Is an average viscosity tenable in lipid bilayers and membranes? A comparison of semi-empirical equivalent viscosities given by unbound probes: a nitroxide and a fluorophore.
Relative variations of fluidity in bilayers and membranes are currently evaluated by numerous physical methods, but comparison between different systems remain difficult because the effects of order (anisotropy) and fluidity are involved in the diffusion coefficients for correlation times, or frictional coefficients) given by experiment. The present report represents an attempt to generalize the use of isotropic liquids as viscosity standards for disordered lipidic systems. It advances a simple check to verify the quasi-isotropic behaviour of probe environments and avoids the introduction of estimated values of the molecular dimensions in Perrin-Einstein relations. The equivalent viscosities obtained with 1,6-diphenyl hexatriene and with 2-pentyl-2'-butyl-4,4'-dimethyl oxazolidinoxyl are strikingly similar in egg lecithin vesicles above 0 degrees C, while in dipalmitoylphosphatidylcholine dispersions above their transition temperature, a discrepancy of about 30% seems to remain, even at high temperatures.


Short-term outcomes of second kidney transplantation compared with those of first transplantation in Japanese patients: a single-center, retrospective, observational study.
Among patients who undergo kidney transplantation, a subsequent second kidney transplantation (TX2) is often necessary. The TX2 outcomes remain controversial, however, and only limited data are available on clinical outcomes of TX2 in Japanese patients. This study aimed to assess graft and patient survival rates of TX2 and compared these rates with those of first kidney transplantation (TX1) in Japanese patients. Of the 898 kidney transplantations performed between 2010 and 2019 at our institution, 33 were TX2. We performed survival analysis using weighted Kaplan-Meier analysis and Cox proportional hazards analysis with propensity score matching, specifically inverse probability of treatment weighting (IPTW). Death-censored graft survival (DCGS) rates at 1, 3, and 5 years for the TX1 versus TX2 groups were 99.3, 97.9, and 95.0% versus 100, 96.0, and 91.2%, respectively. Overall survival (OS) rates at 1, 3, and 5 years for the TX1 versus TX2 groups were 99.4, 98.9, and 97.8% versus 100, 100, and 94.4%, respectively. Using the log-rank test, IPTW-weighted Kaplan-Meier curves showed no significant differences for TX1 versus TX2 in DCGS (p = 0.535) and OS (p = 0.302). On Cox proportional hazards analysis for TX2 versus TX1, the IPTW-adjusted hazard ratio (HR) for DCGS was 1.75 (95% CI, 0.28-10.9; p = 0.550) and for OS was 2.71 (95% CI, 0.40-18.55; p = 0.311). For patients who require TX2, this treatment is an acceptable option based on the short-term outcomes data for DCGS and OS.


Long-term cultivation of a stable Methylocystis-dominated methanotrophic enrichment enabling tailored production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate).
Methane (CH4) is a readily available feedstock for production of polyhydroxyalkanoates (PHAs). The structure and PHA production capacity of a Methylocystis-dominated methanotrophic enrichment was stable in long-term operation (>175 days) when grown exponentially under non-aseptic conditions in fill-and-draw batch cultures with ammonium as nitrogen source. Cells harvested in the draw step were incubated in the absence of nitrogen with various combinations of CH4 and valerate to assess capacity for synthesis of poly(3-hydroxybutyrate) (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). When fed CH4 alone, only P3HB was produced. When fed CH4 plus valerate, PHBV was synthesized. The mol% of 3-hydroxyvalerate (3HV) increased with added valerate. Oxidation of CH4 was required for valerate assimilation, and the fraction of CH4 oxidized increased with increased mol% 3 HV. By separating PHA accumulation from cell replication, tailored PHA-rich biomass can be generated by addition of co-substrate, while retaining a large inoculum for the next cycle of cell division.


Administration of a VIP-antagonist in vivo modifies ovarian hormone secretion in a rat model with polycystic ovary syndrome.
In the cyclic rat in estrus, the vasoactive intestinal peptide (VIP) has an impact on ovarian function, which depends on the endocrine status of the animal. In this work, we aimed to clarify the participation of VIP in the pathophysiological condition of polycystic ovary syndrome (PCOS) using a model of PCOS induced by estradiol valerate (EV-PCOS) in rats. In the cyclic rat in estrus and in the EV-PCOS model, we analyzed the acute effects of blocking VIP receptors with the use of an antagonist (Ant-VIP) injected into the left or right ovarian bursa on the steroidogenic response and ovarian catecholamine levels. In the cyclic animal in estrus, the treatment with Ant-VIP in the left ovarian bursa resulted in a reduction in testosterone serum levels and in ovarian levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), without changes in 4-hydroxy-3-methoxyphenyl (MHPG) and norepinephrine (NE). When the treatment was applied on the right side, only MHPG levels increased. In the EV-PCOS model, the treatment with Ant-VIP in the left ovarian bursa increased testosterone, estradiol, MHPG, and NE levels. When the treatment was performed on the right side, progesterone levels decreased and estradiol increased, without changes in ovarian catecholamines. The binding of VIP to its receptors differentially regulates steroidogenesis in the cyclic animal in estrus and in the EV-PCOS model. The blocking of VIP signaling produces changes in ovarian catecholamines.


