The negative impact of T cell-mediated rejection on renal allograft survival in the modern era.
The prevalence and long-term impact of T cell-mediated rejection (TCMR) is poorly defined in the modern era of tacrolimus/mycophenolate-based maintenance therapy. This observational study evaluated 775 kidney transplant recipients with serial histology and correlated TCMR events with the risk of graft loss. After a ~30% incidence of a first Banff Borderline or greater TCMR detected on for-cause (17%) or surveillance (13%) biopsies, persistent (37.4%) or subsequent (26.3%) TCMR occurred in 64% of recipients on follow-up biopsies. Alloimmune risk categories based on the HLA-DR/DQ single molecule eplet molecular mismatch correlated with the number of TCMR events (p = .002) and Banff TCMR grade (p = .007). Both a first and second TCMR event correlated with death-censored and all-cause graft loss when adjusted for baseline covariates and other significant time-dependent covariates such as DGF and ABMR. Therefore, a substantial portion of kidney transplant recipients, especially those with intermediate and high HLA-DR/DQ molecular mismatch scores, remain under-immunosuppressed, which in turn identifies the need for novel agents that can more effectively prevent or treat TCMR.


Historical Aspects of Equine Embryo Transfer.
Early embryo transfer in equids was undertaken simultaneously in the early 1970s in Cambridge, England, and Kyoto, Japan. Both groups achieved limited success when flushing the uterine horn ipsilateral to the side of ovulation but the rates improved markedly when the whole uterus was flushed on realization of the continued movement of the embryo throughout the uterine lumen after day 6. Initial transfers of embryos to recipient mares were carried out surgically, but nonsurgical transfer via the cervix has been used subsequently with increasing success, culminating in pregnancy rates of 75%-90% today. Experimental use of embryo transfer in horses and donkeys demonstrated the unique ability of equids to carry to term a full range of interspecies hybrid conceptuses and extraspecies pregnancies created by embryo transfer. Furthermore, splitting of day 4-8 cell embryos and day 6 compact morulae allowed the creation of genetically identical twin foals. But despite these and other significant advances over the past 45 years, a persisting limitation is the relatively low embryo recovery rates from donor mares treated with exogenous gonadotropins in attempts to induce them to superovulate. This is due to the toughness of the ovarian tunica albuginea which forces ovulation through the ventrally situated ovulation fossa where multiple follicles compete with each other and luteinize before they can ovulate properly.


Construction of a new high-copy number shuttle vector of Bacillus thuringiensis.
Construction and characterization of a new cloning shuttle vector for gene transfer and expression in Bacillus thuringiensis. A novel short and high-copy number shuttle vector called pHBLBIV, was constructed for gene transfer and expression in Bacillus thuringiensis. A 1.6-kbp replicon of a relatively high-copy number endogenous plasmid of a selected B. thuringiensis strain was ligated to Escherichia coli pUC18 replicon containing the ampicillin and the erythromycin resistance genes used for the selection of respectively E. coli and B. thuringiensis transformants. The constructed vector was shown to have a high copy number compared with the conventional B. thuringiensis vectors, and used successfully for the transfer of vegetative insecticidal protein-encoding gene (vip) in between B. thuringiensis strains. A new shuttle vector of B. thuringiensis-E. coli named pHBLBIV was constructed. It was characterized by its high copy number, small size and segregational stability. This vector was successfully used for vip gene cloning and transfer in B. thuringiensis. A novel shuttle vector has been constructed, which has demonstrated potential for the cloning and expression of genes in B. thuringiensis.


Sparse and low-rank decomposition of the time-frequency representation for bearing fault diagnosis under variable speed conditions.
Rolling element bearings typically operate with fluctuating speed, leading to nonstationary vibrations. Moreover, bearings vibration signals are frequently hidden by strong distributions, making it difficult to detect clear bearing fault characteristics for diagnosis. Under this circumstance, the key issue is effectively extracting the transient features from the background interference and highlighting the time-varying fault characteristics. To address this issue, a sparse and low-rank decomposition approach is proposed. In this study, the sparsity of the variable defective characteristics and low-rank of background interference is revealed and exploited for bearing fault detection. Firstly, the time-frequency representation (TFR) of the envelope of measured signal is generated by the time-frequency transform. Then, a sparse and low-rank decomposition model is established based on robust principal component analysis (RPCA) to denoise the measured time-frequency representation and gain the sparse component. Finally, a time-frequency reassignment strategy is utilized to further enhance the capability of detecting the faulty characteristics in the decomposed sparse TFR. The synthetic and actual signals are evaluated to illustrate the reliability and efficacy of the proposed technique. The superiority is also validated by comparisons with STFT, synchrosqueezing transform (SST), ridge extraction method, and scaling-basis chirplet transform (SBCT).


Fate of Vibrio parahaemolyticus on shrimp after acidic electrolyzed water treatment.
The objective of this study was to investigate the fate of Vibrio parahaemolyticus on shrimp after acidic electrolyzed water (AEW) treatment during storage. Shrimp, inoculated with a cocktail of four strains of V. parahaemolyticus, were stored at different temperatures (4-30 °C) after AEW treatment. Experimental data were fitted to modified Gompertz and Log-linear models. The fate of V. parahaemolyticus was determined based on the growth and survival kinetics parameters (lag time, λ; the maximum growth rate, μmax; the maximum growth concentration, D; the inactivation value, K) depending on the respective storage conditions. Moreover, real-time PCR was employed to study the population dynamics of this pathogen during the refrigeration temperature storage (10, 7, 4 °C). The results showed that AEW treatment could markedly (p<0.05) decrease the growth rate (μmax) and extend the lag time (λ) during the post-treatment storage at 30, 25, 20 and 15 °C, while it did not present a capability to lower the maximum growth concentration (D). AEW treatment increased the sensitivity of V. parahaemolyticus to refrigeration temperatures, indicated by a higher (p<0.05) inactivation value (K) of V. parahaemolyticus, especially for 10 °C storage. The results also revealed that AEW treatment could completely suppress the proliferation of V. parahaemolyticus in combination with refrigeration temperature. Based on above analysis, the present study demonstrates the potential of AEW in growth inhibition or death acceleration of V. parahaemolyticus on seafood, hence to greatly reduce the risk of illness caused by this pathogen during post-treatment storage.


Light microscopic and ultrastructural localization of immunoreactive substance P in the dorsal horn of monkey spinal cord.
Light- and electron-microscopic localization of substance P in the monkey spinal cord was studied by the peroxidase anti-peroxidase technique with the particular aim of examining types of interactions made by substance P-positive boutons with other neuronal elements in the dorsal horn. By light-microscopy dense labeling for immunoreactive substance P was found in laminae I, II (outer zone) and V (lateral region), consistent with findings in other mammalian species. By electron-microscopy, substance P-positive staining was mostly in unmyelinated and in some thinly myelinated small diameter fibers. Substance P-positive terminals contained both large granular vesicles (80-120 nm diameter), which were filled with reaction product, and clear round vesicles (40-60 nm). Substance P-positive large granular vesicles were sometimes observed near presynaptic sites and in contact with dense projection there. Immunoreactive substance P boutons were small to large in size (1-4 micron), formed synapses with somata and large dendrites and were the central axons of synaptic glomeruli where they were in synaptic contact with numerous small dendrites and spines. Substance P-labeled axons frequently formed synapses with dorsal horn neurons which were also postsynaptic to other types of axons. Substance P-positive profiles participated in numerous puncta adhaerentia with unlabeled cell bodies, dendrites and axons. Only rarely, some suggestive evidence was obtained indicating that axons might synapse onto substance P-containing boutons. Biochemical analysis of monkey spinal cord tissue extracts, undertaken to characterize more precisely the immunoreactive substances, indicated that only substance P and its oxide derivative were detected with the antiserum used in the immunocytochemistry. These morphological findings show that substance P is contained within a class of axon terminals, many of which have been shown previously in the monkey to originate from the dorsal root. The results suggest that modulation of substance P primary afferents terminating in the outer dorsal laminae of the monkey spinal cord occurs in part via axonal inputs onto dorsal horn neurons postsynaptic to the primary afferent.


Acute brain slice elastic modulus decreases over time.
A common benchmark in the brain tissue mechanics literature is that the properties of acute brain slices should be measured within 8 h of the experimental animal being sacrificed. The core assumption is that-since there is no substantial protein degradation during this time-there will be no change to elastic modulus. This assumption overlooks the possibility of other effects (such as osmotic swelling) that may influence the mechanical properties of the tissue. To achieve consistent and accurate analysis of brain mechanics, it is important to account for or mitigate these effects. Using atomic force microscopy (AFM), tissue hydration and volume measurements, we find that acute brain slices in oxygenated artificial cerebrospinal fluid (aCSF) with a standard osmolarity of 300 mOsm/l experience rapid swelling, softening, and increases in hydration within the first 2 hours after slicing. Reductions in elastic modulus can be partly mitigated by addition of chondroitinase ABC enzyme (CHABC). Increasing aCSF osmolarity to 400 mOsm/l does not prevent softening but may hasten equilibration of samples to a point where measurements of relative elastic modulus are consistent across experiments.


Increased large arterial stiffness and impaired acetylcholine induced skin vasodilatation in women with previous gestational diabetes mellitus.
Gestational diabetes is associated with increased risk of developing noninsulin-dependent diabetes (NIDDM) later in life. By the time that a diagnosis of NIDDM is established, functional disturbances in the vascular system may be observed. This study was planned to assess macro- and microvascular function in nonpregnant women without signs of diabetes two to four years after a pregnancy complicated with gestational diabetes. Cross-sectional study. Vascular research laboratory in the obstetric unit of a university hospital. Seventeen nonpregnant, healthy women with a history of gestational diabetes and 20 nonpregnant control women of similar age without previous diabetes. For quantification of the mechanical properties in large arterial vessels the wall movements of the abdominal aorta and left common carotid artery were recorded with an ultrasonic tracking system. Microvascular perfusion in the skin of the hand and foot was recorded by a laser Doppler technique to assess the vasodilatory response induced by transcutaneous acetylcholine. Women in the gestational diabetes group showed evidence of increased wall stiffness in the common carotid artery and a lower maximum incremental velocity of the pulsatile vessel diameter change in both aorta and carotid artery compared with controls. Acetylcholine induced vasodilatation in both hand and foot was lower in women with previous gestational diabetes compared with controls. Abnormal vascular function was found in asymptomatic women with a history of gestational diabetes. It is speculated that these abnormalities might be early evidence of vascular complications associated with subsequent NIDDM.


