Pore-scale hydrodynamics influence the spatial evolution of bacterial biofilms in a microfluidic porous network.
Bacteria occupy heterogeneous environments, attaching and growing within pores in materials, living hosts, and matrices like soil. Systems that permit high-resolution visualization of dynamic bacterial processes within the physical confines of a realistic and tractable porous media environment are rare. Here we use microfluidics to replicate the grain shape and packing density of natural sands in a 2D platform to study the flow-induced spatial evolution of bacterial biofilms underground. We discover that initial bacterial dispersal and grain attachment is influenced by bacterial transport across pore space velocity gradients, a phenomenon otherwise known as rheotaxis. We find that gravity-driven flow conditions activate different bacterial cell-clustering phenotypes depending on the strain's ability to product extracellular polymeric substances (EPS). A wildtype, biofilm-producing bacteria formed compact, multicellular patches while an EPS-defective mutant displayed a linked-cell phenotype in the presence of flow. These phenotypes subsequently influenced the overall spatial distribution of cells across the porous media network as colonies grew and altered the fluid dynamics of their microenvironment.


Immunoglobulin E in extracts of feces from children.
Immunoglobulin E (IgE) was demonstrated by a double antibody radioimmunoassay technique (PRIST) in 5 of 17 unconcentrated fecal extracts from children. Four of the PRIST-positive extracts also had measurable levels of IgE determined by an enzyme-linked immunosorbent test (Enzygnost IgE). However, using a competitive antibody radioimmunoassay technique (RIST), IgE was found in all unconcentrated fecal extracts. The RIST-IgE levels of the extracts were higher and did not correlate to IgE measured by the other methods, nor to the IgE in serum from the same children or to the manifestation of allergy. On the other hand, 4 of the 5 children with measurable PRIST-IgE levels, and 3 of the 4 children with detectable Enzygnost IgE concentrations in the extracts, had elevated serum IgE as well as a history of allergy. Gel filtration studies indicated that IgE determined by the PRIST and Enzygnost IgE methods had been degraded to fragments of lower molecular weight than that of albumin. This study also suggests that the IgE in feces measured by the RIST method is overestimated due to the influence from nonspecific substances of high molecular weight.


Asymptotic solutions for the relaxation of the contact line in the Wilhelmy-plate geometry: The contact line dissipation approach.
The relaxation of straight contact lines is considered in the context of the Wilhelmy-plate experiment: a homogeneous solid plate is moving vertically at constant velocity in a tank of liquid in the partial wetting regime. We apply the contact line dissipation approach to describe the quasistatic relaxation of the contact line toward the stationary state (below the entrainment transition). Asymptotic solutions are derived from the differential equations describing the capillary rise height and the contact angle relaxation for small initial deviations of the height from the final stationary value in the model considering the friction dissipation at the moving contact line, in the model considering the viscous flow dissipation in the wedge, and in the combined model taking into account both channels of dissipation. We find that for all models the time relaxation of the height and the cosine of the contact angle are given by sums of exponential functions up to a second order in the expansion of the small parameter. We analyze the implications which follow when only one dissipation channel is taken into account and compare them to the case when both dissipation channels are included. The asymptotic solutions are compared with experimental results and with numerically obtained solutions which are based on hydrodynamic approach in lubrication approximation with and without a correction factor for finite contact angles. The best description of the experimental data, based on multicriteria testing, is obtained with the combined contact line dissipation model which takes into account both channels of dissipation.


Hepatic lipid metabolism in transition dairy cows fed flaxseed.
Thirty-three Holstein cows averaging 687 kg of body weight were allotted 6 wk before the expected date of parturition to 11 groups of 3 cows blocked within parity for similar calving dates to determine the effects of feeding different sources of fatty acids on blood parameters related to fatty liver and profile of fatty acids in plasma and liver. Cows were fed lipid supplements from 6 wk before the expected date of parturition until d 28 of lactation. Cows within each block were assigned to 1 of 3 isonitrogenous and isoenergetic dietary supplements: control with no added lipids (CO); unsaturated lipids supplied as whole flaxseed (FL; 3.3 and 11.0% of the dry matter in prepartum and postpartum diets, respectively); and saturated lipids supplied as Energy Booster (EB; 1.7 and 3.5% of the DM in prepartum and postpartum diets, respectively). Diets EB and FL had similar ether extract concentrations. Multiparous cows fed EB had lower dry matter intake and milk production, higher concentrations of nonesterified fatty acids and beta-hydroxybutyrate in plasma and triglycerides (TG) and total lipids in liver, and lower concentrations of plasma glucose and liver glycogen than those fed FL and CO. Production of 4% fat-corrected milk was similar among treatments. Multiparous cows fed FL had the highest liver concentrations of glycogen on wk 2 and 4 after calving and lowest concentrations of TG on wk 4 after calving. Liver C16:0 relative percentages in multiparous cows increased after calving whereas those of C18:0 decreased. Relative percentages of liver C16:0 were higher in wk 2 and 4 postpartum for multiparous cows fed EB compared with those fed CO and FL; those of C18:0 were lower in wk 4 postpartum for cows fed EB compared with those fed CO and FL. Liver C18:1 relative percentages of multiparous cows increased after calving and were higher in wk 4 for cows fed EB compared with those fed CO and FL. The inverse was observed for liver C18:2 relative percentages. In general, diets had more significant effects on plasma concentrations of nonesterified fatty acids, beta-hydroxybutyrate, and glucose and liver profiles of fatty acids, TG, total lipids, and glycogen of multiparous than primiparous cows. These data suggest that feeding a source of saturated fatty acids increased the risk of fatty liver in the transition cow compared with feeding no lipids or whole flaxseed. Feeding flaxseed compared with no lipids or a source of saturated fatty acids from 6 wk before calving could be a useful strategy to increase liver concentrations of glycogen and decrease liver concentrations of TG after calving, which may prevent the development of fatty liver in the transition dairy cow.


Relationship between eating behaviors and physical activity among primary and secondary school students: results of a cross-sectional study.
With a view toward developing concerted efforts in fostering healthy eating habits and a physically active lifestyle among young people, a study was carried out to explore associations between eating behavior and physical activity (PA). In the school district, questionnaires were completed at home by parents of primary school children (N = 8612) and by secondary school youth (N = 5250) during a break in the schedule. The rates of response were 79% and 83%, respectively. Inferential and descriptive analyses were performed. The results indicate significant differences between the eating behaviors of young people who engage in 60 minutes of daily PA and those who are sedentary. The physically active children were generally more likely to eat fruit, vegetables, and whole-grain products and to have breakfast (p < .05 among high-school students). The lack of self-confidence (55%) and not enjoying PA (46%) stood out as the greatest obstacles facing adolescents trying to lose weight. There should be particular actions targeting students in the last half of primary school aimed at developing individual accountability and autonomy with respect to healthy eating and PA. These actions should also consider sex differences and those who have more sedentary lifestyles.


The effects of sustained delivery of estrogen on bone strength and cardiovascular panels in osteoporotic female rats.
Osteoporosis and cardiovascular disease (CVD) are common age-related conditions, which are major public health problems leading to an increase in mortality, morbidity, and disability. There have been several connections found between CVD and osteoporosis such as common genetic factors, risk factors, and pathological mechanisms. There is a direct effect of estrogen on CVD and osteoporosis that is demonstrated by the manifestation of estrogen receptors on osteoblasts, osteoclasts, and vascular endothelial and smooth muscle cells. Loss of estrogen has been found to be involved in the pathogenesis of atherosclerosis and bone loss through modulation of other factors including cytokines and oxidized lipids. The goal of this proposed research was to determine if sustained delivery of estrogen is capable of regulating bone cell function while improving cardiovascular panels. Ovariectomized Sprague Dawley rats were administered estradiol at a rate of 5ng/day over an eight-week period. Body weights, estradiol levels, cholesterol levels, and bone strength were determined at 2, 4, and 8 weeks following sustained delivery of estradiol and compared with intact control and ovariectomized control animals. Estrogen replacement resulted in improved cholesterol panels without significant changes in bone flexural strength or improvements in bone porosity. Additional long term studies are needed to determine if the benefits of estrogen replacement outweigh the inherent risks associated with hormone replacement therapies.


Switchable viscosity triggered by CO2 using smart worm-like micelles.
We report two CO2-responsive aqueous solutions having switchable viscosity. The solution of sodium octadecyl sulfate and 2-(dimethylamino)ethanol forms viscoelastic worm-like micelles in the presence of CO2 but not in its absence at 60 °C. Another solution of sodium stearate and sodium nitrate has high viscosity only if CO2 is absent.


Client types in drug-free and methadone treatment: comparison of personality traits.
The Drug-Free Therapeutic Community (TC) and Methadone Maintenance Treatment (MMT) modalities provide environmental conditions that are particularly well suited for examining addict personality characteristics suggested as important to the treatment of addiction. This study examines 174 addicts of two programs to determine how their relatedness to others varies with a self-selected treatment modality. Results indicate a generally low relatedness to others for the sample of addicts studied based on measures of the enduring trait associated with dependency on others and the more situational characteristic of interpersonal behavior. The MMT subsample showed greater social dependency in terms of the more enduring personality trait while the TC subsample was more interpersonally oriented based on the situational context. The absence of a relationship between the two measures suggests that there is a self-selection of treatment types which may serve to compensate for trait-related deficiencies or liabilities in addicts, and that the techniques employed by the approaches interact with these personality attributes that are probably accrued in the midst of learning how to cope with troubled familial settings and life as an addict.