Integrated treatment of suburb diffuse pollution using large-scale multistage constructed wetlands based on novel solid carbon: Nutrients removal and microbial interactions.
In this study, an integrated treatment system was proposed and applied in situ, including detention tank, multistage constructed wetlands (CWs) and wastewater treatment plants (WWTPs), preventing nutrients flowing into Dianchi Lake, in which the treatment performance of multistage CWs were evaluated principally. Results skillfully realized the bypass purification of upstream river at dry reasons, as well as the effective management and treatment of the collected diffuse pollution at rainy reasons. The purified water flowing into water bodies could satisfy the Grade III of environmental quality standards for surface water in China with the average effluent concentrations of COD, NH4+-N, TN and TP decreased to 10 (51.2-72.7%), 0.5 (67.2-83.0%), 1.0 (71.2-79.6%) and 0.15 (72.3-89.4%) mg L-1, respectively. High-throughput sequencing results indicated that the application of poly-3-hydroxybutyrate-cohyroxyvelate-sawdust (PS) blends could enrich norank_f_Anaerolineaceae (7.95%) and Bradyrhizobium (10.2%), which were distinct from the dominant genera of Pleurocapsa (13.0%) in gravel-based CWs. Functional genes and metabolism analysis uncovered that the heterotrophic denitrification was the main pathway of nitrogen removal with the abundance of genes encoding TCA cycle, glycolysis and denitrification process up-regulated. In addition, molecular ecological network (MEN) analysis suggested the denitrification genes were positively correlated with the predominant microbes in PS-based CWs, favorable for denitrifiers to transfer and utilize electron donors during denitrification process. This study proved that the developed PS blends as carbon supplies in CWs and the proposed integrated treatment system are effective methods for watershed management, providing valuable reference to low-pollution wastewater treatment in practical engineering projects.


Clinical Phenotype and Contagiousness of Early Breakthrough SARS-CoV-2 Infections after BNT162b2 COVID-19 mRNA Vaccine: A Parallel Cohort Study in Healthcare Workers.
We evaluated the clinical protection of BNT162b2 mRNA vaccine in healthcare workers (HCWs) and how COVID-19 manifestations and contagiousness change as the time since first dose increases. A matched (1:2 ratio) parallel cohort study was performed. During the first three months of vaccination campaign, HCWs of the entire health district ASL Città di Torino (Turin, Italy) were classified according to SARS-CoV-2-positivity in respect of the vaccination schedule: post-first-dose (fHCWs, <12 days), partially (PHCWs, ≥12 from first dose to ≤7 days after the second), and totally vaccinated (THCWs, ≥8 days after the second dose). Age-/sex-matched unvaccinated controls were randomly selected from all the SARS-CoV-2-positivity detected in the same district and period. Previous infections were excluded. Clinical and virologic data (ORF1ab gene cycle threshold values, Ct) were recorded. In total, 6800 HCWs received at least one dose, and 55 tested positive subsequently: 20 fHCWs, 25 PHCWs, 10 THCWs. Furthermore, 21.8% of breakthrough infections were in male, with a median age of 49 years (32-56), and 51.4% occurred while SARS-CoV-2 B.1.1.7 variant was predominant. The incident relative risk was 0.13 (0.12-0.15) for PHCWs and 0.06 (0.05-0.07) for THCWs. Compared to controls (n = 110), no difference was observed in fHCWs, while PHCWs and THCWs showed higher prevalence of asymptomatic infections, fewer signs/symptoms with a milder systemic involvement, and significantly higher Ct values (PHCWs 30.3 (24.1-35.5) vs. 22.3 (19.6-30.6), p = 0.023; THCWs 35.0 (31.3-35.9) vs. 22.5 (18.2-30.6), p = 0.024). Duration of symptoms was also shorter in THCWs (5 days (3-6) vs. 9 (7-14), p = 0.028). A linear increase of 3.81 points in Ct values was observed across the groups by vaccination status (p = 0.001) after adjusting for age, sex, comorbidities, and time between COVID-19 onset and swab collection. BNT162b2 decreased the risk of PCR-confirmed infections and severe disease, and was associated with a virologic picture of lesser epidemiologic concern as soon as 12 days after the first vaccine dose.


Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients.
To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm. Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement. Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement. Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.


Smoking Is Associated with Sex-Specific Effects on Bone Microstructure in Older Men and Women.
Smoking is a risk factor for fracture, but the mechanism by which smoking increases fracture risk is unclear. Musculoskeletal health was compared with dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HR-pQCT), trabecular bone score, and vertebral fracture assessment in current and past smokers and nonsmokers from a multiethnic study of adults ≥ age 65. Skeletal indices were adjusted for age and weight. Participants (n = 311) were mean age (±SD) 76.1 ± 6.5 years, mostly female (66.0%) and non-white (32.7% black/39.4% mixed race/26.3% white). Mean pack-years was 34.6 ± 20.4. In men (n = 106), weight and BMI were lower (both p < 0.05) in current vs past smokers. Male smokers consumed half the calcium of never and past smokers. BMD by DXA did not differ by smoking status at any skeletal site in either sex. Current male smokers had 13.5%-15.3% lower trabecular bone score vs never and past smokers (both p < 0.05). By HR-pQCT, trabecular volumetric BMD was 26.6%-30.3% lower and trabeculae were fewer, thinner and more widely spaced in male current vs past and never smokers at the radius (all p < 0.05). Cortical indices did not differ. Tibial results were similar, but stiffness was also 17.5%-22.2% lower in male current vs past and never smokers (both p< 0.05). In women, HR-pQCT trabecular indices did not differ, but cortical porosity was almost twice as high in current vs never smokers at the radius and 50% higher at the tibia (both p < 0.05). In summary, current smoking is associated with trabecular deterioration at the spine and peripheral skeleton in men, while women have cortical deficits. Smoking may have sex-specific skeletal effects. The consistent association with current, but not past smoking, suggests the effects of tobacco use may be reversible with smoking cessation.


Range-wide differential adaptation and genomic offset in critically endangered Asian rosewoods.
In the billion-dollar global illegal wildlife trade, rosewoods have been the world's most trafficked wild product since 2005. Dalbergia cochinchinensis and Dalbergia oliveri are the most sought-after rosewoods in the Greater Mekong Subregion. They are exposed to significant genetic risks and the lack of knowledge on their adaptability limits the effectiveness of conservation efforts. Here, we present genome assemblies and range-wide genomic scans of adaptive variation, together with predictions of genomic offset to climate change. Adaptive genomic variation was differentially associated with temperature and precipitation-related variables between the species, although their natural ranges overlap. The findings are consistent with differences in pioneering ability and in drought tolerance. We predict their genomic offsets will increase over time and with increasing carbon emission pathway but at a faster pace in D. cochinchinensis than in D. oliveri. These results and the distinct gene-environment association in the eastern coastal edge of Vietnam suggest species-specific conservation actions: germplasm representation across the range in D. cochinchinensis and focused on hotspots of genomic offset in D. oliveri. We translated our genomic models into a seed source matching application, seedeR, to rapidly inform restoration efforts. Our ecological genomic research uncovering contrasting selection forces acting in sympatric rosewoods is of relevance to conserving tropical trees globally and combating risks from climate change.


Hepatitis A Seropositivity among First-Year Students of the Medical University in Isfahan, Iran.
Students of medicine are prone to contact with various infectious agents such as hepatitis A virus (HAV). Infection with HAV may lead to morbidity and in rare cases, mortality. We evaluated the seroprevalence of HAV among 1(st)-year medical students to assess the necessity of vaccination/preventive immunoglobulin in this at-risk population. This cross-sectional study was carried out in 2007 among 403 1(st)-year medical students in Isfahan, Iran. Participants filled out a questionnaire including items on demographic characteristics, medical history, and hygiene. Then, the anti-HAV IgG antibody was assessed using the ELISA method (Diagnostic Bioprobes, Dia-Pro, Milan, Italy). Among the 403 students invited to attend the study, 361 ones (89.5%) agreed to participate (61.1% female), with a mean age of 19.8 ± 2.6 years. Of the participants, 272 (75.3%) students were seropositive. Seropositivity was not associated with gender (P = 0.222), but was associated with the number of family members (P < 0.001), residence place (P = 0.003), age (P < 0.001), and the type of drinking water (P = 0.008). One of the four medical college students of our society is prone to hepatitis A infection. Accordingly, vaccination/preventive immunoglobulin is suggested for this population; however, whether a prior serological screening is cost-effective needs further evaluation by epidemiologic data from our society.


