Carbon and energy footprint of the hydrate-based biogas upgrading process integrated with CO2 valorization.
The present paper aims at assessing the carbon and energy footprint of an energy process, in which the energy excess from intermittent renewable sources is used to produce hydrogen which reacts with the CO2 previously separated from an innovative biogas upgrading process. The process integrates a hydrate-based biogas upgrading section and a CO2 methanation section, to produce biomethane from the biogas enrichment and synthetic methane from the CO2 methanation. Clathrate hydrates are crystalline compounds, formed by gas enclathrated in cages of water molecules and are applied to the selective separation of CO2 from biogas mixtures. Data from the experimental setup were analyzed in order to evaluate the green-house gas emissions (carbon footprint CF) and the primary energy consumption (energy footprint EF) associated to the two sections of the process. The biosynthetic methane production during a single-stage process was 0.962Nm3, obtained mixing 0.830Nm3 of methane-enriched biogas and 0.132Nm3 of synthetic methane. The final volume composition was: 73.82% CH4, 19.47% CO2, 0.67% H2, 1.98% O2, 4.06% N2 and the energy content was 28.0MJ/Nm3. The functional unit is the unitary amount of produced biosynthetic methane in Nm3. Carbon and energy footprints are 0.7081kgCO2eq/Nm3 and 28.55MJ/Nm3, respectively, when the electric energy required by the process is provided by photovoltaic panels. In this scenario, the overall energy efficiency is about 0.82, higher than the worldwide average energy efficiency for fossil methane, which is 0.75.


PKC-isoform specific regulation of receptor desensitization and KCNQ1/KCNE1 K+ channel activity by mutant α1B-adrenergic receptors.
Activation of a specific protein kinase C (PKC) isoform during stimulation of Gq protein-coupled receptors (GqPCRs) is determined by homologous receptor desensitization that controls the spatiotemporal formation of downstream Gq signalling molecules. Furthermore, GqPCR-activated PKC isoforms specifically regulate receptor activity via a negative feedback mechanism. In the present study, we investigated the contribution of several phosphorylation sites in the α1B-adrenergic receptor (α1B-AR) for PKC and G protein coupled receptor kinase 2 (GRK2) to homologous receptor desensitization and effector modulation. We analyzed signalling events downstream to human wildtype α1B-ARs and α1B-ARs lacking PKC or GRK2 phosphorylation sites (Δ391-401, α1B-ΔPKC-AR and Δ402-520, α1B-ΔGRK-AR) by means of FRET-based biosensors in HEK293 that served as online-assays of receptor activity. K+ currents through KCNQ1/KCNE1 channels (IKs), which are regulated by both phosphatidylinositol 4,5-bisphosphate (PIP2)-depletion and/or phosphorylation by PKC, were measured as a functional readout of wildtype and mutant α1B-AR receptor activity. As a novel finding, we provide evidence that deletion of PKC and GRK2 phosphorylation sites in α1B-ARs abrogates the contribution of PKCα to homologous receptor desensitization. Instead, the time course of mutant receptor activity was specifically modulated by PKCβ. Mutant α1B-ARs displayed pronounced homologous receptor desensitization that was abolished by PKCβ-specific pharmacological inhibitors. IKs modulation during stimulation of wildtype and mutant α1B-ARs displayed transient inhibition and current facilitation after agonist withdrawal with reduced capability of mutant α1B-ARs to induce IKs inhibition. Pharmacological inhibition of the PKCβ isoform did not augment IKs reduction by mutant α1B-ARs, but shifted IKs modulation towards current facilitation. Coexpression of an inactive (dominant-negative) PKCδ isoform (DN-PKCδ) abolished IKs facilitation in α1B-ΔGRK-AR-expressing cells, but not in α1B-ΔPKC-AR-expressing cells. The data indicate that the differential modulation of IKs activity by α1B-ΔGRK- and α1B-ΔPKC-receptors is attributed to the activation of entirely distinct novel PKC isoforms. To summarize, specific phosphorylation sites within the wildtype and mutant α1B-adrenergic receptors are targeted by different PKC isoforms, resulting in differential regulation of receptor desensitization and effector function.


Fractional-order time-sharing-control-based wireless power supply for multiple appliances in intelligent building.
The wired power transmission is usually adopted to supply power for the devices in the traditional buildings. With the development of intelligent buildings, the way of wired power supply would greatly increase the complexity and consumption of laying the lines. To improve the flexibility of power supply and reduce the cost of wiring, wireless power transfer technology has been used in smart buildings. However, it remains a fundamental challenge to create a simple wireless power transfer system in which power can be wirelessly transferred to multiple appliances. Therefore, this paper proposes a wireless power transfer scheme based on fractional-order time-sharing control for a variety of household appliances in intelligent building. In the proposed scheme, only one fractional-order capacitor in the transmitter is needed to realize the time-sharing resonant charging. In contrast, the traditional multiple-receiver systems require complicated control scheme, for example, controlling a plurality of sets of series-parallel capacitors through a series of relay switches. To demonstrate the method, a 150 W LED TV with 300 kHz and a 5 W mobile phone charger with 127 kHz serve as the actual loads. The experimental results show that the proposed system can supply power to the TV and the mobile phone by a time-sharing way wirelessly.


More rapid relief of pain with isosorbide dinitrate oral spray than with sublingual tablets in elderly patients with angina pectoris.
To evaluate the possibility of improving clinical practice in the treatment of angina pectoris, the duration of relief of pain with isosorbide dinitrate (ISDN) oral spray and sublingual tablets were compared in elderly patients with chronic stable angina pectoris. Nine patients (mean age 67 years) were studied in a randomized crossover trial. The patients underwent bicycle ergometry, which resulted in typical chest pain associated with electrocardiographic ST-segment depression in all 9. The patients received ISDN oral spray or sublingual tablets immediately on termination of exercise. At least 6 hours later another ergometry test was performed and the patients were crossed over to the other drug. ISDN spray relieved pain in all patients at a mean duration of 61.6 +/- 24.4 seconds after administration, whereas the duration of relief of pain by ISDN sublingual tablets was 112.4 +/- 70 seconds. The difference was highly significant (p less than 0.0005). It is concluded that clinical practice of treatment of angina pectoris in the elderly can be improved by using ISDN oral spray rather than sublingual tablets. The spray is effective at twice the rapidity of the sublingual tablet.


Liver purine nucleoside phosphorylase in Camelus dromedarius: purification and properties.
1. Purine nucleoside phosphorylase (purine nucleoside:orthophosphate ribosyl transferase, EC 18.104.22.168) was purified to electrophoretic homogeneity from the liver of Camelus dromedarius. 2. The enzyme appears to be a dimer with a 44,000 subunit mol. wt and displays non-linear kinetics with concave downward curvature in double reciprocal plots with respect to both inosine and orthophosphate as variable substrates. 3. The effect of thiol compounds on the enzyme activity and of pH on kinetic parameters is reported.


Fractal model of anomalous diffusion.
An equation of motion is derived from fractal analysis of the Brownian particle trajectory in which the asymptotic fractal dimension of the trajectory has a required value. The formula makes it possible to calculate the time dependence of the mean square displacement for both short and long periods when the molecule diffuses anomalously. The anomalous diffusion which occurs after long periods is characterized by two variables, the transport coefficient and the anomalous diffusion exponent. An explicit formula is derived for the transport coefficient, which is related to the diffusion constant, as dependent on the Brownian step time, and the anomalous diffusion exponent. The model makes it possible to deduce anomalous diffusion properties from experimental data obtained even for short time periods and to estimate the transport coefficient in systems for which the diffusion behavior has been investigated. The results were confirmed for both sub and super-diffusion.


Expression of the third member of the serum amyloid A gene family in mouse adipocytes.
Three homologous genes that code for three related proteins comprise the serum amyloid A (SAA) family in the mouse. Endotoxin induces equally vigorous expression of mRNAs for the three SAA genes in liver. In extrahepatic tissues SAA1 and/or SAA2 mRNAs have been found only in kidney and intestine, however, SAA3 is expressed in all extrahepatic tissues thus far examined. This observation raised the question: is SAA3 mRNA expressed by a single cell system dispersed throughout all tissues, or by differentiated cells of each tissue? This question was explored in various tissues by in situ hybridization with a single-stranded cRNA probe specific for SAA3 mRNA. We found expression in the liver of SAA3 mRNA by other cells as well as by hepatocytes. A common feature among extrahepatic tissues was SAA3 mRNA expression in adipocytes. SAA3 mRNA was also found in two nonadipose cells, Leydig cells of the testis, and some of the cells located in parafollicular zones of the spleen.


Inhibition of cyclic nucleotide phosphodiesterase during exposure to WI-38 cells to prostaglandin E1.
Short term incubation of WI-38 cultures with 5.7 micron prostaglandin E1 (PGE1) caused cyclic AMP phosphodiesterase activity in fibroblast homogenates to fall by 25 to 35% as compared to controls. The PGE1-induced decline in phosphodiesterase activity coincided with a rapid increase in intracellular cyclic AMP levels in response to the hormone and was rapidly reversed by washing the cultures free of the prostaglandin before homogenizing the cells. The effect of PGE1 on WI-38 phosphodiesterase activity was localized to the enzyme form(s) present in 27,000 times g supernatant fractions of cell homogenates. These data suggest that the pattern of cyclic AMP accumulation in WI-38 fibroblasts exposed to PGE1 may be related, at least in part, to decreased phosphodiesterase activity during hormone stimulation.


Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of bone marrow mesenchymal stromal cells.
The capacity of bone marrow mesenchymal stromal cells (BMSCs) to be induced into chondrocytes has drawn much attention for cell-based cartilage repair. BMSCs represent a small proportion of cells of the bone marrow stromal compartment and, thus, culture expansion is a necessity for therapeutic use. However, there is no consensus on how BMSCs should be isolated nor expanded to maximize their chondrogenic potential. During embryonic development pluripotent stem cells differentiate into chondrocytes and form cartilage in a hypoxic microenvironment. Freshly harvested human BMSCs were isolated and expanded from the aspirates of six donors, under either hypoxic conditions (3% O2) or normoxic conditions (21% O2). A colony-forming unit fibroblastic (Cfu-f) assay was used to determine the number of cell colonies developed from each donor. BMSCs at passage 2 (P2) were characterized by flow cytometry for the phenotypic expression of cell surface markers on mesenchymal stem cells. BMSCs at P2 were subsequently cultured in vitro as three-dimensional cell pellets in a defined serum-free chondrogenic medium under normoxic and hypoxic conditions. Chondrogenic differentiation of the BMSCs was characterized by biochemical and histological methods and by quantitative gene-expression analysis. After 14 days of culture, the number of BMSC colonies developed under hypoxia was generally higher (8% to 38% depending on donor) than under normoxia. BMSCs were positive for the cell surface markers CD13, CD29, CD44, CD73, CD90, CD105 and CD151, and negative for CD34. Regardless of the oxygen tension during pellet culture, hypoxia-expanded BMSC pellets underwent a more robust chondrogenesis than normoxia-expanded BMSC pellets after three weeks of culture, as judged by increased glycosaminoglycan synthesis and Safranin O staining, along with increased mRNA expression of aggrecan, collagen II and Sox9. Hypoxic conditions enhanced the mRNA expression of hypoxia inducible factor-2 alpha (HIF-2α) but suppressed the mRNA expression of collagen X in BMSC pellet cultures regardless of the oxygen tension during BMSC isolation and propagation. Taken together, our data demonstrate that isolation and expansion of BMSCs under hypoxic conditions augments the chondrogenic potential of BMSCs. This suggests that hypoxia-mediated isolation and expansion of BMSCs may improve clinical applications of BMSCs for cartilage repair.


Seasonally related effects on natural organic matter characteristics from source to tap in Korea.
In this study, natural organic matter (NOM) characteristics were investigated over three years of monthly monitoring to determine the effect of seasonal variations on NOM levels from source to tap. Liquid chromatography with organic carbon detection (LC-OCD) was used to determine NOM characteristics and the level of reduction of biodegradable dissolved organic carbon (BDOC). The average dissolved organic matter concentration in the source water (Lake Paldang, Korea) was not significantly different between summer and winter. However, the distribution of NOM components, such as biopolymers, building blocks, low molecular weight (MW) neutrals and acids, identified by LC-OCD, varied seasonally. While high MW NOM was preferentially removed by coagulation/sedimentation/rapid sand filtration (CSR), no seasonal effects were observed on the removal of high MW NOM. CSR and biological activated carbon (BAC) filtration showed a better efficiency of BDOC removal in winter and summer, respectively. High concentrations of chlorine used in the treatment plants in summer resulted in 10% higher DOC concentrations during disinfection. Overall NOM removal efficiencies from source to tap were 45% and 35% for summer and winter, respectively. Principal component analysis also indicated that seasonal variations (principal component 1) showed the strongest positive correlation with the overall performance of water treatment. The long-term monitoring of drinking water treatment processes showed that seasonal variations were important factors affecting NOM characteristics during water treatment.


Effects of Medicinal Plants on Fungal Community Structure and Function in Hospital Grassplot Soil.
Hospital grassplot soil is an important repository of pathogenic fungi exposed to the hospital environment, and the diffusion of these fungi-containing soil particles in the air increases the risk of nosocomial fungal infections. In this study, from the perspective of soil microbes-plant holobiont, four medicinal plants Mirabilis jalapa, Artemisia argyi, Viola philippica, and Plantago depressa were used as materials, based on ITS high-throughput amplicon sequencing and simulated pot experiments to explore the effect of medicinal plants on the fungal community in hospital grassplot soil, in order to provide a new exploration for hospital grassplot soil remediation. The results showed that the fungal community ecological guilds in primary test soil was mainly pathogen, and the abundance of animal pathogen with potential threats to human reached 61.36%. After planting medicinal plants, the composition and function of soil fungal community changed significantly. Although this change varied with plant species and growth stages, all samples collected in the pot experiment showed that the pathogen abundance decreased and the saprotroph abundance increased. In addition, 45 of the 46 core fungal genera defined in all potted samples were present in primary test soil, and many of them were human potential pathogens. These findings imply that the idea of enhancing soil quality in hospital grassplot soil by planting specific plants is feasible. However, the initial fungal community of the hospital grassplot soil has a certain stability, and it is difficult to completely eliminate the threat of pathogenic fungi by planting medicinal plants.


The genus Shirozuella Sasaji (Coleoptera, Coccinellidae, Shirozuellini) from the Chinese mainland.
The genus Shirozuella Sasaji, 1967 from the Chinese mainland is reviewed. Eight species are recognized, including four new species: Shirozuella motuoensissp. n., Shirozuella tibetinasp. n., Shirozuella unciformasp. n., and Shirozuella guoyueisp. n. Male genitalia of Shirozuella parenthesis Yu and Shirozuella quadrimacularis are described for the first time. All species are described and illustrated. A key and distribution map to the known species from the Chinese mainland are given.


Propidium uptake and ATP release in A549 cells share similar transport mechanisms.
The lipid bilayer of eukaryotic cells' plasma membrane is almost impermeable to small ions and large polar molecules, but its miniscule basal permeability in intact cells is poorly characterized. This report describes the intrinsic membrane permeability of A549 cells toward the charged molecules propidium (Pr2+) and ATP4-. Under isotonic conditions, we detected with quantitative fluorescence microscopy, a continuous low-rate uptake of Pr (∼150 × 10-21 moles (zmol)/h/cell, [Pr]o = 150 μM, 32°C). It was stimulated transiently but strongly by 66% hypotonic cell swelling reaching an influx amplitude of ∼1500 (zmol/h)/cell. The progressive Pr uptake with increasing [Pr]o (30, 150, and 750 μM) suggested a permeation mechanism by simple diffusion. We quantified separately ATP release with custom wide-field-of-view chemiluminescence imaging. The strong proportionality between ATP efflux and Pr2+ influx during hypotonic challenge, and the absence of stimulation of transmembrane transport following 300% hypertonic shock, indicated that ATP and Pr travel the same conductive pathway. The fluorescence images revealed a homogeneously distributed intracellular uptake of Pr not consistent with high-conductance channels expressed at low density on the plasma membrane. We hypothesized that the pathway consists of transiently formed water pores evenly spread across the plasma membrane. The abolition of cell swelling-induced Pr uptake with 500 μM gadolinium, a known modulator of membrane fluidity, supported the involvement of water pores whose formation depends on the membrane fluidity. Our study suggests an alternative model of a direct permeation of ATP (and other molecules) through the phospholipid bilayer, which may have important physiological implications.


Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.
To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis. We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry. Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2 = 18784, p < 0.001; χ2 = 47.1, p < 0.001; χ2 = 20, p < 0.001). The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.


The association between future self-continuity and problematic mobile video gaming among Chinese college students: the serial mediation of consideration of future consequences and state self-control capacity.
To explore the relationship between future self-continuity and problematic mobile video gaming among Chinese college students and to examine the serial mediation of consideration of future consequences and state self-control capacity on the association between future self-continuity and problematic mobile video gaming, based on Identity-Based Motivation Theory. The Problematic Mobile Video Gaming Scale, Future Self-continuity Scale, Consideration of Future Consequences Scale, and Short Version of State Self-control Capacity Scale were administered to a sample comprising 800 college students (338 males accounting for 42.3%). Multivariate analysis and latent variables analysis were utilized to explore the separate mediating role consideration of future consequences and state self-control capacity played in the association between future self-continuity and problematic mobile video gaming, and their serial mediation also was investigated. The Bootstrap method was employed to test the significance of these mediation effects. The negative association between future self-continuity and problematic mobile video gaming was moderately found. Students with increased consideration of future consequences from higher levels of future self-continuity have decreased their problematic mobile video gaming. Future self-continuity significantly positively predicted state self-control capacity, which in turn significantly negatively predicted problematic mobile video gaming. The serial mediation was also found. The findings revealed why differences in identification with the current and future selves become influencing factors in problematic mobile video gaming. This study observed the mediating role that consideration of future consequences and state self-control capacity play in the association between future self-continuity and problematic mobile video gaming.


Beating uncontrolled eating: Training inhibitory control to reduce food intake and food cue sensitivity.
In our food-rich environment we must constantly resist appealing food in order to maintain a healthy lifestyle. Previous studies have found that food-specific inhibition training can produce changes in eating behaviour, such as a reduction in snack consumption. However, the mechanisms that drive the effect of inhibition training on eating behaviour remain unknown. Identifying the mechanism underlying food-specific inhibition training could lead to more targeted training interventions increasing the potential efficacy of such interventions. In the current study, we investigated directly whether training-induced effects on inhibitory control might underlie the predicted change in eating behaviour. Healthy individuals who scored high on uncontrolled eating were randomly assigned to receive six online training sessions over six consecutive days of either food-specific response inhibition training (active group; n = 21) or response inhibition training without food stimuli (control group; n = 20). We measured pre- and post-training inhibitory control in the context of food and food cue sensitivity, as well as food consumption in a bogus taste test. As expected, food-specific inhibition training decreased snack consumption in the bogus taste test relative to control training. However, the active training did not improve inhibitory control towards food, nor did it reduce food cue sensitivity above and beyond the control training. Future studies are needed to investigate the potential underlying mechanism of food-specific inhibition training, as it remains unclear what drives the reliable effect on eating behaviour.