Incretin effect due to increased secretion and decreased clearance of insulin in normal humans.
To assess the contribution of changes in insulin secretion and clearance to the incretin effect (greater insulinemia after oral than after intravenous glucose), 10 healthy subjects were studied after oral glucose (1 g/kg body wt) and again when glucose was infused intravenously at rates to match arterialized plasma glucose concentrations after oral glucose. Although basal and integrated plasma glucose did not differ between oral and intravenous glucose, integrated responses of insulin (3.3 +/- 0.5 vs. 1.8 +/- 0.4 mU ml-1.240 min-1, P less than .001), C-peptide (456.5 +/- 58.5 vs. 327.9 +/- 46.3 ng.ml-1.240 min-1, P = .002), gastric inhibitory polypeptide, (16.8 +/- 3.5 vs. -2.8 +/- 1.0 micrograms.ml-1.240 min-1, P less than .001), and insulin secretion (6.6 +/- 1.1 vs. 4.7 +/- 0.7 U.240 min-1, P = .003) were greater with oral than intravenous glucose. However, insulin clearance, whether calculated as the molar ratio of integrated C-peptide to integrated insulin responses (6.9 +/- 0.7 vs. 14.2 +/- 3.8, P = .005) or from the formula insulin clearance equals insulin secretion divided by integrated insulin responses (1.1 +/- 0.2 vs. 2.5 +/- 0.7 L.min-1.m-2, respectively, P = .002), was less for oral than for intravenous glucose. Therefore, the incretin effect is mediated both by increased secretion and decreased clearance of insulin.


Regional blood flow in resting and stimulated sciatic nerve of diabetic rats.
The role of ischemia in the pathogenesis of diabetic peripheral neuropathy remains uncertain. We used the distribution of [14C]butanol to measure resting regional sciatic nerve blood flow in normal, anesthetized rats and in rats with acute experimental diabetes from streptozotocin administration. Regional flows in hind limb biceps femoris muscle and skin were simultaneously measured. In additional diabetic rats, these blood flows were compared in both limbs after proximal electrical stimulation of one sciatic trunk (10 shocks/s) for 15 min. One month after streptozotocin administration, 8 of 11 test rats were hyperglycemic. Resting nerve blood flow in the hyperglycemic rats--5.6 +/- 3.07 ml.min-1.100 g-1--was significantly less than that in the controls (9.4 +/- 3.9 ml.min-1.100 g-1, P = 0.002). Muscle blood flow was normal and skin blood flow decreased in these rats. Calculated tissue vascular resistances were elevated in all three tissues. Stimulation of one sciatic trunk in five other diabetic rats resulted in a stimulated nerve blood flow of 15.7 +/- 7.7 ml.min-1.100 g-1, and nerve blood flow in the resting control limb was 7.7 +/- 4.3 ml.min-1.100 g-1 (P = 0.009). Muscle blood flow increased approximately fourfold on the stimulated side but skin blood flow did not increase. Resting sciatic nerve blood flow is modestly decreased in acute streptozotocin-induced diabetes, but the neural blood vessels are still responsive to the increase in nerve metabolic activity associated with nerve stimulation.


The MC4 receptor agonist RO27-3225 inhibits NLRP1-dependent neuronal pyroptosis via the ASK1/JNK/p38 MAPK pathway in a mouse model of intracerebral haemorrhage.
Inflammasome-mediated pyroptosis is an important neuronal cell death mechanism. Previous studies reported that activation of melanocortin MC4 receptor exerted neuroprotection in several neurological diseases. Here, we have investigated the role of MC4 receptor activation with RO27-3225 in suppressing neuronal pyroptosis after experimental intracerebral haemorrhage (ICH) and the underlying mechanism. One hundred and sixty-nine male CD1 mice were used. ICH was induced by injection of bacterial collagenase into the right-side basal ganglia. RO27-3225, a selective agonist of MC4 receptor, was injected intraperitoneally at 1 hr after ICH. To elucidate the underlying mechanism, we used the specific MC4 receptor antagonist HS024 and NQDI-1, a specific inhibitor of the apoptosis signalling-regulating kinase 1 (ASK1). Neurological tests, Western blot, Fluoro-Jade C, TUNEL, and immunofluorescence staining were conducted. Expression of MC4 receptor and the NOD-like receptor family, pyrin domain containing 1 (NLRP1) inflammasome in brain were increased after ICH. RO27-3225 treatment decreased neuronal pyroptosis and neurobehavioural deficits at 24 and 72 hr after ICH. RO27-3225 reduced the expression of p-ASK1, p-JNK, p-p38 MAPK, NLRP1 inflammasome, cleaved caspase-1, and IL-1β after ICH. HS024 pretreatment prevented the effects of RO27-3225. Similar to RO27-3225, NQDI-1 alone improved neurological functions and down-regulated ASK1/JNK/p38MAPK expression after ICH. RO27-3225 suppressed NLRP1-dependent neuronal pyroptosis and improved neurological function, possibly mediated by activation of MC4 receptor and inhibition of ASK1/JNK/p38 MAPK signalling pathways, after experimental ICH in mice. The MC4 receptor may be a promising therapeutic target for the management of ICH.


Correction: Bio-catalytic nanocompartments for in situ production of glucose-6-phosphate.
Correction for 'Bio-catalytic nanocompartments for in situ production of glucose-6-phosphate' by M. Lomora et al., Chem. Commun., 2017, 53, 10148-10151.


Recent Advances in Severe Asthma: From Phenotypes to Personalized Medicine.
This review focuses on recent clinical and translational discoveries in severe and uncontrolled asthma that now enable phenotyping and personalized therapies in these patients. Although asthma is common in both children and adults and typically responds to standard therapies, a subset of individuals with asthma experience severe and/or persistent symptoms despite appropriate therapies. Airflow obstruction leading to frequent symptoms requiring higher levels of controller therapy is the cardinal feature of severe asthma, but the underlying molecular mechanisms, or endotypes, are diverse and variable between individuals. Two major risk factors that contribute to severe asthma are genetics and environmental exposures that modulate immune responses, and although these often interact in complex manners that are not fully understood, certain endotypes converge in severe asthma. A number of studies have evaluated various features of patients with severe asthma and classified patients into phenotypes with clinical relevance. This phenotyping is now incorporated into clinical practice and can be used to guide advanced biological therapies that target specific molecules and inflammatory pathways that contribute to asthma pathogenesis.


Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation.
This study compared the efficacy and safety of sertraline to placebo in treating panic disorder. 178 out-patients with panic disorder who exhibited at least four panic attacks during the four weeks prior to screening and three during the two weeks of lead-in were randomly assigned to 12 weeks of double-blind treatment with sertraline (50, 100 or 200 mg) or placebo. Sertraline was superior to placebo in reducing the number of panic attacks, situational attacks, unexpected attacks, limited symptom attacks, and time spent worrying (all P < 0.01) and the Hamilton Anxiety Scale (P < 0.05), although Clinical Global Impression (Improvement) did not significantly differentiate groups at 12 weeks and at end-point. No serious adverse events were associated with sertraline. No dose relationship was found for adverse events; overall drop-out rates were not different for sertraline or placebo, although more sertraline-treated subjects discontinued for adverse events, typically early in the study. Only dry mouth and ejaculation failure (primarily ejaculation delay) were associated significantly with sertraline. Sertraline was effective and safe in reducing panic attacks. Higher doses were no more effective than the 50 mg dose.


The exploration of quantum dot-molecular beacon based MoS2 fluorescence probing for myeloma-related Mirnas detection.
Highly sensitive and reliable detection of multiple myeloma remains a major challenge in liquid biopsy. Herein, for the first time, quantum dot-molecular beacon (QD-MB) functionalized MoS2 (QD-MB @MoS2) fluorescent probes were designed for the dual detection of multiple myeloma (MM)-related miRNA-155 and miRNA-150. The results indicate that the two probes can effectively detect miRNA-155 and miRNA-150 simultaneously with satisfactory recovery rates, and the limit of detections (LODs) of miRNA-155 and miRNA-150 in human serum are low to 7.19 fM and 5.84 fM, respectively. These results indicate that our method is the most sensitive detection so far reported and that the designed fluorescent probes with signal amplification strategies can achieve highly sensitive detection of MM-related miRNAs for MM diagnosis.


The association between cigarette smoking and health care service utilization among middle-aged and elderly adults in China.
To assess the associations between tobacco use and health care service utilization in Chinese individuals aged more or equal to 40 years old. This research was a cross-sectional study using data from eight provinces in China, and the final sample consisted of 4,733 observations (4,749 participants) aged more or equal to 40 years old. The dependent variable was health care utilization measured by outpatient and inpatient service utilization. Descriptive statistics were used to summarize the socio-demographic characteristics of the sample according to smoking status. The association between tobacco use and health care service utilization was examined by an instrumental variable (IV) probit model. Of the respondents interviewed in 2020, 3,116 (65.84%) were never smokers, 654 (13.82%) were smokers with the smoking index (SI) <400, and 963(20.34%) were smokers with SI≥400. Smokers with SI <400 reported a 6.80% higher probability of using outpatient services. Smokers with SI <400 and SI≥400 reported a 3.10 and 4.20% higher average probability of using ≥3 outpatient visits than never smokers, respectively. Additionally, smokers with SI <400 and SI≥400 reported a 6.30 and 6.20% higher average probability of using inpatient services than those who had not smoked. Moreover, smokers with SI≥400 were more likely to have had ≥2 hospital visits than nonsmokers. Smokers make greater use of health care services. Control of smoking may ease the burden of related health care utilization.


