Optimising assessment of dark adaptation data using time to event analysis.
In age-related macular degeneration (AMD) research, dark adaptation has been found to be a promising functional measurement. In more severe cases of AMD, dark adaptation cannot always be recorded within a maximum allowed time for the test (~ 20-30 min). These data are recorded either as censored data-points (data capped at the maximum test time) or as an estimated recovery time based on the trend observed from the data recorded within the maximum recording time. Therefore, dark adaptation data can have unusual attributes that may not be handled by standard statistical techniques. Here we show time-to-event analysis is a more powerful method for analysis of rod-intercept time data in measuring dark adaptation. For example, at 80% power (at α = 0.05) sample sizes were estimated to be 20 and 61 with uncapped (uncensored) and capped (censored) data using a standard t-test; these values improved to 12 and 38 when using the proposed time-to-event analysis. Our method can accommodate both skewed data and censored data points and offers the advantage of significantly reducing sample sizes when planning studies where this functional test is an outcome measure. The latter is important because designing trials and studies more efficiently equates to newer treatments likely being examined more efficiently.


Active Surveillance of Thyroid Microcarcinomas: a Critical View.
There has been an increasing interest on active surveillance for papillary thyroid microcarcinomas (PTMC) in the literature. We will analyze the contributions of those authors who support this approach in most patients with low-risk tumors. The development of molecular methods to effectively detect aggressive PTMC at the fine-needle aspiration biopsy will enable the sound indication of immediate surgery in those patients, assuring the other individuals with the far more frequent indolent PTMC will undergo active surveillance with less anxiety. Several studies compared the quality of life between patients with PTMC who underwent active surveillance with immediate total thyroidectomy. However, thyroid lobectomy is a quite acceptable intermediate alternative for most patients with PTMC, with less surgical morbidity. It is important to wait for worldwide validation, with reports from low- and middle-income areas, before recommending the routine adoption of active surveillance for patients with PTMC, due to difficult logistic obstacles in those environments.


[Therapy of Achilles tendon rupture in athletes. Advantages of fibrin gluing].
Fibrin gluing of the ruptured Achilles tendon represents an alternative to tenorrhaphy. A report is presented on 17 cases, with particular emphasis on the surgical technique, the results of follow-up, and the findings of CT scanning.


Breeding practices, growth, and carcass potential of fat-tailed Washera sheep breed in Ethiopia.
On-farm survey of farmers' breeding practices, breeding objectives, and selection criteria and on-station feedlot performance evaluation of Washera sheep were undertaken in Ethiopia. The survey revealed that most (79.8%) of the farmers had no breeding ram. The mating system was predominantly uncontrolled. A majority (75.5%) of the sheep owners reported that they herded their sheep flock by mixing with other livestock species mainly with cattle. During grazing, 44.6% of the farmers mix their sheep flock with neighboring sheep flocks. The major sheep production objective was to generate income from the sale of live sheep. Fast growth, appearance, coat color, and pedigree performance were important ram selection criteria, respectively. Ability to breed at early age, pedigree information, mothering ability, and lambing interval were important selection criteria for ewe, respectively. The on-station performance study involved evaluation of feedlot gains and carcass production under five levels of feeding regimes (300, 400, 500, 600, and 700 g day(-1) of concentrate feed) for a period of 93 days. The results indicated that the feedlot growth and carcass performance of Washera sheep were very high, with average daily weight gains of up to 126 g and carcass weight of 16 kg, with the optimal level of supplementation for Washera sheep being at 500 g of concentrate per day for a period of 93 days.


Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts.
Sequestration of tumor necrosis factor-alpha (TNFalpha) by TNF-receptor immunoglobulin G (IgG)-Fc fusion proteins can limit heart failure progression in rodent models. In this study we directly injected an adeno-associated viruses (AAV)-2 construct encoding a human TNF receptor II IgG-Fc fusion protein (AAV-TNFRII-Fc) into healthy baboon hearts and assessed virally encoded gene expression and clinical response. Adult baboons received direct cardiac injections of AAV-TNFRII-Fc ( approximately 5 x 10(12) viral/genomes/baboon) or an equivalent dose of AAV-2 empty capsids, and were analyzed after 5 or 12 weeks. Viral genomes were restricted to the myocardium, and routine analyses (blood cell counts, clinical chemistries) remained unremarkable. Echocardiograms were unchanged but electrocardiograms revealed marked ST- and T-wave changes consistent with myocarditis only in baboons receiving AAV-TNFRII-Fc. TNFRII serum levels peaked at approximately 3 times the baseline levels at 1-2 weeks postinjection and subsequently declined to baseline levels. TNFRII-Fc protein and transcripts were detected in the heart at harvest. After AAV injection, anti-AAV-2 antibody levels increased in all baboons, while anti-TNFRII-Fc could not be detected. Baboons that received AAV-TNFRII-Fc developed myocardial infiltrates including CD8+ cells. Thus, a cellular immune response to cardiac delivery of AAV encoding foreign proteins may be an important consideration for AAV-based cardiac gene therapy.


Connexins, gap junctions and peripheral neuropathy.
Gap junctions (GJs) have emerged as an important molecular component of peripheral myelinated fibers following the discovery of mutations affecting the GJ protein connexin32 (Cx32) in patients with the X-linked Charcot-Marie-Tooth neuropathy (CMT1X). CMT1X is the second most common CMT form and is caused by over 400 different mutations in the GJB1 gene encoding Cx32. In peripheral nerves, Cx32 is expressed by Schwann cells and forms reflexive GJs through non-compact myelin areas, which allow the diffusion of ions and small molecules including second messengers across apposed cell membranes connecting directly the Schwann cell perinuclear cytoplasm with the adaxonal cell compartment inside the myelin sheath. GJs formed by Cx32 play an important role in the homeostasis of myelinated axons. Patients with CMT1X typically present with a progressive peripheral neuropathy characterized by mixed demyelinating and axonal features electrophysiologically and pathologically, which may be accompanied by transient or chronic CNS myelin dysfunction. Both in vitro and in vivo models of the disease indicate that most Cx32 mutations cause loss of function and inability of the mutant Cx32 to form functional GJs. Increased understanding of CMT1X pathogenesis will lead to the development of effective therapies for this currently incurable disease.


Coordination of nuclear and chloroplast gene expression in plant cells.
Plastid proteins are encoded in two genomes, one in the nucleus and the other in the organelle. The expression of genes in these two compartments in coordinated during development and in response to environmental parameters such as light. Two converging approaches reveal features of this coordination: the biochemical analysis of proteins involved in gene expression, and the genetic analysis of mutants affected in plastid function or development. Because the majority of proteins implicated in plastid gene expression are encoded in the nucleus, regulatory processes in the nucleus and in the cytoplasm control plastid gene expression, in particular during development. Many nucleus-encoded factors involved in transcriptional and posttranscriptional steps of plastid gene expression have been characterized. We are also beginning to understand whether and how certain developmental or environmental signals perceived in one compartment may be transduced to the other.


Design and implementation of a near-miss reporting system at a large, academic pediatric anesthesia department.
Current incident reporting systems encourage retrospective reporting of morbidity and mortality and have low participation rates. A near miss is an event that did not cause patient harm, but had the potential to. By tracking and analyzing near misses, systems improvements can be targeted appropriately, and future errors may be prevented. An electronic, web based, secure, anonymous reporting system for anesthesiologists was designed and instituted at The Children's Hospital, Denver. This portal was compared to an existing hospital incident reporting system. A total of 150 incidents were reported in the first 3 months of operation, compared to four entered in the same time period 1 year ago. An anesthesia-specific anonymous near-miss reporting system, which eases and facilitates data entry and can prospectively identify processes and practices that place patients at risk, was implemented at a large, academic, freestanding children's hospital. This resulted in a dramatic increase in reported events and provided data to target and drive quality and process improvement.


Effect of sulfur hexafluoride gas and post-annealing treatment for inductively coupled plasma etched barium titanate thin films.
Aerosol deposition- (AD) derived barium titanate (BTO) micropatterns are etched via SF6/O2/Ar plasmas using inductively coupled plasma (ICP) etching technology. The reaction mechanisms of the sulfur hexafluoride on BTO thin films and the effects of annealing treatment are verified through X-ray photoelectron spectroscopy (XPS) analysis, which confirms the accumulation of reaction products on the etched surface due to the low volatility of the reaction products, such as Ba and Ti fluorides, and these residues could be completely removed by the post-annealing treatment. The exact peak positions and chemicals shifts of Ba 3d, Ti 2p, O 1 s, and F 1 s are deduced by fitting the XPS narrow-scan spectra on as-deposited, etched, and post-annealed BTO surfaces. Compared to the as-deposited BTOs, the etched Ba 3d 5/2 , Ba 3d 3/2 , Ti 2p 3/2 , Ti 2p 1/2 , and O 1 s peaks shift towards higher binding energy regions by amounts of 0.55, 0.45, 0.4, 0.35, and 0.85 eV, respectively. A comparison of the as-deposited film with the post-annealed film after etching revealed that there are no significant differences in the fitted XPS narrow-scan spectra except for the slight chemical shift in the O 1 s peak due to the oxygen vacancy compensation in O2-excessive atmosphere. It is inferred that the electrical properties of the etched BTO film can be restored by post-annealing treatment after the etching process. Moreover, the relative permittivity and loss tangent of the post-annealed BTO thin films are remarkably improved by 232% and 2,695%, respectively.


Efficient Separation of Acetylene and Carbon Dioxide in a Decorated Zeolite.
The almost identical molecular sizes and volatilities of acetylene and carbon dioxide make their separation extremely challenging in industry. Reported here is the efficient separation of acetylene and carbon dioxide (v/v=2/1, which is relevant to that in the industrial cracking stream) in faujasite zeolites decorated with atomically-dispersed copper(II) sites under ambient conditions. In situ neutron powder diffraction and inelastic neutron scattering confirm that the confined copper(II) site displays chemoselective yet reversible binding to acetylene, whereas adsorbed carbon dioxide molecules are stabilized by weak host-guest supramolecular interactions with the framework oxygen centers, thus resulting in the efficient separation of these two gases under flow conditions. A designed adsorption-purging-desorption system based upon Cu@FAU is established for the recovery of high purity acetylene (98-99 %) from the mixture of acetylene and carbon dioxide, offering an unprecedented separation factor of 22.2 with an effective dynamic uptake of acetylene of 1.51 mmol g-1 at 298 K.


