Molecularly Imprinted Polyacrylamide with Fluorescent Nanodiamond for Creatinine Detection.
Creatinine measurement in blood and urine is an important diagnostic test for assessing kidney health. In this study, a molecularly imprinted polymer was obtained by incorporating fluorescent nanodiamond into a creatinine-imprinted polyacrylamide hydrogel. The quenching of peak nanodiamond fluorescence was significantly higher in the creatinine-imprinted polymer compared to the non-imprinted polymer, indicative of higher creatinine affinity in the imprinted polymer. Fourier transform infrared spectroscopy and microscopic imaging was used to investigate the nature of chemical bonding and distribution of nanodiamonds inside the hydrogel network. Nanodiamonds bind strongly to the hydrogel network, but as aggregates with average particle diameter of 3.4 ± 1.8 µm and 3.1 ± 1.9 µm for the non-imprinted and molecularly imprinted polymer, respectively. Nanodiamond fluorescence from nitrogen-vacancy color centers (NV- and NV0) was also used to detect creatinine based on nanodiamond-creatinine surface charge interaction. Results show a 15% decrease of NV-/NV0 emission ratio for the creatinine-imprinted polymer compared to the non-imprinted polymer, and are explained in terms of changes in the near-surface band structure of diamond with addition of creatinine. With further improvement of sensor design to better disperse nanodiamond within the hydrogel, fluorescent sensing from nitrogen-vacancy centers is expected to yield higher sensitivity with a longer range (Coulombic) interaction to imprinted sites than that for a sensor based on acceptor/donor resonance energy transfer.


A cost analysis of a long-term prospective study of patients treated with immediately loaded implant-supported mandibular overdentures.
The economic burden for patients seeking treatment with implant-supported prostheses has not been given adequate attention. To document long-term costs from a prospective trial on edentulous patients treated with mandibular implant-supported overdentures and 2 loading protocols. The direct clinical and time costs for 35 patients receiving an immediate-loading protocol (ILP) and 40 patients with a conventional-loading protocol, over 14 years of observation, were analyzed in 2016 Canadian dollars as a base year. Quality of life (QoL) for the ILP was measured using the OHIP-20 questionnaire. The ILP was associated with higher complication costs ($870.77 ± 692.24 vs $85.73 ± 133.14) with resultant higher maintenance costs ($1746.37 ± 892.68 vs $853.04 ± 276.21) (P < .05). OHIP results showed a sustained improvement in QoL through the first 5 year of follow-up. A worsening of QoL, specifically the functional-related OHIP scores, was noted at 14 years. Incremental cost-effectiveness ratios indicated that the accrued maintenance costs for the ILP made the treatment less cost-effective over time. This long-term study confirmed that ILP is associated with higher maintenance costs and varying subjective QoL measurements. Clinical treatment protocols should be evaluated over a long period and address different perspectives.


Decomposition of Jones and Mueller matrices in terms of four basic polarization responses.
A simple new method is introduced to analyze the polarization of light by media. This method decomposes a Jones matrix into a linear combination of four basic matrices that represent different polarization responses. The Mueller matrix expressed in terms of the response coefficients of the basic matrices demonstrates a highly symmetric form that spells out the physical origins of each matrix element. Randomness in the response coefficients gives rise to depolarization that appears only in the diagonal elements of a Mueller matrix. The decomposition of a Mueller matrix gives both the depolarization and polarization characteristics relating directly to the anisotropic optical properties.


A prospective study of body size in different periods of life and risk of premenopausal breast cancer.
The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer.


Human choriogonadotropin (hCG): comparisons between determinations of intact hCG, free hCG beta-subunit, and "total" hCG + beta in serum during the first half of high-risk pregnancy.
We have studied the concentrations of intact human choriogonadotropin (hCG) and the free hCG beta-subunit in blood samples from singleton pregnancies at risk for habitual or threatened abortion. The samples were obtained weekly between the 6th and 12th weeks and in the 14th and 16th weeks of gestational age. The concentrations of intact hCG, of the free hCG beta-subunit, and of "total" hCG (i.e., intact hCG and the free hCG beta-subunit: hCG + beta) were measured in serum by specific immunoassays. The distributional statistics (the 5th, 50th, and 95th percentiles) of "total" hCG + beta and of intact hCG showed very similar patterns, whereas the response curves for the free hCG beta-subunit showed very much lower serum concentrations. From these data we also estimated distributional statistics of the percent molar ratios of free hCG beta-subunit to intact hCG. We conclude that (a) the relatively small proportion of free hCG beta-subunit in serum during the first half of singleton pregnancy is far too low to interfere with the applied "total" hCG assay, as compared with the serum values obtained for intact hCG, and (b) the percent molar ratios of free hCG beta-subunit to intact hCG, or to "total" hCG + beta, never exceeded 1.0% throughout the period of pregnancy studied.


Cassava mosaic disease and its management in Southeast Asia.
Status of the current outbreak of cassava mosaic disease (CMD) in Southeast Asia was reviewed. Healthy cassava seed production and dissemination systems have been established in Vietnam and Cambodia, along with integrated disease and pest management systems, to combat the outbreak. Cassava (Manihot esculenta Crantz) is one of the most important edible crops in tropical and subtropical regions. Recently, invasive insect pests and diseases have resulted in serious losses to cassava in Southeast Asia. In this review we discuss the current outbreak of cassava mosaic disease (CMD) caused by the Sri Lankan cassava mosaic virus (SLCMV) in Southeast Asia, and summarize similarities between SLCMV and other cassava mosaic begomoviruses. A SATREPS (Science and Technology Research Partnership for Sustainable Development) project "Development and dissemination of sustainable production systems based on invasive pest management of cassava in Vietnam, Cambodia and Thailand", was launched in 2016, which has been funded by The Japan International Cooperation Agency (JICA) and The Japan Science and Technology Agency (JST), Japan. The objectives of SATREPS were to establish healthy seed production and dissemination systems for cassava in south Vietnam and Cambodia, and to develop management systems for plant diseases and insect pests of cassava. To achieve these goals, model systems of healthy seed production in Vietnam and Cambodia have been developed incorporating CMD-resistant planting materials through international networks with The International Center for Tropical Agriculture (CIAT) and The International Institute of Tropical Agriculture (IITA).


Meaning Salience and Meaning in Life Prospectively Predict Lower Distress During the COVID-19 Pandemic.
The COVID-19 pandemic is a widespread source of stress with adverse mental health impacts. Meaning in life, both as a trait and as momentary awareness of what is personally meaningful (meaning salience), is associated with positive health outcomes and may buffer against the deleterious effects of stress. This project examines prospective associations between baseline meaning salience (daily, post-laboratory stressor) and meaning in life with perceived stress during COVID-19. A community sample of healthy adults (n = 147) completed a laboratory stress protocol in 2018-2019, where perceived stress, meaning in life, and meaning salience (daily, post-stressor) were assessed. During April and July 2020 (n = 95, and 97, respectively), participants were re-contacted and reported perceived stress. General linear mixed-effects models accounting for repeated measures of stress during COVID-19 were conducted. Partial correlations holding constant baseline perceived stress showed that COVID-19 perceived stress was correlated with daily meaning salience (r = -.28), post-stressor meaning salience (r = -.20), and meaning in life (r = -.22). In mixed-effects models, daily and post-stressor meaning salience and higher meaning in life, respectively, predicted lower perceived stress during COVID-19, controlling for age, gender, and baseline perceived stress. Individuals more capable of accessing meaning when exposed to laboratory stress reported lower perceived stress during a global health crisis. Despite study limitations concerning generalizability, results support meaning in life and meaning salience as important aspects of psychological functioning that may promote well-being by affecting stress appraisals and available resources for coping.


Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.
Ivabradine, a new I(f) inhibitor which acts specifically on the pacemaker activity of the sinoatrial node, is a pure heart rate lowering agent. Ivabradine has shown anti-ischaemic and anti-anginal activity in a placebo-controlled trial. The objective of this study was to compare the anti-anginal and anti-ischaemic effects of ivabradine and the beta-blocker atenolol. In a double-blinded trial, 939 patients with stable angina were randomized to receive ivabradine 5 mg bid for 4 weeks and then either 7.5 or 10 mg bid for 12 weeks or atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks. Patients underwent treadmill exercise tests at randomization (M(0)) and after 4 (M(1)) and 16 (M(4)) weeks of therapy. Increases in total exercise duration (TED) at trough at M(4) were 86.8+/-129.0 and 91.7+/-118.8 s with ivabradine 7.5 and 10 mg, respectively and 78.8+/-133.4 s with atenolol 100 mg. Mean differences (SE) when compared with atenolol 100 mg were 10.3 (9.4) and 15.7 (9.5) s in favour of ivabradine 7.5 and 10 mg (P<0.001 for non-inferiority). TED at M(1) improved by 64.2+/-104.0 s with ivabradine 5 mg and by 60.0+/-114.4 s with atenolol 50 mg (P<0.001 for non-inferiority). Non-inferiority of ivabradine was shown at all doses and for all criteria. The number of angina attacks was decreased by two-thirds with both ivabradine and atenolol. Ivabradine is as effective as atenolol in patients with stable angina.


Infection resisters: targets of new research for uncovering natural protective immunity against Mycobacterium tuberculosis.
"Infection resisters" are broadly defined as individuals who despite significant exposure to Mycobacterium tuberculosis remain persistently unreactive to conventional detection assays, suggesting that they remain uninfected or rapidly clear their infection early on following exposure. In this review, we highlight recent studies that point to underlying host immune mechanisms that could mediate this natural resistance. We also illustrate some additional avenues that are likely to be differently modulated in resisters and possess the potential to be targeted, ranging from early mycobacterial sensing leading up to subsequent killing. Emerging research in this area can be harnessed to provide valuable insights into the development of novel therapeutic and vaccine strategies against M. tuberculosis.