The association between early-life gut microbiota and childhood respiratory diseases: a systematic review.
Data from animal models suggest a role of early-life gut microbiota in lung immune development, and in establishing susceptibility to respiratory infections and asthma in humans. This systematic review summarises the association between infant (ages 0-12 months) gut microbiota composition measured by genomic sequencing, and childhood (ages 0-18 years) respiratory diseases (ie, respiratory infections, wheezing, or asthma). Overall, there was evidence that low α-diversity and relative abundance of particular gut-commensal bacteria genera (Bifidobacterium, Faecalibacterium, Ruminococcus, and Roseburia) are associated with childhood respiratory diseases. However, results were inconsistent and studies had important limitations, including insufficient characterisation of bacterial taxa to species level, heterogeneous outcome definitions, residual confounding, and small sample sizes. Large longitudinal studies with stool sampling during the first month of life and shotgun metagenomic approaches to improve bacterial and fungal taxa resolution are needed. Standardising follow-up times and respiratory disease definitions and optimising causal statistical approaches might identify targets for primary prevention of childhood respiratory diseases.


A unification of mosaic structures in the human genome.
The human genome is a mosaic structure on many levels: there exist cytogenetic bands, GC composition bands (isochores) and clusters of broadly expressed genes. How might these inter-relate? It has been proposed that to optimize gene regulation, housekeeping genes should concentrate on transcriptionally competent chromosomal domains. Prior evidence suggests that regions of high GC and R bands are associated with such domains. Here we report that broadly expressed genes cluster in regions of high GC, and in R and lightest Giemsa bands. This is not only a confirmation of the adaptive hypothesis, but is also the first direct systematic evidence of a general interdependence of expression patterns with base composition and chromosome structure.


[The subfractional composition of the blood plasma in benign tumors and cancer of the breast based on the data from laser correlational spectroscopy].
LCS was performed in 35 patients with mammary cancer, 59 patients with benign breast tumours and 35 healthy people. 39 samples were taken from inhabitants of Odessa, 89 from St.-Petersburg. Differences were discovered between blood plasma spectra of Odessa and St.-Petersburg residents. Spectra of blood plasma in patients with mammary tumours differed from those of healthy people. LCS may be used for screening, for forming the groups of risk and for diagnosis of mammary gland tumours.


Both abundant and rare fungi colonizing Fagus sylvatica ectomycorrhizal root-tips shape associated bacterial communities.
Ectomycorrhizal fungi live in close association with their host plants and form complex interactions with bacterial/archaeal communities in soil. We investigated whether abundant or rare ectomycorrhizal fungi on root-tips of young beech trees (Fagus sylvatica) shape bacterial/archaeal communities. We sequenced 16S rRNA genes and fungal internal transcribed spacer regions of individual root-tips and used ecological networks to detect the tendency of certain assemblies of fungal and bacterial/archaeal taxa to inhabit the same root-tip (i.e. modularity). Individual ectomycorrhizal root-tips hosted distinct fungal communities associated with unique bacterial/archaeal communities. The structure of the fungal-bacterial/archaeal association was determined by both, dominant and rare fungi. Integrating our data in a conceptual framework suggests that the effect of rare fungi on the bacterial/archaeal communities of ectomycorrhizal root-tips contributes to assemblages of bacteria/archaea on root-tips. This highlights the potential impact of complex fine-scale interactions between root-tip associated fungi and other soil microorganisms for the ectomycorrhizal symbiosis.


Virtual non-contrast in second-generation, dual-energy computed tomography: reliability of attenuation values.
To evaluate the reliability of attenuation values in virtual non-contrast images (VNC) reconstructed from contrast-enhanced, dual-energy scans performed on a second-generation dual-energy CT scanner, compared to single-energy, non-contrast images (TNC). Sixteen phantoms containing a mixture of contrast agent and water at different attenuations (0-1400 HU) were investigated on a Definition Flash-CT scanner using a single-energy scan at 120 kV and a DE-CT protocol (100 kV/SN140 kV). For clinical assessment, 86 patients who received a dual-phase CT, containing an unenhanced single-energy scan at 120 kV and a contrast enhanced (110 ml Iomeron 400 mg/ml; 4 ml/s) DE-CT (100 kV/SN140 kV) in an arterial (n=43) or a venous phase, were retrospectively analyzed. Mean attenuation was measured within regions of interest of the phantoms and in different tissue types of the patients within the corresponding VNC and TNC images. Paired t-tests and Pearson correlation were used for statistical analysis. For all phantoms, mean attenuation in VNC was 5.3±18.4 HU, with respect to water. In 86 patients overall, 2637 regions were measured in TNC and VNC images, with a mean difference between TNC and VNC of -3.6±8.3 HU. In 91.5% (n=2412) of all cases, absolute differences between TNC and VNC were under 15HU, and, in 75.3% (n=1986), differences were under 10 HU. Second-generation dual-energy CT based VNC images provide attenuation values close to those of TNC. To avoid possible outliers multiple measurements are recommended especially for measurements in the spleen, the mesenteric fat, and the aorta.


NaCl sealing Strategy-Assisted synthesis CoO-Co heterojunctions as efficient oxygen electrocatalysts for Zn air batteries.
Developing highly efficient, low-cost, and stable bifunctional oxygen electrocatalysts is essential for the wide popularization of rechargeable Zn-air batteries. Combining zero-dimensional metal nanoparticles with two-dimensional metal oxide nanosheets is an appealing strategy to balance performance and cost. However, the precise construction of these composites remains a great challenge, and their interaction mechanisms lack thorough study. Herein, a cobalt-oxide-based bifunctional oxygen electrocatalyst comprising a rich Co-CoO heterointerface (CoO/Co@NG) was synthesized via a NaCl sealing-assisted pyrolysis strategy. The NaCl crystals played the role of a closed nanoreactor, which facilitated the formation of a CoO-Co heterojunction. Experimental results and theoretical calculations confirmed that the ingeniously constructed heterojunction expedited the oxygen reduction reaction and oxygen evolution reaction kinetics, which is superior to Pt/C. When serving as the air electrode in an assembled liquid-state Zn-air battery, the battery shows high power density (215 mW cm-2), specific capacity (710 mAh gzn-1), and outstanding durability (720 h at 10 mA cm-2). This work provides an innovative avenue to design high-performance heterojunction electrocatalysts for perdurable Zn-air batteries.


Decrease in circulating immune complexes during hemodialysis.
Raji cell radioimmunoassay and Clq solid phase radioimmunoassay were used to determine serially circulating immune complexes in a patient with rapidly progressive glomerulonephritis who was receiving hemodialysis therapy. Initiation of hemodialysis was associated with a significant decrease in detectable immune complexes which, in turn, was associated with improvement and stabilization of renal function. We suggest that hemodialysis may remove immune complexes from the circulation and that it could be of therapeutic benefit in selected patients with presumed immune complex-mediated glomerulonephritis.


Controlled release of a contraceptive steroid from biodegradable and injectable gel formulations: in vitro evaluation.
The purpose of this study was to investigate the effects of formulation factors including varying wax concentration, drug loading and drug particle size, on drug release characteristics from both pure oil and gel formulations prepared with a combination of derivatized vegetable oil (Labrafil 1944 CS) and glyceryl palmitostearate (Precirol ATO 5), using levonorgestrel as a model drug. The effects of varying drug loadings, different drug particle sizes, and wax (Precirol) concentrations on in-vitro drug release rates were evaluated, and the mechanisms of drug release from the gels were determined. Zero-order drug release rates from the 10% Precirol gel formulations containing 0.25, 0.50 and 2.00% w/v drug loadings were lower than those observed for oil formulations containing identical drug loadings. Higher zero-order release rates were observed from formulations containing smaller drug particles suspended in both oil and gel formulations. The mechanism of drug release from gels containing less than 0.25% w/w drug was diffusion-controlled. Increasing the wax concentrations in the gels from 5% w/w to 20% w/w significantly decreased the diffusivity of the drug through the gel formulations and markedly increased the force required to inject the gels from two different sizes of needles. This study shows how modification of the physicochemical properties of the gel formulations by changing the drug particle size, wax concentration and drug loading, affects drug release characteristics from the system.


A novel ETA antagonist (BQ-123) inhibits endothelin-1-induced phosphoinositide breakdown and DNA synthesis in rat vascular smooth muscle cells.
The effects of a novel cyclic pentapeptide (BQ-123), an endothelin (ET) antagonist selective for the ETA receptor subtype, on phosphoinositide breakdown and DNA synthesis stimulated by ET-1 were studied in cultured rat vascular smooth muscle cells (VSMC). BQ-123 competitively inhibited the binding of [125I]ET-1 to VSMC with the apparent Ki of 4 x 10(-9) M. BQ-123 dose-dependently inhibited formation of inositol-1,4,5-trisphosphate and [3H]thymidine uptake stimulated by ET-1. These data suggest that the ET-1-induced DNA synthesis in VSMC is mainly mediated by ETA receptor subtype.


Effect of Crisis Response Planning on Patient Mood and Clinician Decision Making: A Clinical Trial With Suicidal U.S. Soldiers.
The study examined the immediate effect of crisis interventions on the emotional state of acutely suicidal soldiers and clinician decision making. Soldiers (N=97) presenting to a military emergency department or behavioral health clinic were randomly assigned to receive a contract for safety (N=32), standard crisis response plan (S-CRP; N=32), or enhanced crisis response plan (E-CRP; N=33). Soldiers completed self-report scales before and after the intervention. Clinicians blinded to treatment group assignment rated participants' suicide risk level and made a decision about inpatient psychiatric admission. Larger reductions in negative emotional states occurred in S-CRP and E-CRP. Larger increases in positive emotional states occurred in E-CRP. Clinician suicide risk ratings did not differ across treatment groups. Participants in E-CRP were less likely to be psychiatrically admitted. The CRP immediately reduces negative emotional states among acutely suicidal soldiers. Discussing a patient's reasons for living during a CRP also reduces the likelihood of inpatient psychiatric admission.