Wnt/β-catenin signaling enhances osteoblastogenic differentiation from human periodontal ligament fibroblasts.
Wnt/β-catenin signaling has been known to influence bone formation and homeostasis. In this study, we investigated the canonical Wnt signaling regulation of osteogenic differentiation from periodontal ligament (PDL) fibroblasts. Stimulating PDL fibroblasts with lithium chloride (LiCl), a canonical Wnt activator, significantly increased mineralized nodule and alkaline phosphatase (ALP) activity in a time- and dose-dependent manner. LiCl up-regulated protein expression of osteogenic transcription factors, including the runt-related gene 2, Msx2, and Osterix 2, in the PDL fibroblasts. Treatment of these cells with LiCl also increased the mRNA levels of ALP, FosB, and Fra1 in a dose-dependent manner. Blockage of canonical Wnt signaling by treating the cells with DKK1 inhibited Wnt1-stimulated mRNA expression of these osteogenic factors. Furthermore, pretreatment with DKK1 reduced the ALP activity and matrix mineralization stimulated by Wnt1. Collectively, these results suggest that canonical Wnt signaling leads to the differentiation of PDL fibroblasts into osteogenic lineage with the attendant stimulation of osteogenic transcription factors.


Online social networking technologies, HIV knowledge, and sexual risk and testing behaviors among homeless youth.
This study evaluates associations between online social networking and sexual health behaviors among homeless youth in Los Angeles. We analyzed survey data from 201 homeless youth accessing services at a Los Angeles agency. Multivariate (regression and logistic) models assessed whether use of (and topics discussed on) online social networking technologies affect HIV knowledge, sexual risk behaviors, and testing for sexually transmitted infections (STIs). One set of results suggests that using online social networks for partner seeking (compared to not using the networks for seeking partners) is associated with increased sexual risk behaviors. Supporting data suggest that (1) using online social networks to talk about safe sex is associated with an increased likelihood of having met a recent sex partner online, and (2) having online sex partners and talking to friends on online social networks about drugs and partying is associated with increased exchange sex. However, results also suggest that online social network usage is associated with increased knowledge and HIV/STI prevention among homeless youth: (1) using online social networks to talk about love and safe sex is associated with increased knowledge about HIV, (2) using the networks to talk about love is associated with decreased exchange sex, and (3) merely being a member of an online social network is associated with increased likelihood of having previously tested for STIs. Taken together, this study suggests that online social networking and the topics discussed on these networks can potentially increase and decrease sexual risk behaviors depending on how the networks are used. Developing sexual health services and interventions on online social networks could reduce sexual risk behaviors.


Schizophrenia: A developmental disorder with a risk of non-specific but avoidable decline.
The onset of schizophrenia is determined by biological and social risk factors operating predominantly during development. These result in subtle deviations in brain structure and cognitive function. Striatal dopamine dysregulation follows, causing abnormal salience and resultant psychotic symptoms. Most people diagnosed as having schizophrenia do not progressively deteriorate; many improve or recover. However, poor care can allow a cycle of deterioration to be established, stress increasing dopamine dysregulation, leading to more stress consequent on continuing psychotic experiences, and so further dopamine release. Additionally, long-term antipsychotics can induce dopamine supersensitivity with resultant relapse and eventually treatment resistance. Some patients suffer loss of social and cognitive function, but this is a consequence of the hazards that afflict the person with schizophrenia, not a direct consequence of genetic predisposition. Thus, brain health and cognition can be further impaired by chronic medication effects, cardiovascular and cerebrovascular events, obesity, poor diet, and lack of exercise; drug use, especially of tobacco and cannabis, are likely to contribute. Poverty, homelessness and poor nutrition which become the lot of some people with schizophrenia, can also affect cognition. Regrettably, the model of progressive deterioration provides psychiatry and its funders with an alibi for the effects of poor care.


Is the Peroxiredoxin 2/Thioredoxin/Thioredoxin Reductase system in human erythrocytes designed for redox signaling?
In human erythrocytes H2O2 is mainly consumed by glutathione peroxidase, catalase and peroxiredoxin 2 (Prx2). Our previous analyses indicate that Prx2's peroxidase activity is subjected to a strong but quickly reversible inhibition (see companion abstract). If this activity is inhibited then the main role of Prx2 cannot be to eliminate H2O2. What functional advantages could then such an inhibition confer?We set up and validated a kinetic model of H2O2 metabolism human erythrocytes that shows quantitative agreement with extensive experimental observations. We then applied it to analyze the behavior of Prx2 and Trx under the H2O2 exposure dynamics that erythrocytes face in circulation. The significance of Prx2 inhibition was assessed by comparing the behavior of this model with that of an otherwise identical model lacking inhibition.Our analysis shows that Prx2 inhibition leads to 25-40% lower NADPH consumption under low to moderately high H2O2 supply (<0.8µM H2O2/s). Further, the inhibition extends the range where the concentrations of potential redox signaling readouts - H2O2, Prx2 sulfenic acid, Prx2 disulfide and Trx disulfide- show a proportional response to changes in H2O2 supply, covering practically the whole physiological range of the latter. This is desirable for analogic signal transduction and allows the Prx2/Trx/TrxR system to reliably transduce changes in H2O2 supply as changes in thiol oxidation. Finally, the inhibition allows other less abundant peroxiredoxins in the erythrocyte to be oxidized by H2O2 at physiological H2O2 supplies.Altogether, these results suggest that the postulated reversible inhibition of Prx2's peroxidase facilitates signal transduction by the peroxiredoxins and spares NADPH.We acknowledge: fellowship SFRH/BD/51199/2010, grants PEst-C/SAU/LA0001/2013-2014, PEst-OE/QUI/UI0612/2013, PEst-OE/QUI/UI0313/2014, and FCOMP-01-0124-FEDER-020978 co-financed by FEDER through the COMPETE program and by FCT (project PTDC/QUI-BIQ/119657/2010).