Asynchronous Changepoint Estimation for Spatially Correlated Functional Time Series.
We propose a new solution under the Bayesian framework to simultaneously estimate mean-based asynchronous changepoints in spatially correlated functional time series. Unlike previous methods that assume a shared changepoint at all spatial locations or ignore spatial correlation, our method treats changepoints as a spatial process. This allows our model to respect spatial heterogeneity and exploit spatial correlations to improve estimation. Our method is derived from the ubiquitous cumulative sum (CUSUM) statistic that dominates changepoint detection in functional time series. However, instead of directly searching for the maximum of the CUSUM-based processes, we build spatially correlated two-piece linear models with appropriate variance structure to locate all changepoints at once. The proposed linear model approach increases the robustness of our method to variability in the CUSUM process, which, combined with our spatial correlation model, improves changepoint estimation near the edges. We demonstrate through extensive simulation studies that our method outperforms existing functional changepoint estimators in terms of both estimation accuracy and uncertainty quantification, under either weak or strong spatial correlation, and weak or strong change signals. Finally, we demonstrate our method using a temperature data set and a coronavirus disease 2019 (COVID-19) study. Supplementary materials accompanying this paper appear online. Supplementary materials for this article are available at 10.1007/s13253-022-00519-w.


Shiga toxin-producing E. coli O104:H4 outbreak 2011 in Germany: radiological features of enterohemorrhagic colitis.
In 2011 a nationwide outbreak of Shiga toxin-producing E. coli (STEC) O104:H4 infection occurred in Germany with severe hemorrhagic colitis and hemolytic-uremic syndrome (HUS). We defined abdominal radiologic findings in these patients and correlated them with clinical parameters. 23 patients (7 men; age: 48 ± 19 years) with O104:H4 colitis and/or HUS received abdominal CT (n = 12) or radiographs (n = 11). Colonic distension, air-fluid levels, and free intraabdominal air were assessed. Colonic wall thickening, contrast enhancement, pericolic stranding, and ascites were evaluated on CT. Laboratory parameters and clinical presentation were reviewed. Chi-square test, Student's t-test, McNemar's test and Spearman correlation were performed. Colonic lumen distension was seen in 16/23 patients (69.6 %). The ascending colon (11/23 patients; 47.8 %) and transverse colon (12/23 patients; 52.2 %) were dilated significantly more often (p = 0.006 and p = 0.003, respectively) than the descending colon (1/23; 4.3 %). All 12 patients undergoing CT scanning had abnormally thickened colonic wall segments, 3 (25 %) had pancolic involvement and 9 (75 %) had segmental involvement. The descending colon was predominantly affected (11/12 patients; 91.7 %) and thickened significantly more often than other colonic segments (p < 0.001). The segmental type of STEC O104:H4 colitis mainly affects the descending colon with upstream distension of the transverse/ascending colon and differs from other types of colitis.


Influence of de qi on the immediate analgesic effect of SP6 acupuncture in patients with primary dysmenorrhoea and cold and dampness stagnation: a multicentre randomised controlled trial.
The aim of this multicentre randomised controlled trial was to investigate the contribution of de qi to the immediate analgesic effect of acupuncture in patients with primary dysmenorrhoea and the specific traditional Chinese medicine diagnosis cold and dampness stagnation. Eighty-eight patients with primary dysmenorrhoea and cold and dampness stagnation were randomly assigned to de qi (n=43) or no de qi (n=45) groups and underwent 30 min of SP6 acupuncture. The de qi group received deep needling at SP6 with manipulation using thick needles; the no de qi group received shallow needling with no manipulation using thin needles. In both groups the pain scores and actual de qi sensation were evaluated using a visual analogue scale for pain (VAS-P) and the acupuncture de qi clinical assessment scale (ADCAS), respectively. Both groups showed reductions in VAS-P, with no signficant differences between groups. ADCAS scores showed 43/43 and 25/45 patients in de qi and no de qi groups, respectively, actually experienced de qi sensation. Independent of original group allocation, VAS-P reductions associated with actual de qi (n=68) were greater than those without (28.4±18.19 mm vs 14.6±12.28 mm, p=0.008). This study showed no significant difference in VAS-P scores in patients with primary dysmenorrhoea and cold and dampness stagnation immediately after SP6 acupuncture designed to induce or avoid de qi sensation. Both treatments significantly reduced VAS-P relative to baseline. Irrespective of group allocation, patients experiencing actual de qi sensation demonstrated larger reductions in pain score relative to those without, suggesting greater analgesic effects. Chinese Clinical Trial Registry (ChiCTR-TRC-13003086); Results.


Preparation and in vitro evaluation of FGF-2 incorporated carboxymethyl chitosan nanoparticles.
Fibroblast growth factor 2 (FGF-2) is a multi-functional protein involving in wound healing. However, FGF-2 is easily degradable in vivo, which limited its use for wound treatment. In this study, we investigated a drug-delivery model for FGF-2 via incorporation with biodegradable carboxylmethyl chitosan (CMCS). CMCS nanoparticles (NPs) could be synthesized by ionic gelation using CaCl2 as a crosslinking reagent with the CMCS:CaCl2 ratio of 1:0.8. Synthesized CMCS NPs had a diameter of 32.68±6.83nm, and were non-toxic at concentrations up to 2.5mg/ml. Incorporated CMCS:FGF-2 NPs had a diameter of 34.83±5.89nm and incorporation efficiency was 95%. CMCS:FGF-2 NPs released 36.36% and 58.47% of FGF-2 after 48h incubation in two different pH of 7.4 and 5.8, respectively. The incorporation and release processes did not have a significant effect on FGF-2 activity. Simultaneously, CMCS:FGF-2 NPs could protect FGF-2 from the degradation of trypsin in vitro. Our results laid the groundwork for the manufacturing of protein incorporated CMCS NPs for bio-applications.


[The double chisel--a new nasal osteotome (author's transl)].
A new chisel for performing osteotomy in rhinoplasty is described. It is double barrelled and consists of two flat chisels jointed together. Its advantage is that it permits clean division of the nasal bones and in combination with "in and out fracturing" contour irregularities are almost completely avoided.


Comparison of unenhanced magnetic resonance imaging and ultrasound in detecting very small hepatocellular carcinoma.
In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱ are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years. To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously. In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US. The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US (P < 0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S7-8 was identified in 51.7%. Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.


Rapid alterations to marine microbiota communities following an oil spill.
Field data from the first several days after an oil spill is rare but crucial for our understanding of a spill's impact on marine microbiota given their short generation times. Field data collected within days of the Texas City "Y" oil spill showed that exposure to crude oil can rapidly imbalance populations of marine microbiota, which leads to the proliferation of more resistant organisms. Vibrionales bacteria were up to 48 times higher than background concentrations at the most impacted sites and populations of the dinoflagellate Prorocentrum texanum increased significantly as well. Laboratory microcosm experiments with a natural plankton community showed that P. texanum grew significantly faster under oiled conditions but monocultures of P. texanum did not. Additional laboratory experiments with natural communities from Tampa Bay, Florida showed similar results although a different species dominated, P. minimum. In both cases, tolerance to the presence of crude oil was enhanced by higher sensitivity of grazers led to a release from grazing pressure and allows Prorocentrum species to dominate after an oil spill. The results suggest careful monitoring for Vibrionales and Prorocentrum during future spills would be beneficial given the potential implications to human health.


Chemotherapy-induced nausea, vomiting, and fatigue--the role of individual differences related to sensory perception and autonomic reactivity.
In spite of antiemetics, postchemotherapy side effects continue to be common and may affect compliance to cancer treatment. Among the known factors associated with increased symptom severity are: younger age, treatment toxicity, expected severity, and distress, but little is still known about the role of other factors. The aim of our study was to investigate the role of individual differences related to sensory perception for posttreatment side effects. Hundred and twenty-five women receiving adjuvant chemotherapy for breast cancer completed measures of absorption, autonomic perception, somatosensory amplification, trait anxiety, and expected severity at baseline. Pretreatment distress and posttreatment nausea, vomiting, and fatigue were assessed at the 1st, 4th, 6th and last cycles of chemotherapy. While univariate analyses showed several factors to be associated with side effects, only absorption and pretreatment distress remained independent predictors of nausea and fatigue when controlling for the remaining factors. Posttreatment vomiting was only predicted by expected severity of vomiting. Chemotherapy-induced side effects are related to increased autonomic nervous system activity, and absorption has been associated with increased autonomic nervous system reactivity to stress. The results suggest that individuals with high absorption may be at greater risk for developing side effects. Improved precision in identifying patients at risk of experiencing more severe side effects after cancer treatment will increase the ability to target treatments aimed at reducing these side effects.


Detection and identification of imperatorin metabolites in rat, dog, monkey, and human liver microsomes by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry and Compound Discoverer software.
Imperatorin, a furanocoumarin that widely exists in many umbelliferous herbs, has been demonstrated to have a variety of pharmacological effects, including anti-inflammatory, antiosteoporosis, and antitumor activities. The purpose of this study was to investigate the metabolism of imperatorin using liver microsomes. The metabolites were generated by individually incubating imperatorin with rat, dog, monkey, and human liver microsomes. To trap the reactive metabolites during microsomal metabolism, glutathione (GSH) was included in the incubation. A LC technique coupled with benchtop orbitrap MS with full mass/data-dependent tandem mass spectrometry acquisition mode was used to detect and identify the generated metabolites. The possible structures of the metabolites were characterized according to their accurate masses and fragment ions. Under the current conditions, a total of 10 metabolites, including four GSH adducts, were identified. The results indicated that imperatorin underwent extensive metabolic reactions including hydroxylation, oxidation, glucuronidation, and GSH conjugation. This study provides essential data on the metabolism of imperatorin, which will be helpful for us to understand the safety and efficacy of this bioactive compound.


Spontaneous cervical intradural disc herniation associated with ossification of posterior longitudinal ligament.
Intradural herniation of a cervical disc is rare; less than 35 cases have been reported to date. A 52-year-old man with preexisting ossification of posterior longitudinal ligament developed severe neck pain with Lt hemiparesis while asleep. Neurological exam was consistent with Brown-Séquard syndrome. Magnetic resonance images showed a C5-6 herniated disc that was adjacent to the ossified ligament and indenting the cord. The mass was surrounded by cerebrospinal fluid signal intensity margin, and caudally the ventral dura line appears divided into two, consistent with the "Y-sign" described by Sasaji et al. Cord edema were noted. Because of preexisting canal stenosis and spinal cord at risk, a laminoplasty was performed, followed by an anterior C6 corpectomy. Spot-weld type adhesions of the posterior longitudinal ligament to the dura was noted, along with a longitudinal tear in the dura. An intradural extra-arachnoid fragment of herniated disc was removed. Clinical exam at 6 months after surgery revealed normal muscle strength but persistent mild paresthesias. It is difficult to make a definite diagnosis of intradural herniation preoperatively; however, the clinical findings and radiographic signs mentioned above are suggestive and should alert the surgeon to look for an intradural fragment.