GLUT4 Is Not Necessary for Overload-Induced Glucose Uptake or Hypertrophic Growth in Mouse Skeletal Muscle.
GLUT4 is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine whether GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by unilateral synergist ablation. After 5 days, muscle weights and ex vivo [3H]-2-deoxy-d-glucose uptake were assessed. Overload-induced muscle glucose uptake and hypertrophic growth were not impaired in muscle-specific GLUT4 knockout mice, demonstrating that GLUT4 is not necessary for these processes. To assess which transporters mediate overload-induced glucose uptake, chemical inhibitors were used. The facilitative GLUT inhibitor cytochalasin B, but not the sodium-dependent glucose cotransport inhibitor phloridzin, prevented overload-induced uptake demonstrating that GLUTs mediate this effect. To assess which GLUT, hexose competition experiments were performed. Overload-induced [3H]-2-deoxy-d-glucose uptake was not inhibited by d-fructose, demonstrating that the fructose-transporting GLUT2, GLUT5, GLUT8, and GLUT12 do not mediate this effect. To assess additional GLUTs, immunoblots were performed. Overload increased GLUT1, GLUT3, GLUT6, and GLUT10 protein levels twofold to fivefold. Collectively, these results demonstrate that GLUT4 is not necessary for overload-induced muscle glucose uptake or hypertrophic growth and suggest that GLUT1, GLUT3, GLUT6, and/or GLUT10 mediate overload-induced glucose uptake.


I Do It, but I Decide With Whom.
Social interactions and communication shape the desires and preferences of men and women. While it is true that some men have modified their behavior due to feminist women, the same happened with some women, who changed attraction patterns thanks to new alternative masculinities (NAM). This study examines the latter, focusing on social interactions mediated by language, as a crucial element to impact and change the desires of people. For this purpose, six autobiographical interviews were conducted with women aged 19-39 years, from two different countries and continents, paying attention to the narratives of their sexual-affective relationships. Using the communicative methodology, interactions have been analyzed from verbal communication and nonverbal communication, based on the consequences of the actions rather than intentionality. The results of this study show how dialogic communicative acts with NAMs influenced some women who first defended or justified actions of male perpetrators to later prefer to support female survivors against their perpetrators. Analysis reveals that communicative acts grounded in such language that enacted the desire of NAM for women of solidarity have shaped some memories of women of relationships with dominant traditional masculinities (DTM) and, ultimately, contributed to change their attraction and election patterns.


Efficacy and safety of short- and long-term, regular and on-demand regimens of phosphodiesterase type 5 inhibitors in treating erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis.
We performed a meta-analysis to evaluate the efficacy and safety of short-term (≤6 months) and long-term (>6 months), regular (OaD) and on-demand (PRN) regimens of phosphodiesterase type 5 inhibitors (PDE5-Is) in treating erectile dysfunction (ED) after nerve-sparing radical prostatectomy (NSRP). We conducted a literature search in August 2016. Sources included PubMed, EMBASE, and MEDLINE databases. The main outcome was International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, and the secondary outcome was treatment-emergent adverse events (TEAEs). Eight articles involving 13 randomized controlled trials (RCTs) were used in this analysis: they suggested that PDE5-Is can improve the IIEF-EF distinctly in comparison with placebo in short and long term (mean difference [MD]: 2.26, 95% confidence interval [CI]: 1.45-3.08, P<0.00001, and MD: 4.5, 95% CI: 3.6-5.4, P<0.00001), and long-term use of PDE5-Is (>6 months) can improve the IIEF-EF distinctly in comparison with short-term use of PDE5-Is (≤6 months) (MD: 3.9, 95% CI: 3.01-4.8, P<0.00001). OaD of PDE5-Is significantly improved the IIEF-EF compared to placebo in short and long term (MD: 4.08, 95% CI: 3.2-4.97, P<0.00001, and MD: 4.74, 95% CI: 3.79-5.69, P<0.00001). No significant differences were found in IIEF-EF changes between PRN and placebo (≤6 months) (MD: 2.64, 95% CI: -0.87 to 6.14, P=0.14), and between PRN and OaD group (>6 months) (MD: -0.58, 95% CI: -9.86 to 8.74, P=0.91). There were more TEAEs in PDE5-Is group in comparison with placebo (odds ratio [OR]: 1.55, 95% CI: 1.26-1.91, P<0.0001), and TEAEs in OaD group were not significantly different from those seen in PRN group (OR: 1.05, 95% CI: 0.78-1.4, P=0.77). Our meta-analysis suggests that PDE5-Is are efficient and safe for treatment of ED after NSRP, and we should choose the regular regimen for short term and regular or on-demand regimen for long term. Further high-quality RCTs are needed to validate this result.


Intraspecific trait variation and adaptability of Stipa krylovii: Insight from a common garden experiment with two soil moisture treatments.
Understanding patterns of intraspecific trait variation can help us understand plant adaptability to environmental changes. To explore the underlying adaptation mechanisms of zonal plant species, we selected seven populations of Stipa krylovii, a dominant species in the Inner Mongolia Steppe of China, and evaluated the effects of phenotypic plasticity and genetic differentiation, the effects of climate variables on population trait differentiation, and traits coordinated patterns under each soil moisture treatment. We selected seeds from seven populations of S. krylovii in the Inner Mongolia Steppe, China, and carried out a soil moisture (2) × population origin (7) common garden experiment at Tianjin City, China, and measured ten plant traits of S. krylovii. General linear analyses were used to analyze how soil moisture and population origin affected each trait variation, Mantel tests were used to analyze population trait differentiation-geographic distance (or climatic difference) relationships, regression analyses were used to evaluate trait-climatic variable relationships, and plant trait networks (PTNs) were used to evaluate traits coordinated patterns. Both soil moisture and population origin showed significant effects on most of traits. Aboveground biomass, root-shoot ratio, leaf width, specific leaf area, and leaf nitrogen (N) content were significantly correlated with climate variables under the control condition. Specific leaf area and leaf N content were significantly correlated with climate variables under the drought condition. By PTNs, the hub trait(s) was plant height under the control condition and were aboveground biomass, root length, and specific leaf area under the drought condition. This study indicates that both phenotypic plasticity and genetic differentiation can significantly affect the adaptability of S. krylovii. In addition, soil moisture treatments show significant effects on trait-climate relationships and traits coordinated patterns. These findings provide new insights into the adaptive mechanisms of zonal species in the semiarid grassland region.


Development and testing of culturally adapted road hazard communication designs.
This study was conducted to assess comprehension of existing road hazard communication designs (RHCDs) in relation to culturally adapted designs among commercial vehicle drivers using a two-part study. In study 1, nine participants were recruited and their comprehension of 20 existing RHCDs was tested. Results of the analysis revealed that only 50% of the designs met the acceptance criterion of 67% set by the International Organization for Standardization (ISO). Culturally adapted symbols were then developed for the 10 symbols which failed to meet the ISO acceptance criterion through a longitudinal focus group discussion involving the nine participants. In study 2, 226 commercial vehicle drivers were drawn from four bus terminals. Results of a paired-samples t test showed that comprehension of the culturally adapted designs was significantly better than comprehension of their equivalent existing designs. The findings are discussed in the context of extant literature and practice.


Influence of water soluble fillers in hydroxypropylmethylcellulose matrices on in vitro and in vivo drug release.
The purpose of this study was to investigate the effect of fillers in gel-forming matrix on in vivo drug release after oral dosing. A further purpose was to predict the in vivo performance from in vitro dissolution test. Three controlled-release acetaminophen tablets containing hydroxypropylmethylcellulose (HPMC) with or without highly water soluble fillers, lactose or polyethylene glycol 6000 (PEG6000), were prepared. Water penetration into the matrix was enhanced by addition of fillers in the matrices, but the three tablets showed similar in vitro dissolution profiles, indicating that fillers in the HPMC matrices little affected the in vitro drug release. In contrast, the fillers in HPMC matrices did affect the in vivo performance in dogs. The absorption profile of HPMC matrix with PEG6000 was the fastest, followed by that with lactose and without water soluble filler, in that order. As the matrix with PEG6000 had a large amount of water and gelated a large portion of the matrix when in contact with water, the gel layer would be disintegrated by the gastrointestinal motility. It was found that dissolution of gel-forming HPMC matrices under mechanical stress by glass beads well correlated with the in vivo performance of the matrix, with little correlation by the conventional paddle method.


Calcium supplements: do they help or harm?
Current recommendations for calcium intake call for 1,000 mg per day for women ages 19-50 and 1,200 mg per day for women over age 50 to ensure bone health. Given recent concerns that calcium supplements may raise risk for cardiovascular disease and kidney stones, women should aim to meet this recommendation primarily by eating a calcium-rich diet and taking calcium supplements only if needed to reach the RDA goal (often only approximately 500 mg per day in supplements is required).


Biases in attention and interpretation in adolescents with varying levels of anxiety and depression.
This is the first study to investigate multiple cognitive biases in adolescence simultaneously, to examine whether anxiety and depression are associated with biases in attention and interpretation, and whether these biases are able to predict unique variance in self-reported levels of anxiety and depression. A total of 681 adolescents performed a Dot Probe Task (DPT), an Emotional Visual Search Task (EVST), and an Interpretation Recognition Task. Attention and interpretation biases were significantly correlated with anxiety. Mixed results were reported with regard to depression: evidence was found for an interpretation bias, and for an attention bias as measured with the EVST but not with the DPT. Furthermore, interpretation and attention biases predicted unique variance in anxiety and depression scores. These results indicate that attention and interpretation biases are unique processes in anxiety and depression. They also suggest that anxiety and depression are partly based on similar underlying cognitive mechanisms.


Midazolam for upper gastrointestinal endoscopy.
A water-soluble benzodiazepine, midazolam, was used in 400 patients undergoing upper gastrointestinal endoscopy, alone or in combination with pentazocine and compared with 68 patients given diazepam (Valium). In the last 200 patients the endoscopist used midazolam without the presence of an anaesthetist. The absence of injection pain was the most notable feature of midazolam. The degree of co-operation was similar in all groups but the operating conditions were significantly better when midazolam was combined with pentazocine. There was no significant difference in recovery times between the groups as assessed by the pegboard test. Midazolam is an acceptable alternative to diazepam for upper gastrointestinal endoscopy.