[Effect of acupuncture serum on intracellular Ca2+ concentration in cultured neurons].
To study the humoral factor of acupuncture in improving functional activities of the organism. Neurons of the cerebral cortex from the new born rats were taken to be cultured in a strictly controlled medium. Seven to ten days later, fluorescein-molecular probe Fluo-3AM was used for staining intracellular Ca(2+). Ca(2+) concentration and its changes after application of acupuncture serum were measured by using a laser confocal microscope. Normal serum and acupuncture serum were derived from the normal control rats and the rats undergoing electro-acupuncture of "Baihui (GV 20)", "Zusanli (ST 36)", "Quchi (LI 11)" and "Sanyinjiao (SP 6)" for 2 weeks. After application of normal serum, the intracellular Ca(2+) concentration increased strikingly immediately at the beginning, and gradually got stable afterwards. When acupuncture serum was added to the culture fluid, Ca(2+) concentration lowered significantly. These results suggest that bioactive substances in serum collected from rats undergoing acupuncture can affect the intracellular Ca(2+) concentration of the cerebral neurons, and the humoral factor may participate in the effect of acupuncture in regulating functional activities of the organism.


Zuo-Gui and You-Gui pills, two traditional Chinese herbal formulas, downregulated the expression of NogoA, NgR, and RhoA in rats with experimental autoimmune encephalomyelitis.
Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs. Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage). ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage. Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs.


Multi-institutional assessment of ureteroscopic laser papillotomy for chronic flank pain associated with papillary calcifications.
We evaluated the long-term safety, efficacy and durability of ureteroscopic laser papillotomy for chronic flank pain associated with renal papillary calcifications. We reviewed the medical records of all patients who underwent ureteroscopic laser papillotomy in the absence of free urinary calculi at our institutions from 1998 through 2008. Success was defined as patient report of significant pain relief. The duration of response was considered the time from papillotomy to repeat papillotomy in the same renal unit, patient report of recurrent pain or final followup. Ureteroscopic Ho:YAG laser papillotomy was done a total of 176 times in 65 patients, including 147 unilateral and 29 bilateral procedures. Of the patients 39 underwent multiple procedures (2 to 12). Symptomatic followup was available in 50 patients (146 procedures) during a mean of 38 months. Significantly less pain was reported after 121 procedures (83%). The mean duration of response per procedure was 26 months and 30 patients (60%) had a mean remission duration of greater than 1 year. Postoperatively hospital admission was required after 14 procedures (8%). There was no significant change in the mean estimated glomerular filtration rate during a mean 41.3-month followup. Seven of the 65 patients (11%) had hypertension before papillotomy. In 3 of the 49 patients (6.1%) with adequate followup new hypertension developed during a mean of 38 months. Ureteroscopic laser papillotomy is safe and effective. In patients with papillary calcifications and characteristic chronic, noncolicky pain this procedure provides significant, moderately durable symptom relief.


Selective synthesis of β-alkylpyrroles.
β-Alkylpyrroles are key structural motifs found in many natural products and biologically active compounds as well as functional organic materials. For this reason, synthetic chemists continue to be interested in construction of the framework of β-alkylpyrroles. Due to sufficient aromaticity and π-excessive nature of pyrroles, a straightforward approach to β-alkylpyrroles should be electrophilic aromatic substitution (S(E)Ar) toward the pyrrole ring. However, since a primary nucleophilic site of pyrroles is an α-position, some "trick" is required to direct incoming alkyl electrophiles toward a β-position. This Concept article focuses on presenting previous efforts that have been devoted to the synthesis of β-alkylpyrroles, mainly through the S(E)Ar route.


Utility of Three-Dimensional Transesophageal Echocardiography for Mitral Annular Sizing in Transcatheter Mitral Valve Replacement Procedures: A Cardiac Computed Tomographic Comparative Study.
Three-dimensional (3D) transesophageal echocardiographic (TEE) imaging is frequently used as an initial screening tool in the evaluation of patients who are candidates for transcatheter mitral valve replacement (TMVR). However, little is known about the imaging correlation with the gold standard, computed tomographic (CT) imaging. The aims of this study were to test the quantitative differences between these two modalities and to determine the best 3D TEE parameters for TMVR screening. Fifty-seven patients referred to the heart valve clinic for TMVR with prostheses specifically designed for the mitral valve were included. Mitral annular (MA) analyses were performed using commercially available software on 3D TEE and CT imaging. Three-dimensional TEE imaging was feasible in 52 patients (91%). Although 3D TEE measurements were slightly lower than those obtained on CT imaging, measurements of both projected MA area and perimeter showed excellent correlations, with small differences between the two modalities (r = 0.88 and r = 0.92, respectively, P < .0001). Correlations were significant but lower for MA diameters (r = 0.68-0.72, P < .0001) and mitroaortic angle (r = 0.53, P = .0001). Receiver operating characteristic curve analyses showed that 3D TEE imaging had a good ability to predict TMVR screening success, defined by constructors on the basis of CT measurements, with ranges of 12.9 to 15 cm2 for MA area (area under the curve [AUC] = 0.88-0.91, P < .0001), 128 to 139 mm for MA perimeter (AUC = 0.85-0.91, P < .0001), 35 to 39 mm for anteroposterior diameter (AUC = 0.79-0.84, P < .0001), and 37 to 42 mm for posteromedial-anterolateral diameter (AUC = 0.81-0.89, P < .0001). Three-dimensional TEE measurements of MA dimensions display strong correlations with CT measurements in patients undergoing TMVR screening. Three-dimensional TEE imaging should be proposed as a reasonable alternative to CT imaging in this vulnerable population.


Preparation and characterization of curdlan with unique single-helical conformation and its assembly with Congo Red.
Elucidating the structure-activity relationship of curdlan is hampered by a lack of characterization with unique specific conformations (i.e., single- or triple-helix). In this study, single-helical curdlan is generated in dilute NaOH solutions at 35-50 °C, and characterized with NMR, SAXS, and GPC. The conformational transition from coil to single-helix and the intramolecular hydrogen bond interaction are explored using NMR. It is found that the two aforementioned types of curdlan interact with Congo Red in very different ways. Single-helical curdlan can encapsulate Congo Red to form a stable, supramolecular dye assembly, which is demonstrated by the shortest distance between the H3 of curdlan and the phenyl groups of Congo Red, and also the same self-diffusion coefficients of Congo Red and curdlan. In contrast, random-coil curdlan interacts weakly with Congo Red and cannot enwrap it. This study offers insight into the specific structure-activity relationship of beta-(1,3)-glucans.


Effects of aldosterone on Na+ transport in the toad bladder. II. The anaerobic response.
The action of aldosterone on active Na+ transport was assessed under aerobic and anaerobic conditions in the isolated urinary bladder of the toad, Bufo marinus. Aldosterone augmented the short-circuit current (Isc) under rigorous anaerobiosis. Four lines of evidence indicate that the increase in anaerobic Isc does not represent an equivalent increase in active Na+ transport: 1. Net Na transport, determined by isotopic fluxes, was the same in the aldosterone-treated and control quarter-bladders, and significantly greater than the simultaneously measured Isc-2. Amiloride, an inhibitor of the apical entry of Na+, did not reduce the steroid-dependent increase in the anaerobic Isc-3. Substitution of choline for Na+ in the mucosal medium reduced the magnitude of the anaerobic Isc values but did not eliminate the effect of aldosterone. 4. Addition of ouabain, a potent inhibitor of the Na+ pump, partially inhibited the effect of aldosterone on the anerobic Isc but a significant hormonal increment remained. The source of the anaerobic Isc was not identified; an effort was made, however, to determine the dependence of this current on glycolysis. During anaerobiosis, aldosterone increased the integral Isc by 42% but did not alter lactate production. These results suggest that the steroid-dependent increase in the anaerobic Isc may involve effects on permeability properties of the epithelium rather than on active transport systems.


Sedation in the Intensive Care Unit. The basis of the problem.
The authors briefly discuss the advantages and limits of sedation in critically ill patients. They also focus the importance of an individualized sedative approach which provides pain relief and modulates stress response, allowing patients to be easily arousable and cooperative as necessary.


Ureaplasma urealyticum and Mycoplasma hominis sensitivity to bacteriocins produced by two Lactobacilli strains.
The purpose of the present study was to determine the inhibitory activities of two bacteriocins, produced by lactobacilli, against genital mycoplasmas. In this study, infections produced by genital mycoplasmas were studied; of these, 1.3% were caused by Mycoplasma hominis, 10.7% by Ureaplasma urealyticum and 5.6% by U. urealyticum + M. hominis. U. urealyticum was isolated from 75 out of 123 patients with genital mycoplasmas, while M. hominis was isolated from 9 patients (7.3%) and both U. urealyticum and M. hominis from 39 patients (31.7%). Bacteriocins, L23 and L60, produced by Lactobacillus fermentum and L. rhamnosus, respectively, appear to be two novel inhibitors of bacterial infection with potential antibacterial activity. Both bacteriocins proved to be active against 100% of strains tested; MICs of bacteriocin L23 ranged between 320 and 160 UA ml(-1) for 78% of the M. hominis strains and between 320 and 80 UA ml(-1) for 95% of the U. urealyticum strains. In addition, bacteriocin L60 was still active at 160 UA ml(-1) for a high percentage (56%) of M. hominis strains, and at 80 UA ml(-1) for 53% of the U. urealyticum strains. Interestingly, these antimicrobial substances produced by lactobacilli showed an inhibitory activity against genital mycoplasmas even when diluted. Altogether, our study indicates that the bacteriocins, L23 and L60, are good candidates for the treatment or prevention of genital infections in women.