Testosterone and progesterone metabolism in the human neuroblastoma cell line SH-SY5Y.
The ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens and progesterone was studied by incubating the cells in the presence of labeled testosterone (T) or progesterone (P) to measure, respectively, the formation of dihydrotestosterone (DHT) or dihydroprogesterone (DHP) (5 alpha-reductase activity). The 3 alpha-hydroxysteroid dehydrogenase activity was studied by evaluating the conversion of labeled DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). The results show that undifferentiated neuroblastoma cells possess a significant 5 alpha-reductase activity, as shown by the considerable conversion of T into DHT; moreover, this enzymatic activity seems to be significantly stimulated following cell differentiation induced by the phorbol ester TPA, but not after differentiation induced by retinoic acid (RA). The 5 alpha-reductase(s) present in SH-SY5Y cells is also able to convert P into DHP. In undifferentiated cells, this conversion was about 8 times higher than that of T into DHT. Under the influences of TPA and RA, the formation of DHP followed the same pattern observed for the formation of DHT. SH-SY5Y cells also appear to possess the enzyme 3 alpha-hydroxysteroid dehydrogenase, since they are able to convert DHT into 3 alpha-diol. This enzymatic activity is not altered following TPA-induced differentiation and appears to be decreased following treatment with RA. It is suggested that the SH-SY5Y cell line may represent a useful "in vitro" model for the study of the mechanisms involved in the control of androgen and P metabolism in nervous cells.


Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study.
Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III-IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99-1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80-1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74-1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65-1.47, p = 0.93). NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.


Mechanism of the amelioration of the protein digestibility of whole marinated eggs by strong alkali pickling: Physicochemical properties, gel structure, and proteomics.
Marinated egg is one of the traditional egg products in China; however, its low digestibility has limited its further industrial application. In this study, the mechanism involved in the amelioration of the protein digestibility of whole marinated eggs by strong alkali pickling was investigated. The results revealed that the water content of strong alkali-pickled whole marinated egg (SPME) exhibited an increasing trend during the alkali pickling process. Furthermore, as the pickling process progressed, the hardness, net charge, and β-sheets of the SPME first increased and then decreased, and the stability of the secondary structure of the SPME gradually decreased. In addition, long-term strong alkali pickling damaged the gel properties and protein structure of SPME, which resulted in the degradation of the protein. Thus, the alkali pickling significantly enhanced the digestibility of the SPME protein and the number of peptides present in the enzymolysis product of SPME. In summary, strong alkali pickling effectively improved the protein digestibility of marinated egg.


Effect of electroacupuncture on the intestinal microflora in rats with stress urinary incontinence.
To examine the effect of electroacupuncture on the urodynamics and gut microbiota of rats with stress urinary incontinence (SUI). Thirty 2-month-old female Sprague-Dawley (SD) rats were randomly assigned to 4 groups: normal (N), model (M), nonacupoint electric acupuncture control (NAAC), and electroacupuncture (EA). An SUI rat model was established through vaginal balloon dilatation and bilateral oophorectomy. After various treatments, urodynamic tests were performed, and feces were collected. 16S rRNA sequencing analysis was used to investigate SUI-related changes in the intestinal flora. After treatment, compared with those of the M group, the leak point pressure and maximum bladder capacity of the electroacupuncture groups increased (P<0.05). The species community compositions of the N and M groups differed at the genus level, and there were 15 differentially abundant bacterial genera (P<0.05). The Blautia proportion was increased by electroacupuncture treatment (P<0.05) and was significantly positively correlated with the electroacupuncture treatment of SUI (according to Spearman correlation analysis). Electroacupuncture treatment can improve signs of urine leakage in rats with SUI rats by increasing the leak point pressure and maximum bladder capacity. The enrichment of Blautia by electroacupuncture treatment enrichment may be related to SUI sign improvement.


The impact of fathers' drinking on cognitive loss among social drinkers.
This chapter examines cognitive loss in social drinkers. The question of concern is whether the relationship between increased levels of alcohol consumption and reduced sober cognitive performance is misspecified. In particular, does reduced abstraction performance in social drinkers result from parental heavy drinking rather than, as we have proposed, from social drinkers' current use of alcohol. Because offspring of alcoholics may be at high risk for cognitive deficits even in childhood, these deficits may be transmitted in alcoholic families. Thus, the relationship between increased drinking and sober cognitive loss might be eliminated if parental drinking is controlled. We report here, however, that the effects of current alcohol use on abstraction performance in a representative sample of employed men and women cannot be accounted for by fathers' drinking. Our findings indicate the need for further research on both the cognitive effects of parental drinking and current alcohol use.


Effect of S-adenosyl-L-methionine administration on plasma levels of sulphur-containing amino acids in patients with liver cirrhosis.
An impaired transsulphuration pathway has been described in patients with liver cirrhosis. The defective metabolic step is located at the site of S-adenosyl-L-methionine (SAMe) formation from methionine. In a placebo-controlled study, we measured the fasting plasma levels of sulphur-containing amino-acids in cirrhotic patients with hypermethioninemia and/or severe hepatocellular failure, during treatment with exogenous SAMe (1.2 g i.v. for 3 days, followed by an oral administration of 1.2 g for an additional 30 days; 8 cases) or saline and placebo tablets (8 cases). All subjects were initially treated during hospital admission, and completed the oral study as out-patients. In patients given SAMe, long-term treatment doubled the plasma concentration of the secondary sulphur-containing amino acid cystine (from 36 [SD 18] mumol.l(-1) to 67 [36]) and taurine (from 42 [13] mumol.l(-1) to 89 [33]), which were on average low-normal at baseline, without any change in the concentration of methionine, of neutral amino acids, and of polyamines. No changes in plasma amino acids were observed in the control group. Two-factor, repeated measures of analysis of variance revealed differences between SAMe- and placebo-treated patients, consistent with an effect of long-term SAMe administration on secondary sulphur-containing amino acids. The potential therapeutic advantage of such treatment remains to be determined in clinical studies.


Use of transcutaneous electrical nerve stimulation along with functional tasks for immediate pain relief in individuals with knee osteoarthritis.
Knee pain is the major complaint in individuals with knee osteoarthritis (OA), and the effects of transcutaneous electrical nerve stimulation (TENS) on knee pain are controversial. The present study applied TENS along with functional tests to investigate its effect on pain level in individuals with mild-to-moderate knee OA. Twenty volunteers with knee OA classification of graded 2-3 performed four functional tests (stair climb test [SCT], timed up and go test [TUG], 6-minute walk test [6-MWT], knee extensor strength test [KES], and 2-step test from the locomotive syndrome risk test [LSR_2ST]) while wearing either an active or inactive TENS. Knee pain level before and after each test was self-accessed by the Visual Analogue Scale (VAS). The effect of TENS (active vs. inactive) on pain level was submitted to statistical analyses. Knee pain during SCT, TUG, and LSR_2ST tests was significantly lower when subjects used the active TENS, compared with using the inactive unit. The effect of the active TENS on pain level was also more significant in subjects with no anxiety or depression. The results provided evidence of immediate pain relief in individuals with mild-to-moderate knee OA when TENS is applied along with functional activities, that usually induced pain in people with knee OA. The use of transcutaneous electrical nerve stimulation (TENS) in pain management is still unclear. In this study, the analgesic effects of TENS in people with knee osteoarthritis (OA) were found effective when applied along with functional activities. Therefore, study findings provided clinical evidence for the use of TENS during functional activities as a conservative approach to reduce knee OA pain.


Case-control study of prostatic cancer in Kyoto, Japan: demographic and some lifestyle risk factors.
Demographic risk factors for prostatic cancer were examined in a case-control study of 100 triplets of prostatic cancer patients and age-, hospital-, and admission date-matched control series of benign prostatic hyperplasia (BPH) patients and general hospital patients. A higher risk of prostatic cancer was associated with the following factors: 1) long-term occupation in transport or communication (relative risk [RR] = 4.92, 95% confidence interval [CI]: 1.18-20.5) as compared with hospital controls; 2) the wife having a lower educational level (RR = 1.88, 95%CI: 1.02-3.45) as compared with hospital controls; 3) no past episode of hypertension as compared with BPH controls (RR = 2.30, 95%CI: 1.27-4.15); 4) having several sisters (more than four) as compared with both BPH and hospital controls (RR = 3.82, 95%CI: 1.35-10.8 and RR = 2.94, 95%CI: 1.08-8.03 respectively); 5) dense body hair as compared with hospital controls (RR = 4.28, 95%CI: 1.19-15.4). No significant links were found with blood type, daily drug use, head hair, skin color, body type, smoking habits, religion, body weight, and mental characteristics.


Sexual and reproductive health in young people with congenital heart disease: a systematic review of the literature.
Improved survival in young people with congenital heart disease (CHD) alters the significance of a range of developmentally important subjects, such as sexual and reproductive health. The aim of this study was to determine the level of knowledge about sexual and reproductive health issue in young people with CHD. We undertook a systematic review of the literature from 1966 to March 2004, searching Medline, Psych Info, and Em base using a broad range of search terms. Additionally, we searched the literature for published guidelines on standards of care for young people with CHD. We identified ten articles that examined patients,' understanding of their heart disease. Seven of them specifically investigated knowledge of sexual and reproductive health as it related to cardiac disease. In general, young people have a poor understanding of their heart disease. They appear to have a particularly poor grasp of sexual and reproductive health issues, yet they are interested in these issues. Therefore, health care programs for young people with CHD should incorporate sexual and reproductive health information and include anticipatory counseling and health risk screening.