Microincision phacoemulsification combined with sutureless transpupillary passive silicone oil removal.
To evaluate the outcomes of combined microincision phacoemulsification with sutureless transpupillary silicone oil (SO) removal using an irrigation probe of bimanual irrigation/aspiration. We conducted a single-center retrospective study, including patients who had undergone phacoemulsification with transpupillary removal of SO, which had been used for intraocular tamponade after a previous pars plana vitrectomy. Outcome measures were corrected distance visual acuity (CDVA), refractive error, intraocular pressure (IOP), and endothelial cell count (ECC) evaluated preoperatively and postoperatively at 3-month follow-up. Any intraoperative or postoperative complications, duration of surgery, and final retinal status at 3 months were also noted. Seventy-four eyes (74 patients) were analyzed. The mean interval between SO placement and cataract surgery was 4.73 months (standard deviation [SD]: 1.02). CDVA improved in 66 (89.2%) eyes and remained the same in 8 (10.8%) eyes (P < 0.001). The mean postoperative spherical equivalent was -0.96D (SD: 0.75) at 3 months (P < 0.001). There was a significant drop in IOP from 15.08 mmHg (SD: 2.67) preoperatively to 11.64 mmHg (SD: 2.02) postoperatively (P < 0.001). The average ECC loss was only 5.7% at 3 months postoperatively. The mean surgical duration was 17.20 min (SD: 7.02). One patient had retinal redetachment and required resurgery. At 3 months, the retina was attached in all patients. Combined microincision phacoemulsification with transpupillary passive SO removal using irrigation probe of bimanual irrigation/aspiration is a safe, effective, and less invasive technique that offers the main advantage of reduced surgical trauma, and should be reserved for patients with a stable retina, not requiring additional surgical intervention.


End-inspiratory molar mass step correction for analysis of infant multiple breath washout tests.
A refined software algorithm was recently proposed for the analysis of infant multiple breath washout (MBW) measurements. The proposed algorithm uses the change in end-inspiratory molar mass between the wash-in and wash-out curves (EIMM-step) to define the required step response correction of the MM signal and is assumed to provide an accurate evaluation of complete washout of the tracer gas, in comparison to the current software algorithm which applies the change in end-expiratory molar mass (EEMM)-step. We aimed to evaluate the use of the EIMM-step method in a broad range of infants. We performed retrospective analyses comparing the EIMM- and EEMM-step change methods in MBW data collected from infants with cystic fibrosis (CF), infants born preterm, and healthy infants using an ultrasonic flowmeter. We found that the EIMM-step correction significantly increased LCI and functional residual capacity (FRC) in infants with CF, preterm infants, and healthy infants compared with the EEMM-step method. In addition, more than half the measurements that were technically acceptable and repeatable using the EEMM-step correction in healthy infants were excluded after using the EIMM-step correction. We found a large difference between the EIMM- and EEMM-steps in healthy infants indicating incomplete washout, suggesting the need for a longer washout time with using the EIMM-step analysis method. The data indicates that the EIMM-step analysis method may have the potential to generate false abnormal LCI values in individuals without lung disease. Revised normative data may be required if this method is universally adopted. Pediatr Pulmonol. 2017;52:10-13. © 2016 Wiley Periodicals, Inc.


SU(2/1) superchiral self-duality: a new quantum, algebraic and geometric paradigm to describe the electroweak interactions.
We propose an extension of the Yang-Mills paradigm from Lie algebras to internal chiral superalgebras. We replace the Lie algebra-valued connection one-form A, by a superalgebra-valued polyform A ˜ mixing exterior-forms of all degrees and satisfying the chiral self-duality condition A ˜ = * A ˜ χ , where χ denotes the superalgebra grading operator. This superconnection contains Yang-Mills vectors valued in the even Lie subalgebra, together with scalars and self-dual tensors valued in the odd module, all coupling only to the charge parity CP-positive Fermions. The Fermion quantum loops then induce the usual Yang-Mills-scalar Lagrangian, the self-dual Avdeev-Chizhov propagator of the tensors, plus a new vector-scalar-tensor vertex and several quartic terms which match the geometric definition of the supercurvature. Applied to the SU(2/1) Lie-Kac simple superalgebra, which naturally classifies all the elementary particles, the resulting quantum field theory is anomaly-free and the interactions are governed by the super-Killing metric and by the structure constants of the superalgebra.


Comparison of the duration of estradiol administration and the effect on pregnancy outcome of day 3 vitrified-warmed embryo transfer cycle: a randomized controlled trial.
Based on the fact that the follicular phase in the menstrual cycle has length variation, it has been assumed that the duration of oestrogen (E2) administration could also be variable; therefore, for the first time, this randomized clinical trial study was conducted to investigate and compare the duration of estradiol administration and the effect on pregnancy outcomes in the cleavage-stage frozen embryo transfer (FET) cycle. We included women aged 20-40 with a normal uterus on hysteroscopy between September and December 2022 and who were divided randomly into three groups: group A [n = 79; 8-11 days of oestrogen before progesterone (P4) supplementation], group B (n = 78; 12-14 days of oestrogen before P4 supplementation), and group C (n = 76; 15-18 days of estrogen before P4 supplementation). Serum levels for E2 on the initial progesterone day and P4 on the transfer day were measured. The effect of the duration of E2 administration on clinical pregnancy and pregnancy loss was investigated. We found no significant differences between the three groups in the clinical pregnancy rate (P = 0.696) and clinical abortion rate (P = 0.925) according to the duration of the E2. There was no significant difference in the E2, P4 levels, and endometrial thickness in pregnant vs. non-pregnant women. The mean of the E2 and P4 levels was 300.03 ± 22.21 and 25.36 ± 5.78, respectively. Our findings suggest that variation in the length of E2 administration (8-18 days) before progesterone initiation in day 3 FET cycles does not affect pregnancy outcome and transfer time can be flexibly arranged.


Effect of hyaluronan and deoxycholate on transperitoneal insulin and albumin transport in vitro.
In patients with end-stage renal disease on peritoneal dialysis, the peritoneum is effectively utilized as an endogenous semipermeable membrane. Chemical agents may alter the structure of the peritoneum and induce changes in its transfer properties. The purpose of our in vitro study was to compare the influence of sodium hyaluronan (a cytoprotective glycosaminoglycan, 2000 kDa, 40 mg/dL) and sodium deoxycholate (an intense oxidative stress factor, 414 Da, 104 mg/dL) on the transfer of insulin (5.8 kDa, 100 mg/dL) and albumin (68 kDa, 1000 mg/dL) through isolated rabbit parietal peritoneum. We used a mathematical model to calculate the transport rate of solutes from the interstitial to the mesothelial side of peritoneal membrane (I-->M) and in the opposite direction (M-->I) in three separate series of experiments: Control conditions without chemical agents Before (15-60 minutes) and after (75-120 minutes) introduction of sodium hyaluronan into the experimental system Before (15 -75 minutes) and after (90-150 minutes) introduction of sodium deoxycholate into the experimental system The results are expressed as a diffusive permeability coefficient P in centimeters per second. During the 120 minutes of the control stage, the rate of insulin and albumin bidirectional passage remained constant. Values of P +/- standard error of the mean did not correlate with the molecular weight of the compounds and measured 0.145 +/- 0.033 x 0.0001 cm/s and 0.146 +/- 0.022 x 0.0001 cm/s for insulin, and 0.271 +/- 0.056 x 0.0001 cm/s and 0.315 +/- 0.057 x 0.0001 cm/s for albumin in the I-->M and M-->I transport directions respectively. Application of sodium hyaluronan did not change the bidirectional transport of either solute. However sodium deoxycholate caused the values of P to increase by 142% (p < 0.05) for insulin I-->M transfer and by 102% (p < 0.02) for insulin M-->I transport. Albumin passage increased by 193% (p < 0.01) for both transfer directions. We conclude that, in vitro, sodium deoxycholate but not sodium hyaluronan increases the bidirectional peritoneal transport of insulin and albumin. In the case of larger molecular weight solutes, the modification is greater.


Physical working conditions as covered in European monitoring questionnaires.
The prevalence of workers with demanding physical working conditions in the European work force remains high, and occupational physical exposures are considered important risk factors for musculoskeletal disorders (MSD), a major burden for both workers and society. Exposures to physical workloads are therefore part of the European nationwide surveys to monitor working conditions and health. An interesting question is to what extent the same domains, dimensions and items referring to the physical workloads are covered in the surveys. The purpose of this paper is to determine 1) which domains and dimensions of the physical workloads are monitored in surveys at the national level and the EU level and 2) the degree of European consensus among these surveys regarding coverage of individual domains and dimensions. Items on physical workloads used in one European wide/Spanish and five other European nationwide work environment surveys were classified into the domains and dimensions they cover, using a taxonomy agreed upon among all participating partners. The taxonomy reveals that there is a modest overlap between the domains covered in the surveys, but when considering dimensions, the results indicate a lower agreement. The phrasing of items and answering categories differs between the surveys. Among the domains, the three domains covered by all surveys are "lifting, holding & carrying of loads/pushing & pulling of loads", "awkward body postures" and "vibrations". The three domains covered less well, that is only by three surveys or less, are "physical work effort", "working sitting", and "mixed exposure". This is the fırst thorough overview to evaluate the coverage of domains and dimensions of self-reported physical workloads in a selection of European nationwide surveys. We hope the overview will provide input to the revisions and updates of the individual countries' surveys in order to enhance coverage of relevant domains and dimensions in all surveys and to increase the informational value of the surveys.