Lessons learned from a prenatal diagnosis program for thalassemia in Thailand.
To assess the outcome of a thalassemia screening program at community hospitals by determining the proportion of at-risk couples able to obtain a prenatal diagnosis (PND) in relation to gestational age (GA). We accessed records documenting prenatal screening for thalassemia in lower northern Thailand between January 2014 and December 2016. The proportion of at-risk pregnancies able to obtain a PND was determined and median GAs at the time of at-risk notification were compared. Reasons for failures to obtain PNDs were analyzed. Among 4633 screen-positive couples, 259 (5.6%) were identified as at-risk while 23 were excluded due to unconfirmed outcomes. Forty-one declined a PND and were excluded from the final calculations. Of the 195 remaining couples, 140 (71.8%) obtained a PND. Their median GA at the time of at-risk notification was 12.4 (5.6-29.1) weeks, which was earlier than the median GA of 17.7 (6.9-34.6) weeks for couples not undergoing PND (P < .001). Risks for various types of thalassemia and GA were associated with the chances of achieving a PND. In practice, one quarter of couples identified as at-risk were unable to obtain a PND. Time-influencing factors seem to be a major determinant.


Impact of Brief Nicotine Messaging on Nicotine-Related Beliefs in a U.S. Sample.
The current study pilot tested the effect of a single, brief exposure to nicotine education messages on beliefs about nicotine, nicotine-replacement therapy (NRT), E-cigarettes, and cigarettes with reduced nicotine content (RNC). Five hundred and twenty-one U.S. adults (aged ≥18 years) completed a 15-minute survey on Amazon Mechanical Turk in 2018. After completing items on sociodemographics, literacy, and cancer risk behaviors, participants were randomized in a 2:1:1 ratio to 1 of 3 conditions: nicotine education (n=263), sun safety education (attention control, n=128), or no message control (n=130). All participants completed items regarding nicotine, NRT, E-cigarette, and RNC cigarette beliefs, as well as norms about nicotine use, behavioral control regarding cigarette/tobacco use, and intention to use cigarettes, NRT, E-cigarettes, and RNC cigarettes in the next 12 months. Analyses were conducted in 2019. Following exposure, nicotine education participants reported fewer false beliefs about nicotine (p<0.001), NRT (p<0.001), E-cigarettes (p<0.05), and RNC cigarettes (p<0.05) compared with the control conditions. Nicotine messaging doubled the probability of a correct response (false, 78.3% vs 36.8%) to nicotine is a cause of cancer and dramatically reduced the probability of responding don't know to this item (5.3% vs 26.0%). There was no impact of the intervention on beliefs about other substances within cigarette, norms, or behavioral intentions. Findings from the current study support the hypothesis that a brief nicotine messaging intervention-similar to the messages likely to be seen on warning labels or in media campaigns-is likely to correct misperceptions of nicotine, NRT, E-cigarettes, and RNC cigarettes.


Assessing the impact of handwashing soaps on the population dynamics of carbapenemase-producing and non-carbapenemase-producing Enterobacterales.
Carbapenemase-producing bacteria have persistent environmental reservoirs in handwashing sinks. This study assessed the impact of handwashing soaps on the population dynamics of carbapenemase-producing Enterobacterales (CPE) and non-CPE. A number of isolates were grown in minimal media with or without two hand soaps marketed for use in health care. Soap A led to increased growth of all isolates except for Escherichia coli. Soap B did not lead to increased growth. The main difference between the formulations was that Soap B contained DMDM hydantoin, a preservative agent and sensitizer. These results show that environmental persistence of CPE may be sustained by common handwashing practices with soap, but further research is required.


Bifidobacterium longum R0175 protects mice against APAP-induced liver injury by modulating the Nrf2 pathway.
Acetaminophen (APAP) overdose is the most common driver of drug-induced liver injury (DILI) worldwide, and the gut microbiome plays a crucial role in this process. In this study, we estimated the effect of Bifidobacterium longum R0175 on APAP-induced liver injury in mice and discovered that B. longum R0175 alleviated liver injury by diminishing inflammation, reducing oxidative stress levels, inhibiting hepatocyte death and improving APAP-induced microbiome dysbiosis. Further studies revealed that the antioxidative effects of B. longum R0175 were primarily due to activation of the Nrf2 pathway, which was supported by the Nrf2 pathway inhibitor ML385 counteracting these ameliorative effects. B. longum R0175 modified intestinal metabolites, especially the key metabolite sedanolide, which could activate the Nrf2 pathway and contribute to the protective effects against APAP-induced liver injury. Moreover, we found that sedanolide exhibited close interrelationships with specific microbial taxa, indicating that this factor may be derived from gut microbes. In conclusion, our work demonstrated that B. longum R0175 could reduce oxidative damage, inflammation and hepatocyte death by activating the Nrf2 pathway. Importantly, we identified the microbiota-derived metabolite sedanolide, which was first discovered in the mouse intestine, as a key agonist of the Nrf2 pathway and primary effector of B. longum R0175 in APAP challenge. These findings provide new perspectives for APAP overdose therapy and demonstrate the enormous potential of B. longum R0175 in alleviating acute liver injury.


Effect of the fatty acid composition of ingested fats on rat liver intermediary metabolism.
The influence of a single load of medium chain triglycerides (MCT) or long chain triglycerides (LCT) on different intermediary metabolites of the rat liver was studied. Resultes showed that acetyl-CoA increased more after MCT than after LCT. MCT are more ketogenic than LCT. Mitochondrial and cytoplasmic redox state was greatly reduced after MCT. It is particularly interesting to note that MCT produced an increase in malate and citrate levels, whereas LCT had only a minor influence on these substances.


Contaminated soil phytoremediation by Cyperus laxus Lam. cytochrome p450 EROD-activity induced by hydrocarbons in roots.
Laboratory and greenhouse experiments with Cyperus laxus Lam were conducted to determine the rate and extent of phytoremediation and the effect of hydrocarbons on the cytochrome P450 EROD (7-ethoxyresorufin-O-deethylase) enzymatic activity in roots. Plants were cultivated on hydrocarbon-contaminated soil (HCS) and spiked perlite. Phytoremediation was evaluated using 6.5 kg HCS (173 +/- 15 mg total petroleum hydrocarbons [TPH] g(-1) of dry soil) pots at different moisture contents; the average removal rate was 3.46-0.25 mg TPH g(-1) dry soil month(-1) and 48% was removed when moisture was kept at 60%. The aromatic hydrocarbon fraction was the mostly removed, 60%; aliphatic, 51%; and polar 24% after 24-month experiments. In unplanted pots, TPH concentration did not exhibit significant differences with respect to the initial concentration. We confirmed that the presence of hydrocarbons induced ERODactivity up to 6.5-fold. Moreover, short-term experiments (up to 13 d) with spiked perlite demonstrated that two EROD activities in roots contributed to the total detected; 60% was found in the cytosolic and 40% in the microsomal fraction. To our knowledge, this is the first work that tries to build links between the hydrocarbon-inducible character of ERODactivity in roots and the phytoremediation ability of C. laxus in highly contaminated soils.


Lymphadenopathy post-COVID-19 vaccination with increased FDG uptake may be falsely attributed to oncological disorders: A systematic review.
Coronavirus disease 2019 (COVID-19) has caused a global pandemic that continues to cause numerous deaths to date. Four vaccines have been approved by the Food and Drug Administration as of July 2021 to prevent the transmission of COVID-19: Pfizer, Moderna, AstraZeneca, and Janssen. These vaccines have shown great efficacy and safety profile. One side effect that has been widely reported is post-COVID-19 vaccination lymphadenopathy. Due to the mimicry of the lymphadenopathy for metastases in some oncologic patients, there have been reports of patients who underwent biopsies that showed pathologic confirmation of benign reactive lymphadenopathy secondary to the COVID-19 vaccine. Therefore, understanding the incidence of lymphadenopathy post-COVID-19 vaccinations will help guide radiologists and oncologists in their management of patients, both present oncologic patients, and patients with concerns over their newly presenting lymphadenopathy. A systematic literature search was performed using several databases to identify relevant studies that reported lymphadenopathy post-COVID-19 vaccination. Our results revealed that several cases have been detected in patients undergoing follow-up fluorodeoxyglucose (FDG)-positron emission tomography-computerized tomography scans where lymph nodes ipsilateral to the vaccine injection site show increased uptake of FDG. Thus, knowledge of the incidence of lymphadenopathy may help avoid unnecessary biopsies, interventions, and changes in management for patients, especially oncologic patients who are at risk for malignancies.


2D-3D Cs2PbI2Cl2-CsPbI2.5Br0.5 Mixed-Dimensional Films for All-Inorganic Perovskite Solar Cells with Enhanced Efficiency and Stability.
The phase instability of cesium lead halide perovskite is still a substantial challenge hindering its application. A 2D-3D all-inorganic Cs2PbI2Cl2-CsPbI2.5Br0.5 perovskite solar cell was successfully developed to address this issue. The 2D Cs2PbI2Cl2 phase distributed among the grain boundaries of the 3D CsPbI3-xBrx grains. The existence of Cs2PbI2Cl2 effectively facilitated the (100) preferential crystal orientation of the CsPbI2.5Br0.5 crystals, promoting the carrier transport. The smooth transition region between the (003)2D//(001)3D interface indicated the formation of a 2D-3D heterostructure. Due to the improved crystal quality, high uniformity, and repeatability, the efficiency of the solar cells with areas of 0.09, 1, and 2 cm2 significantly improved to 15.09%, 12.74%, and 10.01%, respectively. The power conversion efficiency (PCE) retained 95.3% of the initial efficiency after 60 days in a nitrogen atmosphere at room temperature and 80% of the initial efficiency at a humidity of 70 ± 10% relative humidity (RH) under continuous heating at 80 °C for 12 h.