The Infrared Thermography Toolbox: An Open-access Semi-automated Segmentation Tool for Extracting Skin Temperatures in the Thoracic Region including Supraclavicular Brown Adipose Tissue.
Infrared thermography (IRT) is widely used to assess skin temperature in response to physiological changes. Yet, it remains challenging to standardize skin temperature measurements over repeated datasets. We developed an open-access semi-automated segmentation tool (the IRT-toolbox) for measuring skin temperatures in the thoracic area to estimate supraclavicular brown adipose tissue (scBAT) activity, and compared it to manual segmentations. The IRT-toolbox, designed in Python, consisted of image pre-alignment and non-rigid image registration. The toolbox was tested using datasets of 10 individuals (BMI = 22.1 ± 2.1 kg/m2, age = 22.0 ± 3.7 years) who underwent two cooling procedures, yielding four images per individual. Regions of interest (ROIs) were delineated by two raters in the scBAT and deltoid areas on baseline images. The toolbox enabled direct transfer of baseline ROIs to the registered follow-up images. For comparison, both raters also manually drew ROIs in all follow-up images. Spatial ROI overlap between methods and raters was determined using the Dice coefficient. Mean bias and 95% limits of agreement in mean skin temperature between methods and raters were assessed using Bland-Altman analyses. ROI delineation time was four times faster with the IRT-toolbox (01:04 min) than with manual delineations (04:12 min). In both anatomical areas, there was a large variability in ROI placement between methods. Yet, relatively small skin temperature differences were found between methods (scBAT: 0.10 °C, 95%LoA[-0.13 to 0.33 °C] and deltoid: 0.05 °C, 95%LoA[-0.46 to 0.55 °C]). The variability in skin temperature between raters was comparable between methods. The IRT-toolbox enables faster ROI delineations, while maintaining inter-user reliability compared to manual delineations. (Trial registration number (ClinicalTrials.gov): NCT04406922, [May 29, 2020]).


Characterization of paracetamol UDP-glucuronosyltransferase activity in human liver microsomes.
A specific high performance liquid chromatographic assay has been developed for the measurement of paracetamol glucuronide formation by the microsomal fraction of human liver. The procedure has been used to characterize paracetamol glucuronidation kinetics in human livers microsomes and to assess the substrate specificity of the paracetamol UDP-glucuronosyltransferase (UDPGT) activity. Paracetamol glucuronidation followed Michaelis-Menten kinetics, suggesting the involvement of a single form of UDPGT, or possibly two or more forms of UDPGT with similar affinities for paracetamol, in this reaction. Mean apparent Km and Vmax values were 7.37 +/- 0.99 mM and 4.76 +/- 1.35 nmol/min/mg, respectively. Addition of the non-ionic detergent Brij 58 to microsomal incubations resulted in approximately 50% activation of microsomal paracetamol UDPGT-activity. This contrasts to the approximately three-fold activation of 4-methylumbelliferone, morphine and 4-nitrophenol glucuronidation observed following Brij 58 treatment of human liver microsomes. The glucuronidated xenobiotics chloramphenicol, digitoxigenin monodigitoxoside, 4-hydroxybiphenyl, 4-methylumbelliferone, morphine, 1-naphthol and 4-nitrophenol were screened for inhibitory effects on paracetamol glucuronidation. Of these compounds, only digitoxigenin monodigitoxoside and 1-naphthol were found to cause significant inhibition of paracetamol UDPGT activity. Along with the results of previous studies of the kinetics and inhibitor profile of human liver glucuronidation reactions (Miners et al., Biochem Pharmacol 37: 665-671, 1988 and 37: 2839-2845, 1988), these data indicate that the model glucuronidated substrates paracetamol, morphine and 4-methyllumbelliferone may be used to differentiate at least four human liver UDPGT isozyme activities.


New boundaries of liver imaging: from morphology to function.
From an invisible organ to one of the most explored non-invasively, the liver is, today, one of the cornerstones for current cross-sectional imaging techniques and minimally invasive procedures. After the achievements of US, CT and, most recently, MRI in providing highly accurate morphological and structural information about the organ, a significant scientific development has gained momentum for the last decades, coupling morphology to liver function and contributing far most to what we know today as precision medicine. In fact, dedicated tailor-made investigations are now possible in order to detect and, most of all, quantify physiopathological processes with unprecedented certitude. It is the intention of this review to provide a better insight to the reader of several functional imaging techniques applied to liver imaging. Contrast enhanced imaging, diffusion weighted imaging, elastography, spectral computed tomography and fat and iron assessment techniques are commonly performed clinically. Diffusion kurtosis imaging, magnetic resonance spectroscopy, T1 relaxometry and radiomics remain largely limited to advanced clinical research. Each of them has its own value and place on the diagnostic armamentarium and provide unique qualitative and quantitative information regarding the pathophysiology of diseases, contributing at a large scale to model therapeutic decisions and patient follow-up. Therefore, state-of-the-art liver imaging acts today as a non-invasive surrogate biomarker of many focal and diffuse liver diseases.


The meaning of wild: Genetic and adaptive consequences from large-scale releases of domestic mallards.
The translocation of individuals around the world is leading to rising incidences of anthropogenic hybridization, particularly between domestic and wild congeners. We apply a landscape genomics approach for thousands of mallard (Anas platyrhynchos) samples across continental and island populations to determine the result of over a century of supplementation practices. We establish that a single domestic game-farm mallard breed is the source for contemporary release programs in Eurasia and North America, as well as for established feral populations in New Zealand and Hawaii. In particular, we identify central Europe and eastern North America as epicenters of ongoing anthropogenic hybridization, and conclude that the release of game-farm mallards continues to affect the genetic integrity of wild mallards. Conversely, self-sustaining feral populations in New Zealand and Hawaii not only show strong differentiation from their original stock, but also signatures of local adaptation occurring in less than a half-century since game-farm mallard releases have ceased. We conclude that 'wild' is not singular, and that even feral populations are capable of responding to natural processes. Although considered paradoxical to biological conservation, understanding the capacity for wildness among feral and feral admixed populations in human landscapes is critical as such interactions increase in the Anthropocene.


Phenotypic, chemical component and molecular assessment of genetic diversity and population structure of Morinda officinalis germplasm.
Morinda officinalis How (MO) is a perennial herb distributed in tropical and subtropical regions, which known as one of the "Four Southern Herbal Medicines". The extent of genetic variability and the population structure of MO are presently little understood. Here, nine morphological traits, six chemical components and Single nucleotide polymorphism (SNP) markers were used in integrative research of MO germplasm variation among 88 individuals collected from ten populations across four geographical provinces of China. Both phenotype and chemical composition have significant genetic variation, and there is a certain correlation between them such as root diameter and the nystose content, as well as geographical distribution. The principal component analysis (PCA) showed the leaf length, leaf width, nystose, 1F-furanosaccharide nystose, and the section color were the major contributors to diversity. The cluster analysis based on phenotypic and oligosaccharide data distinguished three significant groups, which was consistent with the result of a corresponding analysis with 228,615 SNP markers, and importantly, they all showed a significant correlation with geographical origin. However, there was little similarity between two cluster results. The Shannon's information index (I) varied from 0.17 to 0.53 with a mean of 0.37, suggesting a high level of genetic diversity in MO populations, which mainly existed among individuals within populations, accounting for 99.66% of the total according to the analysis of molecular variance (AMOVA) results. Each population also maintains the connection because of certain gene communication, so that the genetic differentiation between populations was not very significant. The STRUCTURE software was used to analyse the population structure and the result showed that 88 accessions were clustered into three groups, and 67% of them were pure type, which was also confirmed through PCA. The comprehensive study of phenotypic, chemical and molecular markers will provide valuable information for future breeding plans and understanding the phylogenetic relationship of MO population.


Stimulation of SV40 DNA replication by the human c-myc enhancer.
In earlier studies we had shown that a transcriptional enhancer sequence exists about 2 kb upstream of the human c-myc gene. The core sequence necessary for enhancer activity was defined therein as a 21 bp nucleotide element, which also showed autonomous replicating activity [EMBO J. (1988) 7, 3135-3142; EMBO J. (1989) 8, 4273-4279]. Recently, several reports have substantiated the notion that transcription and replication can be concertedly regulated in a larger number of cases than expected. In this report, we took the simian virus 40 (SV 40) ori/promoter as a model system. The SV40 enhancer is known to enhance transcription from its ori/promoter, but to reduce its replication (probably due to a negative feedback). The SV40 enhancer was replaced by the c-myc enhancer core in order to see its effect upon SV40 DNA replication and transcription. The results showed that besides stimulating transcription, the c-myc enhancer promoted SV40 DNA replication in monkey CosI cells. Stimulation was only observed when the c-myc enhancer was inserted in the 'up-to-down' orientation to the SV40 promoter. The promoting function of the c-myc enhancer on DNA replication correlated with the transcriptional activation function, as determined by systematic point mutations introduced within the 21 bp core sequence.


The Social Factors Influencing Cover Crop Adoption in the Midwest: A Controlled Comparison.
Increased funding and resources have become available in recent years for agricultural producers to plant cover crops to improve soil health and prevent nutrient loss and erosion; however, cover crop adoption remains relatively low and has been uneven across different Midwestern counties. This study employed a controlled comparison method to investigate the social factors affecting cover crop adoption in Iowa, Illinois, and Indiana. In each state, the authors compared pairs of neighboring counties, where one county was a relatively higher adopter and the other was a lower adopter of cover crops, while controlling for variations in climate conditions. Results show that there were multiple factors explaining the difference in cover crop adoption among county pairs. Social factors included attitudes toward cover crops; conservation agency influence; presence of cover crop experts, advocates, and/or entrepreneurs; and collaboration between agencies and the private sector. Other important factors included topography, cattle raising, organic production, and local incentive-based programs. Among these, collaborations between agencies and the private sector played the most important role in explaining why some counties had higher rates of cover crop adoption compared to their neighbors.


Mystery of the lost gallstone-Part 1.
If gallbladder perforation occurs during laparoscopic cholecystectomy, every spilled gallstone should be retrieved to minimize possible late gallstone-related septic complications.


Determination of creatine and phosphocreatine in muscle biopsy samples by capillary electrophoresis with contactless conductivity detection.
A capillary electrophoresis method with contactless conductivity detection was evaluated as a new approach for quantification of creatine and phosphocreatine in human quadriceps femoris biopsy samples. The running buffers employed consisted of 1 M acetic acid at a pH of 2.3 for the determination of creatine and 50 mM 3-(N-morpholino)propanesulfonic acid/30 mM histidine at a pH of 6.4 for the determination of phosphocreatine in the centrifuged muscle extracts. The limits of detection for creatine and phosphocreatine were found to be 2.5 and 1.0 μM, respectively. Creatine and phosphocreatine were determined in six human muscle biopsy samples and the results were found comparable to those of a standard enzymatic assay. The procedures developed for creatine and phosphocreatine also allow the determination of creatinine as well as adenosine diphosphate and adenosine triphosphate.