Assessing the toxicity and risk of salt-impacted winter road runoff to the early life stages of freshwater mussels in the Canadian province of Ontario.
In temperate urbanized areas where road salting is used for winter road maintenance, the level of chloride in surface waters has been increasing. While a number of studies have shown that the early-life stages of freshwater mussels are particularly sensitive to salt; few studies have examined the toxicity of salt-impacted winter road runoff to the early-life stages of freshwater mussels to confirm that chloride is the driver of toxicity in this mixture. This study examines the acute toxicity of field-collected winter road runoff to the glochidia of wavy-rayed lampmussels (Lampsilis fasciola) (48 h exposure) and newly released juvenile fatmucket mussels (Lampsilis siliquoidea) (<1 week old; 96 h exposure) under different water hardness. The chronic toxicity (28 d) to older juvenile L. siliquoidea (7-12 months old) was also investigated. The 48-h EC50 and 96-h LC50 for L. fasciola glochidia and L. siliquoidea juveniles exposed to different dilutions of road run-off created with moderately hard synthetic water (∼80 mg CaCO3/L) were 1177 (95% confidence interval (CI): 1011-1344 mg Cl-/L) and 2276 mg Cl-/L (95% CI: 1698-2854 mg Cl-/L), respectively. These effect concentrations correspond with the toxicity of chloride reported in other studies, indicating that chloride is likely the driver of toxicity in salt-impacted road-runoff, with other contaminants (e.g., metals, polycyclic aromatic hydrocarbons) playing a de minimis role. Toxicity data from the current study and literature and concentrations of chloride in the surface waters of Ontario were used to conduct a probabilistic risk assessment of chloride to early-life stage freshwater mussels. The assessment indicated that chronic exposure to elevated chloride levels could pose a risk to freshwater mussels; further investigation is warranted to ensure that the most sensitive organisms are protected.


Daclizumab for the treatment of relapsing-remitting multiple sclerosis.
Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Over the last two decades, the number of therapeutic options for the treatment of relapsing remitting MS (RRMS) has been constantly growing, providing new treatment options to patients. Areas covered: Herein, the authors review the recently approved monoclonal antibody daclizumab for the treatment of RRMS. Based on original articles, they discuss its mode of action and evaluate its efficacy and safety profile compared to other available agents. Expert opinion: The IL-2 receptor modulator daclizumab is a new highly effective agent for the treatment of RRMS with novel immunomodulatory properties. Compared to interferon-beta i.m., daclizumab is more effective in reducing relapse rates and MRI activity. However, its use is limited by the risk of autoimmune disorders and hepatotoxicity. Similar to other monoclonal antibodies for RRMS, therapy with daclizumab needs a strict preselection and monitoring of patients based on individual risk benefit assessment. Given its substantial effectiveness, daclizumab can be an attractive option for patients with highly active MS.


Stromal-epithelial interaction induces GALNT14 in prostate carcinoma cells.
Cell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors. To investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing. RNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an age-dependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score. Overall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14.


Transperitoneal laparoscopic pyeloplasty in children: does upper urinary tract anomalies affect surgical outcomes?
To assess the feasibility and outcomes of laparoscopic pyeloplasty in children with complex ureteropelvic junction obstruction (UPJO) and compare to children with iso-lated UPJO without associated urinary tract abnormalities. Medical records of 82 consecutive children submitted to transperitoneal laparoscopic pyeloplasty in a 12-year period were reviewed. Eleven cases were con-sidered complex, consisting of atypical anatomy including horseshoe kidneys in 6 patients, pelvic kidneys in 3 patients, and a duplex collecting system in 2 patients. Patients were di-vided into 2 groups: normal anatomy (group 1) and complex cases (group 2). Demographics, perioperative data, outcomes and complications were recorded and analyzed. Mean age was 8.9 years (0.5-17.9) for group 1 and 5.9 years (0.5-17.2) for group 2, p=0.08. The median operative time was 200 minutes (180-230) for group 1 and 203 minutes (120-300) for group 2, p=0.15. Major complications (Clavien ≥3) were 4 (5.6%) in group 1 and 1 (6.3%) in group 2, p=0.52. No deaths or early postoperative complications such as: urinoma or urinary leakage or bleeding, occurred. The success rate for radiologic improvement and flank pain improvement was comparable between the two groups. Re-garding hydronephrosis, significant improvement was present in 62 patients (93.4%) of group 1 and 10 cases (90.9%) of group 2, p=0.99. The median hospital stay was 4 days (IQR 3-4) for group 1 and 4.8 days (IQR 3-6) for group 2, p=0.27. Transperitoneal laparoscopic pyeloplasty is feasible and effective for the management of UPJO associated with renal or urinary tract anomalies.


Substrate stiffness influences the outcome of antitumor drug screening in vitro.
Substrate stiffness has been proven to play a critical role in vitro tumor proliferation; however, pharmacological studies on antitumor drug screening are still routinely carried out in regular plastic culture plates. In the article, polydimethylsiloxane (PDMS) substrates with different stiffness (mimicking articular cartilage, collagenous bone and mammary tumor respectively) and plastic substrate were employed to establish the mechanical microenvironment for the in vitro drug screening platform. We studied the influences of stiffness on the responses of MCF-7 cells to typical antitumor drugs, cisplatin and taxol. Results showed that for both the treatment IC50 value to MCF-7 cells decreased significantly (p < 0.01) on the rigid substrate, indicating that MCF-7 cells on soft substrate have a resistance to cytotoxicity of antitumor drugs. The sensitivity of MCF-7 cells on rigid substrate to drug cytotoxicity was attributed to the increased cell cycle progression, implying that agents proven to be effective in vitro by conventional screening approach might be inefficient in a soft microenvironment in vivo. We conclude that stiffness of the substrates, as a critical mechanical factor, should be concerned for screening antitumor agents in vitro. As an extrapolation, the extensively used drug screening system needs to be revalued and redesigned.


[Comparison of the rate of body weight increase in children fed with cow's milk formulas and children with alimentary sensitivity, fed with milk-replacing mixtures].
The aim of this study was a comparison of body weight increase rate in two groups of children up to 18 months of age. The first group was fed with cow s milk formula. The second group due to allergy or cow milk intolerance was fed with milk-replacing mixtures: hydrolyzates with higher rate of protein hydrolysis or soya preparations. In the analysed group of 332 children, 135 children were fed with cow's milk formulas, 142 children were given no-milk diet based on protein hydrolyzates and another 55 were fed with soya mixtures. The average body weight increase values were analysed in three months periods of half-years of life and in relation to gender and type of feeding. The obtained results were analysed statistically. There were statistically significant greater mean monthly increments of body weight in male children fed with cow's milk formulas as compared to male children fed with hydrolyzates in the first quarter and in the first half-year of life and male infants fed with soya mixtures. In subsequent three and six months periods no statistically significant differences in mean monthly values of body weight increase in relation to type of nutrition were found.


Multiple cutaneous melanomas associated with gastric and brain metastases.
The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified.


School-community partnerships: a cluster-randomized trial of an after-school soccer program.
Identifying community-based programs that increase physical activity among diverse youth could yield sustainable tools to reduce obesity and obesity disparities. To evaluate the impact of a community-based after-school soccer and youth development program, America SCORES, on students' physical activity, weight status, and fitness. Cluster-randomized trial. Study measures were collected in the fall (baseline), winter (midpoint), and spring (end point) of the 2009-2010 school year. After-school programs in 6 schools within a large urban school district. All 4th and 5th grade students in after-school programs at the study schools were eligible. Three schools were randomized to receive the SCORES after-school program, delivered via the train-the-trainer model. Change in minutes of after-school moderate-to-vigorous physical activity (MVPA), fitness (maximal oxygen consumption), and body mass index over 1 school year. Participants (n = 156) were diverse (42% Latino, 32% Asian, and 12% African American) and 76 (49%) had a body mass index at or above the 85th percentile. There were no significant group differences in the change in physical activity, fitness, or weight status among all students. However, among students with a body mass index at or above the 85th percentile, SCORES significantly increased MVPA after school (3.4 min/d; 95% CI, 0.3-6.5) and on Saturdays (18.5 minutes; 95% CI, 3.4-33.6). Existing community-based programs such as SCORES can increase physical activity among low-income youth, particularly those most at risk for weight-related comorbidities. While evaluating existing programs presents special challenges, partnerships between communities, schools, and researchers are an important component of translational research to address obesity. clinicaltrials.gov Identifier: NCT01156103.


Structural and mechanistic studies of mofegiline inhibition of recombinant human monoamine oxidase B.
Mechanistic and structural studies have been carried out to investigate the molecular basis for the irreversible inhibition of human MAO-B by mofegiline. Competitive inhibition with substrate shows an apparent K(i) of 28 nM. Irreversible inhibition of MAO-B occurs with a 1:1 molar stoichiometry with no observable catalytic turnover. The absorption spectral properties of mofegiline inhibited MAO-B show features (lambda(max) approximately 450 nm) unlike those of traditional flavin N(5) or C(4a) adducts. Visible and near-UV circular dichroism spectra of the mofegiline-MAO-B adduct shows a negative peak at 340 nm with an intensity similar to that of N(5) flavocyanine adducts. The X-ray crystal structure of the mofegiline-MAO-B adduct shows a covalent bond between the flavin cofactor N(5) with the distal allylamine carbon atom as well as the absence of the fluorine atom. A mechanism to explain these structural and spectral data is proposed.


Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex.
The spatial-temporal sequence of cerebral blood flow (CBF), cerebral blood volume (CBV) and blood velocity changes triggered by neuronal activation is critical for understanding functional brain imaging. This sequence follows a stereotypic pattern of changes across different zones of the vasculature in the olfactory bulb, the first relay of olfaction. However, in the cerebral cortex, where most human brain mapping studies are performed, the timing of activity evoked vascular events remains controversial. Here we utilized a single whisker stimulation model to map out functional hyperemia along vascular arbours from layer II/III to the surface of primary somatosensory cortex, in anesthetized and awake Thy1-GCaMP6 mice. We demonstrate that sensory stimulation triggers an increase in blood velocity within the mid-capillary bed and a dilation of upstream large capillaries, and the penetrating and pial arterioles. We report that under physiological stimulation, response onset times are highly variable across compartments of different vascular arbours. Furthermore, generating transfer functions (TFs) between neuronal Ca2+ and vascular dynamics across different brain states demonstrates that anesthesia decelerates neurovascular coupling (NVC). This spatial-temporal pattern of vascular events demonstrates functional diversity not only between different brain regions but also at the level of different vascular arbours within supragranular layers of the cerebral cortex.