SPI1 activates TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells.
Glioma stem cells (GSCs) exhibit diverse molecular subtypes with the mesenchymal (MES) population representing the most malignant variant. The oncogenic potential of Salmonella pathogenicity island 1 (SPI1), an oncogenic transcription factor, has been established across various human malignancies. In this study, we explored the association between the SPI1 pathway and the MES GSC phenotype. Through comprehensive analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas glioma databases, along with patient-derived GSC cultures, we analyzed SPI1 expression. Using genetic knockdown and overexpression techniques, we assessed the functional impact of SPI1 on GSC MES marker expression, invasion, proliferation, self-renewal, and sensitivity to radiation in vitro, as well as its influence on tumor formation in vivo. Additionally, we investigated the downstream signaling cascades activated by SPI1. Our findings revealed a positive correlation between elevated SPI1 expression and the MES phenotype, which in turn, correlated with poor survival. SPI1 enhanced GSC MES differentiation, self-renewal, and radioresistance in vitro, promoting tumorigenicity in vivo. Mechanistically, SPI1 augmented the transcriptional activity of both TGF-β1 and FKBP12 while activating the non-canonical PI3K/Akt pathway. Notably, inhibition of TGF-β1/PI3K/Akt signaling partially attenuated SPI1-induced GSC MES differentiation and its associated malignant phenotype. Collectively, our results underscore SPI1's role in activating TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12, thereby supporting the aggressive MES phenotype of GSCs. Therefore, SPI1 emerges as a potential therapeutic target in glioma treatment.


A scanning electron microscope study of concanavalin A receptors on retinal rod cells labeled with latex microspheres.
Con A-methacrylate microsphere conjugates prepared by a two-step glutaraldehyde reaction were used to label Con A-binding sites on bovine rod photoreceptor cells for visualization by scanning electron microscopy. A dense distribution of markers was observed on the surface of the rod outer segment, the inner segment, and the synaptic region. Disk membranes also appear to be heavily labeled with the Con A-microsphere conjugates. The Con A inhibitor, alpha-methyl mannoside, inhibited the binding of the conjugate to the surface of these visual cells.


GENETIC INTERACTIONS AND NATURAL SELECTION IN LOUISIANA IRIS HYBRIDS.
Hybridization between divergent lineages has long been assumed to give rise to unfavorable interactions between the parental genomes. These deleterious genetic interactions are further assumed to result in the production of hybrid offspring with decreased levels of viability and/or fertility. To test this assumption, we investigated the role of both nuclear and cytonuclear epistatic interactions in determining the frequencies of F2 genotypes produced in crosses between two species of Louisiana iris, Iris fulva and I. brevicaulis. Overall, these crosses revealed a significant deficit of intermediate hybrid genotypes accompanied by an excess of parental-like genotypes, suggesting that genetic interactions may promote postmating reproductive isolation between these species. However, analyses of single and multilocus segregation patterns revealed a variety of negative and positive interactions between the genomes of the parental taxa at the nuclear and cytonuclear levels. Taken together, these results indicate that the traditional view that interactions between divergent genomes are always deleterious is an oversimplification. Rather, it seems likely that crosses between divergent lineages can lead to the production of both fit and unfit hybrid genotypes.


Collagen Synthesis-Promoting Effects of Andiroba Oil and its Limonoid Constituents in Normal Human Dermal Fibroblasts.
The seed oil of andiroba (Carapa guianensis, Meliaceae) was found to promote collagen synthesis in normal human dermal fibroblasts. To characterize the active constituents of this oil, the collagen synthesis-promoting activities of 10 principal limonoid constituents, gedunin (1), 6α-acetoxygedunin (2), 7-deacetoxy-7-oxogedunin (3), 7-deacetoxy-7α-hydroxygedunin (4), andirolide H (5), 6α-hydroxygedunin (6), methyl angolensate (7), 17β-hydroxyazadiradione (8), and carapanosides C (9) and R (10), were examined. Among them, 1-4, 6, 7, and 9 were found to significantly promote collagen synthesis without cytotoxicity at the effective concentrations.


From Kaua'i to Hawai'i Island: Interisland Differences in Emergency Contraceptive Pill Availability.
Emergency contraceptive pills (ECPs) are medications used after unprotected intercourse, underprotected intercourse, or sexual assault to decrease the risk of pregnancy. Availability of ECPs in Hawai'i's retail pharmacies was last assessed in 2007, following over-the-counter access to levonorgestrel ECPs (LNG-ECP) for women age 18 years or older and prior to U.S. Food and Drug Administration (FDA) approval of prescription-only ulipristal acetate (UPA). We conducted a county-by-county subanalysis from a larger observational population-based study on statewide availability of ECPs in Hawai'i's pharmacies. In the original study, researchers called all 198 unique retail pharmacies in Hawai'i between December 2013 and June 2014. Only 3% of pharmacies had UPA immediately available on-site in the state, with UPA available on Kaua'i and O'ahu only. At least one form of LNG-ECPs was available in 82% of pharmacies in 2013-2014, roughly the same as 2007 (81%) (P=0.9) when Lana'i and Moloka'i lacked access. Currently, only Moloka'i lacks retail pharmacy access to ECPs. When controlling for general inflation, the 2013-2014 mean price for name brand LNG-ECP fell within the reported range of 2007 prices. Generic LNG-ECPs were substantially lower in price than name brand LNG-ECPs in 2007 and 2013-2014. Availability of UPA is limited and significantly lower compared to LNG-ECPs. Availability of LNG-ECPs statewide has remained stable and the arrival of generics has decreased prices.


Assessment of ovarian vascularization in the polycystic ovary by three-dimensional power Doppler ultrasonography.
To assess whether there are differences in ovarian echogenicity and vascularization as assessed by three-dimensional power Doppler angiography (3D-PDA) between women with polycystic ovaries (PCO) and women with normal ovaries (NO). Eighty-three women were classified into two groups according to the 2003 Rotterdam consensus criteria. The NO group comprised women (n = 45) with regular menstrual cycles and proven fertility, whereas the PCO group comprised women (n = 38) with oligo-anovulation, clinical and/or biochemical features of hyperandrogenism, and polycystic ovary morphology at two-dimensional ultrasound. All women were evaluated by means of 3D-PDA. The parameters studied in both groups were follicle number per ovary (FNPO), ovarian volume (OV), mean gray value (MG) and three vascular indices: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The PCO group showed a higher mean OV as well as FNPO. No differences in MG, VI, FI and VFI were found between the groups. 3D-PDA indices are not useful for discriminating between normal and polycystic ovaries.


[The first Congolese case of cervical clear cell adenocarcinoma].
The authors report the first Congolese case of uterine cervix clear cell adenocarcinoma in a menopausal multipara, whose mother had not been treated by diethystilboestrol (DES). The histological diagnosis was made on embedded-paraffin samples, stained by HE and PAS. Discharged from hospital on parents' request in order to be on infusion and brew-based traditional treatment, the patient died at home two months after diagnosis.


Applying fault tree analysis to the prevention of wrong-site surgery.
Wrong-site surgery (WSS) is a rare event that occurs to hundreds of patients each year. Despite national implementation of the Universal Protocol over the past decade, development of effective interventions remains a challenge. We performed a systematic review of the literature reporting root causes of WSS and used the results to perform a fault tree analysis to assess the reliability of the system in preventing WSS and identifying high-priority targets for interventions aimed at reducing WSS. Process components where a single error could result in WSS were labeled with OR gates; process aspects reinforced by verification were labeled with AND gates. The overall redundancy of the system was evaluated based on prevalence of AND gates and OR gates. In total, 37 studies described risk factors for WSS. The fault tree contains 35 faults, most of which fall into five main categories. Despite the Universal Protocol mandating patient verification, surgical site signing, and a brief time-out, a large proportion of the process relies on human transcription and verification. Fault tree analysis provides a standardized perspective of errors or faults within the system of surgical scheduling and site confirmation. It can be adapted by institutions or specialties to lead to more targeted interventions to increase redundancy and reliability within the preoperative process.


Probing protein orientation near charged nanosurfaces for simulation-assisted biosensor design.
Protein-surface interactions are ubiquitous in biological processes and bioengineering, yet are not fully understood. In biosensors, a key factor determining the sensitivity and thus the performance of the device is the orientation of the ligand molecules on the bioactive device surface. Adsorption studies thus seek to determine how orientation can be influenced by surface preparation, varying surface charge, and ambient salt concentration. In this work, protein orientation near charged nanosurfaces is obtained under electrostatic effects using the Poisson-Boltzmann equation, in an implicit-solvent model. Sampling the free energy for protein G B1 D4' at a range of tilt and rotation angles with respect to the charged surface, we calculated the probability of the protein orientations and observed a dipolar behavior. This result is consistent with published experimental studies and combined Monte Carlo and molecular dynamics simulations using this small protein, validating our method. More relevant to biosensor technology, antibodies such as immunoglobulin G are still a formidable challenge to molecular simulation, due to their large size. With the Poisson-Boltzmann model, we obtained the probability distribution of orientations for the iso-type IgG2a at varying surface charge and salt concentration. This iso-type was not found to have a preferred orientation in previous studies, unlike the iso-type IgG1 whose larger dipole moment was assumed to make it easier to control. Our results show that the preferred orientation of IgG2a can be favorable for biosensing with positive charge on the surface of 0.05 C/m(2) or higher and 37 mM salt concentration. The results also show that local interactions dominate over dipole moment for this protein. Improving immunoassay sensitivity may thus be assisted by numerical studies using our method (and open-source code), guiding changes to fabrication protocols or protein engineering of ligand molecules to obtain more favorable orientations.