Comparison of the Clinical Manifestations between Acute Vogt-Koyanagi-Harada Disease and Acute Bilateral Central Serous Chorioretinopathy.
To compare clinical, angiographic, and optical coherence tomographic characteristics between eyes with acute Vogt-Koyanagi-Harada (VKH) disease and eyes with acute bilateral central serous chorioretinopathy (CSC), and to demonstrate distinguishing features between the two diseases in confusing cases. The medical records of 35 patients with VKH disease and 25 patients with bilateral CSC were retrospectively reviewed. Characteristics according to slit-lamp biomicroscopy, ophthalmoscopy, fundus photography, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography were compared between the two diseases. Five of 35 patients (10 of 70 eyes, 14.3%) with VKH disease were initially misdiagnosed as CSC patients, and six of 25 patients (12 of 50 eyes, 24%) with bilateral CSC were initially misdiagnosed as patients with VKH disease. Pigment epithelial detachment in CSC and optic disc hyperemia in VKH disease show the highest positive predictive values of 100% for each disease. Optic disc hyperemia in VKH disease and pigment epithelial detachment in bilateral CSC are the most specific clinical manifestations of each disease at initial patient presentation.


Textural characterization of media composed of compacted pieces of cardboard and polyethylene using a gas tracer method.
The aim of this work is the experimental determination of effective transport properties of porous media consisting of compacted pieces of cardboard and polyethylene (PE). The proposed method itself is more general and can be applied to many different materials and contexts. Three major transport properties were determined: porosity, tortuosity factor and permeability. Three parameters characterizing the media were varied over a wide range: the bulk density, the size of the elements entering the mix, and the proportion of cardboard and PE in the mix. The properties were measured by means of a specially designed experimental device based on miscible gas tracing. The porosity and tortuosity factor were simultaneously determined by parametric identification, based on the experimental sample output response to an inlet gas concentration step change compared to the results of a direct numerical model. Permeability was calculated in the standard way from the measurement of the pressure drop across the sample. The reproducibility of the measurements was very good. It was found that changing the material density of the medium significantly affects all three structural properties. When the bulk density is varied between 300 and 900 kg m(-3), the tortuosity factor varies in a range as large as 18-8 and the permeability decreases by a ratio of 2-3. The tortuosity factor shows unusual variation, characterized by a decrease when density is increased above 500 kg m(-3). The size of the elements does not significantly affect the structural properties of the medium in the range of parameters studied.


Risk factors for recurrence in stage II/III colorectal cancer patients treated with curative surgery: The impact of postoperative tumor markers and an infiltrative growth pattern.
We evaluated the capacity of clinicopathological factors to predict recurrence in stage II/III colorectal cancer (CRC) patients after curative resection. We retrospectively examined 386 stage II/III CRC patients who underwent curative resections between April 2008 and August 2013. We assessed the predictive power of pre- and postoperative tumor marker levels, lymphatic and venous invasion, and infiltrative growth patterns using Cox's proportional hazards model. Of 206 stage II and 180 stage III patients, 26 (13%) and 46 (26%) patients, respectively, developed recurrences with median follow-up times of 51 and 45 months, respectively. Independent risk factors for recurrence were lymphatic invasion (hazard ratio [HR], 5.99; P = 0.0006) and infiltrative growth patterns (HR, 4.02; P = 0.017) in stage II patients; and elevated preoperative carcinoembryonic antigen levels (HR, 3.22; P = 0.004), elevated postoperative carbohydrate antigen 19-9 levels (HR, 5.08; P = 0.005), and infiltrative growth patterns (HR, 3.19; P = 0.037) in stage III patients. High-recurrence risk can be identified in stage II/III CRC patients by assessing perioperative serum tumor marker levels, lymphatic invasion, and infiltrative growth patterns. Intensive follow-up for patients with these risk factors may help detect recurrences promptly and improve survival. J. Surg. Oncol. 2016;114:368-374. © 2016 Wiley Periodicals, Inc.


Hepatogenic pulmonary angiodysplasia treated with coil-spring embolization.
Coil-spring embolization is a procedure for treatment of pulmonary arteriovenous malformations. Herein is described a patient with hepatogenic pulmonary angiodysplasia ("pulmonary spiders") managed with this technique.


The human leukocyte photoreactivating enzyme.
A photoreactivating enzyme from human leukocytes has been isolated and characterized. The enzyme requires DNA irradiated with ultraviolet light (220-300 nm) as substrate, and visible light (300-600 nm) for catalysis. In the reaction, the enzyme converts cyclobutyl pyrimidine dimers in the DNA to monomer pyrimidines. The enzyme has an apparent monomer molecular weight of 40,000 and tends to form aggregates. The pH optimum of 7.2 and absence of a requirement for metal ions are similar to the requirements of the Escherichia coli enzyme; however, the ionic strength optimum of 0.05 is much lower than those for other photoreactivating enzymes. The demonstration that human cells possess photoreactivating enzyme implies that a direct test by photoreactivation may be made of the role of pyrimidine dimers in the induction of abnormal cell growth.


Adsolubilization of 2-naphthol into adsorbed layers of triblock PEO-PPO-PEO copolymers on hydrophobic silica particles.
Adsolubilization of 2-naphthol into an adsorbed layer of triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, Pluronics) copolymers on hydrophobically modified silica particles has been investigated. Four kinds of Pluronics (P103, P105, P123, and F108) were employed in order to understand the effect of the hydrophobicity of the surfactants on the adsolubilization. The amount of the Pluronics adsorbed of the maximum/saturation adsorption level was increased with a decrease in the HLB value, suggesting that the more hydrophobic Pluronics (P103 and P123) adsorb preferentially onto the hydrophobic silica surface over the more hydrophilic Pluronics (P105 and F108). The greater adsorbed amount of the more hydrophobic surfactants resulted in a greater amount of 2-naphthol adsolubilized into the adsorbed Pluronics layers. In the case of simultaneous addition of the Pluronics and 2-naphthol, the amount adsolubilized into the adsorbed P123 and P103 layers increased in their low-surfactant-concentration regime, reached a maximum, and then decreased with a further increase in the Pluronics concentration. On the other hand, for both the P105 and F108 copolymers, a decrease in the adsolubilized amount was not observed over the whole range of copolymer concentration investigated. This difference is attributed to a difference in the hydrophobicity of the micellar aggregates in solution and of the adsorbed layers on the hydrophobic surface. When 2-naphthol was added after replacement of the Pluronics supernatant by a surfactant-free solution, the final decrease in the adsolubilization was insignificant for all the Pluronics. Indeed, the maximum amount of adsolubilization was comparable to the corresponding amount obtained in the case of simultaneous addition.


Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors: a Danish population-based cohort study.
To examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting. We enrolled all postmenopausal patients diagnosed with stage I-III estrogen receptor positive breast cancer during the years 2007-2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥ 1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure. We enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92-14.28] and 13.40 [95% CI 12.36-14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50-1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48-1.02]). Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy.


A preliminary communication. Isolation and positive confirmation of chlordecone in rabbit oviductal fluid.
Chlordecone (10 mg/kg, sc in corn oil) was administered to mature female rabbits once daily for five days. Analysis of oviductal fluid collected from these rabbits over the course of this experiment confirmed the presence of chlordecone. It is reasonable to suggest that chlordecone may reduce mammalian fertility during the preimplantation period by producing deleterious effects on respective gametes and/or the embryo. The mechanisms by which chlordecone may interfere with fertilization and reproduction is discussed.


Influence of contractile tension development on dynamic strength measurements of the plantarflexors in man.
The influence of the contractile tension rise time on isokinetic force-angle records has been inferred from static force-time curves but has not been experimentally determined. The purpose of this study is thus to describe the influence of the contractile rise time on the force-angle curves produced during maximal voluntary, acceleration controlled, isokinetic plantarflexions at 30 degrees/s. Since we could not measure directly the period of force development unbiased by changes in muscle length during the movements, we devised an experimental strategy which allowed the computation of the dynamic force-time curve. Thus in five normal men, we first recorded force-angle curves produced during maximal voluntary plantarflexion movements preceded by maximal static pre-loading (D:-10 degrees Max) in order to eliminate the period of tension development from the force-angle record. Next, we recorded force-angle curves produced during maximal voluntary contractions initiated from two different starting angles without pre-loading (D:-10 degrees Min and D:0 degrees Min) to include the period of tension rise. The dynamic force-time curve was computed by correcting these force-angle curves (D:-10 degrees Min and D:0 degrees Min) for the hypothetical loss in force due to muscle shortening. We compared the relative (to remove the effects of force magnitude) computed dynamic force-time curves with relative static force-time curves measured at three different angles. We found the shape and several other parameters of all three static and both computed dynamic force-time curves to be similar (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacology of ACC-9653 (phenytoin prodrug).
ACC-9653, the disodium phosphate ester of 3-hydroxymethyl-5,5-diphenylhydantoin, is a prodrug of phenytoin with advantageous physicochemical properties. ACC-9653 is rapidly converted enzymatically to phenytoin in vivo. ACC-9653 and phenytoin sodium have equivalent anticonvulsant activity against seizures induced by maximal electroshock (MES) in mice following i.p., oral, or i.v. administration. The ED50 doses were 16 mg/kg for i.v. ACC-9653 and 8 mg/kg for i.v. phenytoin sodium. ACC-9653 and phenytoin sodium have similar antiarrhythmic activity against ouabain-induced ventricular tachycardia in anesthetized dogs. The total doses of ACC-9653 or phenytoin sodium necessary to convert the arrhythmia to a normal sinus rhythm were 24 +/- 6 and 14 +/- 3 mg/kg, respectively. Only phenytoin sodium displayed in vitro antiarrhythmic activity against strophanthidin-induced arrhythmias in guinea pig right atria. In anesthetized dogs, a high dose of ACC-9653 (31 mg/kg) was infused over 15, 20, and 30 min and the responses were compared to an equimolar dose of phenytoin sodium (21 mg/kg). The ACC-9653 and phenytoin sodium treatments produced similar marked reductions in diastolic blood pressure and contractile force (LVdP/dt). The maximum effects of each treatment occurred at the time of maximum phenytoin sodium levels. Acute toxicity studies of ACC-9653 and phenytoin sodium were carried out in mice, rats, rabbits, and dogs by i.v., i.m., and i.p. routes of administration. The systemic toxic signs of both agents were similar and occurred at approximately equivalent doses. Importantly, the local irritation of ACC-9653 was markedly less than phenytoin sodium following i.m. administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling.
Papillomavirus E6 oncoproteins associate with LXXLL motifs on target cellular proteins to alter their function. Using a proteomic approach, we found the E6 oncoproteins of cutaneous papillomaviruses Bovine Papillomavirus Type 1 (BPV-1) E6 and human papillomavirus (HPV) types 1 and 8 (1E6 and 8E6) associated with the MAML1 transcriptional co-activator. All three E6 proteins bind to an acidic LXXLL motif at the carboxy-terminus of MAML1 and repress transactivation by MAML1. MAML1 is best known as the co-activator and effector of NOTCH-induced transcription, and BPV-1 E6 represses synthetic NOTCH-responsive promoters, endogenous NOTCH-responsive promoters, and is found in a complex with MAML1 in stably transformed cells. BPV-1-induced papillomas show characteristics of repressed NOTCH signal transduction, including suprabasal expression of integrins, talin and basal type keratins, and delayed expression of the NOTCH-dependent HES1 transcription factor. These observations give rise to a model whereby papillomavirus oncoproteins, including BPV-1 E6, and the cancer-associated HPV-8 E6 repress NOTCH-induced transcription, thereby delaying keratinocyte differentiation.