Screening of tissue-specific genes and promoters in tomato by comparing genome wide expression profiles of Arabidopsis orthologues.
Constitutive overexpression of transgenes occasionally interferes with normal growth and developmental processes in plants. Thus, the development of tissue-specific promoters that drive transgene expression has become agriculturally important. To identify tomato tissue-specific promoters, tissue-specific genes were screened using a series of in silico-based and experimental procedures, including genome-wide orthologue searches of tomato and Arabidopsis databases, isolation of tissue-specific candidates using an Arabidopsis microarray database, and validation of tissue specificity by reverse transcription-polymerase chain reaction (RT-PCR) analysis and promoter assay. Using these procedures, we found 311 tissue-specific candidate genes and validated 10 tissue-specific genes by RT-PCR. Among these identified genes, histochemical analysis of five isolated promoter::GUS transgenic tomato and Arabidopsis plants revealed that their promoters have different but distinct tissue-specific activities in anther, fruit, and root, respectively. Therefore, it appears these in silico-based screening approaches in addition to the identification of new tissue-specific genes and promoters will be helpful for the further development of tailored crop development.


[Cerebral aneurysms and current methods of treatment].
The authors discuss briefly aneurysms cerebral arteries. In the light of the pertinent literature the hypotheses of their development are reviewed. These aneurysms are probably lesions acquired by individuals with special predispositions, acquired or inborn. The problems of aneurysm diagnosis are reviewed and the methods are discussed of their management, both surgical and intravascular (embolization). Both methods are tentatively compared. In certain cases each method may be an excellent alternative for the other, and in other cases they are mutually complementary extending thus the range of therapeutic possibilities.


AMPK-related kinase 5 (ARK5) enhances gemcitabine resistance in pancreatic carcinoma by inducing epithelial-mesenchymal transition.
AMPK-related kinase 5 (ARK5) is a member of the human AMP-activated protein kinase (AMPK) family, which is associated with increased tumor survival and drug resistance in many cancers. However, the function of ARK5 in pancreatic carcinoma (PC) is unclear. Our study investigated the role of ARK5 in the chemo-resistance of PC and its underlying mechanism. PC cell lines that displayed high expression levels of ARK5 had low sensitivity to gemcitabine (GEM). Suppression of ARK5 increased sensitivity to GEM in PC cell lines. Western blotting and immunofluorescence showed that suppression of ARK5 upregulated expression of E-cadherin and downregulated vimentin expression. Suppression of ARK5 also inhibited the epithelial-mesenchymal transition (EMT) efficiency associated with GEM in PC cell lines and upregulation of ARK5 expression enhanced GEM resistance in PC cell lines by inducing Twist-mediated EMT. In addition, we found that suppression of ARK5 increased GEM sensitivity in PC cell lines under hypoxic conditions. ARK5 increases GEM resistance in PC cell lines via EMT, and suppression of ARK5 increases sensitivity to GEM under both normoxic and hypoxic conditions.


Intracardiac catheter 2-D arrays on a silicon substrate.
The design, fabrication, and characterization of a 7 MHz, two-dimensional (2-D) array transducer built on a silicon substrate is described. The array fits inside a 9-French (2.9 mm O.D.) catheter for use in real-time intracardiac volumetric imaging. The -6 dB fractional bandwidth of the transducer is 30%, the 50 ohm pitch-catch insertion loss is 78 dB, and the interelement crosstalk is -25 dB. Real-time volumetric images in phantoms and in-vitro images of a sheep heart have been acquired yielding measured spatial resolution of 2 mm at a depth of 1 cm. The cardiac structures imaged include ventricular chambers, interventricular septum, mitral and tricuspid valves and real-time 3-D rendered volumes of the tricuspid valve in the open and closed position.


A simple method for the estimation of peritoneal fluid transport.
Evaluating peritoneal fluid kinetics is of great value to the adjustment of peritoneal dialysis prescription. Therefore, in the present study, we developed a simple method, based on a membrane transport model, to evaluate the fluid transport characteristics of the peritoneal membrane in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients' peritoneal ultrafiltration (UF) volume was collected for 2 consecutive months. Membrane transport model and nonlinear least-squares regression analyses were applied to the pooled UF volume for the first month for fluid kinetic simulation and the data from the second month were used to evaluate the reliability and precision of simulated UF values. Seventeen chronic peritoneal dialysis (PD) patients were selected for the present study. Simulated UF values based on the pooled UF volume in the first month correlated significantly with the actual measured UF values in the second month. By Bland-Atman plot, the width between the 95% limits of agreement fell within -133.3 to 154.2 ml with a mean difference of 10.5 ml. Our study showed that applying the fluid transport model and nonlinear least-squares regression analysis to the pooled actual UF value might be a good and simple way to predict peritoneal UF.


MicroRNA 21 blocks apoptosis in mouse periovulatory granulosa cells.
MicroRNAs (miRNAs) play important roles in many developmental processes, including cell differentiation and apoptosis. Transition of proliferative ovarian granulosa cells to terminally differentiated luteal cells in response to the ovulatory surge of luteinizing hormone (LH) involves rapid and pronounced changes in cellular morphology and function. MicroRNA 21 (miR-21, official symbol Mir21) is one of three highly LH-induced miRNAs in murine granulosa cells, and here we examine the function and temporal expression of Mir21 within granulosa cells as they transition to luteal cells. Granulosa cells were transfected with blocking (2'-O-methyl) and locked nucleic acid (LNA-21) oligonucleotides, and mature Mir21 expression decreased to one ninth and one twenty-seventh of its basal expression, respectively. LNA-21 depletion of Mir21 activity in cultured granulosa cells induced apoptosis. In vivo, follicular granulosa cells exhibit a decrease in cleaved caspase 3, a hallmark of apoptosis, 6 h after the LH/human chorionic gonadotropin surge, coincident with the highest expression of mature Mir21. To examine whether Mir21 is involved in regulation of apoptosis in vivo, mice were treated with a phospho thioate-modified LNA-21 oligonucleotide, and granulosa cell apoptosis was examined. Apoptosis increased in LNA-21-treated ovaries, and ovulation rate decreased in LNA-21-treated ovaries, compared with their contralateral controls. We have examined a number of Mir21 apoptotic target transcripts identified in other systems; currently, none of these appear to play a role in the induction of ovarian granulosa cell apoptosis. This study is the first to implicate the antiapoptotic Mir21 (an oncogenic miRNA) as playing a clear physiologic role in normal tissue function.


The nursing management of enterocutaneous fistulae: a challenge for all.
This article focuses on the principles of managing patients with enterocutaneous fistulae. Successful management involves comprehensive assessment, planning, implementation and evaluation of care and involves all members of the multidisciplinary team in both primary and secondary care. The main challenge for the nursing team is effective containment of the effluent to prevent excoriation of the skin thereby ensuring patient comfort. The article includes suggestions for choice and application of suitable appliances which have been successfully used by the authors. Early involvement in of patient and carer in all aspects of management is recommended for successful discharge of patients into the community.


CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice.
A localized Th2 milieu has been observed in the intestine of subjects with food allergic disorders; however, the role of T cells in the pathophysiology of these disorders remains poorly understood. Our aim was to examine sites of T cell activation in response to food challenge, identify potential factors responsible for T cell recruitment to the gut, and determine the role of T cells in disease. BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly fed with OVA to induce allergic diarrhea. Local cytokine and chemokine expressions were assessed by quantitative PCR, and cytokine secretion levels in the mesenteric lymph node (MLN) were determined by ELISA. Homing molecule expression was determined by flow cytometry, and the role of CD4(+) T cells in promoting disease was tested by adoptive transfer. Mice developed diarrhea associated with changes in epithelial ion transport, mast cell infiltration, intestinal IgE secretion, and local upregulation of Th2 cytokines and the Th2 chemokines CCL1, CCL17, and CCL22 in the small intestine. T cell activation occurred in the MLN before symptom onset, and a single feed of OVA induced T cell proliferation, alpha(4)beta(7) upregulation, and CD62L downregulation. Cells from the MLN, including purified CD4(+) T cells, were able to transfer allergic diarrhea to naive mice. A gut-homing phenotype induced in the MLN and selective upregulation of Th2 chemoattractants are likely important factors in the gastrointestinal recruitment of pathological Th2-skewed CD4(+) T cells in food allergy.


A spectrophotometric study of the denaturation of deoxyribonucleic acid in the presence of urea or formaldehyde and its relevance to the secondary structure of single-stranded polynucleotides.
1. The thermal denaturation of DNA from rat liver was studied spectrophotometrically. In sodium phosphate buffers denaturation led to a single-stranded form having, at 25 degrees , about 25% of the hypochromism of the intact double helix. 2. The hypochromism of the denatured form was the same in 1mm- as in 10mm-sodium phosphate buffer and was scarcely affected by reaction with formaldehyde. The hypochromism was decreased by about 40% in the presence of 8m-urea. 3. The hypochromism of denatured DNA at low ionic strengths was about the same as that of fragments of reticulocyte ribosomal RNA that were too short to form double-helical secondary structure and about the same as that of RNA after reaction with formaldehyde. 4. The spectrum of DNA was slightly affected by the presence of 8m-urea or 4m-guanidinium chloride. The differences in the spectrum of the native and denatured forms of DNA in 0.1m-sodium phosphate buffer, in 8m-urea-10mm-sodium phosphate buffer and in 4m-guanidinium chloride-10mm-sodium phosphate buffer, pH7.6, were similar but not identical. 5. Denatured rat liver DNA appears to have no double-helical character at 25 degrees in 10mm-sodium phosphate buffer, pH7.6; increasing the buffer concentration to 0.1m leads to a more compact form in which about 40% of the residues form base pairs.