Recognizing and Maximizing the Nexus of Perioperative Medicine and Narrative Medicine.
Perioperative medicine remains an evolving, interdisciplinary subspecialty, which encompasses the unique perspectives and incorporates the respective vital expertise of numerous stakeholders. This integrated model of perioperative medicine and care has a wide-ranging set of clinical, strategic, and operational goals. Among these various programmatic goals, a subset of 4, specific, interdependent goals include (1) enhancing patient-centered care, (2) embracing shared decision-making, (3) optimizing health literacy, and (4) avoiding futile surgery. Achieving and sustaining this subset of 4 goals requires continued innovative approaches to perioperative care. The burgeoning field of narrative medicine represents 1 such innovative approach to perioperative care. Narrative medicine is considered the most prominent recent development in the medical humanities. Its central tenet is that attention to narrative-in the form of the patient's story, the clinician's story, or a story constructed together by the patient and clinician-is essential for optimal patient care. If we can view the health care experience through the patient's eyes, we will become more responsive to patients' needs and, thereby, better clinicians. There is a potential clinical nexus between the perioperative medicine practice and narrative medicine skills, which, if capitalized, can maximize perioperative patient care. There are a number of untapped educational and research opportunities in this fruitful nexus between perioperative medicine and narrative medicine.


La2TeI2: a new layered telluride iodide with unusual electrical properties.
A new layered metal-rich telluride halide, La2TeI2, has been synthesized by heating stoichiometric mixtures of LaI3, La, and Te under argon at 900 degrees C, and its structure has been refined from X-ray powder diffraction data. The compound crystallizes in the 3R-Lu2CCl2 structure type (rhombohedral space group R(-)3m with a = 4.5074(4) A, c = 32.528(2) A, and Z = 3). The crystal structure is composed of infinite layers of edge-sharing, Te-centered metal atom octahedra and iodine atoms separating these layers to form three close-packed I-Ln-Te-Ln-I slabs within the unit cell. The title compound is metallic at room temperature and exhibits an anomaly in the resistivity around 140 K which is closely related to changes in the a lattice parameter with temperature. The chemical bonding and metallic properties of La2TeI2 can be plausibly understood in terms of an ionic description (Ln3+)2Te2-(I-)2(e)2 where two electrons are delocalized in the La 5d conduction band.


Protonation and conformational dynamics of GFP mutants by two-photon excitation fluorescence correlation spectroscopy.
GFP mutants are known to display fluorescence flickering, a process that occurs in a wide time range. Because serine 65, threonine 203, glutamate 222, and histidine 148 have been indicated as key residues in determining the GFP fluorescence photodynamics, we have focused here on the role of histidine 148 and glutamate 222 by studying the fluorescence dynamics of GFPmut2 (S65A, V68L, and S72A GFP) and its H148G (Mut2G) and E222Q (Mut2Q) mutants. Two relaxation components are found in the fluorescence autocorrelation functions of GFPmut2: a 10-100 micros pH-dependent component and a 100-500 micros laser-power-dependent component. The comparison of these three mutants shows that the mutation of histidine 148 to glycine induces a 3-fold increase in the protonation rate, thereby indicating that the protonation-deprotonation of the chromophore occurs via a proton exchange with the solution mediated by the histidine 148 residue. The power-dependent but pH-independent relaxation mode, which is not affected by the E222Q and H148G mutations, is due to an excited-state process that is probably related to conformational rearrangements of the chromophore after the photoexcitation, more than to the chromophore excited-state proton transfer.


Azithromycin impact on neutrophil oxidative metabolism depends on exposure time.
Several antimicrobial agents have already been investigated relating to their influence on neutrophil ROS generation. Azithromycin provides, a dose-related anti-oxidant effect, after 15 min incubation, with the stimulating agent FMLP, as well with PMA or S. aureus. This finding was however obtained with concentrations not considered in therapeutics. Since short incubation times are not representative of the physiological situation, and since azithromycin is characterized by prolonged high concentrations within phagocytes, the same experiments were performed over 2 and 4 h exposures. A time-dependent anti-oxidant effect was then reported. The maximum effect was obtained with PMA (IC50 were 856 and 30 micrograms/ml for 15 min and 4 h incubation times respectively). Time-dependent modifications of neutrophil oxidative metabolism seem to be correlated with intracellular concentrations. Depressed oxidative metabolism might be related neither to azithromycin cellular toxicity, nor to superoxide scavenging properties. By increasing exposure periods, therapeutic concentrations could therefore lead to an anti-inflammatory effect, potentially of clinical interest since associated with bacteriostatic activity.


Chronic pain and infection: mechanisms, causes, conditions, treatments, and controversies.
Throughout human history, infection has been the leading cause of morbidity and mortality, with pain being one of the cardinal warning signs. However, in a substantial percentage of cases, pain can persist after resolution of acute illness, manifesting as neuropathic, nociplastic (eg, fibromyalgia, irritable bowel syndrome), or nociceptive pain. Mechanisms by which acute infectious pain becomes chronic are variable and can include immunological phenomena (eg, bystander activation, molecular mimicry), direct microbe invasion, central sensitization from physical or psychological triggers, and complications from treatment. Microbes resulting in a high incidence of chronic pain include bacteria such as the Borrelia species and Mycobacterium leprae, as well as viruses such as HIV, SARS-CoV-2 and herpeses. Emerging evidence also supports an infectious cause in a subset of patients with discogenic low back pain and inflammatory bowel disease. Although antimicrobial treatment might have a role in treating chronic pain states that involve active infectious inflammatory processes, their use in chronic pain conditions resulting from autoimmune mechanisms, central sensitization and irrevocable tissue (eg, arthropathy, vasculitis) or nerve injury, are likely to cause more harm than benefit. This review focuses on the relation between infection and chronic pain, with an emphasis on common viral and bacterial causes.


IgG anti-IgE autoantibodies in visceral leishmaniasis.
Procedures for IgG depletion in visceral leishmaniasis (VL) and schistosomiasis sera using Sepharose-protein G beads also deplete IgE. In this study, the presence of IgG anti-IgE autoantibodies in sera from patients with VL (n = 10), and hepatic-intestinal schistosomiasis (n = 10) and from healthy individuals (n = 10) was investigated. A sandwich ELISA using goat IgG anti-human IgE to capture serum IgE and goat anti-human IgG peroxidase conjugate to demonstrate the binding of IgG to the IgE captured was performed. VL sera had higher titers (p < 0.05) of IgG anti-IgE autoantibodies (OD = 2.01 +/- 0.43) than sera from healthy individuals (OD = 1.35 +/- 0.16) or persons infected with Schistosoma mansoni (OD = 1.34 +/- 0.18). The immunoblotting carried out with eluates from Sepharose-protein G beads used to deplete IgG from these sera and goat anti-human IgE peroxidase conjugate, showed a similar pattern of bands, predominating the 75 kDa epsilon-heavy chain and also polypeptides resulting from physiological enzymatic digestion of IgE. A frequent additional band immediately above 75 kDa was observed only in VL sera.


The Role of Silicon in Higher Plants under Salinity and Drought Stress.
Although deemed a "non-essential" mineral nutrient, silicon (Si) is clearly beneficial to plant growth and development, particularly under stress conditions, including salinity and drought. Here, we review recent research on the physiological, biochemical, and molecular mechanisms underlying Si-induced alleviation of osmotic and ionic stresses associated with salinity and drought. We distinguish between changes observed in the apoplast (i.e., suberization, lignification, and silicification of the extracellular matrix; transpirational bypass flow of solutes and water), and those of the symplast (i.e., transmembrane transport of solutes and water; gene expression; oxidative stress; metabolism), and discuss these features in the context of Si biogeochemistry and bioavailability in agricultural soils, evaluating the prospect of using Si fertilization to increase crop yield and stress tolerance under salinity and drought conditions.


Revealing DNA interactions with exogenous agents by surface-enhanced Raman scattering.
The standard protocols for DNA analysis largely involve polymerase chain reaction (PCR). However, DNA structures bound to chemical agents cannot be PCR-amplified, and therefore any sequence changes induced by external agents may be neglected. Thus, the development of analytical tools capable of characterizing the biochemical mechanisms associated with chemically induced DNA damage is demanded for the rational design of more effective chemotherapy drugs, understanding the mode of actions of carcinogenic chemicals, and monitoring the genotypic toxicology of environments. Here we report a fast, high-throughput, low-cost method for the characterization and quantitative recognition of DNA interactions with exogenous agents based on surface-enhanced Raman scattering spectroscopy. As representative chemical agents, we selected a chemotherapeutic drug (cisplatin) which forms covalent adducts with DNA, a duplex intercalating agent (methylene blue), and a cytotoxic metal ion (Hg(II)) which inserts into T:T mismatches. Rich structural information on the DNA complex architecture and properties is provided by the unique changes of their SERS spectra, which also offer an efficient analytical tool to quantify the extent of such binding.


Investigating the awareness level about diabetes mellitus and associated factors in Tarlai (rural Islamabad).
To determine the baseline level of awareness amongst a rural community about Diabetes Mellitus (irrespective of type 1 or type 2), its risk factors and complications. This was a cross-sectional survey conducted at the community of Tarlai, Islamabad, Pakistan, in January of 2008. A structured questionnaire was used and 300 adults (age > or = 18 years) were assessed on their knowledge regarding awareness of Diabetes Mellitus, its risk factors and complications. All data collected was entered into SPSS version 10.0. The data was re-validated and analyzed. Out of the three hundred adults subjected to the survey, only 129 (43%) adults had any awareness of Diabetes Mellitus. Adults with no regular, scheduled exercise were 221 (73.7%) and 256 (85.3%) did not have healthy eating habits. Awareness of risk factors was present in 42 (14%) while awareness of the complications associated with the disease was 65 (22%). Adults which reported as never going for regular checkups to any clinic or hospital were 232 (77%). Family history of diabetes mellitus was statistically significantly associated with awareness about diabetes mellitus (65% vs 32%, p < 0.001), people who were in contact regularly with health care providers were more aware about diabetes and the associated risk factors than those who were not (71% vs 35%, p < 0.001). Sex was not associated (p = 0.28) with awareness about diabetes mellitus, nor was the educational status (p = 0.46). Majority of adults were unaware of Diabetes Mellitus itself and associated risk factors. Raising public awareness of the disease through outreach programmes and mass media should be planned and implemented.