DTNB-Based Quantification of In Vitro Enzymatic N-Terminal Acetyltransferase Activity.
We here describe a quick and easy method to quantitatively measure in vitro acetylation activity of not only N-terminal acetyltransferase (NAT) enzymes, but acetyltransferases using acetyl-coenzyme A as an acetyl donor in general.


Shifting of cell cycle arrest from the S-phase to G2/M phase and downregulation of EGFR expression by phytochemical combinations in HeLa cervical cancer cells.
Cervical cancer is a major human papillomavirus-related disease and is the fourth leading cause of death by cancer among women. Plants are an important source of anticancer compounds and many of them are currently used in the treatment of cancer. Several reports suggest the efficacy of plant-derived compounds increases when used in combination. This study was carried out to evaluate the effect of four plant-derived compounds such as curcumin (C), ellagic acid (E), quercetin (Q), and resveratrol (R) when used alone or in combinations using HeLa cervical cancer cells. All four phytocompounds showed effective cytotoxic activities in targeting HeLa cervical cancer cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. The selected phytocompound combinations C + E, C + Q, and Q + R work synergistically while the combination C + R shows additive effects. All four phytocompounds reduce cell migration as determined by in vitro wound-healing assay. The expression level of the epidermal growth factor receptor is significantly downregulated both in individual and combination. The flow cytometry analysis of cell cycle indicates that individual drugs curcumin, ellagic acid, quercetin, and resveratrol, each with 20 µM effectively arrested cell cycle at the S-phase while the combination of drugs (10 + 10 µM) at the G2/M phase.


The art of interprofessional psychosocial communication: Optimizing patient interfaces with psychiatric specialists in liver transplantation.
Psychiatric and substance use disorders (SUD) commonly cause and contribute to advanced liver diseases and psychosocial phenomena remain some of the most challenging matters that liver transplantation (LT) teams encounter. Patients are often most focused on biomedical aspects of their treatment and LT course rather than subtler psychosocial factors which must be addressed alongside medical and surgical problems. This means that patients may not accept teams' recommendations for psychiatric and SUD treatment despite their primary role in treating liver disease and promoting successful LT. Alcohol-related liver disease is the archetype of these challenges. A crucial, actionable, and rarely discussed factor in creating a therapeutic interface between liver patients and psychiatric and SUD specialists is medical and surgical clinicians' interprofessional psychosocial communication (IPC; i.e., a clinician's personal ability to communicate effectively with patients about psychiatric and substance-related matters). In this article, we describe three crucial IPC timepoints during a typical ALD transplantation timeline, briefly review and synthesize diverse literature and perspectives into an overview of potential IPC pitfalls, propose practical IPC strategies for institutions and clinicians, and indicate future areas of study.


Cytochrome unfolding pathways from computational analysis of crystal structures.
We have developed a model to study the role of geometrical factors in influencing the early stages of unfolding in three cytochromes: cyt c', cyt c-b562 and cyt c. Each stage in unfolding is quantified by the spatial extension λ̂i of n-residue segments, and by their angular extension 〈βn〉. Similarities and differences between and among the three cytochromes in the unfolding of helical and non-helical regions can be determined by analyzing the data for each signature separately. Definite conclusions can be drawn when spatial and angular changes are considered in tandem. To facilitate comparisons, we present graphical portraits of the three cytochromes at the same stage of unfolding, and in relation to their native state structures. We also display specific segments at different stages of unfolding to illustrate differences in stability of defined domains thereby allowing us to make specific predictions on the unfolding of corresponding internal and terminal helices in cyt c' and cyt c-b562. Our work accords with an earlier experimental report on the presence and persistence of a hydrophobic core in cyt c.


Reflective narratives on unfolding ethics case vignettes: integration into the physiology course of first-year medical students.
Reflective narrative writing on unfolding ethics case vignettes has the potential to promote values like empathy among medical students, which will prove useful in their future. The objective of this study was to explore the scope of guided reflective narratives on unfolding ethics case vignettes integrated into physiology teaching to promote empathy among first-year medical students. First-year medical students (n = 150) were presented with unfolding case vignettes exploring ethical issues, as part of their physiology curriculum, with questions and prompts for a guided reflective narrative. Feedback about the program was obtained through a semistructured questionnaire. The contents of the students' reflective narratives and feedback were analyzed. The narratives revealed that students empathized with the various individuals involved in medical treatment and research, which was also reflected in student feedback (n = 116; 79%) and high Likert scale scores (74%). The program was considered effective by students in broadening their perspective and promoting critical thinking (n = 129; 88%). Through analysis of reflections, a rubric that would enable the evaluation of students' empathy on a scale of increasing ability to look at a situation from another's point of view emerged. This rubric could be used to quantitatively assess the impact of similar programs. Although divided in their individual opinions, the study population was able to relate to all individuals involved in medical practice and research, recognizing the need for fair and ethical practices. The content analysis led to the development of a rubric to grade empathy.NEW & NOTEWORTHY Unfolding case vignettes exploring ethical issues were introduced into the physiology curriculum of first-year medical students. The effectiveness of guided reflections following the case vignettes was explored. The analysis of the reflections and feedback on the program revealed that students became more empathetic. The reflections broadened their perspective and encouraged critical thinking. The analysis led to development of a rubric to grade the level of empathy, which can be used for quantitative assessment of empathy.


Febrile and other occasional seizures.
Seizures with fever that result from encephalitis or meningitis usually occur late in the course of febrile illness, and are focal and prolonged. Febrile seizures are by far the most common affecting 5% of the population, followed by posttraumatic seizures and those observed in the setting of a toxic, infectious, or metabolic encephalopathy. This chapter reviews the clinical presentation of the three most common forms, due to fever, trauma, and intoxication. Febrile seizures carry no cognitive or mortality risk. Recurrence risk is increased by young age, namely before 1 year of age. Febrile seizures that persist after the age of 6 years are usually part of the syndrome of Generalized epilepsy febrile seizures plus. These febrile seizures have a strong link with epilepsy since non-febrile seizures may occur later in the same patient and in other members of the same family with an autosomal dominant transmission. Complex febrile seizures, i.e., with focal or prolonged manifestations or followed by focal defect, are related to later mesial temporal epilepsy with hippocampal sclerosis; risk factors are seizure duration and brain malformation. Prophylactic treatment is usually not required in febrile seizures. Early onset of complex seizures is the main indication for AED prophylaxis. Early posttraumatic seizures, i.e., within the first week, are often focal and indicate brain trauma: contusion, hematoma, 24 hours amnesia, and depressed skull fracture are major factors of posttraumatic epilepsy. Prophylaxis with antiepileptic drugs is not effective. Various psychotropic drugs, including antiepileptics, may cause seizures.


Activation of plasminogen by tissue activator is increased specifically in the presence of certain soluble fibrin(ogen) fragments.
Tissue activator-mediated plasminogen activation is potentiated both by fibrin and by some soluble fibrin(ogen) fragments. The potentiating effect of the different fragments decreases in the order fibrin monomer greater than D-dimer greater than Y greater than D EGTA greater than Dcate greater than X. Fibrinogen and the fragments Ecate, E EGTA and E fibrin have almost no effect. The existence of a fibrin polymer is apparently not a prerequisite for this potentiating effect. The plasminogen activation by various urokinase preparations is not potentiated by fibrin and fibrin(ogen) fragments.


Oligodendrocytes upregulate blood-brain barrier function through mechanisms other than the PDGF-BB/PDGFRα pathway in the barrier-tightening effect of oligodendrocyte progenitor cells.
White matter lesions are associated with impairment of the blood-brain barrier (BBB), an essential component of the cerebrovasculature. The BBB allows the brain to maintain its highly specialized microenvironment by restricting entry of blood-borne substances including molecules that induce myelin damage. Accumulating evidence suggests that interactions between brain endothelial cells and neighboring cells, including oligodendrocyte progenitor cells (OPCs), are required for the induction and maintenance of BBB function. Here, we compared the ability of OPCs and oligodendrocytes to modulate BBB integrity using co-cultures of rat brain endothelial cells with OPCs or oligodendrocytes. We found that OPCs lowered the brain endothelial permeability to sodium fluorescein, and this enhancement of BBB function was prevented by treatment with AG1296 (a PDGFRα inhibitor). Oligodendrocytes also enhanced BBB integrity. Pharmacological inhibition of PDGFRα did not affect the oligodendrocyte-induced BBB facilitation. These data indicate that oligodendrocytes enhance BBB integrity through pathways other than PDGF-BB/PDGFRα signaling triggered by the brain endothelial cell-derived PDGF-BB. Therefore, our findings suggest that oligodendrocytes constitutively support BBB integrity through soluble factors. Crosstalk between brain endothelial cells and oligodendrocytes could play a facilitatory role in maintaining BBB integrity in the white matter.


