of this specialization. In this study, we tested whether an increase in intracellular calcium is observable upon the bead-muscle contact. The measurement was carried out on cells loaded with the fluorescent calcium indicator fura-2 AM by digitized video microscopy. When polycation-coated beads were added to cells, an increase in intracellular calcium concentration in the range of 5 to 57% of the resting level was observed within 10 sec after bead-muscle contact. Afterward, the calcium level gradually returned to the resting level with a time course of about 3 min. Uncoated beads, which do not induce the formation of acetylcholine receptor clustering, failed to elicit this calcium transient. Removal of extracellular calcium as well as blocking calcium channels with 50 microM verapamil also suppressed this transient induced by the polycation-coated beads. Both treatments are known to suppress the formation of receptor clusters by these beads. These results suggest that the polycation-coated beads cause an influx of calcium by increasing the membrane conductance to this ion. This process may underlie the signaling of the postsynaptic differentiation.


Crowd computing: using competitive dynamics to develop and refine highly predictive models.
A recent application of a crowd computing platform to develop highly predictive in silico models for use in the drug discovery process is described. The platform, Kaggle™, exploits a competitive dynamic that results in model optimization as the competition unfolds. Here, this dynamic is described in detail and compared with more-conventional modeling strategies. The complete and full structure of the underlying dataset is disclosed and some thoughts as to the broader utility of such 'gamification' approaches to the field of modeling are offered.


[Drug-induced lung diseases].
Drug-induced interstitial pneumonias are systematically considered in the differential diagnosis of the interstitial pneumonias. The presentation may be acute, sub-acute or chronic, with the same drug possibly leading to either acute or subacute/chronic interstitial lung disease (e.g. amiodarone). There is no definite diagnostic criterion, the final diagnosis relying on the clinical and imaging features, the chronology of pulmonary manifestations, and the prevalence of reported cases with the suspected drug.


Correction: Crystalline matrix-activated spin-forbidden transitions of engineered organic crystals.
Correction for 'Crystalline matrix-activated spin-forbidden transitions of engineered organic crystals' by Heming Zhang et al., Phys. Chem. Chem. Phys., 2023, 25, 11102-11110, DOI: https://doi.org/10.1039/d3cp00187c.


Multiacquisition Variable-Resonance Image Combination Magnetic Resonance Imaging Used to Study Detailed Bone Apposition and Fixation of an Additively Manufactured Cementless Acetabular Shell.
The ability to utilize magnetic resonance imaging (MRI) to assess bony fixation in 3 dimensions may allow a better understanding of the implant design and bony integration. We hypothesized that a new 3-dimensionally printed cementless highly porous acetabular component (Stryker Trident II TritaniumTM) would show better fixation than an earlier cup from the same manufacturer as assessed by the noninvasive technique of multispectral MRI. Multiacquisition variable-resonance image combination selective metal suppression MRI was performed in 19 patients implanted with a new 3-dimensionally printed cup and 20 patients who had received a previous-generation cup from the same manufacturer at 1-year follow-up. Each cup was graded globally as well as by 9 specific zones. Integration grades were performed for each zone: 0, full bone integration; 1, fibrous membrane present; 2, osteolysis; and 3, fluid present. A mixed-effects logistic regression model was used to compare fixation between the 2 groups. All cups in both cohorts showed greater than 90% estimated global bony integration (3-dimensionally printed cups, 99.4%; regular cups 91.6%) with no osteolysis or fluid observed in any cup. The 3-dimensionally printed cup had 1 of 171 zones (0.6%) graded as fibrous membrane present, while the 2-dimensional group had 15 of 180 zones (8.3%) graded as fibrous. Of note, screw hole regions were omitted but may be read as fibrous membrane areas. Using multiacquisition variable-resonance image combination selective MRI, our analysis showed greater osteointegration and less fibrous membrane formation in the 3-dimensionally printed cups than the control group at 1-year follow-up.