Structural basis for the interaction of protein S1 with the Escherichia coli ribosome.
In Gram-negative bacteria, the multi-domain protein S1 is essential for translation initiation, as it recruits the mRNA and facilitates its localization in the decoding centre. In sharp contrast to its functional importance, S1 is still lacking from the high-resolution structures available for Escherichia coli and Thermus thermophilus ribosomes and thus the molecular mechanism governing the S1-ribosome interaction has still remained elusive. Here, we present the structure of the N-terminal S1 domain D1 when bound to the ribosome at atomic resolution by using a combination of NMR, X-ray crystallography and cryo-electron microscopy. Together with biochemical assays, the structure reveals that S1 is anchored to the ribosome primarily via a stabilizing π-stacking interaction within the short but conserved N-terminal segment that is flexibly connected to domain D1. This interaction is further stabilized by salt bridges involving the zinc binding pocket of protein S2. Overall, this work provides one hitherto enigmatic piece in the 'ribosome puzzle', namely the detailed molecular insight into the topology of the S1-ribosome interface. Moreover, our data suggest novel mechanisms that have the potential to modulate protein synthesis in response to environmental cues by changing the affinity of S1 for the ribosome.


[Silicon forms and its role in infant food].
This paper presents an attempt to assess the total content of silicon and its potentially bioavailable forms to the baby body in milk nutrient and baby foods. The measurements of the total and bioavailable silicon were conducted with the use of two analytical methods. The method of atomic absorption spectroscopy (AAS) was used for the determination of total silicon content. Bioavailable silicon was determined by means of visible light spectroscopy (VIS) with ammonium molybdate. In the group milk products the largest amount of total silicon was found in Mlekovita milk -0.54 mg/l, and Humana 2 milk formula contained the largest amount of ionised silicon-0.24 mg/l. In baby foods manufactured by Gerber the total amount of silicon was high and the average content stood at 27 mg/kg in dry matter. The largest amount of total silicon was found in Vegetables and Ham-48.19 mg/kg in dry matter, as well as bioavailable silicon--4.13 mg/kg in dry matter. Compare level of silicon in milk nutrient and baby foods to silicon content in human milk 0.05 mg/l, it was found that large excess of silicon in this foodstuffs.


Application of maxillofacial miniplating and microplating systems to the hand.
During the past several years, a profound change in our approach to bone stabilization in the hand has occurred. Today, standard management of almost any fracture requiring open reduction as well as most arthrodeses and osteotomies will incorporate rigid fixation employing one of the maxillofacial systems. Many of the early concerns, such as increased complexity of the procedure, the need for extensive periosteal stripping, bulkiness of the plates (with potential palpation, tenderness, and the impingement on tendon and joint motion), and the anticipated frequent need for removal, have been allayed. Thinner plates, the smallest screws from the miniplating systems, and the introduction of the microplating systems (Luhr and Synthes) have obviated much of the anticipated difficulty with tendon gliding and have made the necessity for subsequent plate removal a rarity in our practice. The use of these systems allows much earlier mobilization postoperatively, reducing the incidence of joint stiffness and tendon adhesion. This paper discusses our series of 143 patients (average follow-up time over 18 months) and the application of miniplating and microplating systems for a variety of fractures, osteotomies, and arthrodeses in the hand.


The expression of thymidine phosphorylase suppresses spontaneous apoptosis of cancer cells in esophageal squamous cell carcinoma.
Thymidine phosphorylase (TP) is an enzyme which converts thymidine to thymine. TP is expressed in a variety of human carcinomas and is known to be a potent angiogenic factor. A recent in vitro study indicated that TP is involved in the intracellular apoptotic signal transduction pathway. The aim of this study was to investigate the correlations between the expression of TP, microvessel density (MVD) and the occurrence of spontaneous apoptosis in esophageal squamous cell carcinoma (ESCC). The expression of TP, intratumoral MVDs and percentages of apoptotic cancer cells, expressed by the apoptotic index (AI), of 155 tumors from 155 patients with ESCC were analyzed by immunohistochemistry and compared. Positive TP expression in cancer and stromal cells was detected in 89 (57.4%) and 104 (67.1%) cases, respectively. The mean MVD and mean AI of the 155 tumors were 288/mm(2) (range: 36-668/mm(2)) and 2.1% (range: 0-20.4%). The mean MVD of 104 tumors with TP-positive stromal cells (336/mm(2)) was higher than that of 51 tumors with TP-negative stromal cells (188/mm(2), p < 0.001). However, the mean MVD of 89 tumors with TP-positive cancer cells (293/mm(2)) did not differ from that of 66 tumors with TP-negative cancer cells (280/mm(2), p = 0.509). On the other hand, the mean AI of 89 tumors with TP-positive cancer cells (1.2%) was lower than that of 66 tumors with TP-negative cancer cells (3.4%, p < 0.001). However, the mean AI of 104 tumors with TP-positive stromal cells (1.9%) did not differ from that of 51 tumors with TP-negative stromal cells (2.6%, p = 0.058). No significant correlation between the MVDs and the AIs was observed (rho = -0.067, p = 0.409). In ESCC, TP may play an important role in tumor progression by increasing microvessels and suppressing apoptosis of cancer cells.


Vulvodynia - an evolving disease.
Vulvodynia is a common vulval pain syndrome that occurs most commonly in reproductive women of all ages. It can, in some cases, present for the first time after menopause. Up to about 15% of adult women have had symptoms of vulvodynia, with 4-5% currently symptomatic. Since there are no specific tests for diagnosis, vulvodynia is a diagnosis of exclusion. The condition is commonly associated with other chronic pain disorders and can be exceedingly debilitating, resulting in sexual dysfunction, severe depression and/or anxiety. It can significantly impair quality of life. Goals for long-term team approach management should be discussed with the patient at the commencement of each intervention as effectiveness of therapy is not assured. Currently, there is no intervention that effects cure in all individuals and a combination of pharmacological therapy, psychotherapy and physiotherapy, reserving surgery as a last-line option, is the best option for treatment. There are no long-term data on how long women will have symptoms and, if resolved, what provokes symptoms again in the future, whilst correlation between the etiology of vulvodynia and efficacy of treatment is not known.


Does the siphon effect of cerebrospinal fluid shunting develop in vivo? Report of a case casting doubt on the presence of this phenomenon.
A 52-year-old male underwent lumboperitoneal shunting after external decompressive craniectomy. His postoperative course was accompanied by remarkable displacement of the intracranial structures to the opposite side of craniectomy. This phenomenon, probably caused by the siphon effect of cerebrospinal fluid shunting, resolved after cranioplasty. This observation provides the evidence casting doubt on the presence of the siphon effect due to atmospheric pressure in patients without the association of skull defect or open cranial sutures.


Mechanisms of hypoxia responses in renal tissue.
pO2 in the kidney is maintained at relatively stable levels by a unique and complex functional interplay between renal blood flow, GFR, O2 consumption, and arteriovenous O2 shunting. The fragility of this interplay makes the kidney susceptible to hypoxic injury. Cells in the kidney utilize various molecular pathways that allow them to respond and adapt to changes in renal oxygenation. This review provides an integrative perspective on the role of molecular hypoxia responses in normal kidney physiology and pathophysiology, and discusses their therapeutic potential for the treatment of renal diseases.


[Pharmacokinetics of cefatrizine administered in repeated doses].
Twelve healthy volunteers received cefatrizine orally at doses equal to 500 mg every 12 h for 5 days. Cefatrizine was assayed by high performance liquid chromatography in plasma and urines collected after the first and/or the last administration. Cefatrizine absorption was rapid; its peak plasma level was reached at time 1.79 +/- 0.07 h following the first dose, it was equal to 7.37 +/- 0.31 micrograms.ml-1. Its apparent elimination half-life was equal to 1.50 +/- 0.05 h, it explains the lack of accumulation with time during multiple administrations every 12 hours. Comparisons between peak plasma concentration and area under curves following the first and last dosing showed significant (p less than 0.01) but weak (close to 15%) reduction of these 2 parameters with time which could be explained by a slight reduction of cefatrizine absorption with time. In conclusion, cefatrizine does not accumulate when administered repeatedly at a dose equal to 500 mg every 12 h in young adult, and its pharmacokinetics is virtually linear with time.


Diaryl-Pyrano-Chromenes Atropisomers: Stereodynamics and Conformational Studies.
The dynamic scenario of di-aryls-pyrano-chromenes was investigated using DFT calculations. The symmetry of the chromene scaffold and the presence of two ortho-substituted aryls substituents can generate two syn/anti diastereoisomers and conformational enantiomers with different rotational barriers. The relative conformations and configurations were derived using NOESY-1D experiments. Depending on the energies related to the conformational exchange, the experimental energy barriers were determined through Dynamic NMR, Dynamic HPLC or kinetic studies. The atropisomeric pairs were resolved in the latter scenario, and their absolute configuration was assigned using the ECD/TD-DFT method.