Genomic view on the peopling of India.
India is known for its vast human diversity, consisting of more than four and a half thousand anthropologically well-defined populations. Each population differs in terms of language, culture, physical features and, most importantly, genetic architecture. The size of populations varies from a few hundred to millions. Based on the social structure, Indians are classified into various caste, tribe and religious groups. These social classifications are very rigid and have remained undisturbed by emerging urbanisation and cultural changes. The variable social customs, strict endogamy marriage practices, long-term isolation and evolutionary forces have added immensely to the diversification of the Indian populations. These factors have also led to these populations acquiring a set of Indian-specific genetic variations responsible for various diseases in India. Interestingly, most of these variations are absent outside the Indian subcontinent. Thus, this review is focused on the peopling of India, the caste system, marriage practice and the resulting health and forensic implications.


Kinetic analysis of the binding of guanine nucleotides to bovine brain rhoB p20, a ras p21-like GTP-binding protein.
We have investigated the kinetics of the binding of guanine nucleotides to bovine brain rhoB p20, a ras p21-like GTP-binding protein with GTPase activity. The initial velocities of the binding of guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) to GDP-bound rhoB p20 and the dissociation of GDP from this protein were markedly increased by decreasing Mg2+ concentrations. The initial velocity of the binding of GTP gamma S to GDP-free rhoB p20 was not affected by changing Mg2+ concentrations. These results indicate that the dissociation of GDP from rhoB p20 limits the binding of GTP to this protein, and suggest that there is a factor stimulating the dissociation of GDP from rhoB p20 and thereby stimulating the binding of GTP to this protein in mammalian tissues. Consistently, the factor stimulating the dissociation of GDP, but not of GTP gamma S, from rhoB p20 was detected in bovine brain cytosol.


The dynamics of income and neighborhood context for population health: do long-term measures of socioeconomic status explain more of the black/white health disparity than single-point-in-time measures?
Socioeconomic status, though a robust and strong predictor of health, has generally been unable to fully explain the health gap between blacks and whites in the United States. However, at both the individual and neighborhood levels, socioeconomic status is often treated as a static factor with only single-point-in-time measurements. These cross-sectional measures fail to account for possible heterogeneous histories within groups who may share similar characteristics at a given point in time. As such, ignoring the dynamic nature of socioeconomic status may lead to the underestimation of its importance in explaining health and racial health disparities. In this study, I use national longitudinal data to investigate the relationship between neighborhood poverty and respondent-rated health, focusing on whether the addition of a temporal dimension reveals a stronger relationship between neighborhood poverty and health, and a greater explanatory power for the health gap between blacks and whites. Results indicate that long-term neighborhood measures are stronger predictors of health outcomes and explain a greater amount of the black/white health gap than single-point measures.


The interrelated process of becoming independent in user participation for young persons living with disabilities.
User participation is important in the delivery of health- and social services. Yet, our knowledge regarding how user participation is experienced from the perspective of those who use these services is limited. This study aims to develop knowledge regarding how young persons living with disabilities experience becoming independent in user participation. This qualitative study is inspired by Constructivist Grounded Theory. Nine young persons between 16 and 25 years of age and living with a disability, participated in the interviews. The results revealed that user participation for young persons is a socially situated, relational, and skills-dependent process. User participation is characterized as a process, consisting of increasing skills, gradually reducing parental support, and responding to interactions with professionals. The three categories are strongly reciprocal and interrelated, forming the unifying core category of Striving towards independence in user participation. We theorize about the Interrelated process of becoming independent in user participation for young persons with disabilities. This theory highlights the need to understand the interrelatedness of user participation, allowing for a recognition of the complexity of user participation, showing it as a process involving developing skills, and gradually becoming independent and skilled in user participation.Implications for rehabilitationYoung persons with disability rely on support from parents as well as professionals to become independent in user participationProfessionals should acknowledge that user participation is a learning process and allow for time and resources to aid this processFocusing on increasing health literacy alone is not sufficient to ensure user participation for young persons with disability.


How does context influence the delivery of mental health interventions for asylum seekers and refugees in low- and middle-income countries? A qualitative systematic review.
Low- and middle-income countries (LMICs) host the majority of the world's refugees. Evidence suggests that refugees and asylum seekers have high mental health needs compared to the host country population. However, they face many social, economic and culture barriers to receiving mental health care and benefitting from mental health interventions. This paper examines how these contextual factors affect the implementation of mental health interventions for refugees and asylum seekers in LMICs. We conducted a qualitative systematic review searching 11 databases and 24 relevant government and non-governmental organisation (NGO) websites. We spoke with academic experts and NGO professionals for recommendations, and conducted forwards and backwards citation tracking. From 2055 records in abstract and title screening, and then 99 in full-text screening, 18 eligible studies were identified. Qualitative thematic synthesis was conducted on eligible papers. Three main thematic clusters were identified around: (1) support during a time of pressure and insecurity, and the need for intervention flexibility through facilitator and participant autonomy; (2) different cultural conceptions of mental health, and how interventions negotiated these differences; and (3) the importance of facilitator skills, knowledge, characteristics and relationships to intervention implementation. Evidence suggests that intervention coordinators and developers should continue to: (1) think broadly about the range of social influences on mental health, addressing structural issues where possible; (2) offer flexibility with intervention style, content and timings; and (3) encourage building research capacity in LMICs while acknowledging pre-existing mental health knowledge and practice.


Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway.
Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear. Cell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice. The results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo. In current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.


Postoperative adjuvant chemotherapy is associated with a lower incidence of colorectal adenomas in patients with previous colorectal cancer.
The effects of chemotherapeutic agents on the development of colorectal adenomas in patients with previous colorectal cancer (CRC) are not defined. Therefore, we evaluated the potential effect of adjuvant chemotherapy on the incidence of colorectal adenomas in patients with previous CRC. We selected patients with low-risk stage II CRC with or without postoperative 5-fluorouracil-based adjuvant chemotherapy to reduce selection bias. Among 1808 patients with stage II CRC who underwent colonoscopic surveillance after curative resection of CRC between 2006 and 2013, 192 patients were retrospectively enrolled in this study after matching for age and sex. The patients were divided into 96 patients receiving and 96 patients not receiving 5-fluorouracil-based chemotherapy. Forty patients (41.7%) exhibited colorectal adenomas among 96 patients who received adjuvant chemotherapy, compared with 50 patients (52.1%) with colorectal adenomas among 96 patients who received surgery only. The incidence rate of advanced adenoma was significantly lower in the chemotherapy group than in the nonchemotherapy group (3.1% vs 10.4%, P = .044). After adjustment for clinically relevant factors such as body mass index, aspirin use, metformin use, number of follow-up colonoscopies, and operation type, adjuvant chemotherapy was found to be associated with a decreased incidence of advanced adenoma (odds ratio, .151; 95% confidence interval, .035-.653; P = .011) in patients with stage II CRC. The results showed that chemotherapy in patients with CRC may be associated with a lower risk of colorectal advanced adenoma development.


Demarcating geographic regions using community detection in commuting networks with significant self-loops.
We develop a method to identify statistically significant communities in a weighted network with a high proportion of self-looping weights. We use this method to find overlapping agglomerations of U.S. counties by representing inter-county commuting as a weighted network. We identify three types of communities; non-nodal, nodal and monads, which correspond to different types of regions. The results suggest that traditional regional delineations that rely on ad hoc thresholds do not account for important and pervasive connections that extend far beyond expected metropolitan boundaries or megaregions.


Computed Tomography-Guided Catheter Aspiration and Thrombolysis of Hypertensive Basal Ganglionic Hematomas: Technique and Short-Term Outcome Comparison.
Minimally invasive techniques of hematoma evacuation with or without the use of thrombolytic agents to lyse the clots have shown promising outcomes compared to open surgical evacuation. However, there is a dearth of literature in developing nations. The objective in this study was to evacuate spontaneous hypertensive basal ganglionic hemorrhages using computed tomography (CT)-guided catheter insertion, hematoma aspiration, and lysis with thrombolytic agents and analyze the efficacy and outcomes. Ten patients with spontaneous basal ganglionic hemorrhage underwent CT-guided clot catheter insertion, followed by aspiration of hematoma and clot lysis using 25,000 IU urokinase instilled every 12 hours. Details including symptoms, clinical and radiologic findings, efficacy of the technique, functional outcomes during follow-up, length of stay, and cost were recorded. Relevant details for 12 age- and sex-matched conservatively treated patients were compared. Functional outcome in the catheter group at 6 months was better than the medically managed group, with improved mean Glasgow Outcome Scale score (0.4 vs. 0.08), reduced modified Rankin scale score (-0.8 vs. -0.25), and reduced National Institutes of Health Stroke Scale score (-6.8 vs. -1.5 points). However, it was not statistically significant. Average hematoma volume reduction in the catheter group was 83.14%. In the medically managed group, 2 of 12 patients (16.6%) had hematoma expansion, 6 patients (50%) developed hydrocephalus, and 2 patients (16.6%) died. In the catheter group, 4 of 10 patients (40%) developed mild pneumocephalus that resolved. The evacuation of hypertensive basal ganglionic hematomas is feasible with basic neurosurgical instruments and existing resources (e.g., CT scan) with improved functional outcome compared with conservative treatment alone.