Nomogram for the Prediction of 30-Day Readmission in Acute Pancreatitis.
A prediction model for 30-day readmission in patients with acute pancreatitis (AP) was needed. To develop a nomogram to predict 30-day readmission in patients with AP and validate the usefulness of serum indicators after discharge for the prediction of 30-day readmission. This was a retrospective cohort study enrolling patients with the first attack of AP. Baseline characteristics, clinical profiles, and serum indicators after discharge were compared. Multivariate logistic regression analysis and a nomogram were employed to determine the independent risk factors for 30-day readmission. A total of 7.32% (121/1653) of the patients were readmitted within 30 days after discharge. Different etiologies (biliary pancreatitis (adjusted odds ratio (AdjOR), 9.63; 95% confidence interval (CI), 1.28-72.52; P = 0.028), other causes (AdjOR, 9.37; 95% CI, 1.15-76.12, P = 0.026), mixed causes (AdjOR, 10.76; 95% CI, 1.27-91.35; P = 0.03) compared with alcoholic pancreatitis)), infected pancreatitis necrosis (IPN) (AdjOR, 2.3; 95% CI, 1.2-4.42; P = 0.013), total bilirubin level ≥ 20.5 µmol/L (AdjOR, 2.42; 95% CI, 1.23-4.77; P = 0.01), glucose level ≥ 6.1 mmol/L (AdjOR, 1.93; 95% CI, 1.16-3.19; P = 0.011), and albumin level < 40 g/L (AdjOR, 4.25; 95% CI, 2.44-7.41; P < 0.001) were independently associated with 30-day readmission. A nomogram incorporating these factors demonstrated good discrimination, calibration, and clinical utility. Serum indicators after discharge added predictive value compared with clinical variables alone (AUC, 0.78 vs. 0.685; P = 0.0001). The nomogram combining etiology, IPN, and serum indicators after discharge has favorable predictive performance for 30-Day readmission. The close monitoring and reexamination of serum indicators are essential for AP patients at high risk.


Histological antiphospholipid-associated nephropathy versus lupus nephritis in patients with systemic lupus erythematosus: an observational cross-sectional study with longitudinal follow-up.
Renal involvement is a severe complication in systemic lupus erythematosus (SLE). Moreover, a subset of SLE patients develop the anti-phospholipid syndrome (APS), characterised by the occurrence of anti-phospholipid antibodies in combination with macro- and microvascular thrombotic manifestations, including acute and chronic antiphospholipid-associated nephropathy (APLN). Clinical presentations of lupus nephritis and APLN are similar and a renal biopsy is necessary to differentiate between the conditions. Our aim with this study was to investigate the occurrence of histopathological findings consistent with APLN (hAPLN) in renal biopsies from SLE patients and to investigate associations with anti-phospholipid antibody specificities, clinical manifestations, HLA-DRB1 alleles, and long-term renal outcome. Consecutive renal biopsies from 112 SLE patients with renal involvement were investigated and evaluated for findings of hAPLN; in all there were 236 renal biopsies. Data from biopsy reports and clinical information were collected. Autoantibodies against cardiolipin and β2-glycoprotein-1 were measured by enzyme-linked immunosorbent assay. A lupus anticoagulant test was determined with a modified Dilute Russel Viper Venom method. HLA genotyping was performed by sequence-specific primer PCR. Renal outcome was determined at study end. The prevalence of hAPLN was 14.3% among SLE patients with renal involvement. Compared to patients with pure lupus nephritis, occurrence of hAPLN was associated with intima changes (odds ratio (OR) = 24; 95% confidence interval (CI), 3.0 to 189.8; P < 0.0001), hypertensive vascular changes (OR = 7.8; 95% CI, 1.6 to 39.4; P = 0.01), inflammatory infiltrates (OR = 6.5; 95% CI, 1.7 to 25.1; P = 0.007) and tubular atrophy (OR = 13.1; 95% CI, 1.7 to 103.6; P = 0.002). hAPLN was associated with the presence of cardiolipin antibodies (OR = 3.3; 95% CI, 1.0 to 10.8; P = 0.05) and triple anti-phospholipid antibody positivity (OR = 4.2; 95% CI, 1.3 to 13.7; P = 0.02). Patients with hAPLN were more hypertensive (OR = 3.8; 95% CI, 1.2 to 12.3; P = 0.03) and had higher levels of creatinine as compared to lupus nephritis patients (median 116 versus 75 μmol/L; P < 0.0001). We found significantly higher frequency of HLA-DRB1*13 (OR = 5.1; 95% CI, 1.7 to 15.4; P = 0.03) and development of end-stage renal disease (OR = 5.8; 95% CI, 1.7 to 19.7; P = 0.008) in hAPLN compared with lupus nephritis. hAPLN is a severe and often unrecognized condition in SLE patients with renal involvement. We have demonstrated an increased risk for development of renal impairment and a genetic predisposition in hAPLN patients compared to lupus nephritis patients.


Challenges in liver cancer and possible treatment approaches.
Globally, liver cancer is the most frequent fatal malignancy; in the United States, it ranks fifth. Patients are often diagnosed with liver cancer in advanced stages, contributing to its poor prognosis. Of all liver cancer cases, >90% are hepatocellular carcinomas (HCCs) for which chemotherapy and immunotherapy are the best options for therapy. For liver cancer patients, new treatment options are necessary. Use of natural compounds and/or nanotechnology may provide patients with better outcomes with lower systemic toxicity and fewer side effects. Improved treatments can lead to better prognoses. Finally, in this review, we present some of the problems and current treatment options contributing to the poor outcomes for patients with liver cancer.


Corpus callosum growth in normal and growth-restricted fetuses.
The aim of this study was to characterize the normal ultrasonographic growth of the corpus callosum (CC) in normal and in growth-restricted fetuses throughout gestation. This was a prospective cross-sectional study. Consecutive routine biometric measurements and fetal organ scans were obtained in patients undergoing elective fetal anatomical surveys or evaluation of the fetal growth between 16 to 33 weeks. Special attention was given to the CC of the fetal brain. In addition, we evaluated the growth of the CC in growth-restricted fetuses throughout pregnancy. Two hundred and fifty two normal fetuses were scanned between 16 and 36 weeks of gestation. A regression line of the CC was established through gestation and a second-degree correlation was found between gestational age and CC outer margin. Twenty four growth-restricted fetuses were also evaluated in which the growth of the CC was significantly below both the 25(th) and 50(th) percentiles in 77.3% and 95.5%, respectively, for the same gestational age. We provide nomograms for the ultrasonographic dimensions of the fetal CC that allows for prenatal diagnosis of abnormal dimensions of CC. The significance of abnormal CC growth in growth-restricted fetuses should be further evaluated.


Academic and non-academic predictors of academic performance in medical school: an exploratory cohort study.
Medical schools should also evaluate applicants' non-academic characteristics in the search for successful students and future physicians, but ideal non-academic criteria have not yet been found. We followed two successive generations of medical students at the University of Split School of Medicine (USSM) to assess both academic and non-academic constructs as predictors of academic performance, defined as medical school grade point average (GPA). We also interviewed some of the participants to gain additional insight for future studies. We measured study GPA in first and last year, as well as attitudes towards science, motivation, emotional intelligence, self-esteem, and perceived personal incompetence in first year. We also obtained their scores on existing medical school enrollment criteria, the State Graduation Exam (SGE) and high-school GPA. Regression models were constructed for predictors of GPA in the last year of medical school. Four structured pilot interviews were conducted to explore participants' perceptions of necessary traits for medical school and later practice. Regression analysis showed that only SGE predicted final academic performance in medical school (β=0.35, 95% confidence interval (CI)=0.06-0.64), while none of the non-academic constructs we assessed predicted this outcome of education. The two generations did not significantly differ in any variable except that intrinsic motivation was higher in the generation that enrolled in 2011 (OR=1.47, 95%CI=1.12-1.93, P=0.005). None of the non-academic constructs predicted academic performance in medical school. Their use as selection criteria may not be warranted as they could impact the academic quality of enrolling medical students.


Oxygen excess ratio control of PEM fuel cell systems with prescribed regulation time.
In this paper, we focus on addressing the air supply problem for fuel cells. The air supply system faces a challenge: operating at maximum load consumes a significant amount of power, while insufficient air can lead to oxygen starvation problems in fuel cells. An important metric, the oxygen excess ratio, indicates whether the fuel cell is receiving the appropriate amount of air. Unfortunately, directly measuring this ratio is generally impractical. To overcome this limitation, we propose a fixed-time observer that reconstructs the oxygen excess ratio within a short predetermined period. By utilizing this reconstructed index, we introduce a cascaded double-loop controller. Specifically, both the external and internal loops are regulated using a modified prescribed time control strategy. This approach enables the regulation of the oxygen excess ratio to the optimal value within a prescribed short time. The advantages of our proposed method are validated through hardware in-loop experiments, showcasing its superiority over conventional finite-time control techniques.


Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study.
Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB). To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice. This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors. During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45-4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03-1.42) and male sex (aSHR, 1.58; 95% CI, 1.04-2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4-year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%-1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%-2.0%). Severe flares with hepatic decompensation were observed in 1%-2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.


An evaluation of three materials as barriers to coronal microleakage in endodontically treated teeth.
Barrier Dentin Sealant, glass ionomer cement, and TERM were evaluated as possible barriers to coronal microleakage. The root canals of 70 extracted teeth were accessed, cleaned and shaped, and then obturated with gutta-percha and sealer. The teeth were divided into four groups, one for each barrier material evaluated and one control group. Subgroups were stored in a humidor or immersed in artificial saliva for 7 days and then placed in methylene blue dye. Barrier Dentin Sealant and TERM groups demonstrated the lowest dye penetration measurements. The difference between them was not statistically different. Glass ionomer cement demonstrated the greatest dye penetration and was statistically different from the other two barrier materials.