Early Referral to Coronary Artery Bypass Grafting Following Acute Coronary Syndrome, Trends and Outcomes from the Acute Coronary Syndrome Israeli Survey (ACSIS) 2000-2010.
Limited information exists on whether changes in medical practices over the study decades have affected the outcomes of acute coronary syndrome (ACS) patients who undergo early coronary artery bypass surgery (CABG) during index hospitalisation. Data on trends for early CABG referral and associated outcomes were obtained among 11,485 ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010. Among 11,485 patients, 566 (5%) were referred to early CABG. These patients displayed higher risk characteristics, including Killip class >II, anterior myocardial infarction, greater left ventricular dysfunction, and more frequent use of mechanical ventilation and intra-aortic balloon pump (all p<0.01). Nevertheless, mortality rates of patients referred to early CABG vs. treated with percutaneous coronary intervention (PCI) or medically, was similar (11.4% vs. 10.2%; log-rank p-value=0.40). There was a significant decline in the referral trend over the study decade (6.7% - 1.7%; p<0.001). One year survival was similar between patients referred to early CABG during the late (years: 2006-2010) vs. early (years: 2000-2005) period (85.7% vs. 90%; log-rank p-value=0.15), whereas, among patients who didn't undergo early CABG, and underwent percutaneous coronary intervention (PCI) or medical management only, enrolment during the late periods was associated with a significant survival benefit (91.5% vs. 88.1%; log-rank p-value<0.001). Over the study decade there was a significant decline in referral for early CABG, without a difference in the one-year mortality between the early and non-early CABG group.


From Ethnomethodologist to Data Lover: How I Became a Keen Advocate for Using Administrative Data.
This article is a personal reflection on a professional journey from ethnographer to keen analyst of administrative data. Using a knitter's analogy, I describe using the thread of administrative information, armed with one stick (social science methods) and the second stick, practice-relevant, theory-informed research.


Complete amino acid sequence of the B875 light-harvesting protein of Rhodopseudomonas sphaeroides strain 2.4.1. Comparison with R26.1 carotenoidless-mutant strain.
The complete amino acid sequence was determined for the alpha- and beta-chains of the B875 light-harvesting protein purified from photosynthetic membranes of Rhodopseudomonas sphaeroides 2.4.1. The sequence of the B875-alpha-polypeptide was identical to that reported for the R26.1 carotenoidless mutant [(1985) Biochim. Biophys. Acta 806, 185-186] and contained 58 amino acid residues with a blocked methionine and a glutamic acid at the N- and C-termini, respectively. The B875-beta-polypeptide contained 48 amino acid residues with alanine and phenylalanine as respective N- and C-termini; although otherwise identical, the leucine at position 29 in the wild-type strain was replaced by proline in the mutant. This radical amino acid substitution occurred within the central hydrophobic domain of the beta-polypeptide chain and is thought to result in a weakening of the structure of the alpha/beta heterodimer since it was not possible to isolate the intact pigment-protein complex from the R26.1 mutant strain.


Heterogeneity of tumor endothelial cells and drug delivery.
To date anti-angiogenic therapy has been used for cancer therapy widely, yielding promising results. However, it has been elucidated that current anti-angiogenic drug has several issues to be solved, such as side-effects and drug resistance. It has been reported that tumor endothelial cells (TECs) differ from normal counterparts. In addition, it was shown that the TECs are heterogeneous according to the malignancy status of tumor. The development of novel strategy for targeting tumor vasculature is required. Recently, we have developed an active targeting system, which targets TECs specifically. In this review, we will discuss how TECs in tumor vasculature are heterogeneous and offer new perspectives on a drug delivery system, which can target heterogeneous tumor blood vessels from a viewpoint of personalized medicine.


Surface modification of zirconia with polydopamine to enhance fibroblast response and decrease bacterial activity in vitro: A potential technique for soft tissue engineering applications.
The quality of soft-tissue integration plays an important role in the short- and long-term success of dental implants. The aim of the present study was to provide a surface modification approach for zirconia implant abutment materials and to evaluate its influence on fibroblast behavior and oral bacteria adhesion, which are the two main factors influencing the quality of peri-implant soft-tissue seal. In this study, polydopamine (PDA)-coated zirconia was prepared and the surface characteristics were evaluated using scanning electron microscopy, atomic force microscopy, a contact-angle-measuring device, X-ray photoelectron spectroscopy, and Raman spectroscopy. The responses of human gingival fibroblasts (HGFs) to PDA-coated zirconia; i.e., adhesion, proliferation, morphology, protein synthesis, and gene expression, were analyzed. Additionally, the adhesion of Streptococcus gordonii and Streptococcus mutans to zirconia after PDA coating was assessed by scanning electron microscopy and live/dead staining. The material surface analyses suggested the successful coating of PDA onto the zirconia surface. The PDA coating significantly increased cell adhesion and proliferation compared with pristine zirconia. HGFs exhibited a high degree of spreading and secreted a high level of collagen type I on PDA-modified disks. Upregulation of integrin α5, β1, β3 and fibronectin was noted in HGFs cultured on PDA-coated zirconia. The number of adherent bacteria decreased significantly on zirconia after PDA coating. In summary, our result suggest that PDA is able to modify the surface of zirconia, influence HGFs' behavior and reduce bacterial adhesion. Therefore, this surface modification approach holds great potential for improving soft-tissue integration around zirconia abutments in clinical application.