Simultaneous GPS-tracking of parents reveals a similar parental investment within pairs, but no immediate co-adjustment on a trip-to-trip basis.
Parental care benefits the offspring, but comes at a cost for each parent, which in biparental species gives rise to a conflict between partners regarding the within-pair distribution of care. Pair members could avoid exploitation by efficiently keeping track of each other's efforts and coordinating their efforts. Parents may, therefore, space their presence at the nest, which could also allow for permanent protection of the offspring. Additionally, they may respond to their partner's previous investment by co-adjusting their efforts on a trip-to-trip basis, resulting in overall similar parental activities within pairs. We investigated the coordination of parental care measured as nest attendance and foraging effort in the Lesser black-backed gull (Larus fuscus), a species with long nest bouts that performs extended foraging trips out of sight of their partner. This was achieved by GPS-tracking both pair members simultaneously during the entire chick rearing period. We found that the timing of foraging trips (and hence nest attendance) was coordinated within gull pairs, as individuals left the colony only after their partner had returned. Parents did not match their partner's investment by actively co-adjusting their foraging efforts on a trip-by-trip basis. Yet, pair members were similar in their temporal and energetic investments during chick rearing. Balanced investment levels over a longer time frame suggest that a coordination of effort may not require permanent co-adjustment of the levels of care on a trip-to-trip basis, but may instead rather take place at an earlier stage in the reproductive attempt, or over integrated longer time intervals. Identifying the drivers and underlying processes of coordination will be one of the next necessary steps to fully understand parental cooperation in long-lived species.


Failure mechanisms of total hip resurfacing: implications for the present.
In the past decade, there has been a renewed interest in hip resurfacing due to recent design improvements. It is unclear whether the recent improvements have accounted for all of the previous failure mechanisms. We determined the long-term performance of hip resurfacing, while paying special attention to the mechanisms of failure. We retrospectively reviewed 62 patients (65 hips) who had Indiana conservative hip prostheses implanted between 1977 and 1981. Forty-one of 62 joints had failed, representing a failure rate of 66%. The time to failure averaged 9.7 years with a range of 6 months to 21.5 years. There were 23 femoral failures (37%). Eleven were caused by femoral fracture, and 12 were caused by femoral loosening. All late femoral failures (greater than 10 years postoperatively) showed narrowing of the femoral neck secondary to stress shielding. There were 18 acetabular failures (29%) with 10 failing secondary to polyethylene wear and eight failing secondary to acetabular loosening. Failure of the Indiana conservative hip prosthesis continues over time related to femoral and acetabular failure mechanisms. These data should be considered in the context of growing enthusiasm for resurfacing with new bearing surfaces and cementless fixation.


Thulium fiber laser: ready to dust all urinary stone composition types?
To evaluate whether stone dust can be obtained from all prevailing stone composition types using the thulium fiber laser (TFL) for lithotripsy. Where applicable, stone dust was further characterized by morpho-constitutional analysis. Human urinary stones were submitted to in vitro lithotripsy using a FiberLase U2 TFL generator with 150 µm silica core fibers (IPG Photonics®, IPG Medical™, Marlborough, MA, USA). Laser settings were 0.05 J, 320 Hz and 200 μs. A total of 2400 J were delivered to each stone composition type. All evaluated stones had a > 90% degree of purity (calcium oxalate monohydrate, calcium oxalate dihydrate, uric acid, carbapatite, struvite, brushite and cystine). Spontaneously floating stone particles were considered as stone dust and collected for analysis by scanning electron microscopy and Fourier transform infrared spectroscopy. Stone dust could be retrieved from all evaluated urinary stones after TFL lithotripsy. Most stone dust samples revealed changes in crystalline organization, except for calcium oxalate monohydrate and carbapatite, which conserved their initial characteristics. Mean maximal width of stone dust particles did not exceed 254 µm. The TFL is capable to produce stone dust from all prevailing stone types. Morpho-constitutional changes found in stone dust suggest a photothermal interaction of laser energy with the stone matrix during TFL lithotripsy.


Randomized clinical study on the analgesic effect of local infiltration versus spinal block for hemorrhoidectomy.
Postoperative analgesia and early recovery are important for hospital discharge. The primary objective of this study was to compare the analgesic effectiveness of perianal infiltration and subarachnoid anesthesia for hemorrhoidectomy. The secondary objective was to compare time to discharge, adverse effects and complications. Randomized, prospective and comparative study at Dr. Mário Gatti Hospital. Forty patients aged 18-60, in American Society of Anesthesiologists physical status category 1 or 2, were included. The local group (LG) received local infiltration (0.75% ropivacaine) under general anesthesia; the spinal group (SG) received subarachnoid block (2 ml of 0.5% bupivacaine). Analgesic supplementation consisted of fentanyl for LG and lidocaine for SG. Postoperative pain intensity, sphincter relaxation, lower-limb strength, time to discharge, analgesic dose over one week and adverse effects were assessed. Eleven LG patients (52.4%) required supplementation, but no SG patients. Pain intensity was higher for LG up to 120 min, but there were no differences at 150 or 180 min. There were no differences in the need for paracetamol or tramadol. Times to first analgesic supplementation and hospital discharge were longer for SG. The adverse effects were nausea, dizziness and urinary retention. Pain intensity was higher in LG than in SG over the first 2 h, but without differences after 150 and 180 min. Time to first supplementation was shorter in LG. There were no differences in doses of paracetamol and tramadol, or in adverse effects. ClinicalTrials.gov NCT02839538.


Nano-assemblies consisting of Pd/Pt nanodendrites and poly (diallyldimethylammonium chloride)-coated reduced graphene oxide on glassy carbon electrode for hydrogen peroxide sensors.
Non-enzymatic hydrogen peroxide (H2O2) sensors were fabricated on the basis of glassy carbon (GC) electrode modified with palladium (Pd) core-platinum (Pt) nanodendrites (Pt-NDs) and poly (diallyldimethylammonium chloride) (PDDA)-coated reduced graphene oxide (rGO). A facile wet-chemical method was developed for preparing Pd core-Pt nanodendrites. In this approach, the growth of Pt NDs was directed by Pd nanocrystal which could be regarded as seed. The PDDA-coated rGO could form uniform film on the surface of GC electrode, which provided a support for Pd core- Pt NDs adsorption by self-assembly. The morphologies of the nanocomposites were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction (spectrum). Electrocatalytic ability of the nanocomposites was evaluated by cyclic voltammetry and chronoamperometric methods. The sensor fabricated by Pd core-Pt NDs/PDDA-rGO/GCE exhibited high sensitivity (672.753 μA mM(-1) cm(-2)), low detection limit (0.027 μM), wider linear range (0.005-0.5mM) and rapid response time (within 5s). Besides, it also exhibited superior reproducibility, excellent anti-interference performance and long-term stability. The present work could afford a viable method and efficient platform for fabricating all kinds of amperometric sensors and biosensors.


What is it about your face that tells me what you want from me? Emotional appeals are associated with specific mental images.
Emotional facial expressions have a communicative function. Besides information about the internal states (emotions) and the intentions of the expresser (action tendencies), they also communicate what the expresser wants the observer to do (appeals). Yet, there is very little research on the association of appeals with specific emotions. The present study has the aim to study the mental association of appeals and expressions through reverse correlation. Using reverse correlation, we estimated the observer-specific internal representations of expressions associated with four different appeals. A second group of participants rated the resulting expressions. As predicted, we found that the appeal to celebrate was uniquely associated with a happy expression and the appeal to empathize with a sad expression. A pleading appeal to stop was more strongly associated with sadness than with anger, whereas a command to stop was comparatively more strongly associated with anger. The results show that observers internally represent appeals as specific emotional expressions.


HYDIN loss-of-function inhibits GATA4 expression and enhances atrial septal defect risk.
Mutations affecting cardiac structural genes can lead to congenital heart diseases (CHDs). Axonemal Central Pair Apparatus Protein (HYDIN) is a ciliary protein previously linked to congenital cardiomyopathy. However, the role of HYDIN in the aetiology of CHDs is thus far unknown. Herein, we explore the function of HYDIN in heart development and CHDs. The function of HYDIN in cardiac differentiation was assessed in vitro using HYDIN siRNAs, HYDIN overexpression, and HYDIN short hairpin RNA (shRNA)-GATA binding protein 4 (GATA4) cDNA rescue constructs in the human embryonic stem cell (hESC) line HES3. To assess Hydin's function in vivo, we generated shRNA-mediated Hydin knockdown transgenic mice. We characterized the functional mechanisms of the most common human HYDIN variant associated with atrial septal defect (ASD) risk (71098693 mutant, c.A2207C) in cardiac-differentiating HES3 cells. HYDIN functions as a positive regulator of human cardiomyocyte differentiation and promotes expression of cardiac contractile genes in hESC cells. This is mediated through GATA4, a critical transcription factor in heart development. Cardiac-specific Hydin knockdown in vivo leads to Gata4 downregulation and enhanced atrial septal defect (ASD) risk in mice. The c.A2207C HYDIN mutation reduces GATA4 expression in hESC cells. HYDIN loss-of-function inhibits GATA4 expression and enhances ASD risk. We also establish the regulation of a key transcription factor in heart development by a ciliary protein.


Glucose metabolism in obesity: influence of body fat distribution.
The dose-response relationships between portal venous insulin concentrations and hepatic glucose production and between peripheral insulin concentrations and peripheral glucose utilization were determined in 8 nonobese and 17 obese premenopausal women with either upper or lower body fat localization. The glucose production dose-response curves for the two obese groups were shifted to the right at all levels of portal insulinemia. The upper body obese women had a greater rightward shift compared to the lower body obese women. The peripheral glucose utilization dose-response curve was shifted to the right in the lower body obese women, but maximal glucose utilization was normal. The upper body obese women had both a greater rightward shift and a marked reduction in maximal glucose utilization. The insulin concentrations that had half-maximal effects on glucose production and utilization were similar in each group. These results indicate that the liver is not inherently more sensitive to insulin than peripheral tissues. Obesity is associated with a moderate diminution of hepatic and peripheral insulin sensitivity. Upper body fat localization in obese women is characterized by a greater diminution in insulin sensitivity and decline in peripheral insulin responsivity than is lower body fat localization. The marked peripheral insulin resistance in the former group may account for the increased prevalence of glucose intolerance.