Gene transfer and metabolic modulators as new therapies for pulmonary hypertension. Increasing expression and activity of potassium channels in rat and human models.
Chronic Hypoxic Pulmonary Hypertension (CH-PHT) is characterized by pulmonary artery (PA) vasoconstriction and cell proliferation/hypertrophy. PA smooth muscle cell (PASMC) contractility and proliferation are controlled by cytosolic Ca++ levels, which are largely determined by membrane potential (E(M)). E(M) is depolarized in CH-PHT due to decreased expression and functional inhibition of several redox-regulated, 4-aminopyridine (4-AP) sensitive, voltage-gated K+ channels (Kv1.5 and Kv2.1). Humans with Pulmonary Arterial Hypertension (PAH) also have decreased PASMC expression of Kv1.5 and Kv2.1. We speculate this "K+-channelopathy" contributes to PASMC depolarization and Ca++ overload thus promoting vasoconstriction and PASMC proliferation. We hypothesized that restoration of Kv channel expression in PHT and might eventually be beneficial. Two strategies were used to increase Kv channel expression in PASMCs: oral administration of a metabolic modulator drug (Dichloroacetate, DCA) and direct Kv gene transfer using an adenovirus (Ad5-Kv2.1). DCA a pyruvate dehydrogenase kinase inhibitor, promotes a more oxidized redox state mimicking normoxia and previously has been noted to increase K+ current in myocytes. Rats were given DCA in the drinking water after the development of CH-PHT and hemodynamics were measured approximately 5 days later. We also tested the ability of Ad5-Kv2.1 to increase Kv2.1 channel expression and function in human PAs ex vivo. The DCA-treated rats had decreased PVR, RVH and PA remodeling compared to the control CH-PHT rats (n=5/group, p<0.05). DCA restored Kv2.1 expression and PASMC Kv current density to near normoxic levels. Adenoviral gene transfer increased expression of Kv2.1 channels and enhanced 4-AP constriction in human PAs. Increasing Kv channel function in PAs is feasible and might be beneficial.


Improvement of in vitro gynogenesis induction in onion (Allium cepa L.) using polyamines.
The effects of polyamines on gynogenetic embryogenesis and regeneration of plantlets in onion were studied. Whole flowers from two onion genotypes, 'Valcatorce INTA' cultivar and 'Torrentina' population, were used as initial explants. Embryo induction was greatest with a combined treatment of 2 mM putrescine and 0.1 mM spermidine. Addition of putrescine alone, with a few exceptions, did not have any significant effect on either embryo induction or haploid plantlet production for both onion genotypes. 'Torrentina' showed a higher embryo generation capacity (9.5%) than 'Valcatorce INTA' (2.8%). Fast regeneration of embryos was achieved (from 60 to 90 days) as compared to a previously reported time of 46-152 days. The use of spermidine (0.1 mM) after 15 days of culture promoted further embryo maturation and plantlet formation. 'Torrentina' produced more haploid plants (1.90%). This is the first report of successful use of polyamines for induction of gynogenic embryos and regeneration of onion plantlets.


Double Layer at the Pt(111)-Aqueous Electrolyte Interface: Potential of Zero Charge and Anomalous Gouy-Chapman Screening.
We report, for the first time, the observation of a Gouy-Chapman capacitance minimum at the potential of zero charge of the Pt(111)-aqueous perchlorate electrolyte interface. The potential of zero charge of 0.3 V vs. NHE agrees very well with earlier values obtained by different methods. The observation of the potential of zero charge of this interface requires a specific pH (pH 4) and anomalously low electrolyte concentrations (<10-3 m). By comparison to gold and mercury double-layer data, we conclude that the diffuse double layer structure at the Pt(111)-electrolyte interface deviates significantly from the Gouy-Chapman theory in the sense that the electrostatic screening is much better than predicted by purely electrostatic mean-field Poisson-Boltzmann theory.