How do organizations and social policies 'acculturate' to immigrants? Accommodating skilled immigrants in Canada.
While the idea of acculturation (Berry 1997) was originally proposed as the mutual change of both parties (e.g., immigrants and the host society), the change processes of host societies are neglected in research. A grounded theory study explored the efforts of human service organizations to 'acculturate' to an increasingly diverse immigrant population, through interviews conducted with service providers serving Mainland Chinese immigrants. Acculturation efforts of human service organizations (mezzo-level acculturation) were often needs-driven and affected by the political will and resultant funding programs (macro-level forces). Even with limitations, human service organizations commonly focused on hiring Mainland Chinese immigrants to reflect the changing demographics of their clientele and creating new programs to meet the language and cultural backgrounds of the clients. To contextualize these organizational efforts, an analysis of how policy changes (macro-level acculturation) interact with organizational practice is presented. Finally, the meaning of acculturation for the host society is discussed.


Improvement of walking speed and gait symmetry in older patients after hip arthroplasty: a prospective cohort study.
Retraining walking in patients after hip or knee arthroplasty is an important component of rehabilitation especially in older persons whose social interactions are influenced by their level of mobility. The objective of this study was to test the effect of an intensive inpatient rehabilitation program on walking speed and gait symmetry in patients after hip arthroplasty (THA) using inertial sensor technology. Twenty-nine patients undergoing a 4-week inpatient rehabilitation program following THA and 30 age-matched healthy subjects participated in this study. Walking speed and gait symmetry parameters were measured using inertial sensor device for standardized walking trials (2*20.3 m in a gym) at their self-selected normal and fast walking speeds on postoperative days 15, 21, and 27 in patients and in a single session in control subjects. Walking speed was measured using timing lights. Gait symmetry was determined using autocorrelation calculation of the cranio-caudal (CC) acceleration signals from an inertial sensor placed at the lower spine. Walking speed and gait symmetry improved from postoperative days 15-27 (speed, female: 3.2 and 4.5 m/s; male: 4.2 and 5.2 m/s; autocorrelation, female: 0.77 and 0.81; male: 0.70 and 0.79; P <0.001 for all). After the 4-week rehabilitation program, walking speed and gait symmetry were still lower than those in control subjects (speed, female 4.5 m/s vs. 5.7 m/s; male: 5.2 m/s vs. 5.3 m/s; autocorrelation, female: 0.81 vs. 0.88; male: 0.79 vs. 0.90; P <0.001 for all). While patients with THA improved their walking capacity during a 4-week inpatient rehabilitation program, subsequent intensive gait training is warranted for achieving normal gait symmetry. Inertial sensor technology may be a useful tool for evaluating the rehabilitation process during the post-inpatient period.


Functional and Nonclinical Similarity of ABP 980, a Biosimilar of Trastuzumab.
The in vitro and in vivo pharmacologic assessment of ABP 980 similarity to its reference product is intended to compare the activity of ABP 980 and trastuzumab and support the overall conclusion of similarity based on a comprehensive analytical and functional evaluation. This work complements the primary assessment of functional similarity with additional in vitro assays, binding studies, and non-clinical studies including human epidermal growth factor receptor-2 (HER2) kinetic binding, HER2 signaling, HER2 internalization, synergy with docetaxel chemotherapy, FcγR kinetic binding, primary natural killer and monocyte cell binding, antibody-dependent cellular phagocytosis activity, in vivo xenograft studies, and toxicokinetic parameters. The results contribute to the totality of evidence with respect to functional similarity and support that ABP 980 is similar to trastuzumab in all primary and secondary mechanisms of action. These results also support the scientific justification of extrapolation to all approved indications of trastuzumab given the established functional similarity of the two products and the same mechanisms of action across all conditions of use.