Robotic Transrectal Computed Tomographic Ultrasound with Artificial Neural Network Analysis: First Validation and Comparison with MRI-Guided Biopsies and Radical Prostatectomy.
There is still a lack of availability of high-quality multiparametric magnetic resonance imaging (mpMRI) interpreted by experienced uro-radiologists to rule out clinically significant PC (csPC). Consequently, we developed a new imaging method based on computed tomographic ultrasound (US) supported by artificial neural network analysis (ANNA). Two hundred and two consecutive patients with visible mpMRI lesions were scanned and recorded by robotic CT-US during mpMRI-TRUS biopsy. Only significant index lesions (ISUP ≥2) verified by whole-mount pathology were retrospectively analyzed. Their visibility was reevaluated by 2 blinded investigators by grayscale US and ANNA. In the cohort, csPC was detected in 105 cases (52%) by mpMRI-TRUS biopsy. Whole-mount histology was available in 44 cases (36%). In this subgroup, mean PSA level was 8.6 ng/mL, mean prostate volume was 33 cm3, and mean tumor volume was 0.5 cm3. Median PI-RADS and ISUP of index lesions were 4 and 3, respectively. Index lesions were visible in grayscale US and ANNA in 25 cases (57%) and 30 cases (68%), respectively. Combining CT-US-ANNA, we detected index lesions in 35 patients (80%). The first results of multiparametric CT-US-ANNA imaging showed promising detection rates in patients with csPC. US imaging with ANNA has the potential to complement PC diagnosis.


Nanopore Cas9-targeted sequencing enables accurate and simultaneous identification of transgene integration sites, their structure and epigenetic status in recombinant Chinese hamster ovary cells.
The integration of a transgene expression construct into the host genome is the initial step for the generation of recombinant cell lines used for biopharmaceutical production. The stability and level of recombinant gene expression in Chinese hamster ovary (CHO) can be correlated to the copy number, its integration site as well as the epigenetic context of the transgene vector. Also, undesired integration events, such as concatemers, truncated, and inverted vector repeats, are impacting the stability of recombinant cell lines. Thus, to characterize cell clones and to isolate the most promising candidates, it is crucial to obtain information on the site of integration, the structure of integrated sequence and the epigenetic status. Current sequencing techniques allow to gather this information separately but do not offer a comprehensive and simultaneous resolution. In this study, we present a fast and robust nanopore Cas9-targeted sequencing (nCats) pipeline to identify integration sites, the composition of the integrated sequence as well as its DNA methylation status in CHO cells that can be obtained simultaneously from the same sequencing run. A Cas9-enrichment step during library preparation enables targeted and directional nanopore sequencing with up to 724× median on-target coverage and up to 153 kb long reads. The data generated by nCats provides sensitive, detailed, and correct information on the transgene integration sites and the expression vector structure, which could only be partly produced by traditional Targeted Locus Amplification-seq data. Moreover, with nCats the DNA methylation status can be analyzed from the same raw data without prior DNA amplification.


Is the modern high potential dairy cow suitable for organic farming conditions?
It is not acceptable to compromise animal welfare in any system of farming. Feeding should be aimed at meeting the nutritional requirements at the various stages of production. This paper deals with the detrimental effects that organic, extensive or low input farming systems may have on the energy status in early lactation of the high potential dairy cow. Bovine ketosis is the most important disease resulting from insufficient energy intake in early lactation. It is also important to realize that ketosis is a part of the so-called periparturient disease complex, which includes milk fever, mastitis, retained placenta, endometritis and poor fertility also. All these diseases are interrelated and reflect to a large extent the nutritional status of the animal. If organic dairy farming is to be successful the breeding programmes have to divert from selection for high yields as a main goal, to more emphasis on a flatter lactation curve, less production diseases and longevity.


Phylogenetic Resolution in Juglans Based on Complete Chloroplast Genomes and Nuclear DNA Sequences.
Walnuts (Juglans of the Juglandaceae) are well-known economically important resource plants for the edible nuts, high-quality wood, and medicinal use, with a distribution from tropical to temperate zones and from Asia to Europe and Americas. There are about 21 species in Juglans. Classification of Juglans at section level is problematic, because the phylogenetic position of Juglans cinerea is disputable. Lacking morphological and DNA markers severely inhibited the development of related researches. In this study, the complete chloroplast genomes and two nuclear DNA regions (the internal transcribed spacer and ubiquitin ligase gene) of 10 representative taxa of Juglans were used for comparative genomic analyses in order to deepen the understanding on the application value of genetic information for inferring the phylogenetic relationship of the genus. The Juglans chloroplast genomes possessed the typical quadripartite structure of angiosperms, consisting of a pair of inverted repeat regions separated by a large single-copy region and a small single-copy region. All the 10 chloroplast genomes possessed 112 unique genes arranged in the same order, including 78 protein-coding, 30 tRNA, and 4 rRNA genes. A combined sequence data set from two nuclear DNA regions revealed that Juglans plants could be classified into three branches: (1) section Juglans, (2) section Cardiocaryon including J. cinerea which is closer to J. mandshurica, and (3) section Rhysocaryon. However, three branches with a different phylogenetic topology were recognized in Juglans using the complete chloroplast genome sequences: (1) section Juglans, (2) section Cardiocaryon, and (3) section Rhysocaryon plus J. cinerea. The molecular taxonomy of Juglans is almost compatible to the morphological taxonomy except J. cinerea (section Trachycaryon). Based on the complete chloroplast genome sequence data, the divergence time between section Juglans and section Cardiocaryon was 44.77 Mya, while section Rhysocaryon diverged from other sections in the genus Juglans was 47.61 Mya. Eleven of the 12 small inversions in the chloroplast genomes provided valuable phylogenetic information for classification of walnut plants at section and species levels. Our results are valuable for future studies on Juglans genetic diversity and will enhance the understanding on the phylogenetic evolution of Juglandaceae.


Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China.
Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before and during the outbreak and contact-tracing information from Hunan province. Daily contacts were reduced seven- to eightfold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0 to 14 years of age are less susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults 15 to 64 years of age (odds ratio 0.34, 95% confidence interval 0.24 to 0.49), whereas individuals more than 65 years of age are more susceptible to infection (odds ratio 1.47, 95% confidence interval 1.12 to 1.92). Based on these data, we built a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. Although proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40 to 60% and delay the epidemic.


Safe surgery: validation of pre and postoperative checklists.
to develop, evaluate and validate a surgical safety checklist for patients in the pre and postoperative periods in surgical hospitalization units. methodological research carried out in a large public teaching hospital in the South of Brazil, with application of the principles of the Safe Surgery Saves Lives Programme of the World Health Organization. The checklist was applied to 16 nurses of 8 surgical units and submitted for validation by a group of eight experts using the Delphi method online. the instrument was validated and it was achieved a mean score ≥1, level of agreement ≥75% and Cronbach's alpha >0.90. The final version included 97 safety indicators organized into six categories: identification, preoperative, immediate postoperative, immediate postoperative, other surgical complications, and hospital discharge. the Surgical Safety Checklist in the Pre and Postoperative periods is another strategy to promote patient safety, as it allows the monitoring of predictive signs and symptoms of surgical complications and the early detection of adverse events.


Prosthetic polyester-based hybrid mesh for repairing of perineal hernia in dogs.
This study involves the use of a new multifunctional prosthetic mesh for treatment of the perineal hernia without complications. The prosthetic mesh is a hybrid platform of both synthetic and natural materials, mainly consisting of a synthetic commercial polyester fabric (CPF) to deliver the required mechanical integrity. The CPF mesh was coated by a natural biodegradable, biocompatible, and antimicrobial layer of chitosan incorporating phenytoin-loaded pluronic nanomicelles for healing promotion and ciprofloxacin-alginate polyelectrolyte complex-based microparticles as antibacterial agent. To evaluate the new developed multifunction polyester-based hybridmesh to repair perineal hernia clinical cases in dogs. The used multifunctional prosthetic mesh is a hybrid of the natural biodegradable, biocompatible, and antimicrobial material used in six cases with perineal hernia. The prosthetic polyester-based hybrid mesh was found very helpful in repairing clinical cases of perineal hernias in six dogs without unwarranted other surgical procedures or complications. The developed mesh proved its feasibility in terms of efficient biocompatibility, stability, sterilizability, and low cost. The prosthetic commercial polyester-based mesh provided the ideal and feasible alternative prosthesis with many advantages.


Introduction and Perspectives.
Classically, metabolism was investigated by studying molecular characteristics of enzymes and their regulators in isolation. This reductionistic approach successfully established mechanistic relationships with the immediate interacting neighbors and allowed reconstruction of network structures. Severely underdeveloped was the ability to make precise predictions about the integrated operation of pathways and networks that emerged from the typically nonlinear and complex interactions of proteins and metabolites. The burden of metabolic engineering is a consequence of this fact-one cannot yet predict with any certainty precisely what needs to be engineered to produce more complex phenotypes. What was and still is missing are concepts, methods, and algorithms to integrate data and information into a quantitatively coherent whole, as well as theoretical concepts to reliably predict the consequence of environmental stimuli or genetic interventions. This introduction and perspective to Domain 3, Metabolism and Metabolic Fluxes, starts with a brief overview of the panoply of global measurement technologies that herald the dawning of systems biology and whose impact on metabolic research is apparent throughout the Domain 3. In the middle section, applications to Escherichia coli are used to illustrate general concepts and successes of computational methods that approach metabolism as a network of interacting elements, and thus have potential to fill the gap in quantitative data and information integration. The final section highlights prospective focus areas for future metabolic research, including functional genomics, eludication of evolutionary principles, and the integration of metabolism with regulatory networks.