Microalbuminuria in normal Korean children.
Although microalbuminuria is known as a predictor of clinical nephropathy and cardiomyopathy, few studies have investigated the incidence and reference range of microalbuminuria in healthy children. This study aimed to establish a reference range and to study the age-related trend for spot urine microalbumin/creatinine ratio in a Korean pediatric population. 352 healthy children were studied from July 2007 through March 2010. Height, weight, serum creatinine, spot urine microalbumin/creatinine ratio, and glomerular filtration rate (GFR) were obtained for each subject. We divided the study population into 5 groups according to age, and compared the spot urine microalbumin/creatinine ratio with other variables using one-way analysis of variance (ANOVA), regression analysis and Pearson's correlation analysis. In this study, the data showed that the spot urine microalbumin/creatinine ratio decreased with age: 1-12 months, 22.72 ± 13.80 mg/mmol (2SD: 3.33-54.40 mg/mmol); 13-28 months, 16.34 ± 9.58 mg/mmol (2SD: 3.16-35.19 mg/mmol); 29-48 months, 13.12 ± 9.74 mg/mmol (2SD: 3.01-41.57 mg/mmol); 4-6 years, 10.58 ± 8.13 mg/mmol (2SD: 0.00-30.19 mg/mmol); and 7-19 years, 5.13±5.44 mg/mmol (2SD: 0.45-14.45 mg/mmol). The spot urine microalbumin/creatinine ratio showed correlation with age, height, height z-score, weight, weight z-score, GFR, body mass index (BMI) and body surface area (BSA). The spot urine microalbumin/creatinine ratio in normal Korean children decreased with age. This ratio could potentially be used to establish reference ranges and cutoff values for Korean children and to predict nephropathy and cardiomyopathy.


Perceived stress, stress coping strategies, and post-traumatic-growth among healthcare professionals during COVID-19 pandemic.
The purpose of this research was to identify the perceived stress, stress coping strategies, and Post-Traumatic-Growth (PTG) among Iranian healthcare professionals. A cross-sectional study was applied. This study was conducted among 402 healthcare professionals in northwestern Iran. Participants completed demographic, perceived stress, stress coping strategies, and PTG questionnaires. Multiple linear regression was employed to identify the predictors of perceived stress and PTG. The overall score of perceived stress was calculated 30.55 (6.18). The problem-oriented strategy was the most common stress coping by healthcare professionals (52.66 (8.72)). Also, the total score of PTG was calculated at 45.72 (30.42). Perceived stress, stress coping strategies (except problem-oriented), and PTG scores were significantly different between hospital and health centres participants (p-value < 0.05). Previous experience in critical situations, crisis-related course, degree, age, department, and stress coping strategies were related to the stress level. Moreover, workplace, department, work experiences, and employment status were the predictors of PTG.


Effect of medical therapy on left ventricular ejection fraction in patients with systolic heart failure and narrow QRS duration with and without ischemic heart disease and left ventricular mechanical dyssynchrony.
We studied 99 consecutive patients with class III-IV systolic heart failure with a left ventricular ejection fraction (LVEF) < or =35% and a QRS duration <120 milliseconds. Patients with cardiac resynchronization therapy were excluded. Echocardiography was performed in all patients before and after optimal standard heart failure therapy. The septal-to-posterior wall motion delay (SPWMD) > or =130 milliseconds on echocardiogram was defined as left ventricular mechanical dyssynchrony (LVMD). Sixty-nine of 99 patients (70%) had ischemic heart disease. During follow-up of 15.2 +/- 9.8 months, LVEF improvement > or =15% was greater patients in nonischemic group (50%, 15/30) than in ischemic group (9%, 6/69; P < 0.001). After adjustment for age, gender, and clinical and echocardiographic characteristics, ischemic heart disease and grade of coronary disease were persistently related to LVEF improvement > or =15% (P = 0.03 and 0.02, respectively). Twenty of 99 patients (20%) had SPWMD > or =130 milliseconds (LVMD group), and 79 of 99 patients (80%) had SPWMD <130 milliseconds (non-LVMD group). LVEF increased in both groups (P = 0.005) during follow-up, but the percentage of patients with LVEF improvement > or =15% in LVMD was greater compared with patients without LVMD (40% versus 16%, respectively, P = 0.03). In conclusion, the improvement of LVEF in patients with systolic heart failure and narrow QRS was greater in patients with nonischemic heart disease and LVMD compared with patients with ischemic heart disease and absence of LVMD during medical therapy without cardiac resynchronization therapy.


West meets East: preliminary results of narrow band imaging with optical magnification in the diagnosis of colorectal lesions: a multicenter Australian study using the modified Sano's classification.
Narrow band imaging with optical magnification (NBI-Z) enables mucosal morphology to be assessed in real time by using light with narrowed band width and magnification of up to 115×. Colorectal lesions detected were assessed with NBI-Z. Histology was predicted using the modified Sano's classification based on capillary network patterns (cn); type I: absent cn (hyperplastic polyp), type II: cn present, surrounding mucosal glands (adenoma), type IIIa: high density cn with tortuosity and lack of uniformity (intramucosal cancer) and type IIIb: nearly avascular cn (invasive cancer). Each lesion was also graded with a confidence level (low/high). High-definition videos (mean 28.2 s; range 12-55) of each lesion assessed with NBI-Z were then taken. This was followed by polypectomy, endoscopic or surgical resection. NBI-Z diagnosis was compared with the final histopathology. To test for interobserver agreement, an endoscopist blinded to the video acquisition process/histology was invited to grade the videos. A total of 50 lesions (2 assessors: 100 studies), with an average size of 8.4 mm (range 3-30), in 32 patients were assessed. Twenty were hyperplastic, 25 adenomas, 2 intramucosal and 3 invasive cancers of which 19 were located in the right and 31 in the left colon. The overall accuracy of NBI-Z in predicting histology was 90%, which increased to 95% (88/93) when lesions were predicted with high confidence. The sensitivity (Sn), specificity (Sp), positive (PPV) and negative predictive values (NPV) in differentiating neoplastic from non-neoplastic lesions with high confidence were 98%, 89%, 93% and 97%, respectively, while the Sn, Sp, PPV and NPV in predicting endoscopic resectability (type II, IIIa vs type I, IIIb) was 100%, 90%, 93% and 100%, respectively. The interobserver agreement between both assessors (κ value) was substantial at 0.89. Using confidence levels, NBI-Z permits prediction of colorectal neoplasia with high accuracies and might allow prompt decisions to be made if a lesion should be left in situ, resected and discarded or biopsied. This approach might lead to substantial time and cost savings and could potentially reduce complications associated with polypectomy and endoscopic resections.


Persistent and Chronic Perioperative Pain After Cancer Surgery.
Persistent and chronic pain after cancer surgery is a complex clinical problem. The etiology of pain in these cases is often multifactorial and, in addition to the surgery itself, can include or overlap with other painful syndromes such as direct effects of tumors, neuropathic pain, and pain syndromes secondary to chemotherapy and/or radiation. There is a growing body of literature which suggests that treating pain in the acute and subacute periods can prevent chronic pain, an important step in reducing the morbidity of this clinical problem. This review describes the incidence of persistent pain after cancer surgery, its pathophysiology, and treatment considerations. Additional research on diagnostic criteria, pathophysiology, and novel medications, restorative therapies, and interventional treatments will be essential to continue to reduce the clinical burden of persistent and chronic perioperative pain after cancer surgery.


Predictive value of long noncoding RNA ZFAS1 in patients with ischemic stroke.
LncRNAs play an essential role in a variety of diseases. Zinc finger antisense 1 (ZFAS1), a newly identified lncRNA, is a transcript antisense to the 5' end of the gene Znfx1. The purpose of this study was to aim to compare the levels of ZFAS1 between ischemic stroke (IS) and healthy control subjects and explore its potential role as a noninvasive biomarker in the diagnosis of IS. A total of 176 patients and 111 healthy controls were included in the study. RT-qPCR was performed to detect the expression of ZFAS1. The results showed that level of ZFAS1 in IS patients was significantly lower than controls (P = 0.0002). Furthermore, we found that the ZFAS1 levels in large-artery atherosclerosis (LAA) strokes were significantly downregulated than those in non-LAA strokes and controls. Meanwhile, ZFAS1 levels in the small vessel occlusion (SVO) group were lower than those in cardioembolism (CE) (P = 0.0197) and controls (P = 0.0041). Multinomial logistic regression analyses showed that the expression of ZFAS1 was not associated with the CE (P = 0.185) and SVO (P = 0.268) stroke groups, while lower ZFAS1 levels (P < 0.003, adjusted OR = 0.218, 95% CI: 0.079-0.597) showed significant associations with increased probability of having LAA strokes, compared to control subjects. The receiver operating characteristic curve analyses indicated that the sensitive of ZFAS1 was 89.39% in differentiating LAA strokes from controls. These results suggest that ZFAS1 might be used as a potential noninvasive biomarker for the diagnosis of LAA stroke.


Xenon as a probe for minority sites on solid surfaces.
Atomic-level microscopies have proved useful to map solid-surface sites directly, but, because of their lack of chemical specificity, they are less adept at identifying unique chemical activity on those sites. Here we present a dual-titration approach developed to probe minority sites on solid surfaces with unique chemical properties of potential relevance to heterogeneous catalysis. Our methodology involves the initial dosing of a chemical probe such as carbon monoxide or ammonia to drive its selective adsorption onto specific sites with particular chemical activity, and the subsequent adsorption of xenon to help identify the nature of those sites. A combination of photoelectron and temperature-programmed desorption spectroscopies are used to characterize the Xe adsorption. The chemistry of oxygen-modified Ni(110) single crystals was probed to test this technique. It was observed that whereas CO does not discriminate among the various sites present on those surfaces, ammonia binds preferentially to the end of -Ni-O rows and modifies their local electrostatic potential. In addition, it was determined that adsorbed CO aids in a reversible surface reconstruction involving the coalescence of fragmented surface -Ni-O rows at high (>350 K) temperatures.