Results of additional pulsatile pulmonary blood flow with bidirectional glenn cavopulmonary anastomosis: positive effect on main pulmonary artery growth and less need for fontan conversion.
Additional antegrade pulsatile pulmonary blood flow obtained by leaving the main pulmonary artery patent during bidirectional cavopulmonary shunt has been shown to give additional benefits to the bidirectional Glenn cavopulmonary anastomosis. We retrospectively evaluated our 20-patient pulsatile Glenn series in order to find out whether these salutary effects were valid or not. Between June 2007 and November 2011, 20 patients (11 girls and 9 boys) with single-ventricle physiology underwent bidirectional cavopulmonary anastomosis. The additional source of blood flow was through the unligated main pulmonary artery in all patients. A retrospective review of our surgical experience was performed focusing on the role of additional pulmonary flow. Medical records and perioperational and postoperative follow-up data including clinical outcomes were retrospectively retrieved and analyzed. Two patients died in the early postoperative period. One patient died in the follow-up period. Mean follow-up time was 23.9 ± 15.7 months. No superior vena cava syndrome and no increase in pulmonary vascular resistance were observed. Improvement of partial oxygen pressure after pulsatile Glenn has been shown in all patients (P = .00). At a mean interval of 22.9 months, main pulmonary artery size continued to increase after pulsatile Glenn cavopulmonary anastomosis (P = .028). Only 1 patient was converted to Fontan type circulation after pulsatile Glenn cavopulmonary anastomosis. The pulsatile cavopulmonary shunt is a useful procedure in the early and intermediate term management of patients with a functional univentricular heart. It improves partial oxygen pressure and the impact of pulsatility on the main pulmonary artery.


Live-cell visualization of gasdermin D-driven pyroptotic cell death.
Pyroptosis is a form of cell death important in defenses against pathogens that can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, GSDMD (gasdermin D), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD. In this work, we performed mutagenesis and molecular modeling to strategically place tags and fluorescent proteins within GSDMD that support native pyroptosis and facilitate live-cell imaging of pyroptotic cell death. Here, we demonstrate that these fusion proteins are cleaved by caspases-1 and -11 at Asp-276. Mutations that disrupted the predicted p30-p20 autoinhibitory interface resulted in GSDMD aggregation, supporting the oligomerizing activity of these mutations. Furthermore, we show that these novel GSDMD fusions execute inflammasome-dependent pyroptotic cell death in response to multiple stimuli and allow for visualization of the morphological changes associated with pyroptotic cell death in real time. This work therefore provides new tools that not only expand the molecular understanding of pyroptosis but also enable its direct visualization.


Impact of expiratory muscle strength training on voluntary cough and swallow function in Parkinson disease.
Cough provides high expiratory airflows to aerosolize and remove material that cannot be adequately removed by ciliary action. Cough is particularly important for clearing foreign particles from the airway in those with dysphagia who may be at risk for penetration/aspiration (P/A). Expiratory muscle strength training (EMST) was tested to improve cough and swallow function. Ten male participants, diagnosed with Parkinson disease (PD), with videofluorographic evidence of penetration or with evidence for aspiration of material during swallow of a thin 30-mL bolus, completed 4 weeks of an EMST program to test the hypothesis that EMST would improve cough and/or swallow function. Measured parameters from an airflow waveform produced during voluntary cough, pre-EMST and post-EMST, included inspiration phase duration, compression phase duration (CPD), expiratory phase peak flow (EPPF), expiratory phase rise time (EPRT), and cough volume acceleration (VA) [ie, the EPPF/EPRT ratio]. The swallow outcome measure was the degree of P/A during the swallow task. There was a significant decrease in the duration of the CPD and EPRT; the decrease in EPRT resulted in a significant increase in cough VA. Significant decreases in the P/A scores were found posttraining. The results demonstrate that EMST is a viable treatment modality for a population of participants with PD at risk of aspiration.


Computed tomography of intrinsic laryngeal and tracheal abnormalities in children.
The use of CT in the evaluation of intrinsic laryngeal and tracheal lesions in 42 children is reported. Computed tomography accurately defined the caliber of the airway and documented the site and extent of narrowed segments as well as revealed detailed information about tissues adjacent to the airway. Documentation of a normal or slightly narrowed airway on CT may obviate the need for more invasive endoscopic procedures. Computed tomography may reveal valuable anatomical information prior to endoscopy and can delineate the length of narrowed segments when endoscopy fails to do so.


Monitoring Health Inequalities at the Municipal Level: Lithuanian Experience.
This study aimed to assess the attitudes of Lithuanian public health professionals towards health inequality monitoring in municipalities. The survey was conducted in public health bureaus (PHBs) and administrations of municipalities in March 2015. All employees of PHBs, all municipal doctors and all employees of health departments were invited to participate in the study (N=318; response rate, 47.2%). The study participants had positive attitudes towards the importance of health inequality monitoring at the municipal level, meanwhile systematic health inequality monitoring was assessed moderately. The majority of the interviewed professionals working at PHBs and municipalities (91.4% and 88.2%, respectively) declared that health indicators were monitored and analysed in their institutions. The respondents acknowledged the importance of routine monitoring of health indicators for assessment of inequalities, but these indicators were not monitored systematically in every municipality and PHB. Public health professionals identified the following measures for better health inequality monitoring: to strengthen intersectoral collaboration, formulate specific objectives of health programmes, promote actions in reducing health inequalities. Public health professionals working at the municipal level outlined the importance of monitoring and reducing health inequalities. However, health inequality monitoring at the municipal level was considered as insufficient.


Evaluation of Shear Bond Strength of Newer Bonding Systems on Superficial and Deep Dentin.
The purpose of this study was to compare the shear bond strength of nanocomposite resin to superficial dentin and deep dentin using two different dentin bonding systems. All teeth were sectioned at various levels (superficial dentin: Dentin within 0.5-1 mm of dentinoenamel junction; deep dentin: Dentin within 0.5 mm of the highest pulp horn) using a Carborundum Disc and embedded in acrylic block of specific size. Selected specimens (60 premolar teeth) were grouped randomly into three groups, the groups were differentiated into superficial dentin, deep dentin, and control group which were further divided into sub Group A and Subgroup B containing 10 teeth each, depending on the bonding agents used. In Subgroup A, Tetric N Bond, and in Subgroup B Single Bond Universal were used. In the control group no bonding agent was used. The specimens were thermocycled for 500 cycles between 5°C and 55°C water bath for 40 s. Finally, the specimens were subjected to shear bond strength study under INSTRON machine (Universal Testing Machine). The maximum shear bond strengths were noted at the time of fracture (de-bonding) of the restorative material. Results were analyzed using ANOVA test, Bonferroni test, and paired t-test. Bond strength values of fifth generation bonding system (Tetric N Bond) showed higher mean shear bond strength compared to seventh generation bonding system (Single Bond Universal). There was a significant fall in bond strength values as one reaches deeper levels of dentin from superficial to deep dentin. There was a significant difference between the bond strength of fifth generation bonding system (Tetric N Bond) and seventh generation bonding system (Single Bond Universal). Decrease in the bond strength values is seen for the deeper level of dentin as compared to superficial dentin.


Validation of the concept risk for decreased cardiac output.
to validate the concept "risk for decreased cardiac output". Six of the eight steps suggested in the technique developed by Walker & Avant were adopted to analyze the concept of the phenomenon under study and the proposal made by Hoskins was used for content validation, taking into account agreement achieved among five experts. the concept "decreased cardiac output" was found in the nursing and medical fields and refers to the heart's pumping capacity while the concept "risk" is found in a large number of disciplines. In regard to the defining attributes, "impaired pumping capacity" was the main attribute of decreased cardiac output and "probability" was the main attribute of risk. The uses and defining attributes of the concepts "decreased cardiac output" and "risk" were analyzed as well as their antecedent and consequent events in order to establish the definition of "risk for decreased cardiac output", which was validated by 100% of the experts. The obtained data indicate that the risk for decreased cardiac output phenomenon can be a nursing diagnosis and refining it can contribute to the advancement of nursing classifications in this context.


An interactive education session and follow-up support as a strategy to improve clinicians' goal-writing skills: a randomized controlled trial.
Recent research indicates that allied health clinicians have difficulty articulating client needs and priorities into specific and measurable goals. As a result, a number of strategies to facilitate improvement in allied health clinicians' goal-setting skills have been recommended in the literature. In order to assist clinicians develop the skills required to set SMART goals, it is necessary that the strategies are rigorously tested. To determine if a 50-minute education session and 3-month email and telephone support programme improves clinicians' SMART goal-writing skill and accurately predicts improved goal-writing behaviour. Concealed random allocation of participants (n = 120) into two parallel groups: (1) intervention group received education on writing goals using the SMART Goal Evaluation Method as part of a workshop on outcome measurement and received 3 months of follow-up support (n = 60); and (2) control group attended a workshop on evidence-based practice (n = 60). Education and follow-up support improved clinicians' SMART goal-writing skills at both the 3- and 6-month review (Yates chi(2) = 4.324, d.f. = 1, P = 0.0375). Structural equation modelling revealed education and follow-up support is an accurate predictor of SMART goal-setting behaviour change at both 3 months (standardized regression weights = 0.21; P = 0.014) and 6 months (standardized regression weights = 0.19; P = 0.02) post intervention. Changes were modest and developed over a 6-month period. This study provides empirical evidence that a programme of educating clinicians in a standardized method of goal setting and providing follow-up support improves allied health clinicians' SMART goal-writing skills.


Importance of Survey Design for Studying the Epidemiology of Emerging Tobacco Product Use Among Youth.
Accurate surveillance is critical for monitoring the epidemiology of emerging tobacco products in the United States, and survey science suggests that survey response format can impact prevalence estimates. We utilized data from the 2014 New Jersey Youth Tobacco Survey (n = 3,909) to compare estimates of the prevalence of 4 behaviors (ever hookah use, current hookah use, ever e-cigarette use, and current e-cigarette use) among New Jersey high school students, as assessed using "check-all-that-apply" questions, with estimates measured by means of "forced-choice" questions. Measurement discrepancies were apparent for all 4 outcomes, with the forced-choice questions yielding prevalence estimates approximately twice those of the check-all-that-apply questions, and agreement was fair to moderate. The sensitivity of the check-all-that-apply questions, treating the forced-choice format as the "gold standard," ranged from 38.1% (current hookah use) to 58.3% (ever e-cigarette use), indicating substantial false-negative rates. These findings highlight the impact of question response format on prevalence estimates of emerging tobacco products among youth and suggest that estimates generated by means of check-all-that-apply questions may be biased downward. Alternative survey designs should be considered to avoid check-all-that-apply response formats, and researchers should use caution when interpreting tobacco use data obtained from check-all-that-apply formats.