Urinary excretion of cyclic AMP in bacterial infections.
Urinary cyclic AMP excretion was found to be increased in patients with severe bacterial infections and normal renal function. The observed changes appeared due to a combination of an increased filtered load plus augmented "nephrogenous" production in some patients; while in others, only an increase in the apparent "nephrogenous" production of cAMP could be found to account for the elevation in the total urinary excretion. Since total serum calcium was found to be low in most of these patients, increased PTH secretion to reduce urinary excretion of calcium may have been responsible for an increase in renal parenchymal production, and subsequent excretion of cyclic AMP. Although speculative, this theory is tenable in that ionized hypocalcemia exists in septic patients.


Acute haemodynamic effects of ibopamine and dopamine on isovolumic relaxation.
The effects of intraduodenal ibopamine (a new orally active inotropic agent claimed to have haemodynamic effects similar to dopamine) on isovolumic relaxation were monitored for 90 min in eight closed-chest anaesthetized dogs. Dopamine and epinine (ibopamine active metabolite) were also infused at graded doses. After 15 min, ibopamine (12 mg/kg) shortened the time constant of isovolumic relaxation, and increased stroke volume and mean aortic pressure. Peak positive dP/dt increased significantly only 10 min later. Heart rate did not change. Dopamine (10 micrograms/kg per min) similarly reduced the time constant, and increased stroke volume, mean aortic pressure, peak positive dP/dt and heart rate. Epinine (10 micrograms/kg per min) caused similar changes in peak positive dP/dt, stroke volume, mean aortic pressure, and accelerated time constant without raising the heart rate. Ibopamine and epinine therefore significantly improved the isovolumic relaxation phase, like dopamine, without however affecting the heart rate.


Fep1, an iron sensor regulating iron transporter gene expression in Schizosaccharomyces pombe.
Schizosaccharomyces pombe cells acquire iron under high affinity conditions through the action of a cell surface ferric reductase encoded by the frp1(+) gene and a two-component iron-transporting complex encoded by the fip1(+) and fio1(+) genes. When cells are grown in the presence of iron, transcription of all three genes is blocked. A conserved regulatory element, 5'-(A/T)GATAA-3', located upstream of the frp1(+), fip1(+), and fio1(+) genes, is necessary for iron repression. We have cloned a novel gene, termed fep1(+), which encodes an iron-sensing transcription factor. Binding studies reveal that the putative DNA binding domain of Fep1 expressed as a fusion protein in Escherichia coli specifically interacts with the 5'-(A/T)GATAA-3' sequence in an iron-dependent manner. In a fep1 Delta mutant strain, the fio1(+) gene is highly expressed and is unregulated by iron. Furthermore, the fep1 Delta mutation increases activity of the cell surface iron reductase and renders cells hypersensitive to the iron-dependent free radical generator phleomycin. Mutations in the transcriptional co-repressors tup11(+) and tup12(+) are phenocopies to fep1(+). Indeed, strains with both tup11 Delta and tup12 Delta deletions fail to sense iron. This suggests that in the presence of iron and Fep1, the Tup11 and Tup12 proteins may act as co-repressors for down-regulation of genes encoding components of the reductive iron transport machinery.


Crucial function of the pre-T-cell receptor (TCR) in TCR beta selection, TCR beta allelic exclusion and alpha beta versus gamma delta lineage commitment.
The analysis of T-cell receptor (TCR) beta selection, TCR beta allelic exclusion and TCR beta rearrangement in gamma delta T cells from normal and pre-TCR-deficient mice has shown that the pre-TCR has a crucial role in T-lymphocyte development: The pre-TCR is by far the most effective receptor that generates large numbers of CD4+8+ T cells with productive TCR beta rearrangements. In the absence of the pre-TCR, TCR beta rearrangement proceeds in developing cells irrespective of whether they already contain a productive TCR beta gene. The pre-TCR directs developing T cells to the alpha beta lineage because gamma delta T cells from pT alpha-/- mice proceed much further in TCR beta rearrangement than gamma delta T cells from wild-type mice. It is argued that the pre-TCR commits developing T cells to the alpha beta lineage by an instructive mechanism, which has largely replaced an evolutionarily more ancient mechanism that involves stochastic alpha beta lineage commitment.