Surgical repair of supposedly multiple defects within the apical part of the muscular ventricular septum.
A distinct defect has been described within the apical part of the muscular ventricular septum, which has multiple orifices when seen from its right ventricular aspect. Closure has been suggested using umbrella devices introduced on a catheter. Such an intervention, however, can be technically difficult in small infants. We have recently seen two examples of this type of complex communication between the apexes of both left and right ventricles. Neither could be closed by catheterization. A surgical approach was used through a modified apical right ventriculotomy. We have also studied two autopsied specimens, which clarify the morphologic arrangement. Both patients were closed successfully, with trivial residual shunt and good biventricular functions. The patients were clinically well at 2-year follow-up. Surgical division of right ventricular trabeculations makes it feasible to identify and repair the septal deficiency, which is a solitary hole. On the basis of our morphologic study, we offer an explanation for the anatomic arrangement that differs from the one proposed by recent previous investigators. If the ventricular incision is appropriately placed, our anatomic studies suggest that it is possible to visualize the solitary opening from its right ventricular aspect, and achieve surgical closure with a single patch.


Salivary response to olfactory food stimuli as a function of dietary restraint and body weight.
The effects of food and non-food odors on salivation rate and the relation between this response, body weight for height and dietary restraint score were investigated in college students. Potential confounding variables, such as dieters' anxiety due to expectations of food consumption, intrusive methods of salivation collection, and the degree of dieting strictness, were controlled. Results indicated that dietary restraint, but not body weight per se, predicted hyper-responsiveness to food cues, supporting the view that self-imposed dietary restriction heightens external salivary responsiveness to food-related stimuli.


Antimalarial drug quinacrine binds to C-terminal helix of cellular prion protein.
Using NMR spectroscopy we show that the cellular prion protein constitutes a target for binding of various acridine and phenothiazine derivatives. We unambiguously map the quinacrine binding site of recombinant human prion protein to residues Tyr225, Tyr226, and Gln227 of helix alpha3, which is located near the "protein X" epitope. The millimolar dissociation constant of the complex suggests that in vivo inhibition of prion propagation occurs after 10000-fold concentration of quinacrine within endolysosomes.


Estimation of height for persons in pictures.
We report three experiments in which subjects estimated the height of persons seen in pictures. In Experiment 1, 50 realistic photographs were used as targets. The correlation between mean estimated height and actual height was .92, and target's sex and the ratios of head to trunk, which included horizontal ratio (i.e., a ratio of head width to shoulder width) and vertical ratio (i.e., a ratio of head height to stature), were found to be effective on height estimates, although target's sex was more effective than ratios of head to trunk. In Experiments 2 and 3, the recognizability of target persons was reduced, respectively, by inverting the person photographs and by degrading the various features of the photographs. The main results were that (1) the correlation between mean estimated height and actual height was .88 for the inverted photographs and was .80, on average, for the degraded drawings; (2) target's sex was consistently influential in both experiments; (3) vertical ratio was effective for the inverted photographs and the mildly degraded drawings but not for the extremely degraded drawings in which only outlines of target persons were depicted; and (4) the estimation for the outlined pictures was likely to be influenced by fit of clothes to targets' bodies. From these findings, person stimuli were considered to provide a stable metric stick of visual space under naturalistic circumstances.


Evolution and function of ubiquitin-like protein-conjugation systems.
Ubiquitin functions by covalently modifying other proteins. In the past few years, a surprising number of other proteins have been identified that, despite often being only slightly similar to ubiquitin, can also be attached to proteins. Newly discovered parallels between the activation of ubiquitin and the biosynthesis of certain enzyme cofactors now hint at the possible evolutionary origins of the ubiquitin system.


ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML).
Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.


Results of a healthcare worker (HCW) survey on environmental awareness as an instrument for the preparation of an environmental report for the University Medicine Greifswald.
Environmental reporting is increasingly important for medical facilities. Currently, hospitals can determine the content of an environmental report as they see fit. To examine the utility and scope of an employee survey as an instrument for the preparation of an environmental report at the University Hospital Greifswald. For this purpose a questionnaire was developed with a focus on environmental behaviour and the significance attached to the protection of the environment. The employees of the University Medicine Greifswald attach an unexpectedly high significance to the protection of the environment. Based on this finding, this potential should be used to promote the optimal implementation of ecological-economic behaviour within the University Medicine. An employee survey is a useful instrument in the preparation of an environmental report.