Visceral adiposity and left ventricular mass and function in patients with aortic stenosis: the PROGRESSA study.
Recent studies have reported that obesity, metabolic syndrome, and diabetes are associated with left ventricular (LV) hypertrophy (LVH) and dysfunction in patients with aortic stenosis (AS). The purpose of this study was to examine the association between amount and distribution of body fat and LVH and systolic dysfunction in AS patients. One hundred twenty-four patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study and underwent Doppler echocardiography and computed tomography scan. Presence and severity of LVH was assessed according to LV mass indexed for height(2.7) and LV dysfunction according to global longitudinal strain (GLS). Computed tomography was used to quantify abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, and total adipose tissue (TAT). Body mass index (BMI) correlated strongly with TAT (r = 0.85), moderately with VAT (r = 0.70), and SAT (r = 0.69), and weakly with the proportion of VAT (VAT/TAT ratio: r = 0.19). In univariate analysis, greater BMI, TAT, VAT, SAT, and VAT/TAT were associated with increased LV mass index and greater VAT and VAT/TAT ratio were associated with reduced GLS. Multivariate analysis revealed that larger BMI (P < 0.0001) and greater VAT/TAT ratio (P = 0.01) were independently associated with higher prevalence of LVH, and only the VAT/TAT ratio (P = 0.03) was independently associated with reduced GLS. The results of this study suggest that total and visceral adiposity are independently associated with LVH in patients with AS. Furthermore, impairment of LV systolic function does not appear to be influenced by total obesity but is rather related to excess visceral adiposity. These findings provide impetus for elaboration of interventional studies aiming at visceral adiposity in the AS population.


Comparison of simultaneous static standing balance data on a pressure mat and force plate in typical children and in children with cerebral palsy.
Balance testing is an important component in treatment planning and outcome assessment for children with Cerebral Palsy (CP). Objective measurement for static standing balance is typically conducted in motion labs utilizing force plates; however, a plantar pressure mat may prove to be a viable alternative for this type of balance assessment. This study examined static standing balance simultaneously on a force plate and a plantar pressure mat in 30 typically developing (TD) and 30 children with CP to determine if valid measures of static standing balance could be obtained in children with CP using a pressure mat. Examination of the data provided evidence that reliable and valid measures of static standing balance can be produced with a plantar pressure mat for both groups. Five variables out of the 21 variables examined were found to be reliable and valid on both devices (pressure mat and force plate) for both subgroups (TD and CP). The variables medial/lateral (ML) average radial displacement, range moved-ML, anterior/posterior average velocity, ellipse area, and area per second were found to have high test-retest reliability (ICC > .6) and possess discriminant validity between the subgroups (TD vs. CP). Additionally, the ellipse area and area per second variables also had the ability to discriminate between GMFCS levels. A normative center of pressure (CoP) balance data set using all 21 variables was also established for typically developing children for both devices (pressure mat and force plate) within this study. The ability to utilize a portable plantar pressure mat for quick and reliable standing balance measurement allows for expanded ability to capture objective data in a variety of settings thereby increasing opportunity for outcomes analysis.


Fatty acids and the control of bilirubin levels in blood.
The evidence that changes in the hepatic intracellular concentration of non-esterified fatty acids affect the clearance of bilirubin from blood by the liver is reviewed. Such a mechanism would in particular explain the rise in plasma bilirubin levels during fasting.


A new method using surface landmarks to locate resuscitative endovascular balloon occlusion of the aorta based on a retrospective CTA study.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) can timely prevent the wounded from fatal hemorrhage. However, blind insertion of REBOA in field or emergency room may result in catheter malposition and serious complications. We aim to develop a new method based on surface landmarks to guide the accurate placement of REBOA in zone III of aorta without fluoroscopy. A retrospective study was conducted in a university hospital, including 57 subjects who underwent computed tomography angiography (CTA) from April to December in 2019. External distances and intravascular lengths were measured by three-dimensional reconstruction of CT images, including the distances from the insertion site of femoral artery to the xiphoid process (FA-Xi), the midpoint between the xiphoid process and the umbilicus (FA-mXU), the umbilicus (FA-Ui), the midpoint of the zone III of aorta (FA-mZIII), the lowest renal artery (FA-LRA), and aortic bifurcation (FA-AB). The distal and proximal ideal margin and predicted accuracy were calculated by curvature plane reconstruction. The predicted probability of balloon positioning in zone III by different methods was compared. The mean age of all patients was 60 years (SD = 9.4). The average length of zone III of aorta was 9.4 cm (SD = 1.0), and the length of FA-mZIII on the right and left sides were 24.4 cm (SD = 2.1), 23.8 cm (SD = 2.1), respectively. FA-Xi was longer than FA-LRA, and FA-Ui was shorter than FA-AB (paired two-tailed test, p < 0.001). Using three methods including the optimal quartering distances, the optimal distances below the xiphoid and above the umbilicus to predict the length of REBOA catheter positioning in zone III showed no statistically significant difference. The predicted accuracy of catheter positioning in zone III on the left and right sides guided by FA-mXU were 84.2% and 86%. The midpoint between the xiphoid process and the umbilicus may be a new surface landmark for people of normal weight to guide rapid positioning REBOA in zone III of aorta without fluoroscopy.


National trends in repair for type B aortic dissection.
Thoracic endovascular aortic repair (TEVAR) first gained in popularity for repair of type B aortic dissections (TBADs) in the early 2000's. We aimed to describe patients undergoing open repair, TEVAR, and no repair and analyze factors associated with repair within 14 days of presentation in the contemporary era. We used the MarketScan database to find patients with TBAD between 2014 and 2017. To assess factors associated with early repair, univariable, and multivariable log-binomial regression were used. There were 2613 patients admitted with TBAD between 2014 and 2017 across the United States, of whom 38.4% underwent repair within 14 days of admission (25.3% open repair and 13.1% TEVAR). The incidence of repair within 14 days decreased over the study period (43% of the study cohort in 2014 to 26.4% in 2017) primarily due to a decrease in open repairs from 30.8% of patients in 2014 to 12.5% in 2017. In multivariable analysis, older age, Middle Atlantic location, diabetes mellitus, insulin use, antiplatelet use, and more recent year were associated with lower likelihood of early repair; male sex, peripheral vascular disease, and the presence of extremity ischemia, rupture, shock, and acidosis were associated with higher likelihood of repair. Overall, repair of TBAD within 14 days of presentation declined from 2014 to 2017, with a steady rate of TEVAR but declining rate of open repairs. Further investigation into provider- and hospital-specific factors as they relate to likelihood of repair is needed.


[A Case of Advanced Rectal Cancer with Left Hydronephrosis Treated with Left Ureter-Sparing Laparoscopic High Anterior Resection after Chemotherapy].
A 47-year-old woman with a complaint of weight loss for the past 5 months was referred to our hospital. Colonoscopy revealed advanced rectal cancer 20 cm from the anal verge. The patient had left hydronephrosis caused by ureteral invasion. Firstly, we performed transverse colostomy and left nephrostomy. After 8 courses of capecitabine, oxaliplatin plus bevacizumab( CAPOX plus Bmab)therapy, colonoscopy and computed tomography revealed shrinkage of both the primary and metastatic lesions. Laparoscopic high anterior resection was performed, and the left ureter was successfully preserved. The patient received chemotherapy after surgery. Neither local recurrence nor enlargement of metastases has been observed 8 months after surgery.


Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer.
In colorectal cancer (CRC), 20-50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II-IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32-11.69); 3.72 (1.99-6.95); 2.58 (1.18-5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64-5.73); 3.41 (1.55-7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38-7.04) and OS, HR 3.20 (1.39-7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0-53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.


ACE2: the molecular doorway to SARS-CoV-2.
The angiotensin-converting enzyme 2 (ACE2) is the host functional receptor for the new virus SARS-CoV-2 causing Coronavirus Disease 2019. ACE2 is expressed in 72 different cell types. Some factors that can affect the expression of the ACE2 are: sex, environment, comorbidities, medications (e.g. anti-hypertensives) and its interaction with other genes of the renin-angiotensin system and other pathways. Different factors can affect the risk of infection of SARS-CoV-2 and determine the severity of the symptoms. The ACE2 enzyme is a negative regulator of RAS expressed in various organ systems. It is with immunity, inflammation, increased coagulopathy, and cardiovascular disease. In this review, we describe the genetic and molecular functions of the ACE2 receptor and its relation with the physiological and pathological conditions to better understand how this receptor is involved in the pathogenesis of COVID-19. In addition, it reviews the different comorbidities that interact with SARS-CoV-2 in which also ACE2 plays an important role. It also describes the different factors that interact with the virus that have an influence in the expression and functional activities of the receptor. The goal is to provide the reader with an understanding of the complexity and importance of this receptor.


Time-traveling seeds reveal that plant regeneration and growth traits are responding to climate change.
Studies assessing the biological impacts of climate change typically rely on long-term, historic data to measure trait responses to climate through time. Here, we overcame the problem of absent historical data by using resurrected seeds to capture historic plant-trait data for a number of plant regeneration and growth traits. We collected seed and seedling trait measurements from resurrected historic seeds and compared these with modern seed and seedling traits collected from the same species in the same geographic location. We found a total of 43 species from southeastern Australia for which modern/historic seed pairs could be located. These species were located in a range of regions that have undergone different amounts of climate change across a range of temperature, precipitation, and extreme measures of climate. There was a correlation between the amount of change in climate metrics, and the amount of change in plant traits. Using stepwise model selection, we found that for all regeneration and growth trait changes (except change in stem density), the most accurate model selected at least two measures of climate change. Changes in extreme measures of climate, such as heat-wave duration and changes in climate variability, were more strongly related to changes in regeneration and growth traits than changes in mean climate metrics. Across our species, for every 5% increase in temperature variability, there was a threefold increase in the probability of seed viability and seed germination success. An increase of 1 d in the maximum duration of dry spells through time led to a 1.5-fold decrease in seed viability and seeds became 30% flatter/thinner. Regions where the maximum heat-wave duration had increased by 10 d saw a 1.35-cm decrease in seedling height and a 1.04-g decrease in seedling biomass. Rapid responses in plant traits to changes in climate may be possible; however, it is not clear whether these changes will be fast enough for plants to keep pace with future climate change.