Arsenate microbial reducing behavior regulated by the temperature fields in landfills.
Attention should be paid to the As(V) reducing behavior in landfills under different temperature fields. In this study, microcosm tests were conducted using enrichment culture from a landfill. The results revealed that the reduction rate of As(V) was significantly affected by the temperature field, with the highest reduction rate observed at 50 °C, followed by 35 °C, 25 °C, and 10 °C. Different As cycling pathways were observed under various temperature fields. At room and medium temperatures, As4S4 was detected, indicating that both biomineralization and methylation processes occurred after As(V) reduction. However, only biogenic methylation was observed under high or low temperatures, indicating that the viability and adaptability of microorganisms varied depending on the temperature field and As contents. Pseudomonas was found to be the primary genus and dominant As(V) reduction bacteria (ARB) in all reactors. The study revealed that Pseudomonas accounted for a significant proportion of arsC genes, ranging from 87.29% to 97.59%, while arsCs genes were predominantly found in Bacillales and Closestridiales, with a contribution ranging from 89.17% to 96.59%. Interestingly, Bacillus and Clostridium were found to possess arsA genes in their metagenome-ssembled genome, resulting in a higher As(V) reducing rate under medium and high temperatures. These findings underscore the importance of temperature in modulating As(V) reducing behavior and As cycling, and could have implications for managing As pollution in landfill sites.


[Torsion of testicular appendages: a case of acute scrotum due to torsion of the hydatid of Morgagni].
The torsion of testicular appendages is the most frequent cause of acute scrotum in pediatric patients. The Authors report a case of Morgagni's hydatid torsion and stress that surgical exploration is the best therapeutical choice whenever the etiological diagnosis is uncertain.


Formation and contamination of PCDD/Fs, PCBs, PeCBz, HxCBz and polychlorophenols in the production of 2,4-D products.
The concentrations and profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), pentachlorobenzene (PeCBz), hexachlorobenzene (HxCBz) and polychlorophenols in 2,4-D were investigated in this study. Two 2,4-D acid and three 2,4-D butyl ester enterprises were selected as typical 2,4-D producers. The total concentrations of 2,3,7,8-PCDD/Fs in the 2,4-D samples ranged from 355 to 35080ngkg(-1) and the corresponding TEQ values were in the range of 13.4 and 694.6ng WHO-TEQkg(-1). The concentrations of total PCBs in the 2,4-D were in the range of 16.1 and 8023ngkg(-1), and the WHO-TEQ values of the PCBs were between 0.057 and 108.3ng WHO-TEQkg(-1), while total PCBs were between 1486 and 47342ngkg(-1). The average emission factors were 414.4μg WHO-TEQt(-1) for PCDD/Fs and 21.9μg WHO-TEQt(-1) for PCBs. The polychlorobenzenes and polychlorophenols impurities may play a key role in the PCBs and PCDD/Fs formation. The impurities of PCDD/Fs and PCBs in 2,4-D may increase the risk for the human and environmental health.


Conservative surgical management of Mersilene mesh suburethral sling erosion.
The aim of this study was to describe conservative surgical management of polyethylene terephthalate (Mersilene, Ethicon, Inc, Somerville, NJ) mesh suburethral sling erosion as an alternative to sling removal. Seven women who had undergone suburethral sling procedures with Mersilene mesh were found to have varying degrees of mesh visible in the vagina at 4 to 12 weeks after the operation. Three women with erosions <5 mm were treated in the office and 4 women who had 6 to 30 mm erosions underwent inpatient surgical revision, which consisted of trimming of mesh when needed, excision of granulation tissue, and re-covering of the erosion in 2 layers. All 7 patients have been followed up for 6 to 37 months. Only 1 woman who underwent inpatient surgical revision had a recurrence (4 mm); this was treated successfully in the office. Vaginal erosions in suburethral sling procedures with Mersilene mesh can be managed initially with our conservative surgical technique.