Estimation and characterization of prostaglandins in the human gastrointestinal tract.
1 Prostaglandin-like material was extracted from muscle and mucosa of surgically removed human stomach, ileum and colon and assayed against prostaglandin E(2) on strips of rat gastric fundus. Superfused human isolated gastric mucosa released prostaglandin-like material and release was increased by stretching or clamping the tissue.2 The relative amounts of extracted biological activity were broadly as follows: gastric antral mucosa > colon muscle > gastric body mucosa approximately ileal mucosa > colon mucosa approximately gastric muscle approximately ileal muscle.3 Prostaglandin E and F were tentatively identified by chromatography and sensitivity to inactivation by alkali.4 Prostaglandin E apparently contributed most to the biological activity, possibly because the assay tissue is more sensitive to prostaglandin E than to F. Chromatography of gastric body mucosal extracts located material running with prostaglandin E(2) and a little with E(1). Colonic muscle and mucosal extracts contained material with R(F) values of prostaglandins E(1), E(2), E(3) and F(1a), whereas F(2a) and F(3a)-like substances were found only in the mucosa. The proportions of prostaglandin F varied between specimens.5 The amount of extracted prostaglandin-like activity was increased by adding cofactors and arachidonic acid, and lessened by homogenization with acid-ethanol.6 The type and amount of activity generated from arachidonic acid by partly purified colonic mucosal prostaglandin synthetase depended on the substrate concentration.7 The possible relationships of prostaglandins to mucus secretion and other physiological and pathological gut functions are discussed.


Assessment of Vigilance and Fatigue.
This article summarizes the definitions of vigilance, fatigue, and sleepiness, as well as tools used in their assessment. Consideration is given to the strengths and limitations of the different subjective and objective tools. Future directions for research are also discussed, as well as the public health importance of continued investigation in this subject.


Mussel-inspired antifouling magnetic activated carbon for uranium recovery from simulated seawater.
Undesirable bio-adhesion of microalgae on adsorbent can influence its adsorption capacity. In this report, we fabricated a novel mussel-inspired antifouling magnetic activated carbons which derived orange peel by integrated biosorption-pyrolysis process (MACs@PDA-Ag), via co-functionalization of poly-dopamine (PDA) and Ag nanoparticles (AgNPs), for the recovery of uranium (VI) from simulated seawater with antimicrobial adhesion performance; this process did not require an additional reducing agent. The effect of pH, concentration, contact time, fouling test against nitzschia closterium f.minutissima (GY-H8) were studied. Compared with MACs (632.91 mg/g at pH 7.0), the calculated maximum adsorption capacity of MACs@PDA-Ag increased to 657.89 mg/g at pH 8.0 and showed good recyclability. These data all fitted well with the Langmuir and pseudo-second order models. The possible removal mechanism by XPS is chelation (catechol hydroxyls, amine/imine units, the metal-oxygen and carboxylic) with uranium (VI). The antifouling tests indicated that the AgNPs-modified materials displayed the antimicrobial adhesion behavior, and the viability of the microorganism was not impacted. Thereby, the direct deposition of AgNPs onto the adsorbent has shown great potential for uranium (VI) recovery with an antifouling benefit and is environmentally friendly.


Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of Late Gadolinium Enhancement.
This study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort. The relationship between LGE and prognosis in DCM is incompletely understood. The authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM. Of 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD endpoint. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern. In DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.


Visualization of the Nucleolus Using 5' Ethynyl Uridine.
Labeling of the nucleolus in Arabidopsis thaliana can be achieved by incorporation of 5'-ethynyl uridine (EU) into bulk RNA. Although EU does not selectively label the nucleolus, the abundance of ribosomal transcripts results in the predominant accumulation of the signal in the nucleolus. Ethynyl uridine has the advantage of being detected via Click-iT chemistry providing a specific signal and low background. While the protocol presented here employs fluorescent dye and allows visualization of the nucleolus by microscopy, this method can also be used for other downstream applications. Though we tested nucleolar labeling only in A. thaliana, in principle it can be applied to other plant species.


Finding New Communities: A Principle of Neuronal Network Reorganization in Alzheimer's Disease.
Background: Graph-theoretical analyses have been previously used to investigate changes in the functional connectome in patients with Alzheimer's disease (AD). However, these analyses generally assume static organizational principles, thereby neglecting a fundamental reconfiguration of functional connections in the face of neurodegeneration. Methods: Here, we focus on differences in the community structure of the functional connectome in young and old individuals and patients with AD. Patients with AD, moreover, underwent molecular imaging positron emission tomography by using [18F]AV1451 to measure tau burden, a major hallmark of AD. Results: Although the overall organizational principles of the community structure of the human functional connectome were preserved even in advanced healthy aging, they were considerably changed in AD. We discovered that the communities in AD are re-organized, with nodes changing their allegiance to communities, thus resulting in an overall less efficient re-organized community structure. We further discovered that nodes with a tendency to leave the communities displayed a relatively higher tau pathology burden. Discussion: Together, this study suggests that local tau pathology in AD is associated to fundamental changes in basic organizational principles of the human connectome. Our results shed new light on previous findings obtained by using the graph theory in AD and imply a general principle of the brain in response to neurodegeneration.