[The inhibitors of the apical sodium-dependent bile acid transporter (ASBT) as promising drugs].
Inhibition of the apical sodium-dependent bile acid transporter (ASBT, also known as IBAT - ileal bile acid transporter, SLC10A2) leads to disruption of the enterohepatic circulation of bile acids and their excretion with fecal masses. This is accompanied by cholesterol utilization for synthesis of new bile acids. ASBT inhibitors are promising drugs for the treatment of such diseases as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, type 2 diabetes mellitus, necrotic enterocolitis, chronic constipation, atherosclerosis. To date the most known chemically synthesized inhibitors are: A3309, SHP626, A4250, 264W94, GSK2330672, SC-435. All of them are at different stages of clinical trials, which confirm the high efficacy and good tolerance of these inhibitors. Current trends in this field also include directed chemical synthesis of ASBT inhibitors, as well as their search among substances of plant origin.


Characterization of nanoporous cavity of quardruply bridged calix[6]arenes by means of hyperpolarized 129Xe NMR.
The bridged calix[6]arenes, which are well known as cavitands to capture ions and molecules, were characterized via the hyperpolarized 129Xe NMR. Also, we could deduce the pathway of a guest molecule into hosts and estimate the pore diameter of bridged calix[6]arenes. The characterized results of nanoporous cavity by the hyperpolarized 129Xe NMR corresponded with the measurement from the X-ray structure. This study showed that the hyperpolarized 129Xe NMR could be used as a promising tool to characterize nanoporous cavity of host compounds with low surface area.


Bronchial microdialysis of cytokines in the epithelial lining fluid in experimental intestinal ischemia and reperfusion before onset of manifest lung injury.
Today, there is no continuous monitoring of the bronchial epithelial lining fluid. This study used microdialysis as a method of continuous monitoring of early lung cytokine response secondary to intestinal ischemia-reperfusion in pigs. The authors aimed to examine bronchial microdialysis for continuous monitoring of IL-1β, TNF-α, IL-8, and fluorescein isothiocyanate Dextran 4,000 Da (FD-4). The superior mesenteric artery was cross-clamped for 120 min followed by 240 min of reperfusion (ischemia group, n = 8). Four sham-operated pigs served as controls. The pigs were anesthetized and normoventilated (peak inspiratory pressure, <20 cm H2O; positive end-expiratory pressure, 7 cm H2O). Samples from bronchial and luminal intestinal and arterial microdialysis catheters (flow-rate of 1 μL/min) were collected during reperfusion in 60-min fractions. Samples were analyzed for TNF-α, IL-1β, IL-8, and FD-4. Data are presented as median (interquartile range). A lung biopsy was collected at the end of the experiment. During reperfusion, there was an increase in bronchial concentrations of both IL-8 (3.70 [1.47-8.93] ng/mL per h vs. controls, 0.61 [0.47-0.91] ng/mL per h; P < 0.001) and IL-1β (0.32 [0.05-0.56] ng/mL per h vs. controls, 0.07 [0.04-0.10] ng/mL per h; P = 0.008). In the intestinal lumen, IL-8 was increased in the ischemia group (6.33 [3.13-9.23] ng/mL per h vs. controls, 0.89 [0.21-1.86] ng/mL per h; P < 0.001). The FD-4 did not differ between groups. Pulmonary vascular resistance and pulmonary shunt increased versus controls. During reperfusion, PaO2/FiO2 ratio decreased in the ischemia group. Histology was normal in both groups. Bronchial microdialysis detects altered levels of cytokines in the epithelial lining fluid and can be used for continuous monitoring of the immediate local lung cytokine response secondary to intestinal ischemia-reperfusion.


Rainwater harvesting in American Samoa: current practices and indicative health risks.
Roof-harvested rainwater (RHRW) is an important alternative source of water that many island communities can use for drinking and other domestic purposes when groundwater and/or surface water sources are contaminated, limited, or simply not available. The aim of this pilot-scale study was to investigate current RHRW practices in American Samoa (AS) and to evaluate and compare the quality of water from common potable water sources including RHRW stored in tanks, untreated stream water, untreated municipal well water, and treated municipal tap water samples. Samples were analyzed using culture-based methods, quantitative polymerase chain reaction (qPCR), and 16S amplicon sequencing-based methods. Based on indicator bacteria (total coliform and Escherichia coli) concentrations, the quality of RHRW was slightly lower than well and chlorinated tap water but exceeded that of untreated stream water. Although no Giardia or Leptospira spp. were detected in any of the RHRW samples, 86% of the samples were positive for Cryptosporidium spp. All stream water samples tested positive for Cryptosporidium spp. Opportunistic pathogens (Pseudomonas aeruginosa and Mycobacterium intracellulare) were also detected in the RHRW samples (71 and 21% positive samples, respectively). Several potentially pathogenic genera of bacteria were also detected in RHRW by amplicon sequencing. Each RHRW system was characterized by distinct microbial communities, 77% of operational taxonomic units (OTUs) were detected only in a single tank, and no OTU was shared by all the tanks. Risk of water-borne illness increased in the following order: chlorinated tap water/well water < RHRW < stream water. Frequent detection of opportunistic pathogens indicates that RHRW should be treated before use. Stakeholder education on RHRW system design options as well as on importance of regular cleaning and proper management techniques could improve the quality of the RHRW in AS.


Treatment of the exposed Achilles tendon using negative pressure wound therapy: a case report.
Exposed tendons after burn injury create a surgical challenge for the treating physician. This is particularly true with regard to the exposed Achilles tendon. This case report reviews the nature of this challenge and traditional solutions, and describes the use of negative pressure wound therapy to facilitate coverage of the Achilles tendon. This therapy may provide a more appropriate therapeutic option for dealing with tendon exposure after severe burns.


Nanoparticle accumulation in angiogenic tissues: towards predictable pharmacokinetics.
Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.


The role of the basic N-terminal region of protein L18 in 5S RNA-23S RNA complex formation.
Of the three proteins, L5, L18 and L25, which bind to 5S RNA, the former two effect the interaction of 5S RNA with 23S RNA. We have used trypsin as a probe to investigate the roles of the proteins in this RNA-RNA assembly, with the following results: (1) In complexes with 5S RNA, the highly basic N-terminal region of L18 is accessible to trypsin. This accessibility is unaffected by L25. However, its presence is essential for stimulating L5 binding. (2) In 5S RNA-protein-23S RNA complexes proteins L5 and L18 are both strongly resistant to proteolysis. (3) No 5S RNA-23S RNA complex formation occurs in the presence of L5 and the C-terminal L18 fragment. Two possible models for the mechanism of RNA-RNA assembly are proposed.


Interaction of receptors for insulin-like growth factor I, platelet-derived growth factor, and fibroblast growth factor in rat aortic cells.
Serum contains various growth factors which regulate the proliferation of cells. We investigated the growth of cultured arterial smooth muscle cells under the influence of insulin-like growth factor I (IGF I), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), and examined the effect of these growth factors on the binding of [125I] IGF I and on the binding of [125I]PDGF to these cells. IGF I, FGF, and PDGF stimulated [6-3H]thymidine incorporation into DNA of confluent cultures of cells which were incubated in modified Dulbecco's modified Eagle medium. However, the effect of these growth factors on DNA synthesis was much more potent in Dulbecco's modified Eagle medium with 1% fetal calf serum. FGF and PDGF potentiated the growth-promoting effect of IGF I. The binding of [125I]IGF I to the cells was increased after a preincubation with FGF and PDGF. The binding was potently increased by FGF (100 ng/ml) after a preincubation time of 30 min. There was an increase in binding during the first 3 h of preincubation followed by a decrease after 4-5 h. PDGF (10-1000 ng/ml) stimulated [125I]IGF I binding only after 2 h of preincubation. The stimulation was dose dependent. Maximal stimulation of the binding was observed after 3 h of preincubation followed by a decrease after 4-5 h of preincubation. Specific binding sites for PDGF on smooth muscle cells could be demonstrated too. A preincubation of confluent cells with IGF I caused a dose-dependent increase in [125I]PDGF binding. These results support the hypothesis that the regulation of the binding of a specific growth factor by a second growth factor is important for the control of cell growth.


Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis.
SignificanceScramblases translocate lipids across the lipid bilayer without consumption of ATP, thereby regulating lipid distributions in cellular membranes. Cytosol-to-lumen translocation across the endoplasmic reticulum (ER) membrane is a common process among lipid glycoconjugates involved in posttranslational protein modifications in eukaryotes. These translocations are thought to be mediated by specific ER-resident scramblases, but the identity of these proteins and the underlying molecular mechanisms have been elusive. Here, we show that CLPTM1L, an integral membrane protein with eight putative transmembrane domains, is the major lipid scramblase involved in efficient glycosylphosphatidylinositol biosynthesis in the ER membrane. Our results validate the long-standing hypothesis that lipid scramblases ensure the efficient translocations of lipid glycoconjugates across the ER membrane for protein glycosylation pathways.


Effect of tribendimidine on adult Echinostoma caproni harbored in mice, including scanning electron microscopic observations.
Food-borne trematodiasis is an emerging public health problem with more than 10% of the world's population at risk of infection, yet there are only 2 drugs available for treatment and morbidity control. We assessed the effect of a promising broad-spectrum anthelmintic drug, i.e., tribendimidine, with an experimental focus on adult Echinostoma caproni. Female NMRI mice were infected with 30 E. caproni for 2 wk and then administered single oral doses of tribendimidine ranging between 25 and 500 mg/kg. Three days post-treatment, mice were necropsied, and adult worms were recovered from their intestines. Worm burden reductions were assessed against untreated control mice. In addition, scanning electron microscopic observations were done on adult E. caproni recovered from mice given a single dose of 150 mg/kg tribendimidine intragastrically 2, 4, and 8 hr post-treatment. Worm burden reductions of 100% were achieved at doses of 125 mg/kg and above. Severe damage of the tegument, including extensive peeling, formation of blebs, and structural loss of the definition of collar and tegumentary spines already occurred within 2 hr after drug administration. Our findings call for further investigations using tribendimidine in other trematode-animal models, because this compound shows promising trematocidal activity.