Occurrence and phenotypic detection of class A carbapenemases among Escherichia coli and Klebsiella pneumoniae blood isolates at a tertiary care center.
Resistance to carbapenems is a significant therapeutic threat. The increasing frequency of car bapenemase enzymes among Gram-negative bacilli makes their early detection and differentiation urgent. Carbapenemases belonging to Class A are most commonly produced by members of family Enterobacteriaceae and are inhibited to various degrees by clavulanic acid. The present study is aimed to determine the occurrence and phenotypic detection of Class A carbapenemases in Escherichia coli and Klebsiella pneumoniae blood isolates from septicemic patients. A total of 75 isolates of K. pneumoniae and 25 E. coli were screened for resistance to carbapenems by using meropenem and imipenem discs and meropenem E-test. Positive strains were then subjected to a modified Hodge test combined with carbapenemase inhibition tests to phenotypically detect and differentiate Class A serine carbapenemases from other classes of carbapenem hydrolyzing enzymes. The screening test showing the number of isolates resistant to meropenem and imipenem were 41 and 35 for K. pneumoniae and nine and four for E. coli, respectively. A total of 25 (33.3%) K. pneumoniae isolates and two (8.0%) E. coli isolates were classified as Class A carbapenemase producers. Multidrug resistance with coexistence of extended spectrum-beta-lactamases occurred in 44.4% isolates. However, all of the isolates were susceptible to colistin, polymyxin B, and tigecycline by disc diffusion test. We conclude from the present study that Class A carbapenemases appear to be the predominant cause of resistance to carbapenems in Enterobacteriaceae at our center and, thus, phenotypic detection based on simple methods should be employed routinely in clinical microbiology laboratories.


The effect of inferior turbinate outfracture on nasal resistance to airflow in vasomotor rhinitis assessed by rhinomanometry.
Twenty-eight patients with nasal obstruction due to vasomotor rhinitis were assessed using anterior rhinomanometry before and six weeks after the operation of out-fracture and amputation of the posterior ends of the inferior turbinates. It was found that the operation did not significantly improve the nasal airway. Though just over half the patients had an objective improvement in nasal airflow, only half of this group reported a subjective improvement in their symptoms.


Biosorption of Cr(VI) from aqueous solution by chemically modified potato starch: equilibrium and kinetic studies.
The biosorption capacity of chemically modified potato starch (CPS) for Cr(VI) from aqueous solution was investigated. The materials derived from carbohydrates are biodegradable and are generally regarded as safe and environmentally acceptable. The hydroxyl, carboxyl and carbonyl groups are responsible for the biosorption process. In the present study, the influence of various important parameters such as pH, time, biosorbent dose and initial Cr(VI) concentration on the biosorption capacity were investigated. The isotherms such as Langmuir, Freundlich and Tempkin were studied. The Freundlich and the Redlich-Peterson isotherms had been well fitted the biosorption of Cr(VI) with chemically modified potato starch. The kinetics of Cr(VI) removal using chemically modified potato starch was well explained by second-order kinetic model. The thermodynamic parameters were also evaluated from the biosorption measurements. Among the various desorbing agents tested, 98.2 percent chromium recovery was achieved with 0.1molL(-1) NaOH.


Synthesis of a precursor dipeptide of thymopentin in organic solvents by an enzymatic method.
The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide of thymopentin(TP-5), Z-Arg-Lys-NH2 in organic solvents was studied. Z-Arg-OMe was used as the acyl donor and Lys-NH2 was used as the nucleophile. An industrial alkaline protease alcalase and trypsin were used to catalyze the synthesis of the target dipeptide in water-organic cosolvent systems. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including organic solvents, water content, temperature, pH, and reaction time on the yield of Z-Arg-Lys-NH2. The optimum conditions using alcalase as the catalyst are pH 10.0, 35 degrees C, in acetonitrile/DMF/Na2CO3-NaHCO3 buffer system (80:10:10, V/V), 6 h, with the dipeptide yield of 71.1%. Compared with alcalase, the optimum conditions for trypsin are pH 8.0, 35 degrees C, in ethanol/Tris-HCl buffer system (80:20, V/V), 4 h, with the dipeptide yield of 76.1%.


Trpc1 as the Missing Link Between the Bmp and Ca2+ Signalling Pathways During Neural Specification in Amphibians.
In amphibians, the inhibition of bone morphogenetic protein (BMP) in the dorsal ectoderm has been proposed to be responsible for the first step of neural specification, called neural induction. We previously demonstrated that in Xenopus laevis embryos, the BMP signalling antagonist, noggin, triggers an influx of Ca2+ through voltage-dependent L-type Ca2+ channels (LTCCs), mainly via CaV1.2, and we showed that this influx constitutes a necessary and sufficient signal for triggering the expression of neural genes. However, the mechanism linking the inhibition of BMP signalling with the activation of LTCCs remained unknown. Here, we demonstrate that the transient receptor potential canonical subfamily member 1, (Trpc1), is an intermediate between BMP receptor type II (BMPRII) and the CaV1.2 channel. We show that noggin induces a physical interaction between BMPRII and Trpc1 channels. This interaction leads to the activation of Trpc1 channels and to an influx of cations, which depolarizes the plasma membrane up to a threshold sufficient to activate Cav1.2. Together, our results demonstrate for the first time that during neural induction, Ca2+ entry through the CaV1.2 channel results from the noggin-induced interaction between Trpc1 and BMPRII.


Systemic and single cell level responses to 1 nm size biomaterials demonstrate distinct biological effects revealed by multi-omics atlas.
Although ultra-small nanoclusters (USNCs, < 2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.


Non-Pharmacological Treatments of Asthma Chronic Obstructive Pulmonary Disease Overlap and Rehabilitation Programs.
Non-pharmacologic treatment is a vital, yet often under-utilized aspect of care for patients with ACO. As patients with ACO are often excluded from clinical trials, management decisions should be based on patient characteristic "phenotypes," such as dyspnea or exacerbation, and considering whether COPD or asthma is more pronounced in the individual patient. Self-management interventions in asthma and COPD have an overwhelming amount of supporting evidence and should be an integral part of ACO management. Additionally, pulmonary rehabilitation has widespread benefits in patients with COPD as well as asthma and should be offered in symptomatic patients with ACO. While the COVID-19 pandemic has highlighted some shortcomings, and introduced several challenges, to the delivery of PR world-wide, it has also presented the opportunity for the development and refinement of new models to deliver PR, such as telerehabilitation. While further research and development are necessary, telerehabilitation offers a promising alternative to reach patients, such as those with ACO, who would benefit from the programming. While future research is needed, we can make a more explicit and judicious use of current best evidence in making therapeutic decisions that includes non-pharmacological interventions in patients with ACO.


Characterization of two major isoforms of juvenile hormone esterase from Trichoplusia ni (Lepidoptera).
The two major isoforms of juvenile hormone (JH) esterase isolated from Trichoplusia ni were fragmented by cyanogen bromide and trypsin digestion. The resulting CNBr or CNBr/trypsin fragments were characterized and compared biochemically by SDS-PAGE, isoelectric focusing, two-dimensional electrophoresis and HPLC. Similar and unique fragments were examined for sequence, antigenic determinants and carbohydrate moieties. The studies identified small regions of the proteins which possess either potentially different sequences or different post-translational modifications. The location of a glycosylated asparagine residue was determined, as well as a region containing an epitope probably composed of a linear sequence of residues. An N-terminal region was identified that contained charge variation between the two isoforms and the sequence was obtained for the only unique CNBr/trypsin fragment detected from that region. These are the first data on mapping of regions of charge variation, epitope location and glycosylation sites for this enzyme from any insect species.


Health literacy and preventive health care use among Medicare enrollees in a managed care organization.
Many older adults in Medicare managed care programs have low health literacy, and this may affect use of preventive services. To determine whether older adults with inadequate health literacy were less likely to report receiving influenza and pneumococcal vaccinations, mammograms, and Papanicolaou smears than individuals with adequate health literacy after adjusting for other covariates. Cross-sectional survey; home interviews with community dwelling enrollees. Medicare managed care enrollees 65 to 79 years old in four US cities (n = 2722). Short Test of Functional Health Literacy in Adults and self-reported preventive service use. In bivariate analyses, self-reported lack of preventive services was higher among individuals with inadequate health literacy than those with adequate health literacy: never had an influenza vaccination: 29% versus 19% (P = 0.000); never had a pneumococcal vaccination: 65% versus 54% (P = 0.000); no mammogram in the last 2 years: 24% versus 17% (P = 0.017); never had a Papanicolaou smear: 10% versus 5% (P = 0.002). After adjusting for demographics, years of school completed, income, number of physician visits, and health status, people with inadequate health literacy were more likely to report they had never received the influenza (OR, 1.4; 95% CI, 1.1-1.9) or pneumococcal vaccination (OR, 1.3; 95% CI, 1.1-1.7), and women were less likely to have received a mammogram (OR, 1.5; 95% CI, 1.0-2.2) or Papanicolaou smear (OR, 1.7; 95% CI, 1.0-3.1). Among Medicare managed care enrollees, inadequate health literacy is independently associated with lower use of preventive health services.


Mapping of mouse carbonic anhydrase-3, Car-3: another locus in the homologous region of mouse chromosome 3 and human chromosome 8.
At least six separate genes determining tissue- and organelle-specific isoforms of carbonic anhydrase are known. We have determined the chromosome location of one of these genes, carbonic anhydrase-3 (Car-3), in the mouse and carried out a linkage analysis of Car-1, Car-2, and Car-3. Car-3 has been assigned to band 3A2 by in situ hybridization. We identified a PstI restriction fragment length polymorphism between Mus spretus and Mus mus domesticus and, by using an interspecific backcross, showed that Car-3 is 2.4 +/- 1.7% SE from both Car-1 and Car-2, calculating genetic distance as percentage recombination. No recombinants were found between Car-1 and Car-2 in 100 backcross offspring, and when these data are combined with earlier results, these two loci are estimated to be 1.2 cM from each other at the 95% confidence interval. The three homologous carbonic anhydrase loci in man had earlier been assigned to 8q22, and the finding of linkage of Car-3 to Car-1 and Car-2 in the mouse adds another locus to the conserved segments on mouse chromosome 3 and human chromosome 8.