MicroRNA-5195-3p mediated malignant biological behaviour of insulin-resistant liver cancer cells via SOX9 and TPM4.
Primary liver cancer is a malignant tumour of the digestive system, ranking second in cancer mortality in China. In different types of cancer, such as liver cancer, microRNAs (miRNAs) have been shown to be dysregulated. However, little is known about the role of miR-5195-3p in insulin-resistant liver cancer. In this study, in vitro and in vivo experiments were conducted to identify the altered biological behaviour of insulin-resistant hepatoma cells (HepG2/IR), and we proved that HepG2/IR cells had stronger malignant biological behaviour. Functional experiments showed that enhanced expression of miR-5195-3p could inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance of HepG2/IR cells, while impaired expression of miR-5195-3p in HepG2 cells resulted in the opposite effects. Bioinformatics prediction and dual luciferase reporter gene assays proved that SOX9 and TPM4 were the target genes of miR-5195-3p in hepatoma cells. In conclusion, our study demonstrated that miR-5195-3p plays a critical role in insulin-resistant hepatoma cells and might be a potential therapeutic target for liver cancer.


Soliris to Stop Immune-Mediated Death in COVID-19 (SOLID-C19)-A Compassionate-Use Study of Terminal Complement Blockade in Critically Ill Patients with COVID-19-Related Adult Respiratory Distress Syndrome.
Eculizumab, a terminal complement (C5)-inhibiting monoclonal antibody, was administered in five mechanically ventilated patients in life-threatening condition due to COVID-19-related acute respiratory distress syndrome (ARDS) between 23 March 2020 and 3 April 2020. Their clinical progress was monitored. The primary endpoint was mortality. One patient was excluded while two passed away. The remaining two patients survived. At the time of this study, the mortality rate in mechanically ventilated COVID-19 patients suffering from ARDS receiving the standard of care as their therapeutic regimen was reportedly as high as 97%. This pilot study demonstrates a 50% mortality rate in patients receiving eculizumab therapy.


An abscess of mitral aortic intervalvular fibrosa mimicking an intracardiac mass.
Abscess of the mitral-aortic intervalvular fibrosa (MAIVF) is a rare occurrence, with its most frequently described causative associations being active or prior endocarditis, prosthetic valves, or native valves with anomalies. We report a case of infective endocarditis (IE) complicated by an abscess of the MAIVF without valvular involvement. This case highlights the importance of this rare clinical entity and of the multimodality imaging approach in reaching an accurate diagnosis and differential diagnosis. A 35-year-old male presented with fatigue and intermittent high-grade fever for a 2-week duration. IE was suspected based on a clinical exam. Transthoracic echocardiography (TTE) demonstrated heterogeneous mass with a size of about 2.9 cm × 2.3 cm coming from the MAIVF, mimicking an intracardiac mass. Color Doppler flow Imaging showed the mass without communication with the surrounding cardiovascular cavities. Cardiac computed tomography angiography (CCTA) revealed a large low-density mass without any enhancement, which was situated adjacent to the left ventricular tract with a severely compressed left atrial chamber. The patient underwent cardiac mass removal under extracorporeal circulation. During the procedure, a large abscess was found to be located in MAIVF. The postoperative course was uneventful. The abscess of MAIVF is a rare entity with a high risk of developing the pseudoaneurysm of MAIVF (p-MAIVF). The periaortic spread of the abscess is a dynamic process in which the inflammation of the deep tissue causes, in the first stage, a MAIVF thickening, which eventually progresses with the formation of an abscess, and subsequently, a pseudoaneurysm. Complications of p-MAIVF include rupture into the left atrium, aorta, or pericardial space leading to hemopericardium, tamponade, and death. The major differential diagnosis for abscess of MAIVF includes p-MAIVF an intracardiac mass. TTE plays a key role in the diagnosis and differential diagnosis of abscesses of MAIVF. CCTA can be a useful adjunct to further characterize abscess spread, three-dimensional spatial relationships with other cardiac structures for preoperative planning, as well as in the evaluation of potential complications such as coronary artery compromise and communication with the aorta, left atrium, or pericardial space. Surgical management is recommended in complicated, symptomatic patients to prevent further expansion of abscesses or pseudoaneurysms. The abscess of MAIVF is a rare complication of endocarditis and surgical trauma in the MAIVF area, TTE remains a first-line imaging modality for clinically suspected periaortic abscess or other IE complications. CCTA has a complementary role to echocardiography in identification, characterization, and preoperative planning.