Antiviral and antibacterial activity of hand sanitizer and surface disinfectant formulations.
Emergent diseases caused by viral and bacterial infections have proven to be a current and future challenge. The occurrence of these diseases is usually accompanied by the lack of vaccines and dedicated therapies leaving prevention as the best strategy to adopt. In that context, and apart from confinement and physical distancing measures, an increase in hygiene actions, namely hand and surface cleaning and disinfection can reduce the infection spread originated from our day-to-day routines. However, during crisis situations the high disinfectants demand can very likely lead to having them running out of stock. This impels many individuals and companies to produce their own disinfectants. Here, we explore the main components of a disinfection formulation, both for hand-rub and surface cleaning. Alcohol and non-alcohol based formulations are described, including the possibility to fine tune the properties of the final product in order to increase public acceptance while maintaining product efficacy. The action mechanisms of the main active principles are also described conjugating information from experimental and theoretical data. Overall, the main aspects to develop a disinfectant formulation are addressed, as well as their function, helping formulation developers to better understand the impact of their choices.


Advances in IgE Testing for Diagnosis of Allergic Disease.
Since its discovery in 1967, IgE antibody detection in skin and blood has identified a state of allergic sensitization and served as a necessary but not sufficient risk factor that requires objective symptoms to make the definitive diagnosis of human allergic disease. More recently, quantitative IgE antibody levels in serum against allergenic extracts, molecules, and epitopes have pushed its application into more accurately identifying the specificity of the allergic response for targeting immunotherapy, predicting allergic symptom severity after allergen exposure, and attempting to distinguish tolerance from food allergy. This review examines new in vivo and in vitro developments in the design, performance, interference, and application of the methods used to identify allergic sensitization. The increasing accepted applications of molecular allergen and allergen epitope-based IgE antibody measurements, especially as applied to food allergy diagnosis and management, are highlighted as state-of-the-art advances. Despite these major advances in allergic sensitization documentation, their ultimate value requires integration by the clinician with the patient's history and pretest probability of disease.


The association of metabolic health obesity with incidence of carotid artery plaque in Chinese adults.
We aimed to evaluate the association between different obese phenotypes with carotid artery plaque (CAP) event. The current retrospective cohort study was performed in 32,778 Chinese adults (19,221 men and 13,557 women, aged 41.9 ± 11.0 years). Obese phenotypes were assessed based on baseline body mass index (<24.0 vs. ≥24.0 kg/m2) and metabolic characteristics (health vs. unhealth). All the participants were further classified into four groups: metabolic health and normal weight (MHNW), metabolic unhealth and normal weight (MUHNW), metabolic health and overweight (MHO), and metabolic unhealth and overweight (MUHO). Ultrasound B-mode imaging was annually performed to evaluate CAP throughout the study. We have identified 2142 CAP cases during 5-year follow-up. Comparing with the MHNW group, the hazard ratios for the risk of incident CAP was 2.44 (95% CI:1.92 and 3.09) for the MUHNW group, 1.52 (95% CI:1.06 and 2.18) for the MHO group, and 1.8 (95% CI:1.4 and 2.33) for the MUHO group. The association was more pronounced in young adults (<65 y) than that in aged adults (≥65 y). Sensitivity analysis generated similar results with the main analysis. MUHNW, MHO, and MUHO were associated with the risk of CAP.


Effects of biodiesels on the physicochemical properties and oxidative reactivity of diesel particulates: A review.
Particulate emissions from the combustion of diesel have always been the main concern, especially in recent years, with continuously stringent particulate emission regulation for diesel engines. To alleviate the problem, biodiesel has been received great attention because of its being environment-friendly, widely available and renewable. The application of biodiesel in diesel engines changes the combustion process, thus varies physicochemical property of the particulate matter (PM) formed, which in turn influences the oxidative reactivity of soot particles. In view of this, it is particularly important to analyze soot particles from the diesel engine fueled with biodiesels. This review focus on the effects of biodiesels on the physicochemical properties of soot particles, such as surface morphology, nanostructure, active surface area, element composition, elemental and organic carbon contents, surface functional groups, sp2 and sp3 hybridizations, etc. The impact of engine operating conditions (i.e. engine load, engine speed, fuel injection timing, fuel injection pressure, exhaust gas recirculation, etc.) on characteristics of soot particles from diesel engines powered by biodiesel is also discussed. Whereafter, the relationships between soot physicochemical characteristics and soot oxidative reactivity are reviewed. Finally, the main conclusions are outlined as well as the proposed research work in the future.


Single Nucleotide Variant in FAS Associates With Organ Failure and Soluble Fas Cell Surface Death Receptor in Critical Illness.
Multiple organ failure in critically ill patients is associated with poor prognosis, but biomarkers contributory to pathogenesis are unknown. Previous studies support a role for Fas cell surface death receptor (Fas)-mediated apoptosis in organ dysfunction. Our objectives were to test for associations between soluble Fas and multiple organ failure, identify protein quantitative trait loci, and determine associations between genetic variants and multiple organ failure. Retrospective observational cohort study. Four academic ICUs at U.S. hospitals. Genetic analyses were completed in a discovery (n = 1,589) and validation set (n = 863). Fas gene expression and flow cytometry studies were completed in outpatient research participants (n = 250). None. In discovery and validation sets of critically ill patients, we tested for associations between enrollment plasma soluble Fas concentrations and Sequential Organ Failure Assessment score on day 3. We conducted a genome-wide association study of plasma soluble Fas (discovery n = 1,042) and carried forward a single nucleotide variant in the FAS gene, rs982764, for validation (n = 863). We further tested whether the single nucleotide variant in FAS (rs982764) was associated with Sequential Organ Failure Assessment score, FAS transcriptional isoforms, and Fas cell surface expression. Higher plasma soluble Fas was associated with higher day 3 Sequential Organ Failure Assessment scores in both the discovery (β = 4.07; p < 0.001) and validation (β = 6.96; p < 0.001) sets. A single nucleotide variant in FAS (rs982764G) was associated with lower plasma soluble Fas concentrations and lower day 3 Sequential Organ Failure Assessment score in meta-analysis (-0.21; p = 0.02). Single nucleotide variant rs982764G was also associated with a lower relative expression of the transcript for soluble as opposed to transmembrane Fas and higher cell surface expression of Fas on CD4+ T cells. We found that single nucleotide variant rs982764G was associated with lower plasma soluble Fas concentrations in a discovery and validation population, and single nucleotide variant rs982764G was also associated with lower organ dysfunction on day 3. These findings support further study of the Fas pathway as a potential mediator of organ dysfunction in critically ill patients.


The JAK2V617F allele burden and STAT3- and STAT5 phosphorylation in myeloproliferative neoplasms: early prefibrotic myelofibrosis compared with essential thrombocythemia, polycythemia vera and myelofibrosis.
Early prefibrotic myelofibrosis (early PMF) is a diagnosis that clinically and histologically mimic essential thrombocythemia (ET), but is important to distinguish from ET, polycythemia vera (PV) and primary myelofibrosis (PMF) due to its different prognosis and clinical evolution. In this study, we assessed the allele burden of JAK2V617F in bone marrow biopsies from patients with these chronic myeloproliferative neoplasms. We correlated our findings with the amount of phosphorylated STAT3 (P-STAT3) and STAT5 (P-STAT5) in megakaryocyte nuclei in the bone marrow. The JAK2V617F allele burden was significantly higher in patients with PV (median: 50.99, range: 23.08-97.29, p < 0.01 and p < 0.01) and PMF (median: 44.13, range: 33.61-92.17, p < 0.05 and p < 0.01) compared with a low allele burden in ET (median: 23.465, range: 8.67-47.92) and early PMF (median: 25.68, range: 0.61-49.13) respectively. In addition, we found a significantly higher phosphorylation of STAT5 and STAT3 in the JAK2V617F positive group than in the negative group. There was no positive correlation between increasing JAK2V617F allele burden and the amount of P-STAT3 and P-STAT5. However, we found low values of P-STAT5 in bone marrow biopsies from patients with ETJAK2V617F+ as compared with patients with early PMFJAK2V617F+. Although this difference was statistically significant, larger studies are needed to firmly support this conclusion.


Greater-omentum lesion-score (GOLS) as a predictor of residual disease in different regions of the peritoneal cavity in patients undergoing interval cytoreductive surgery for advanced ovarian cancer and its potential clinical utility.
The greater omentum(GO) is a common site of residual disease in patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer. The presence of tumor in the GO could predict presence of disease in other peritoneal regions. The goal of this study was to perform a correlation between the greater-omentum lesion-score(GOLS) and presence of disease in different peritoneal regions and determine its potential utility in guiding interval cytoreductive surgery(CRS). This prospective study included 134 patients undergoing interval CRS from July 1, 2018 to June 30, 2020. Each region of Sugarbaker's Peritobneal Cancer Index(PCI) was given a lesion score(LS) from 0 to 3 according to the diameter of the largest tumor in the region. The GOLS was recorded separately from other structures in the region. Correlation between the GOLS and surgical and pathological LS in each region was performed. As the GOLS increased, the incidence of disease(surgical LS) in other regions of the peritoneal cavity increased. Receiver operating characteristic(ROC) curves showed area under curve more than 80% for regions 1-2 and 7-8 indicating a high probability of disease in these regions in patients with GOLS 1-3. The positive predictive value(PPV) of preoperative imaging for GOLS was 95.7%. No cut-off of the GOLS could predict presence of disease on pathology with more than 70% accuracy. Presence of disease in the GO warrants performing upper abdominal exploration and/or cytoreduction and interval CRS should be planned accordingly in these patients. Imaging has a high PPV in detecting disease in the GO.


Novel bacteriochlorophyll e structures and species-specific variability of pigment composition in green sulfur bacteria.
The relative composition of bacteriochlorophyll (BChl) homologs in five different strains of brown-colored green sulfur bacteria was investigated by HPLC-MS/MS and NMR analyses. In addition, the effect of incubation light intensities on homolog distribution was studied in one of the strains (strain Dagow III). A total of 23 different BChl e structures were detected and comprise four homologous porphyrin ring systems and eight different esterifying alcohols. Several BChl e structures are novel. These include a C-8 ethyl, C-12 methyl [E, M] BChl e(F) homolog which was identified by (1)H-NMR analyses of the isolated, main farnesyl homologs (BChl e(F)). In addition, five previously unknown homolog series with dodecanol, pentadecenol, tetradecanol, hexadecenol and phytol as the esterifying alcohols were detected. The composition of BChl e homologs from the five strains of green sulfur bacteria differed with respect to the relative abundance of the homologs (BChl e(F) : 25.6-67.0% of total BChl e content in stationary cultures). In strain Dagow III, the abundance of BChl e(F) homologs decreased upon entry into the stationary phase. In all free-living strains, the abundance of BChl e(F) was increased when the relative carotenoid content was low. The present results provide a detailed picture of pigment composition in chlorosomes and thus will help to elucidate their structure and function. Furthermore, the newly discovered BChl e molecules are valuable biomarkers for the study of the occurrence and metabolism of green sulfur bacteria in past and present ecosystems.