Glucagon effects on plasma cyclic AMP and other reactants in normals and low insulin responders.
The metabolic response to i.v. glucagon was evaluated in 11 normal individuals and 8 healthy low insulin responders. Elevations of plasma cyclic AMP and blood glucose were similar in both groups. Accordingly, no indications were seen of differing hepatic responsiveness to glucagon. In contrast, the groups differed in the course of plasma glycerol during the test.


The effect of tin (IV)-protoporphyrin-IX on bilirubin production and excretion in the rat.
Tin (IV)-protoporphyrin-IX alpha (tin-heme) may have use in treating neonatal jaundice. To evaluate its effect on bilirubin metabolism, we measured bile-bilirubin excretion in adult, male Sprague-Dawley rats (350-500 g). After a 4-h baseline period, tin-heme (100 mumol/kg) or buffer was injected subcutaneously, and bile was collected for 19 h. Bile flow, bile salt excretion, and bile-bilirubin excretion (averaging 600 +/- 60 ng/100 g/min for all animals) remained stable in the control period. Tin-heme treatment did not alter bile flow or bile salt excretion, but within 2 h bilirubin output was significantly reduced. The nadir of output was 5 h after injection when it was 380 +/- 40 ng/100 g/min (p less than 0.001). Cumulative excretion over 19 h was reduced 30.8% (p less than 0.01). To determine if tin-heme interfered with hepatic uptake or excretion of bilirubin, additional animals were administered intravenous bilirubin at 30 mg/kg/h for 3 h after tin-heme injection. Neither peak bile-bilirubin (37.4 +/- 4.68, control; 38.19 +/- 3.81 micrograms/100 g/min, treated) nor cumulative excretion (87.8 +/- 4.7, control; 88.9 +/- 4.2%, treated) were altered. Biliary excretion of tin-heme was measured under various experimental conditions. When administered alone, maximal excretion was 4 h after injection (4.41 +/- 1.58 micrograms/100 g/min); by 15 h, it fell to 0.024 +/- 0.011 microgram/100 g/min; 20-h cumulative tin-heme excretion in bile was 21.8 +/- 3.1% of the administered dose. Intravenous coadministration of albumin or albumin and bilirubin reduced the peak output but did not alter cumulative excretion of tin-heme. These data indicate that tin-heme reduces endogenous bilirubin formation but does not impair hepatic uptake and excretion. Bile is a major excretory route for tin-heme.


Optimizing scale-up fermentation processes.
There are many aims associated with the optimization of fermentation processes. Optimization is expected to increase the yield of the final product but the process must be compliant with good manufacturing practices, the available equipment and the expected final scale of operation. Dealing with genetically modified microorganisms that overproduce recombinant protein has the advantage that the vast majority of the processes use only three different species, namely Escherichia coli, Saccharomyces cerevisiae and Pichia pastoris. Standard processes for each organism are described in textbooks and serve as a basis for the development of a tailored process. This article outlines the general philosophy that we have devised to ensure an efficient approach of scaling up fermentation processes for biopharmaceutical purposes, in a multidisciplinary environment.


Effectiveness of a new cosmetic treatment for melasma.
Melasma treatment is difficult due to extended treatment periods, suboptimal adherence, inconsistent results, and frequent relapses. Kojic acid has been shown to be effective in reducing melasma severity and is now increasingly used in cosmetic treatments. The purpose of the present study was to evaluate the effectiveness of a new cosmetic treatment for melasma at 45 and 90 days. Multicenter prospective study across 20 dermatology clinics/ambulatories. One hundred patients with mild-to-moderate melasma were evaluated. The primary endpoints were changes in mean modified melasma area and severity index (mMASI) score and patient-reported satisfaction at 45 and 90 days. The mean age of patients was 45.19 ± 11.5 years. Most patients were female and Caucasian. Patients presented mixed (65%), epidermal (26%), and dermal (4%) types of melasma. Triggering factors were hormonal contraception (33%), pregnancy (31%), and pharmacological treatment (11%); mean disease duration was 6.7 ± 6.8 years. Overall, a statistically significant decrease in mean mMASI scores was seen at 45 (2.19 ± 0.182 vs 3.29 ± 0.267, P < .0001) and 90 days (1.27 ± 0.128 vs 3.29 ± 0.267, P < .00001). The highest reduction in mMASI scores was observed in patients with dermal melasma. IGA scores showed a statistically significant improvement in pigmentation at 90 days (P < .00001). The novel cosmetic treatment was associated with the improvement of melasma, as assessed by mMASI.


Long range dispersal in checkerspot butterflies: Transplant experiments with Euphydryas gillettii.
Transfers of eggs and larvae from montane Wyoming populations of Euphydryas gillettii south to locations in the central Colorado mountains have resulted in the establishment of at least one Colorado population. This result shows that the previous absence of the species from Colorado was the result of its inability to cross the barrier of the Wyoming Basin, not the ecological unsuitability of Colorado habitats. This, in turn, supports the contention that Euphydryas do not easily disperse long distances.


Real-time tissue elastography (RTE) for noninvasive evaluation of fibrosis in liver diseases in children in comparison to liver biopsy.
To determine the value of real-time tissue elastography (RTE) in pediatric liver diseases in comparison to liver biopsy. RTE was performed on 34 patients (♀, n = 17; ♂, n = 17; range 0-21 years) with various acute and chronic liver diseases: autoimmune hepatitis (n = 5), liver transplantation (n = 5), Wilson's disease (n = 4), hepatopathy of unknown origin (n = 4), unclear cholestatic hepatitis (n = 2), thalassemia major (n = 2), glycogenosis (n = 2), hereditary fructose intolerance (n = 1), alpha-1-antitrypsin deficiency (n = 1), diabetes mellitus type 1 (n = 1), chronic intestinal pseudo-obstruction (n = 1), primary sclerosing cholangitis (n = 1), hepatitis B (n = 1), cirrhosis of unknown origin (n = 1), drug-induced hepatopathy (n = 1), unexplained transaminase elevation (n = 1), and nonalcoholic steatohepatitis (n = 1). Included children were biopsied. RTE was performed on a control group (n = 30; ♀, n = 15; ♂, n = 15). The mean value of strain (MEAN) in arbitrary units and the ratio of blue color-coded harder tissue (AREA) were calculated based on an elasticity histogram of the selected region of interest in liver parenchyma. They were compared with the histologically defined grade of liver fibrosis. In comparison to the scoring systems, a moderate correlation was observed for MEAN and AREA by excluding the F0 patients [MEAN r = -0.575 to -0.645, AREA r = 0.545-0.607 (p < 0.05)]. Differentiation of the control group and low-grade fibrosis (F1) from high-grade fibrosis (F2-4) was significantly possible (p values <0.001 at 5 % significance level). RTE parameters enable a possible differentiation of high fibrosis; however, their correlation with fibrosis stage was moderate. RTE seems to be a promising method in liver fibrosis grading in children.


Strained thiacyclophanes: Reducing properties and gauge of transannular interactions.
The current study involves the investigation of reducing properties of disulfide bonded heteraphanes. The calculated adiabatic electron affinity (AEA) values of heteraphanes are found comparable to that of cystine molecule and are capable of undergoing reversible redox reactions. In aqueous phase, these show high propensity to get reduced. The reaction energies calculated using isodesmic equations reflect the strain associated with the studied thiacyclophane models. Increase in the number of disulfide bonds results in less strain and more stabilization. Through-space transannular interactions in the selected heteraphanes have a decisive influence on the structure stabilization associated with the systems. The results reported in the current study are expected to play a vital role while designing redox driven drug carriers by incorporating these systems in biomolecules.


Slow electroencephalographic oscillations and behavioral measures as predictors of high executive processing in early postmenopausal females: A discriminant analysis approach.
Decline in cognitive function is frequent in early postmenopause. There are postmenopausal females who show high performance while others display low performance in executive function, modulated by the prefrontal cortex. These differences have led to confusing and inconclusive results, which have not been explained entirely by the decline in estrogens, which affect the prefrontal cortex functions. An analysis of brain function and the application of a discriminant analysis can help to clarify the deficits in executive function shown by some postmenopausal females. The objective was to examine electroencephalographic recording during the performance of an executive function test in early postmenopausal females, ten with a high level of performance and ten with a low level of performance. Absolute power of delta, theta, alpha1, alpha2, beta1 and beta2 and the numbers of completed categories, trials, perseverative errors and overall errors were submitted to stepwise discriminant analysis to identify predictor variables. Four predictors emerged as significant of group membership based on cognitive performance, with the high-performance group characterized by more completed categories, more delta power, less theta power and more alpha1 power. These findings suggest that postmenopausal females classified in the high-performance group displayed appropriate temporary activation in slow oscillations during executive processing.


RNA interference-mediated knockdown of a cytochrome P450, CYP6BG1, from the diamondback moth, Plutella xylostella, reduces larval resistance to permethrin.
We have previously reported that a cytochrome P450, CYP6BG1, from Plutella xylostella was found to be overexpressed in 4th instars of a permethrin resistant strain and inducible in the susceptible counterpart. The findings suggested potential involvement of CYP6BG1 in permethrin resistance, hence warranted a functional analysis. To assess the functional link of the gene to permethrin resistance, we adopted RNA interference-mediated gene silencing (RNAi) by dsRNA droplet feeding. Here, real time PCR analyses show that oral delivery of dsRNA can efficiently reduce the expression of CYP6BG1. Knockdown of CYP6BG1 transcript was evident in midgut and larval tissues enclosed in carcass. As a consequence of knockdown, a significant reduction in resistance of larvae fed CYP6BG1 dsRNA was observed after 24 and 48h of exposure to permethrin. In addition, CYP6BG1 dsRNA feeding to larvae led to reduced total P450 activities of microsomal preparations toward model substrates p-nitroanisole and benzyloxyresorufin. These results indicate that the overexpressed CYP6BG1 participate in enhanced metabolism of permethrin, thereby, resistance. The knockdown of a non-overexpressed P450, CYP6BF1v4, from the same resistant P. xylostella strain did not lead to changes in the level of resistance to permethrin, supporting further the specific involvement of CYP6BG1 in the resistance.