Frequency bifurcation in a series-series compensated fractional-order inductive power transfer system.
This paper reveals and analyzes the frequency bifurcation phenomena in the fractional-order inductive power transfer (FOIPT) system with series-series compensation topology. Using fractional calculus theory and electric circuit theory, the circuit model of the series-series compensated FOIPT system is first proposed, then taking the case of a single variable fractional order as an example, three frequency analytical solutions of frequency bifurcation equation are solved by using Taylor expansion method. By analyzing the three bifurcation frequencies solved, it can be found that the frequency bifurcation phenomenon can be effectively eliminated by controlling the fractional order, and the boundary of critical distance and critical load is reduced, thereby expanding the working range of the conventional inductive power transfer (IPT) system. Furthermore, the output power and transfer efficiency at the three bifurcation frequencies are analyzed, it can be observed that the output power and transfer efficiency at the high bifurcation frequency and low bifurcation frequency are close and basically keep constant against the variation of transfer distance, and the output power is obviously higher than that at the intrinsic frequency. In addition, the output power at the three bifurcation frequencies can be significantly improved by adjusting the fractional order. Finally, the experimental prototype of FOIPT is built, and the experimental results verify the validity of theoretical analysis.


A method of treating serous fluid leak from a polytetrafluoroethylene Blalock-Taussig shunt.
A 3 1/2-year-old girl with complex cyanotic congenital heart disease underwent palliation with a modified Blalock-Taussig shunt, for which a 6 mm polytetrafluoroethylene graft was used. Seroma formation with serous leakage occurred. Two periods of conservative management failed. At reoperation, treatment of the graft with intraluminal "fibrin glue" resulted in immediate resolution of the leak.


Fabrication of ultra-stable and high-efficient CoP-based electrode toward seawater splitting at industrial-grade current density.
The mild and rapid construction of economical, efficient and ultrastable electrodes for hydrogen production via water splitting at industrial-grade current density remains extremely challenging. Herein, a one-step mild electroless plating method is proposed to deposit cobalt phosphorus (CoP)-based species on robust nickel net (NN, denoted as Co-P@NN). The tight interfacial contact, corrosion-proof self-supporting substrate and synergistic effect of Co-P@Co-O contribute greatly to the rapid electron transport, high intrinsic activity and long-term durability in the alkaline simulated seawater (1.0 M KOH + 0.5 M NaCl). Attractively, Co-P@Co-O also achieves ultrastable catalysis for over 2880 h with negligible activity attenuation under various alkaline extreme conditions (simulated seawater, high-salt environment, domestic sewage and so on). Furthermore, this work successfully constructs a series of ternary elemental doped (Ni, S, B, Fe and so on) CoP-based catalytic electrodes for highly efficient overall seawater splitting (OSWS). This work demonstrates not only an ideal platform for the versatile strategy of mildly obtaining CoP-based electrocatalysts but also the pioneering philosophy of large-scale hydrogen production.


Observation of mechanical bound states in the continuum in an optomechanical microresonator.
Bound states in the continuum (BICs) are a type of waves that are perfectly confined in the continuous spectrum of radiating waves without interaction with them. Here, we fabricated, with CMOS-compatible processes on a silicon chip, a wheel-shaped optomechanical microresonator, in which we experimentally observed the BIC in the micromechanical domain. The BIC results from destructive interference between two dissipative mechanical modes of the microresonator under broken azimuthal symmetry. Such BICs can be obtained from devices with large and robust supporting structures with variable sizes, which substantially reduces fabrication difficulty and allows for versatile application environments. Our results open a new way of phonon trapping in micromechanical structures with dissipation channels, and produce long phonon lifetimes that are desired in many mechanical applications such as mechanical oscillators, sensors, and quantum information processors.


Time series outlier removal and imputing methods based on Colombian weather stations data.
The time data series of weather stations are a source of information for floods. The study of the previous wintertime series allows knowing the behavior of the variables and the result that will be applied to analysis and simulation models that feed variables such as flow and level of a study area. One of the most common problems is the acquisition and transmission of data from weather stations due to atypical values and lost data; this generates difficulties in the simulation process. Consequently, it is necessary to propose a numerical strategy to solve this problem. The data source for this study is a real database where these problems are presented with different variables of weather. This study is based on comparing three methods of time series analysis to evaluate a multivariable process offline. For the development of the study, we applied a method based on the discrete Fourier transform (DFT), and we contrasted it with methods such as the average and linear regression without uncertainty parameters to complete missing data. The proposed methodology entails statistical values, outlier detection, and the application of the DFT. The application of DFT allows the time series completion, based on its ability to manage various gap sizes and replace missing values. In sum, DFT led to low error percentages for all the time series (1% average). This percentage reflects what would have likely been the shape or pattern of the time series behavior in the absence of misleading outliers and missing data.


Simvastatin inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma through KLF2 signal.
This study aimed to explore the role and specific mechanism of the cholesterol-lowering drug simvastatin in inhibiting oral squamous cell carcinoma (OSCC). The proliferation, apoptosis, and migration levels of OSCC cells were detected by CCK8, quantitative real-time polymerase chain reaction, Western blot, colony formation, TdT-mediated dUTP Nick-End Labeling assay, and wound healing assay. The inhibitory effect of simvastatin in vivo was detected by a mouse xenograft tumor model. Immunohistochemistry and immunofluorescence staining were used to assess the KLF2 and β-catenin expressions in cells and tissues. KLF2 expression in OSCC cells and tissues was downregulated. The addition of KLF2 inducer, GGTI298, inhibited the proliferation and migration of OSCC cells. Simvastatin played a role in inhibiting the proliferation and promoting the apoptosis of OSCC cells. Moreover, it inhibited β-catenin expression and promoted KLF2 expression in OSCC cells. KLF2 siRNA reversed the effect of simvastatin on the proliferation and apoptosis of OSCC cells. KLF2, as a tumor suppressor gene, may be an important marker for diagnosing and treating OSCC. Simvastatin inhibits the progression of OSCC by regulating the KLF2 signal.


Association of age and time of disease with HIV-associated neurocognitive disorders: a Japanese nationwide multicenter study.
There is no detailed information on the association between age, time of disease, and HIV-associated neurocognitive disorders (HAND). In this prospective study involving 17 medical facilities across Japan, we recruited HIV-infected patients to complete a 14-test neuropsychological battery that assess eight neurocognitive domains. HAND were diagnosed by the Frascati criteria. Of 1399 recruited patients, 728 were enrolled. The prevalence of HAND was 25.3% [13.5% asymptomatic neurocognitive impairment, 10.6% mild neurocognitive disorder (MND), and 1.2% HIV-associated dementia (HAD)]. Tests that assess executive and visuospatial functions showed better diagnostic accuracy than other tests for HAND. Multivariate analysis identified age (≥ 50 years) and incomplete virological suppression as risk factors for MND and HAD and current ART as a protective factor. The prevalence of MND and HAD was low in the early stage of infection (6.3% in ≥ 2 to < 6 years), then increased in the later stage [17.3% in ≥ 11 years, p = 0.001 (vs. ≥ 2 to < 6 years)], independent of age or treatment. Older patients were more likely to show MND or HAD in the early stage of HIV infection (26.7 vs. 8.7% for < 2 years and 17.4 vs. 3.1% for ≥ 2 to < 6 years, p = 0.040 and 0.004, respectively) compared to younger ones. In conclusion, MND and HAD were more commonly found in later years since diagnosis of HIV infection and older patients are at risk of neurocognitive impairment at the early stage of HIV infection. Tests for executive and visuospatial functions seem more sensitive than other tests for diagnosing HAND.


Overimitation in Dogs: Is There a Link to the Quality of the Relationship with the Caregiver?
Overimitation, the copying of causally irrelevant or non-functional actions, is well-known from humans but completely absent in other primates. Recent studies from our lab have provided evidence for overimitation in canines. Previously, we found that half of tested pet dogs copied their human caregiver's irrelevant action, while only few did so when the action was demonstrated by an unfamiliar experimenter. Therefore, we hypothesized that dogs show overimitation as a result of socio-motivational grounds. To test this more specifically, here we investigated how the relationship with the caregiver influenced the eagerness to overimitate. Given the high variability in the tendency to overimitate their caregiver, we hypothesized that not only familiarity but also relationship quality influences whether dogs faithfully copy their caregiver. For this purpose, on the one hand we measured the overimitation tendency (with the same test as in the two studies before) and on the other hand the relationship quality between the dogs and their caregivers. Although we found no significant correlation between the two test results, our data might suggest that, on average, dogs who overimitated seemed to show more referential and affiliative behaviours towards the owner than dogs who showed less or no copying of the irrelevant action. Notably, as a group, those dogs that showed the highest level of copying accuracy of the irrelevant action showed the highest level of gazing and synchronization towards the owner.


Effect of level of feed intake on the development of gastrointestinal parasitism in growing lambs.
A study was conducted to examine the role of nutrition in the development of gastrointestinal (GI) parasitism, performance and pathophysiology of parasitism in female lambs. Forty-four months old ewe lambs received for 6 weeks 0, 1500 or 7000 L(3) larvae of Teladorsagia circumcincta in two doses per week. The animals were given access to a pelleted diet to meet energy requirements for gaining weight close to their potential (H) or approximately 50% of it (L). The level of protein in the diet was 20-30% above requirements for both planes of nutrition. Measurements of body weight, serum pepsinogen concentration and faecal egg counts were taken at weekly intervals. All animals were slaughtered 2 weeks after the last larval dosing for estimation of worm count, carcass composition and reproductive tract development. Voluntary intake of infected animals decreased by approximately 10%. Both nutrition and infection influenced lamb performance and carcass composition. However, no direct effects on reproductive tract parameters due to the presence of infection were observed. The level of L(3) infection showed a significant effect not only on faecal egg counts and on worm burden, as it could be expected, but also on the proportion of females to males, which increased significantly with the level of infection. While the plane of nutrition did not show a significant effect on faecal egg counts or on worm burden, surprisingly, both female worm size and their fecundity decreased significantly with the level of nutrition. This response was accompanied by a significant increase in the concentration of circulating eosinophils suggesting that the immune response of lambs consuming high levels of energy was enhanced compared to that of lambs kept on a restricted diet. Results herein show that in young female lambs fed on adequate levels of protein, an improvement in energy supply does not only improve carcass characteristics but clearly enhances the development of resistance to GI nematodes infection. This may have decisive management implications for the control of parasitic infections in sustainable production systems.