Surface changes on dental materials. II. The influence of two different dentifrices on surface roughness measured by laser reflexion and profilometer techniques.
Surface changes on eight different dental materials were investigated, using laser reflexion technique and a profilometer. The tested materials were: Acrylic veneers Isosit, Isosit N, K+B+, Multiplus and K+Bpaste Gold Sjödings C Titanium pure non-rolled titanium Ceram a potential ceramic direct filling material The materials were subjected to brushing in a brushing machine, with a toothpaste-water slurry. Two different toothpastes were used separately; Clinomyn and Colgate. The new ceramic material showed no measurable wear by the brushing. All the other materials were affected to some extent. On titanium increasing values of light intensity were obtained thus indicating a smoother surface. Among the veneer materials K+Bpaste was the most wear resistant.


Preliminary immunological studies in spinal muscular atrophy.
Evidence of impaired cell-mediated immunity in children with spinal muscular atrophy was obtained using lymphocyte transformation with PHA (20 children) and skin tests with tuberculin and DNCB (35 children). Laryngological examination of 16 children demonstrated hypoplasia of lymphatic tissue in Waldeyer's ring and the cervical lymph nodes. An ectodermal defect involving both spinal cord and thymus is suggested.


Disseminated bilateral hyperkeratotic variant of porokeratosis Mibelli.
Clinical, histopathological, and ultrastructural features of a new clinical variant of porokeratosis Mibelli (PM) are presented. We report a solitary case of a patient, male aged 62, who developed disseminated verrucous nodules on the buttocks and the lower extremities 3 years before diagnosis. Histopathologically, all specific signs of the keratinization disorder of PM were demonstrable; in addition, however, multiple cornoid lamellae were found at the margin as well as in the center of the lesions, which only in part showed relationships to the epidermal appendages. In the papillary dermis, numerous ectatic capillaries were conspicuous. Using electron microscopy the same specific abnormalities of the keratinization process as known from classical cases of PM could be demonstrated: autophagocytic cells that revealed perinuclear edematization and vacuolization, accumulation of autophagic vacuoles and heterolysosomes, and dyskeratotic corps ronds-like cells that become transformed to fibrillar or Civatte bodies. Problems of the classification, differential diagnosis, and pathomorphogenesis are discussed.


Group 3 metal initiators with an [OSSO]-type bis(phenolate) ligand for the stereoselective polymerization of lactide monomers.
A series of 1,ω-dithiaalkanediyl-bridged bis(phenols) of the general type [OSSO]H(2) with variable steric properties and various bridges were prepared. The stoichiometric reaction of the bis(phenols) 1,3-dithiapropanediyl-2,2'-bis(4,6-di-tert-butylphenol), 1,3-dithiapropanediyl-2,2'-bis[4,6-di(2-phenyl-2-propyl)phenol], rac-2,3-trans-propanediyl-1,4-dithiabutanediyl-2,2'-bis[4,6-di(2-phenyl-2-propyl)phenol], rac-2,3-trans-butanediyl-1,4-dithiabutane diyl-2,2'-bis[4,6-di(2-phenyl-2-propyl)phenol], rac-2,3-trans-hexanediyl-1,4-dithiabutanediyl-2,2'-bis[4,6-di(2-phenyl-2-propyl)phenol], 1,3-dithiapropanediyl-2,2'-bis[6-(1-methylcyclohexyl)-4-methylphenol] (C(1), R=1-methylcyclohexyl), and 1,4-dithiabutanediyl-2,2'-bis[6-(1-methylcyclohexyl)-4-methylphenol] with rare-earth metal silylamido precursors [Ln{N(SiHMe(2))(2)(3)(thf)(x)] (Ln=Sc, x=1 or Ln=Y, x=2; thf=tetrahydrofuran) afforded the corresponding scandium and yttrium bis(phenolate) silylamido complexes [Ln(OSSO){N(SiHMe(2))(2)}(thf)] in moderate to good yields. The monomeric nature of these complexes was shown by an X-ray diffraction study of one of the yttrium complexes. The complexes efficiently initiated the ring-opening polymerization of rac- and meso-lactide to give heterotactic-biased poly(rac-lactides) and highly syndiotactic poly(meso-lactides). Variation of the ligand backbone and the steric properties of the ortho substituents affected the level of tacticity in the polylactides.