Electrical coupling between primary afferents and amphibian motoneurons.
The short-latency DR-EPSPs resistant to Ca2+-lack and to addition of Mn2+ and Mg2+ result from electrical coupling between primary afferents and spinal motoneurons in frogs and toads. There are two time constants by which the time constant for the decay of the electronic DR-EPSP can be described: 1. the membrane time constant which determines the rate of passive decay of the membrane potential shift produced directly by the presynaptic spike, 2. the rate at which the presynaptic after-depolarization (ADP) declines. The latter value is very large as compared with the postsynaptic membrane time constant. Presynaptic tetanization does not change the magnitude of the initial spike-induced component of the EPSP but its later slowly decaying portion is potentiated markedly as a result of the post-tetanic increase in the amplitude of the ADP. The perfusion with substances blocking potential dependent potassium channels (4-AP and TEA) greatly augments the DR-EPSP due to prolongation of the presynaptic spike and appearance of multiple discharges in the presynaptic fibers. An antidromic electrical coupling between motoneurons and the terminals of primary afferents was demonstrated in the isolated amphibian spinal cord perfused with zero Ca2+, 2 mM Mn2+ solution containing TEA or 4-AP. Under these conditions ventral root volleys may evoke local graded depolarizing potentials in some sensory fibers. Such antidromic coupling potentials can reach the critical level for generating a single or multiple discharge.


Alpha spectrometry and liquid scintillation counting for the measurement of 238Pu, 239Pu, 240Pu, 241Pu, 242Pu and age.
A method for the measurement of the isotopic composition and time since last chemical separation (age) of plutonium is presented. The method includes alpha spectrometric measurement of 238Pu, 239Pu and 240Pu where the ratio of 239Pu and 240Pu was determined using spectral deconvolution, and liquid scintillation counting of 241Pu, after chemical separation of plutonium and americium. For the age determination, the 241Pu determined using liquid scintillation counting was combined with alpha spectrometric measurement of 241Am. The results of the isotopic composition were compared with certified reference materials with known isotopic composition, and the results of the age determination were compared with literature values of the separation dates.


Trends in cervical laminoplasty and 30-day postoperative complications: 10-year results from a retrospective, multi-institutional study of 1095 patients.
This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.


Studying Chemoattractant Signal Transduction Dynamics in Dictyostelium by BRET.
Understanding the dynamics of chemoattractant signaling is key to our understanding of the mechanisms underlying the directed migration of cells, including that of neutrophils to sites of infections and of cancer cells during metastasis. A model frequently used for deciphering chemoattractant signal transduction is the social amoeba Dictyostelium discoideum. However, the methods available to quantitatively measure chemotactic signaling are limited. Here, we describe a protocol to quantitatively study chemoattractant signal transduction in Dictyostelium by monitoring protein-protein interactions and conformational changes using Bioluminescence Resonance Energy Transfer (BRET).


Selective inhibition of CBP/p300 HAT by A-485 results in suppression of lipogenesis and hepatic gluconeogenesis.
The histone acetyltransferases CREB-binding protein (CBP) and its paralogue p300 are transcriptional coactivators which are essential for a multitude of signaling pathways and energy homeostasis. However, the role of CBP/p300 HAT domain in regulating energy balance is still unclear. Here, C57BL/6 mice fed with either normal chow diet (NCD) or high-fat diet (HFD) were administrated with A-485, a recently reported selective inhibitor of CBP/p300 HAT activity for 1 week and the metabolic change was analyzed. The white adipose tissue (WAT) weight and adipocyte size were reduced in A-485-administrated mice, with decreased expressions of lipogenic genes and transcriptional factors. In the liver of A-485-treated mice, the lipid content and lipogenic gene expressions were lowered while the binding of forkhead box O1 (FOXO1) to glucose-6-phosphatase (G6Pc) promoter was reduced, leading to decreased expression of G6Pc. In primary mouse hepatocytes, A-485 abolished cAMP-elicited mRNA expressions of key gluconeogenic enzymes and promoted FOXO1 protein degradation via increasing its ubiquitination. Thus, A-485 inhibits lipogenesis in WAT and liver as well as decreases hepatic glucose production via preventing FOXO1 acetylation, leading to its protein degradation through a proteasome-dependent pathway. The specific inhibition of CBP/p300 HAT will provide a novel therapeutic approach for metabolic diseases.


The effect of a recessionary economy on food choice: implications for nutrition education.
To determine the effect of an economic recession on food choice behaviors. A qualitative study using semistructured, in-depth interviews followed by completion of a nutrition knowledge questionnaire and the Food Choice Questionnaire was conducted. A convenience sample from a metropolitan city in the Midwest. Women with children younger than 18 years in the household who had experienced unemployment, underemployment, or loss of a house because of foreclosure in the previous year participated (n = 25). Reported behaviors for food choices when grocery shopping and dining out and educational resources requested to inform nutrition education programs. Interviews were coded with a matrix derived from participant statements. Common behaviors were grouped and broad themes were identified. Numerous shopping strategies were recently used to save money (eg, buying only sale items, using coupons). Participants believed a healthful diet included a variety of foods with less sugar, salt, and fat. Recipes and menus that required little cost or preparation time and resources to track food expenditures were desired. Nutrition education should include money-saving shopping strategies, facilitate menu planning and cooking skills, and address food resource management to enable participants to acquire sufficient, acceptable, and nutritionally adequate food.


Tattoo Removal as a Resettlement Service to Reduce Incarceration Among Mexican Migrants.
In Mexico, tattooed migrants face discrimination and are at high-risk of incarceration, thus, we assessed whether receiving laser tattoo removal affected the likelihood of incarceration. In 2015-2016, 89 adults ages ≥ 18 years with visible tattoos were recruited at a free-clinic to receive laser tattoo removal or assigned to the wait-list; all completed baseline and 6-month questionnaires. Overall, 97.8% of participants ever migrated to the USA. In multivariate analyses restricted to migrants (n = 87), those receiving laser tattoo removal [Adjusted Odds Ratio (AOR) 0.27, 95% CI 0.07-0.89] and possessing a Mexican Voting card (AOR 0.14; 95% CI 0.03-0.58) were significantly less likely than wait-list participants to be incarcerated at 6-months. Previously incarcerated participants were significantly more likely to be incarcerated at follow-up. Tattoo removal may reduce incarceration among Mexican migrants. Future studies can assess other health and social benefits of tattoo removal for migrants/deportees returning to Mexico.


High prevalence of vaccine-preventable anal human papillomavirus infections is associated with HIV infection among gay, bisexual, and men who have sex with men in Nairobi, Kenya.
Human papillomavirus (HPV) infection is associated with anal cancers and is more prevalent in gay, bisexual, and men who have sex with men (gbMSM), partly due to their vulnerability to HIV infection. Baseline HPV genotype distributions and risk factors can inform the design of next-generation HPV vaccines to prevent anal cancer. A cross-sectional study was conducted among gbMSM receiving care at a HIV/STI clinic in Nairobi, Kenya. Anal swabs were genotyped using a Luminex microsphere array. Multiple logistic regression methods were used to identify risk factors for four HPV outcomes (any HPV, any HR-HPV, and 4- and 9-valent vaccine-preventable HPVs). Among 115 gbMSM, 51 (44.3%) were HIV-infected. Overall HPV prevalence was 51.3%; 84.3% among gbMSM living with HIV and 24.6% among gbMSM without HIV (p < 0.001). One-third (32.2%) had HR-HPV and the most prevalent vaccine-preventable HR-HPV genotypes were 16, 35, 45, and 58. HPV-18 was uncommon (n = 2). The 9-valent Gardasil vaccine would have prevented 61.0% of HPV types observed in this population. In multivariate analyses, HIV status was the only significant risk factor for any HPV (adjusted odds ratio [aOR]:23.0, 95% confidence interval [95% CI]: 7.3-86.0, p < 0.001) and for HR-HPV (aOR: 8.9, 95% CI: 2.8-36.0, p < 0.001). Similar findings were obtained for vaccine-preventable HPVs. Being married to a woman significantly increased the odds of having HR-HPV infections (aOR: 8.1, 95% CI: 1.6-52.0, p = 0.016). GbMSM living with HIV in Kenya are at higher risk of anal HPV infections including genotypes that are preventable with available vaccines. Our findings support the need for a targeted HPV vaccination campaign in this population.


Periprosthetic Joint Infection With Actinomyces radingae May Lead to the Identification of a Neglected Source of Intraoperative Contamination.
Periprosthetic joint infection remains a major complication in arthroplasty. We present the first description of a case of periprosthetic joint infection with Actinomyces radingae, microorganism that is mostly found on the skin of the upper body and might cause particular challenges as it is difficult to culture and specify. Furthermore, a thorough microbiologic workup may indicate the source of infection. In this case, it is possible that perspiration from the surgeon was the source of intraoperative contamination. Intraoperative contamination through perspiration may be important and should be avoided by all means.


Macular detachment associated with an optic pit: optical coherence tomography patterns and surgical outcomes.
To describe the different optical coherence tomography (OCT) patterns in macular detachment associated with an optic disc pit and their long-term evolution following vitrectomy. The data of 5 patients (9-43 years of age) with unilateral macular detachment associated with an optic disc pit, who had at least 1 year of follow-up, were compiled. Pars plana vitrectomy combined with gas tamponade was performed as the primary procedure in all patients. The OCT scans, best-corrected visual acuity (BCVA), and anatomic outcomes were documented. Two main OCT patterns were identified: a multilayer schisis pattern and a serous detachment pattern. Patients with multilayer schisis pattern were older and demonstrated worse mean preoperative (20/160) and postoperative (20/50) BCVA compared to serous detachment pattern patients (20/30 and 20/20, respectively). An average of 2.3 procedures per patient was needed in the multilayer schisis pattern compared to just one procedure in the serous detachment pattern. In 3 patients, additional pneumatic retinopexy was performed with full resolution of the subretinal fluid achieved. Two distinct OCT patterns were observed in eyes with macular detachments with an optic pit, with different clinical features and prognoses. Excellent final visual acuity was obtained in all eyes, including those that required several surgical procedures.