The complete mitochondrial genome sequence of Mustela eversmannii (Carnivora: Mustelidae).
In this study, the complete mitochondrial genome of Steppe polecat, Mustela eversmannii, was sequenced for the first time using muscle tissue. The mitochondrial genome is a circular molecule of 16 463 bp in length and overall base composition is A (32.7%), T (27.3%), C (26.1%), and G (13.9%), which indicates a strong A-T bias. A phylogenetic analysis on the basis of 13 protein-coding genes and two rRNA genes of 10 Mustela species' mitochondrial genomes using maximum likelihood (ML) and Bayesian inference (BI) demonstrated that these Mustela species were clustered into two clades and M. eversmannii was close to M. putorius.


Influence of oxygen uptake through the liver surface on the metabolism of ex vivo perfused liver during hypoxia.
The low quality of transplants having undergone hypoxic injury can lead to postoperative complications. The aim of the present research is to estimate, by means of mathematical modeling, how the process of oxygen uptake through the liver surface influences the metabolism of ex vivo perfused liver under hypoxia. The value of oxygen uptake through the surface was established to depend on the degree of oxygenation of the perfusion medium. A decrease in the oxygenation of the perfusion medium resulted in a decreased oxygen uptake through the liver surface. Stoichiometric modeling of the liver metabolism shows that upon the decreased oxygenation of the perfusion medium more energy is required for the process of oxygen uptake through the surface even at a lower level as compared to the normal oxygen supply. The application of the Pareto optimality allows estimating the optimum distribution of the energy resources in liver under ex vivo conditions. Both upon the normal and decreased oxygenation of the perfusion medium, the phenomenon of "free competition" for the resource was observed, with the energy being optimally distributed among all the metabolic fluxes. Moreover, this energy is also spent on the accompanying processes, e.g. for the transport of interstitial fluid.


Use of oleic-acid functionalized nanoparticles for the magnetic solid-phase microextraction of alkylphenols in fruit juices using liquid chromatography-tandem mass spectrometry.
Magnetic nanoparticles of cobalt ferrite with oleic acid as the surfactant (CoFe2O4/oleic acid) were used as sorbent material for the determination of alkylphenols in fruit juices. High sensitivity and specificity were achieved by liquid chromatography and detection using both diode-array (DAD) and electrospray-ion trap-tandem mass spectrometry (ESI-IT-MS/MS) in the selected reaction monitoring (SRM) mode of the negative fragment ions for alkylphenols (APs) and in positive mode for ethoxylate APs (APEOs). The optimized conditions for the different variables influencing the magnetic separation procedure were: mass of magnetic nanoparticles, 50mg, juice volume, 10mL diluted to 25mL with water, pH 6, stirring for 10min at room temperature, separation with an external neodymium magnet, desorption with 3mL of methanol and orbital shaking for 5min. The enriched organic phase was evaporated and reconstituted with 100µL acetonitrile before injecting 30µL into a liquid chromatograph with a mobile phase composed of acetonitrile/0.1% (v/v) formic acid under gradient elution. Quantification limits were in the range 3.6 to 125ngmL(-1). The recoveries obtained were in the 91-119% range, with RSDs lower than 14%. The ESI-MS/MS spectra permitted the correct identification of both APs and APEOs in the fruit juice samples.


Vestibular Implantation and the Feasibility of Fluoroscopy-Guided Electrode Insertion.
Recent research has shown promising results for the development of a clinically feasible vestibular implant in the near future. However, correct electrode placement remains a challenge. It was shown that fluoroscopy was able to visualize the semicircular canal ampullae and electrodes, and guide electrode insertion in real time. Ninety-four percent of the 18 electrodes were implanted correctly (<1.5 mm distance to target). The median distances were 0.60 mm, 0.85 mm, and 0.65 mm for the superior, lateral, and posterior semicircular canal, respectively. These findings suggest that fluoroscopy can significantly improve electrode placement during vestibular implantation.


Hospital-onset sepsis and community-onset sepsis in critical care units in Japan: a retrospective cohort study based on a Japanese administrative claims database.
Hospital- and community-onset sepsis are significant sepsis subgroups. Japanese data comparing these subgroups are limited. This study aimed to describe the epidemiology of hospital- and community-onset sepsis in critical care units in Japan. We performed a retrospective cohort study using the Japanese Diagnosis and Procedure Combination database. Adult patients admitted to critical care units with sepsis from April 2010 to March 2020 were included. Sepsis cases were identified based on ICD-10 codes for infectious diseases, procedure codes for blood culture tests, and medication codes for antimicrobials. Patients' characteristics, in-hospital mortality, and resource utilization were assessed. The in-hospital mortality between groups was compared using the Poisson regression generalized linear mixed-effect model. Of 516,124 patients, 52,183 (10.1%) had hospital-onset sepsis and 463,940 (89.9%) had community-onset sepsis. Hospital-onset sepsis was characterized by younger age, infrequent emergency hospitalization, frequent surgery under general anesthesia, and frequent organ support upon critical care unit admission compared to community-onset sepsis. In-hospital mortality was higher for hospital-onset than for community-onset sepsis (35.5% versus 19.2%; unadjusted mean difference, 16.3% [95% confidence interval (CI) 15.9-16.7]; adjusted mean difference, 15.6% [95% CI 14.9-16.2]). Mean hospital length of stay was longer for hospital-onset than for community-onset sepsis (47 days versus 30 days; unadjusted mean difference, 17 days [95% CI 16-17]; adjusted mean difference, 13 days [95% CI 12-14]). Patients with hospital-onset sepsis admitted to critical care units in Japan had a poorer prognosis and more resource utilization including organ support rate, number of days with critical care unit surcharge codes, and hospital length of stay than those with community-onset sepsis.


Dissociable large-scale networks anchored in the right anterior insula subserve affective experience and attention.
Meta-analytic summaries of neuroimaging studies point to at least two major functional-anatomic subdivisions within the anterior insula that contribute to the detection and processing of salient information: a dorsal region that is routinely active during attention tasks and a ventral region that is routinely active during affective experience. In two independent samples of cognitively normal human adults, we used intrinsic functional connectivity magnetic resonance imaging to demonstrate that the right dorsal and right ventral anterior insula are nodes in separable large-scale functional networks. Furthermore, stronger intrinsic connectivity within the right dorsal anterior insula network was associated with better performance on a task involving attention and processing speed whereas stronger connectivity within the right ventral anterior insula network was associated with more intense affective experience. These results support the hypothesis that the identification and manipulation of salient information is subserved by at least two brain networks anchored in the right anterior insula that exhibit distinct large-scale topography and dissociable behavioral correlates.


Identification of the novel KIR3DL3*118 allele in a Chinese Han individual.
The novel KIR3DL3*118 allele differs from the closest allele KIR3DL3*01002 by a single missense mutation at CDS nt502 A > G in exon 4.


Ascending aortic dissection causing unilateral absence of perfusion on lung scanning.
A case of an ascending aortic dissection occurring in a patient 8 years after an aortic valve replacement is presented. The patient's initial clinical presentation was thought to be due to pulmonary embolism, and a ventilation-perfusion lung scan demonstrated mismatched absence of perfusion to the entire right lung. Aortography and findings at surgery demonstrated a type A dissection of the ascending aorta. The anatomic relationship of the aorta and pulmonary artery and their common tunica adventitia make the right pulmonary artery susceptible to extrinsic compression after aortic dissection. Although uncommon, dissection of the ascending aorta needs to be considered in patients who have undergone previous aortic valve surgery and demonstrate mismatched unilateral absence of perfusion to the right lung. Because anticoagulation is contraindicated in patients with acute aortic dissection, confirmation of the diagnosis with angiography usually is required.


A HIGH FREQUENCY OF HERITABLE CHANGES IN NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER IN UKRAINE.
Spontaneous mutations are thought to have a stable rate for a given species. If non-adaptive, they appear at low frequencies and are governed by drift. However, environmental factors have been reported to cause spread of non-adaptive mutations in populations, governed by mechanisms, such as genetic assimilation. In the present study, we report a simultaneous appearance of a mutant and apparently non-adaptive C2 vein in Drosophila melanogaster at higher than expected frequencies in several distant populations, which excludes the role of drift or selection as the cause of the reported mutation frequencies. We discuss explanations of the phenomenon, including the role of externalfactors, such as temperature, in the possible genetic assimilation of the trait.


Screening of antimicrobial activity of plants popularly used in Guatemala for the treatment of dermatomucosal diseases.
Ethnobotanical surveys were conducted among traditional healers and local market vendors; about 200 plants used in Guatemala for the treatment of dermatomucosal diseases were detected. By literature review and according to local availability, 89 plants were selected for in vitro screening for antimicrobial activity against the microorganisms usually causing skin and mucosal infections. Ethanolic macerations were prepared and impregnated in absorbent paper; once dried, these were applied over standardized inocula of Candida albicans, Escherichia, coli, Pseudomonas aeruginosa and Staphylococcus aureus. After incubation, inhibition zones were measured, demonstrating that 28 of the plants exhibited some in vitro inhibition of the tested microorganisms.


Opposing kinesin complexes queue at plus tips to ensure microtubule catastrophe at cell ends.
In fission yeast, the lengths of interphase microtubule (iMT) arrays are adapted to cell length to maintain cell polarity and to help centre the nucleus and cell division ring. Here, we show that length regulation of iMTs is dictated by spatially regulated competition between MT-stabilising Tea2/Tip1/Mal3 (Kinesin-7) and MT-destabilising Klp5/Klp6/Mcp1 (Kinesin-8) complexes at iMT plus ends. During MT growth, the Tea2/Tip1/Mal3 complex remains bound to the plus ends of iMT bundles, thereby restricting access to the plus ends by Klp5/Klp6/Mcp1, which accumulate behind it. At cell ends, Klp5/Klp6/Mcp1 invades the space occupied by the Tea2/Tip1/Tea1 kinesin complex triggering its displacement from iMT plus ends and MT catastrophe. These data show that in vivo, whilst an iMT length-dependent model for catastrophe factor accumulation has validity, length control of iMTs is an emergent property reflecting spatially regulated competition between distinct kinesin complexes at the MT plus tip.