Expression patterns of cluster of differentiation 147 impact the prognosis of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) has very low overall survival. According to global cancer statistics, approximately 905677 new cases were reported in 2020, with at least 830180 of them being fatal. Cluster of differentiation 147 (CD147) is a novel, transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development. Based on the reports described previously, we theorize that CD147 may be used as a novel biological indicator to predict the prognosis of HCC. To study this possibility, expression profiles of CD147 and corresponding clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed, and a hazard ratio (HR) was established. To explore the pattern of CD147 expression and its applicability in the prognosis of HCC. To establish HRs and probability points for predicting the prognosis of HCC by correlating CD147 expression with clinical characteristics. To determine if CD147 can be a reliable biomarker in HCC prognosis. The CD147 expression profile in HCC and corresponding clinical data were obtained from TCGA database. The expression patterns of CD147 were then validated by analyzing data from the GEO database. In addition, CD147 immunohistochemistry in HCC was obtained from the Human Protein Atlas. CD147 expression patterns and clinical characteristics in the prognosis of HCC were analyzed by accessing the UALCAN web resource. Accuracy, sensitivity, and specificity of the CD147 expression profile in predictive prognosis were determined by the time-dependent receiver operating characteristic (ROC) curves. Kaplan-Meier curves were plotted to estimate the HR of survival in HCC. Univariate and multivariate Cox regression proportional hazards analyses of CD147 expression levels and clinical characteristics as prognostic factors of HCC were performed. Nomograms were used to establish probability points and predict prognosis. Data from TCGA and GEO databases revealed that CD147 was significantly overexpressed in HCC (P = 1.624 × 10-12 and P = 1.2 × 10-5, respectively). The expression of CD147 and prognosis of HCC were significantly correlated with the clinical characteristics of HCC as per the data from the UALCAN web resource (P < 0.05). Kaplan-Meier analysis of CD147 expression in HCC revealed that the high expression groups showed poor prognosis and an HR of survival > 1 [log-rank test, P = 0.000542, HR (in high expression group): 1.856, 95% confidence interval (CI): 1.308 to 2.636]. ROC curves were plotted to analyze the 1-year, 3-year, and 5-year survival rates. The area under the ROC curve values were 0.675 (95%CI: 0.611 to 0.740), 0.623 (95%CI: 0.555 to 0.692), and 0.664 (95%CI: 0.582 to 9.745), respectively. Univariate Cox analysis of CD147 expression and clinical characteristics of HCC and multivariate Cox analysis of CD147 patterns and pathological tumor-node-metastasis stage showed significant differences (univariate Cox, P = 0.00013, HR: 1.424, 95%CI: 1.884 to 1.707 and P = 0.00066, HR: 1.376, 95%CI: 1.145 to 1.654, respectively; multivariate Cox, P = 0.00578, HR: 1.507, 95%CI: 1.126 to 2.018 and P = 0.00336, HR: 1.443, 95%CI: 1.129 to 1.844, respectively). Nomograms were plotted to establish the probability points and predict prognosis. The total points ranged from 0 to 180, and the C-index value was 0.673 (95%CI: 0.600 to 1.000, P < 0.01). Overexpression of CD147 was correlated with poor prognosis in HCC. The CD147 expression profile combined with clinical characteristics can reliably predict the prognosis of HCC. CD147 can serve as a biomarker to predict the prognosis of HCC.


Cryopreservation of Proteins Using Ionic Liquids: A Case Study of Cytochrome c.
Aqueous ionic liquid (IL) solutions form a glassy state at 77 K over a wide concentration of ILs. They have potential as novel cryopreservation/refolding solvents for proteins. However, even if proteins in glass-forming concentrations of ILs are preserved at 77 K, the recovery of activity and the structure of the proteins after cryopreservation are still unclear. To achieve high recovery of protein activity and structure by removal of ILs after cryopreservation at 77 K, we studied the recovery of activity and structural stability after cryopreservation of bovine heart cytochrome c in aqueous solutions with ILs, including ethylammonium nitrate (EAN) and 1-butyl-3-methylimidazolium thiocyanate ([bmim][SCN]) over wide IL concentrations using UV-vis, Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy. On the whole, although the addition of both ILs induced a decrease of activity and unfolding of the secondary structure of cytochrome c before and after cooling to 77 K, EAN, a weak denaturant, showed a reduction in protein damage (decrease of activity and unfolding of secondary structure) during the reheating process from 77 K (protection ability). In contrast, [bmim][SCN], a strong denaturant, did not have this protective ability. A remarkable result is that although the addition of both ILs caused cytochrome c denaturation, > 90% of activity and structure after cryopreservation (X > 10 mol %IL) was recovered after the removal of both ILs by dialysis. These recoveries after the removal of ILs are slightly higher than the results for dimethyl disulfide (DMSO), another cryoprotectant. The present results indicate that concentrated aqueous IL solutions have potential as one-pot (i.e., solubilization/preservation/refolding) solvents for proteins, which easily aggregate after purification, with comparable results to DMSO.


Rigorous Criteria for the Collapse of Nonlinear Cooperative Networks.
Many real-world complex systems, when hitting a tipping point, undergo irreversible sudden shifts that can eventually take a great toll on humanity and the natural world, such as ecosystem collapses, disease outbreaks, etc. Previous work has adopted approximations to predict the tipping points, but due to the nature of nonlinearity, this may lead to unexpected errors in predicting real-world systems. Here we obtain the rigorous bounds of the tipping points for general nonlinear cooperative networks. Our results offer two rigorous criteria that determine the collapse and survival of such a system. These two criteria are decided by the combined effect of dynamical parameters and interaction topology.


Profiling the transcriptome of Gracilaria changii (Rhodophyta) in response to light deprivation.
Light regulates photosynthesis, growth and reproduction, yield and properties of phycocolloids, and starch contents in seaweeds. Despite its importance as an environmental cue that regulates many developmental, physiological, and biochemical processes, the network of genes involved during light deprivation are obscure. In this study, we profiled the transcriptome of Gracilaria changii at two different irradiance levels using a cDNA microarray containing more than 3,000 cDNA probes. Microarray analysis revealed that 93 and 105 genes were up- and down-regulated more than 3-fold under light deprivation, respectively. However, only 50% of the transcripts have significant matches to the nonredundant peptide sequences in the database. The transcripts that accumulated under light deprivation include vanadium chloroperoxidase, thioredoxin, ferredoxin component, and reduced nicotinamide adenine dinucleotide dehydrogenase. Among the genes that were down-regulated under light deprivation were genes encoding light harvesting protein, light harvesting complex I, phycobilisome 7.8 kDa linker polypeptide, low molecular weight early light-inducible protein, and vanadium bromoperoxidase. Our findings also provided important clues to the functions of many unknown sequences that could not be annotated using sequence comparison.


A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus.
Beta blockers used for the treatment of hypertension may be associated with increased risk for new-onset diabetes mellitus (DM). A search of Medline, PubMed, and EMBASE was conducted for randomized controlled trials of patients taking beta blockers as first-line therapy for hypertension with data on new-onset DM and follow-up for > or =1 year. Twelve studies evaluating 94,492 patients fulfilled the inclusion criteria. Beta-blocker therapy resulted in a 22% increased risk for new-onset DM (relative risk 1.22, 95% confidence interval [CI] 1.12 to 1.33) compared with nondiuretic antihypertensive agents. A higher baseline fasting glucose level (odds ratio [OR] 1.01, 95% CI 1.00 to 1.02, p = 0.004) and greater systolic (OR 1.05, 95% CI 1.05 to 1.08, p = 0.001) and diastolic (OR 1.06, 95% CI 1.01 to 1.10, p = 0.011) blood pressure differences between the 2 treatment modalities were significant univariate predictors of new-onset DM. Multivariate meta-regression analysis showed that a higher baseline body mass index (OR 1.17, 95% CI 1.01 to 1.33, p = 0.034) was a significant predictor of new-onset DM. The risk for DM was greater with atenolol, in the elderly, and in studies in which beta blockers were less efficacious antihypertensive agents and increased exponentially with increased duration on beta blockers. For the secondary end points, beta blockers resulted in a 15% increased risk for stroke, with no benefit for the end point of death or myocardial infarction. In conclusion, beta blockers are associated with an increased risk for new-onset DM, with no benefit for the end point of death or myocardial infarction and with a 15% increased risk for stroke compared with other agents. This risk was greater in patients with higher baseline body mass indexes and higher baseline fasting glucose levels and in studies in which beta blockers were less efficacious antihypertensive agents compared with other treatments.


Diversification in vipers: Phylogenetic relationships, time of divergence and shifts in speciation rates.
Snakes of the cosmopolitan family Viperidae comprise around 329 venomous species showing a striking heterogeneity in species richness among lineages. While the subfamily Azemiopinae comprises only two species, 70% of all viper species are arranged in the subfamily Crotalinae or the "pit vipers". The radiation of the pit vipers was marked by the evolution of the heat-sensing pits, which has been suggested to be a key innovation for the successful diversification of the group. Additionally, only crotalines were able to successfully colonize the New World. Here, we present the most complete molecular phylogeny for the family to date that comprises sequences from nuclear and mitochondrial genes representing 79% of all living vipers. We also investigated the time of divergence between lineages, using six fossils to calibrate the tree, and explored the hypothesis that crotalines have undergone an explosive radiation. Our phylogenetic analyses retrieved high support values for the monophyly of the family Viperidae, subfamilies Viperinae and Crotalinae, and 22 out of 27 genera, as well as well-supported intergeneric relationships throughout the family. We were able to recover a strongly supported sister clade to the New World pit vipers that comprises Gloydius, Ovophis, Protobothrops and Trimeresurus gracilis. Our results agree in many aspects with other studies focusing on the phylogenetics of vipers, but we recover new relationships as well. Despite the addition of new sequences we were not able to resolve some of the poor supported relationships previously suggested. Time of divergence estimates suggested that vipers started to radiate around the late Paleocene to middle Eocene with subfamilies most likely dating back to the Eocene. The invasion of the New World might have taken place sometime close to the Oligocene/Miocene boundary. Diversification analyses suggested a shift in speciation rates during the radiation of a sub-clade of pit vipers where speciation rates rapidly increased but slowed down toward the present. Thus, the evolution of the loreal pits alone does not seem to explain their explosive speciation rates. We suggest that climatic and geological changes in Asia and the invasion of the New World may have also contributed to the speciation shift found in vipers.


Floating aerial LED signage based on aerial imaging by retro-reflection (AIRR).
We propose a floating aerial LED signage technique by utilizing retro-reflection. The proposed display is composed of LEDs, a half mirror, and retro-reflective sheeting. Directivity of the aerial image formation and size of the aerial image have been investigated. Furthermore, a floating aerial LED sign has been successfully formed in free space.