Induction of the c-fos gene product in rat forebrain following cortical lesions and NGF injections.
Neocortical lesions and NGF injections into neocortex induce the immunostaining of Fos, the c-fos gene product, in neuronal nuclei in ipsilateral cortex, and amygdala. Adjacent structures including hippocampus, septal nuclei, globus pallidus, and thalamus were unaffected. It is hypothesized that trophic molecules or other chemicals are released at the injury site and these induce the c-fos gene in cells throughout the ipsilateral hemisphere. Fos induction might mediate metabolic or plasticity responses to the focal injury.


Skin damage caused by scale loss modifies the intestine of chronically stressed gilthead sea bream (Sparus aurata, L.).
The present study was designed to test if the damage caused by scale loss provokes a change in other innate immune barriers such as the intestine and how chronic stress affects this response. Sea bream (Sparus aurata) were kept in tanks at low density (16 kg m-3, LD) or exposed to a chronic high density (45 kg m-3, HD) stress for 4 weeks. Scales were then removed (approximately 50%) from the left flank in the LD and HD fish. Intestine samples (n = 8/group) were examined before and at 12 h, 3 days and 7 days after scale removal. Changes in the morphology of the intestine revealed that chronic stress and scale loss was associated with intestinal inflammation. Specifically, enterocyte height and the width of the lamina propria, submucosa and muscle layer were significantly increased (p < 0.05) 3 days after skin damage in fish under chronic stress (HD) compared to other treatments (LDWgut3d or HDgut0h). This was associated with a significant up-regulation (p < 0.05) in the intestine of gene transcripts for cell proliferation (pcna) and anti-inflammatory cytokine tgfβ1 and down-regulation of gene transcripts for the pro-inflammatory cytokines tnf-α and il1β (p < 0.05) in HD and LD fish 3 days after scale removal compared to the undamaged control (LDgut0h). Furthermore, a significant up-regulation of kit, a marker of mast cells, in the intestine of HDWgut3d and LDWgut3d fish suggests they may mediate the crosstalk between immune barriers. Skin damage induced an increase in cortisol levels in the anterior intestine in HDWgut12 h fish and significant (p < 0.05) down-regulation of mr expression, irrespective of stress. These results suggest glucocorticoid levels and signalling in the intestine of fish are modified by superficial cutaneous wounds and it likely modulates intestine inflammation.


The skeletal maturity of Australian children aged 10-13 years in 2016.
Skeletal maturity can be used as a biological indicator of the tempo of growth in children and adolescents. We present a description of skeletal maturity from a cohort of white Australian children and describe variation in skeletal maturity based on child age. Participants (n = 71; age 10.5-13.9 years) were recruited from the 'Healthy, Active Preschool & Primary Years (HAPPY)' study. Left hand-wrist radiographs were used to determine skeletal maturity using the Tanner-Whitehouse III (TW3) RUS technique. In boys, the mean skeletal maturity offset (bone age - chronological age) was -0.12 ± 0.19 years and 57.9% had delayed skeletal maturity compared to chronological age. Among those with delayed skeletal maturity, the average delay was 0.99 years (range 0.02-2.54 years). In girls, skeletal age was advanced, on average, compared to chronological age by 0.32 ± 0.20 years. Among the 39.4% of girls with delayed skeletal maturity, the average delay was 0.48 years (range: 0.01-2.28). Four children in the sample exhibited a delay in skeletal maturity greater than 2 years. In the context of secular trends towards advanced skeletal maturity observed globally, delayed skeletal maturation in this white, economically privileged cohort are surprising and warrant further exploration.


A proposed method of logarithmic transformation of optical coherence tomography data for use in clinical research.
To evaluate a logarithmic transformation of retinal thickness measurements from optical coherence tomography as a new approach to assess clinically meaningful changes in retinal thickness. Methodologic, evidence-based review. Standard published approaches for assessing change in retinal thickness over time, as measured by optical coherence tomography (OCT), were compared with a new approach based on a logarithmic transformation of the retinal thickness data. Comparative examples were derived using published data from a clinical trial comparing intravitreal corticosteroid injections for diabetic macular edema with standard laser treatment. Comparative examples using Diabetic Retinopathy Clinical Research Network data. Logarithmic transformation of retinal thickness data results in a more normalized distribution of OCT data and allows for data analyses assessing proportionate changes in retinal thickness during follow-up. For analysis of grouped data, a logarithmic transformation of the OCT retinal thickness measurements (logOCT) provides several analytic advantages. Distributions of retinal thickness in groups of eyes with diabetic macular edema, and many other causes of macular thickening, tend to be skewed to the right; the logOCT transformation tends to normalize these distributions, which has value for statistical comparisons. For assessing whether the observed OCT change in a patient is real (and not due to testing variability), a 1-step log scale change exceeds the measurement error for all degrees of retinal thickness in current instruments. In addition, this log scale is similar to the logarithm of the minimum angle of resolution (logMAR) scale used for visual acuity. Steps on the log scale for change in thickness seem to be better related to clinical importance than the actual change in microns because each step on the log scale is the same proportionate change in thickness, with a 3-step change equaling a halving or doubling of thickness, regardless of the baseline value. Transformation of OCT retinal thickness data to logOCT may assist in the assessment of clinically meaningful changes in retinal thickness just as use of the logMAR scale has helped to assess clinically meaningful changes in visual acuity.


Impact of Female Sex on Clinical Outcomes in the FIRE AND ICE Trial of Catheter Ablation for Atrial Fibrillation.
Data on predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation (AF) are limited. We sought to assess the association of baseline covariates with clinical outcomes in the 750 patients with drug-refractory paroxysmal AF enrolled in FIRE AND ICE. In a 2-part analysis, univariate and multivariable Cox regression models were first used to identify baseline patient characteristics predictive of catheter ablation efficacy determined by the clinical end points of (1) atrial arrhythmia recurrence (primary efficacy failure), (2) cardiovascular rehospitalization, and (3) repeat ablation. Propensity score stratification methods were then used to account for differences in baseline characteristics between sexes. Female sex (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.08-1.73; P=0.010) and prior direct current cardioversion (HR, 1.40; 95% CI, 1.07-1.82; P=0.013) were independently associated with atrial arrhythmia recurrence. Female sex (HR, 1.36; 95% CI, 1.02-1.80; P=0.035) and hypertension (HR, 1.48; 95% CI, 1.09-2.00; P=0.013) independently predicted cardiovascular rehospitalization. A longer history of AF (HR, 1.03; 95% CI, 1.00-1.06; P=0.039) increased the rate of repeat ablation. Women continued to have higher rates of primary efficacy failure and cardiovascular rehospitalization after propensity score adjustment, with adjusted HRs of 1.51 (95% CI, 1.16-2.18; P<0.05) and 1.40 (95% CI, 1.15-2.17; P<0.05), respectively. After catheter ablation of paroxysmal AF, female sex was associated with an almost 40% increase in the risks of primary efficacy failure and cardiovascular rehospitalization. Primary efficacy failure was also adversely impacted by a history of direct current cardioversion, whereas hypertension had a negative impact on cardiovascular rehospitalization. History of AF was the only predictor of repeat ablation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01490814.


Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death.
Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li-Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein. Further, p53(A347D) cannot bind or transactivate the majority of canonical p53 target genes. Isogenic cell lines harboring either p53(A347D) or no p53 yield comparable tumorigenic properties, yet p53(A347D) displays remarkable neomorphic activities. Cells bearing p53(A347D) possess a distinct transcriptional profile and undergo metabolic reprogramming. Further, p53(A347D) induces striking mitochondrial network aberration and associates with mitochondria to drive apoptotic cell death upon topoisomerase II inhibition in the absence of transcription. Thus, dimer-forming p53 demonstrates both loss-of-function (LOF) and gain-of-function (GOF) properties compared with the wild-type form of the protein. A mutant p53 (A347D), which can only form dimers, is associated with increased cancer susceptibility in LFS individuals. We found that this mutant wields a double-edged sword, driving tumorigenesis through LOF while gaining enhanced apoptogenic activity as a new GOF, thereby yielding a potential vulnerability to select therapeutic approaches. See related commentary by Stieg et al., p. 1046. See related article by Gencel-Augusto et al., p. 1230. This article is highlighted in the In This Issue feature, p. 1027.


Low-cost and portable colorimetric platform for simultaneous detection of Fe, methanol, and total phenols in wine.
A multi-channel colorimetric device was developed for the low-cost and simultaneous determination of three important parameters in wine safety and quality- total iron (Fe), methanol (MeOH), and total phenols. The detection was performed by assembling light-dependent resistors and light-emitting diodes in a 3D printed chamber, which measured colorimetric signals horizontally transmitting through the microwells of an 8-well strip. This device demonstrated linear relationships (R2 greater than 0.99) for all analytes with detection limits of 0.04 mg/L, 2.26 mg/L, and 3.40 mg/L for Fe, MeOH, and total phenols, respectively. Wine sample measurements showed that the multi-channel device was as accurate as the professional spectrophotometer and could simultaneously provide the three target concentrations to facilitate the analysis. With the merits of low fabrication cost and ease of use, this device could be used as a general platform for multiple-target detection, demonstrating great potential for application in food analysis.


An intraventricular arachnoid cyst.
The computed tomographic appearance and the differential diagnosis in a case of unusual congenital intraventricular arachnoid cyst are presented.