A survey of UK surgical trainees and trainers; latest reforms well understood but perceived detrimental to surgical training.
In the United Kingdom, surgical training reforms as part of modernising medical careers (MMC) became fully operational in 2007. This study aims to establish the level of insight and views about MMC based surgical training amongst surgical trainers and trainees working in the National Health Service. An electronic survey consisting of eight questions was disseminated to surgical trainers and trainees via a web-based link placed on Association of Surgeons in Training website. A total of 138 responses were received. Of those, 77% (n = 107) were from trainees. 92% (n = 127) of respondents understood that the purpose of MMC surgical reforms was to provide structured training. 98% (n = 135) agreed traditional SHO training was poorly structured. Two-thirds (67%, n = 92) believed that MMC will reduce the total time period to complete surgical training. 82% (n = 113) recognised work place assessments as an assessment tool for MMC competencies. 82% (n = 113) were aware that an educational supervisor is assigned to monitor individual training. 70% (n = 96) understood that training is a shared responsibility between trainee, educational supervisor and supervising consultants. However, 69% (n = 95) of respondents believed the standard of surgical training via MMC will deteriorate, 18% (n = 25) anticipated no difference, 8% (n = 11) passed no comments and a mere 5% (n = 7) perceived it as an improvement. This study confirms a generally good level of insight amongst trainers and trainees into the aims and structure of MMC based surgical training. However, the majority believe that ultimately the standard of surgical training is set to fall.


Changes in the antigenicity of the hemagglutinin molecule of H3 influenza virus at acidic pH.
In order to determine the location and biological significance of the acid-induced conformational change in influenza virus hemagglutinin (HA) reported by Skehel et al., monoclonal antibodies were prepared to the molecule before and after treatment at pH 5.0. These antibodies together with monoclonal antibodies to the different antigenic regions of the H3 HA were used in immunoprecipitation and ELISA binding studies to show that antigenic changes accompanied the conformational change in the HA. Treatment at pH 5.2 or less exposed new determinants on the HA while two antigenic regions, located at the tip and interface of the molecule at neutral pH, were lost or modified. Antigenic sites in the loop and hinge regions defined by the available monoclonal antibodies were not affected by the conformational change. Monoclonal antibodies specific for the acid-induced conformation efficiently inhibited hemagglutination of the virus at low pH but were extremely poor inhibitors of virus-induced red blood cell hemolysis at its pH optimum of 5.1. These antibodies were unable to neutralize viral infectivity under neutral or acidic conditions. Antibodies specific for the non-acid-treated HA conformation failed to inhibit hemagglutination at low pH values but were able to both inhibit hemolysis of red blood cells and neutralize virus infectivity. Residual unmodified HA after pH 5.0 treatment could explain the inhibition of hemolysis and infectivity by monoclonal antibodies in each of the different antigenic areas.


Cell mediated immunity to bovine rhinovirus type 1 in calves.
Calves experimentally infected with bovine rhinovirus type 1 developed a mild respiratory disease and exhibited a cell mediated immune (CMI) response, as determined by leukocyte migration inhibition (LMI) and lymphocyte blastogenesis tests. The CMI response to the virus was detected by day 3 post-inoculation using direct and indirect LMI tests. It persisted through day 28, with maximal responses occurring between days 4 and 14. Measurement of cellular immunity by blast transformation, however, was not evidenced until day 12. The humoral antibody response was minimal with serum neutralizing titers ranging from 1:4 to 1:16 and this response was not evident until 3 weeks after inoculation.


A patient-centric analysis to identify key influences in allergic rhinitis management.
Allergic rhinitis (AR) is increasingly becoming a patient self-managed disease. Just under 70% of patients purchasing pharmacotherapy self-select their treatment with no health-care professional intervention often resulting in poor choices, leading to suboptimal management and increased burden of AR on the individual and the community. However, no decision is made without external, influencing forces. This study aims to determine the key influences driving patients' decision-making around AR management. To accomplish this aim, we utilised a social network theory framework to map the patient's AR network and identify the strength of the influences within this network. Adults who reported having AR were interviewed and completed an AR network map and AR severity and quality of life questionnaires. Forty one people with AR completed the study. The AR networks of the participants had a range of 1-11 influences (alters), with an average number of 4 and a median of 5. The larger the impact of AR on their quality of life, the greater the number of alters within their network. The three most commonly identified alters were, general practitioners, pharmacists and the participants' 'own experience'. The strength of the influence of health-care professionals (HCPs) was varied. The proportion of HCPs within the AR network increased as the impact of AR on their quality of life increased. By mapping the AR network, this study demonstrated that there are multiple influences behind patient's decisions regarding AR management but the role of the HCP cannot be dismissed.


Extracellular vesicles secreted by Echinococcus multilocularis: important players in angiogenesis promotion.
The involvement of Echinococcus multilocularis, and other parasitic helminths, in regulating host physiology is well recognized, but molecular mechanisms remain unclear. Extracellular vesicles (EVs) released by helminths play important roles in regulating parasite-host interactions by transferring materials to the host. Analysis of protein cargo of EVs from E. multilocularis protoscoleces in the present study revealed a unique composition exclusively associated with vesicle biogenesis. Common proteins in various Echinococcus species were identified, including the classical EVs markers tetraspanins, TSG101 and Alix. Further, unique tegumental antigens were identified which could be exploited as Echinococcus EV markers. Parasite- and host-derived proteins within these EVs are predicted to support important roles in parasite-parasite and parasite-host communication. In addition, the enriched host-derived protein payloads identified in parasite EVs in the present study suggested that they can be involved in focal adhesion and potentially promote angiogenesis. Further, increased angiogenesis was observed in livers of mice infected with E. multilocularis and the expression of several angiogenesis-regulated molecules, including VEGF, MMP9, MCP-1, SDF-1 and serpin E1 were increased. Significantly, EVs released by the E. multilocularis protoscolex promoted proliferation and tube formation by human umbilical vein endothelial cells (HUVECs) in vitro. Taken together, we present the first evidence that tapeworm-secreted EVs may promote angiogenesis in Echinococcus-infections, identifying central mechanisms of Echinococcus-host interactions.


Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma.
Recent studies have implicated a role for the p50 subunit of the NF-kappa B transcription factor complex in tumorigenesis. Therefore, we investigated the expression of the p50 subunit of the NF-kappa B transcription factor complex in paired normal and non-small cell lung carcinoma (NSCLC) tissues. Here we show that nine of 11 (81.8%) fresh NSCLC tissues expressed from two- to 20-fold higher levels of the p50 subunit than normal lung tissue. Thirteen NSCLC cell lines also exhibited high levels of p50. Alterations in the normal NF-kappa B/rel pathway of regulation may play a role in the genesis of NSCLC.


A novel method to estimate cellular internalization of nanoparticles into gram-negative bacteria: Non-lytic removal of outer membrane and cell wall.
Bacteria efficiently take up small organic molecules and ions. However, the internalization of particulate forms, specifically nanoparticles (NPs) has been understudied and is a newly-emerging area of interest. However, determination of true cellular internalization is challenging owing to the difficulty of separating the aqueous phase from bacteria-associated NPs and, more importantly, of differentiating between internalized and NPs sorbed on bacteria surfaces. In this work, we developed and validated an extraction method which can operationally estimate internalization of metal NPs into Gram-negative bacteria. The outer cell membrane and cell wall, collectively called the periplasm, was successfully removed from bacteria using ethylenediaminetetraacetic acid (EDTA) at an optimized exposure period and concentration, without lysis of bacteria. This was followed by standard digestion and metal measurements. Verification of each step of the methodology was conducted by assessing both cellular and metal behavior. Specifically, the combined approaches of live/dead staining of bacteria, optical density measurements, transmission electron microscopy (TEM) and metal analyses of the supernatant indicated that the method operationally separated externally-sorbed NPs from those internalized actually localized within the bacterial cytoplasm. However, this new method is ideally used alongside other methods in a multi-method approach, to provide improved data quality. Therefore, it should be used with CSLM, FACS, TEM and other available methods.


UNC0638 induces high levels of fetal hemoglobin expression in β-thalassemia/HbE erythroid progenitor cells.
Increased expression of fetal hemoglobin (HbF) improves the clinical severity of β-thalassemia patients. EHMT1/2 histone methyltransferases are epigenetic modifying enzymes that are responsible for catalyzing addition of the repressive histone mark H3K9me2 at silenced genes, including the γ-globin genes. UNC0638, a chemical inhibitor of EHMT1/2, has been shown to induce HbF expression in human erythroid progenitor cell cultures. Here, we report the HbF-inducing activity of UNC0638 in erythroid progenitor cells from β-thalassemia/HbE patients. UNC0638 treatment led to significant increases in γ-globin mRNA, HbF expression, and HbF-containing cells in the absence of significant cytotoxicity. Moreover, UNC0638 showed additive effects on HbF induction in combination with the immunomodulatory drug pomalidomide and the DNMT1 inhibitor decitabine. These studies provide a scientific proof of concept that a small molecule targeting EHMT1/2 epigenetic enzymes, used alone or in combination with pomalidomide or decitabine, is a potential therapeutic approach for HbF induction. Further development of structural analogs of UNC0638 with similar biological effects but improved pharmacokinetic properties may lead to promising therapies and possible clinical application for the treatment of β-thalassemia.