[Study on thermo-sensitive intelligent targeting type drug carriers (I) porous membranes with grafted thermo-sensitive gates].
Thermo-responsive intelligent membranes with linear grafted poly(N-isopropylacrylamide) (PNIPAM) gates on the inner pore surface were prepared, and experiments were carried out on the thermo-responsive gating characteristics. Plasma-graft pore-filling polymerization was used to graft PNIPAM into the pore of the porous flat membranes. The experimental results showed that PNIPAM-grafted PVDF (PNIPAM-g-PVDF) membranes were featured with thermo-responsiveness due to the thermo-responsive swollen-shrunken property of PNIPAM chains grafted on the inner pore surface of the membrane. At temperatures below the lower critical solution temperature (LCST), the linear grafted PNIPAM chains on the inner pore surface were in the swollen state, and the pores in the membrane were closed; in contrast, the grafted PNIPAM chains were in the shrunken state at temperatures above the LCST, and therefore the pores in the membrane were open. The LCST of the thermo-sensitive gates could be adjusted by adding acrylamide (AAM) in the N-isopropylacrylamide (NIPAM) monomer solution, the LCST of the poly(NIPAM-co-AAM) gates increased simply with the increase of the AAM fraction.


Intercostal Nerve Cryoablation for Postoperative Pain Control in Pediatric Thoracic Surgery: A Scoping Review.
Background: Cryoanalgesia uses the application of cold temperatures to temporarily disrupt peripheral sensory nerve function for pain control. This review outlines the principles of cryoablation, clinical applications, and clinical data for its use in pediatric thoracic surgery. Methods: A comprehensive PubMed search was performed using the principal terms and combinations of cryoablation, cryoanalgesia, Nuss, Nuss repair, pectus, pectus excavatum, thoracic surgery, thoracotomy, and chest wall. Pediatric articles were reviewed and included if relevant. Adult articles were reviewed for supporting information as needed. Reference lists of included articles were reviewed for possible additional sources. Discussion: The scientific and clinical principles of cryoablation are outlined, followed by a focused review of current clinical application and outcome data. Conclusion: Postoperative pain is a major challenge following thoracic surgery. Cryoanalgesia is emerging as an adjunct in pediatric thoracic surgery, particularly for the Nuss procedure or minimally invasive repair of pectus excavatum. It effectively controls pain, decreasing postoperative opioid use and hospital length of stay with few short-term complications. Although more long-term studies are needed, early evidence suggests there is reliable return of sensation to the chest wall and long-term neuropathic pain is rare.


[Fibrosing cholangiolitis after administration of methyltestosterone].
A case of intrahepatic cholestasis of great intensity was observed in a patient taking methyltestosterone. In histological examination of liver biopsy specimen evidence was found of fibrosing intralobular cholangiolitis. The histological findings and the clinical course are discussed considering the disease as an atypical liver reaction to methyltestosterone.


Surrogate end points for survival in patients with advanced hepatocellular carcinoma treated with immune checkpoint inhibitors.
Aim: The authors investigated surrogacy of radiology-based end points for clinical trials investigating immune checkpoint inhibitors in advanced hepatocellular carcinoma. Methods: Data were collected from electronic databases reporting median overall survival (OS), median progression-free survival (PFS) and objective response rate (ORR). Weighted Pearson correlation coefficients and 95% confidence intervals (CIs) were calculated. Results: 26 clinical trials (41 treatment arms, 5144 patients) were included. ORR (coefficient: 0.71; 95% CI: 0.52-0.84) and PFS (coefficient: 0.63; 95% CI: 0.21-0.92) were positively correlated with OS. Sensitivity analyses suggested liver function, line of therapy and study phase did not greatly impact results. The COSMIC-312 study negatively impacted the overall weighted correlation. Conclusion: ORR and PFS are positively correlated with OS in patients with advanced hepatocellular carcinoma.


Influence of naloxone on the effects of high frequency transcutaneous electrical nerve stimulation in angina pectoris induced by atrial pacing.
The influence of naloxone on the effects of high frequency transcutaneous electrical nerve stimulation in angina pectoris induced by atrial pacing was studied in 11 patients with severe coronary artery disease. The patients were catheterised and treated with transcutaneous electrical nerve stimulation on two occasions, double blind and in random order, with a single intravenous dose of saline or with a single intravenous dose of 50 mg naloxone. Treatment with transcutaneous electrical nerve stimulation increased tolerance to pacing and significantly improved lactate metabolism with placebo and with naloxone. The positive effects of transcutaneous electrical nerve stimulation were thus reproducible and not reversed by single intravenous doses of naloxone. The results indicate that the effects of transcutaneous electrical nerve stimulation on the heart are not mediated by beta endorphin but they do not exclude activation of more short-acting opioids such as delta or kappa receptor agonists (met-enkephalin or dynorphin or both) because naloxone has a low affinity for these receptors. Non-opioid mechanisms may also be important.


Multiplexed Quantification of Proglucagon-Derived Peptides by Immunoaffinity Enrichment and Tandem Mass Spectrometry after a Meal Tolerance Test.
Proglucagon-derived peptides (PGDPs), which include glucagon-like peptide (GLP)-1, glucagon, and oxyntomodulin, are key regulators of glucose homeostasis and satiety. These peptide hormones are typically measured with immuno-based assays (e.g., ELISA, RIA), which often suffer from issues of selectivity. We developed a multiplexed assay for measuring PGDPs including GLP-1 (7-36) amide, GLP-1 (9-36) amide, glucagon, and oxyntomodulin by mass spectrometry and used this assay to examine the effect of a meal tolerance test on circulating concentrations of these hormones. Participants fasted overnight and were either given a meal (n = 8) or continued to fast (n = 4), with multiple blood collections over the course of 3 h. Plasma samples were analyzed by microflow immunoaffinity (IA)-LC-MS/MS with an isotope dilution strategy. Assay performance characteristics were examined and established during analytical validation for all peptides. Intra- and interassay imprecision were found to be 2.2%-10.7% and 6.8%-22.5%, respectively. Spike recovery was >76%, and dilution linearity was established up to a 16-fold dilution. Immediately after the meal tolerance test, GLP-1 and oxyntomodulin concentrations increased and had an almost identical temporal relationship, and glucagon concentrations increased with a slight delay. IA-LC-MS/MS was used for the simultaneous and selective measurement of PGDPs. This work includes the first indication of the physiological concentrations and modulation of oxyntomodulin after a meal.


[Closed reduction and internal fixation versus transtarsal sinus small incision internal fixation for Sanders type II calcaneal fractures].
To compare the clinical effects of closed reduction and internal fixation with limited transtarsal sinus incision in the treatment of Sanders type II calcaneal fractures. From June 2015 to February 2018, 60 patients with Sanders type II calcaneal fractures were treated by minimally invasive method. According to the different treatment methods, they were divided into two groups: closed prying reduction and internal fixation with hollow nails(group A) and limited transtarsal sinus incision internal fixation (group B). There were 34 cases in group A, including 22 males and 12 females, aged 21 to 60(38.90±3.25) years old, 14 cases of Sanders type IIA, 14 cases of Sanders type IIB and 6 cases of Sanders type IIC. There were 20 cases in group B, including 14 males and 6 females, aged 20 to 59(39.20±2.96) years old, 8 cases of Sanders type IIA, 9 cases of Sanders type IIB and 3 cases of Sanders type IIC. Calcaneal height, calcaneal width, Gissane angle and Bohler angle were measured before and after operation. The complications, hospitalization time and cost were compared. Functional evaluation was performed by AOFAS score system one year after operation. Fifty-four cases were followed up for 6 to 16(11.40±2.55) months and 6 cases were lost. All the wounds healed in grade A without complications such as skin infection and necrosis. There were 1 case of nerve injury in group A, 2 cases of tendon entrapment, 2 cases of nerve injury in group B, there was no significant difference(P>0.05). There was no significant difference in calcaneal width, height, Bohlers angle and Gissane angle between group A and group B (P>0.05). There was no significant difference in AOFAS score between group A and group B(89.2±4.7 vs 88.7±4.8, P>0.05). The hospitalization expenditure and length of stay in group A were(5 021.25±1 047.19) yuan, (6.31±4.75) d, and those in group B were(13 591.35±1 975.21) yuan, (9.65±3.42) d, respectively, with significant difference(P<0.05). Closed reduction and internal fixation is as effective as transtarsal sinus incision reduction and internal fixation for Sanders typeIIfracture. It has the advantages of less trauma and fewer complications. Closed reduction and hollow nail fixation group can significantly shorten hospitalization time, reduce hospitalization costs, and is more economical. It is worth recommending, but attention should be paid to avoid choosing to comminute serious calcaneal fracture.


Visualization of sialoglycoproteins in polyacrylamide gels by acidic ninhydrin reaction.
A new method for staining sialoglycoproteins in polyacrylamide gel after disc electrophoresis is described. The method utilizes the reaction of sialic acids with an acidic ninhydrin reagent which yields a stable color with an absorption maximum at 470 nm. After electrophoresis, the polyacrylamide gel is placed in a test tube and heated with 5 ml of the acidic ninhydrin reagent for 10 min in a boiling water bath. Sialoglycoproteins are detected as brown bands. No additional procedure such as destaining is necessary. When 20 micrograms fetuin, a sialoglycoprotein, per gel is applied, the band remains visible for at least 2 h. Stained gel can be scanned with a gel scanner at 470 nm. When the stained gel was dried on a sheet of polypropylene filter, the color was stable for at least one month. The present method is superior to the method using Stains-all (3,3'-diethyl-9-methyl-4,5,4',5'-dibenzothiacarbocyanine) in specificity and simplicity for the detection of sialoglycoproteins.