The genus Labania Hedqvist 1963 (Hymenoptera, Braconidae: Doryctinae) with description of a new species from Brazil.
In this paper a new species of doryctine wasp of the small and rarely collected genus Labania Hedqvist (Braconidae: Doryctinae) is described and illustrated from Brazil. Labania carolinae sp.n. is similar to Labania minuta Marsh, but it can be easily distinguished by the head yellow, with stemmaticum black, mesosoma and metasoma yellow, legs whitish yellow, propodeum with distinct areola, fore wing vein 1cu-a interstitial with 1M, and long ovipositor.


Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT.
Several trials have shown the activity of thalidomide (THAL) in relapsed multiple myeloma (MM) patients failing PBSCT or conventional chemotherapy. PBSCT is considered standard treatment for most patients requiring therapy for MM; however, patients with VAD-resistant disease may not be able to receive PBSCT due to rapidly advancing disease. We report four cases of VAD-refractory MM salvaged with THAL + VAD followed by PBSCT. All patients underwent stem cell mobilization with cyclophosphamide (Cy) (4.5 g/m(2)) and GMCSF. Melphalan (140-200 mg/m(2)) was given as conditioning. All patients engrafted within 12-16 days after PBSCT. Day +100 evaluation showed the following: very good partial response (n = 1) and complete response (n = 3). After a median follow-up to 153 days, two patients continue to take THAL with no signs of disease progression. One patient developed CHF and was taken off THAL while another patient has died of progressive disease while on THAL (MTD 50 mg). In conclusion, VAD-refractory patients were salvaged with the addition of THAL to VAD. They were subsequently able to undergo autologous PBSCT for MM, which will likely improve their overall survival. This suggests that THAL and other related immunomodulatory drugs may prove useful for initial MM therapy in combination with standard chemotherapy followed by PBSCT.


Gastroprotective effects of new diterpenoid derivatives from Azorella cuatrecasasii Mathias & Constance obtained using a β-cyclodextrin complex with microbial and chemical transformations.
Mulinane diterpenoids isolated from Azorella species have displayed gastroprotective effects in animal models. In this study we have transformed the main constituent, mulin-11,13-dien-20 oic acid from this plant using the filamentous fungus Mucor plumbeus and a β-cyclodextrin inclusion complex and we have obtained two main products with good yields (33% and 15% for compound 4 and 5, respectively) for further preparation of semisynthetic derivatives to evaluate their gastroprotective effects. In addition, one of the compounds isolated from Azorella cuatrecasasii was new (9-epi-13α-hydroxymulinene 1). Six new derivatives 4a-4c and 5a-5c were then prepared by simple chemical transformations. The structures of all compounds were elucidated by spectroscopic means based on 1D and 2D-NMR techniques. Some 8 diterpenes were evaluated for their gastroprotective effects in the ethanol/HCl-induced ulcer model in mice at 20mg/kg. The highest gastroprotective activity was shown by 7α,16-dihydroxymulin-11,13-dien-20-oic acid 5, which was higher than the reference drug lansoprazole, while 16-hydroxymulin-11,13-dien-20-oic acid 4 was as active as lansoprazole.


Artificial colonization as a method for studying the normal habitat of mycobacteria.
Sixteen species of mycobacteria were inoculated into samples of earth which were cultured immediately afterwards and then monthly for six months. Five species, and possibility a sixth, colonized the habitat suggesting that it was natural to them. Experiments of this type should provide a useful approach to field studies of the sources of opportunist mycobacteria.


Characterization of a novel type of adherens junction in meningiomas and the derived cell line HBL-52.
Adhering junctions are generally grouped into desmosomes and adherens junctions based on their ultrastructural appearance and molecular composition. The armadillo-protein plakoglobin is common to both types of junctions, which are otherwise composed of mutually exclusive proteins. This view is based on observations in epithelial tissues but cannot easily be transferred to other cell types and tissues, as has become apparent during the last decade with the identification of new junctional proteins and the investigation of further non-epithelial junctions. Using a broad array of well-characterized specific antibodies against key junctional proteins in immunoblot reactions, high-resolution double-label laser scanning confocal microscopy, and immunoelectron microscopy, we describe a new type of adherens junction in human meningiomas and the human meningioma cell line HBL-52. This novel junction has a unique composition of proteins not found in any other tissue; it contains the desmosomal armadillo-protein plakophilin 2 together with the classic proteins of "epithelial" adherens junctions, i.e., E-cadherin (in some instances replaced by N-cadherin), alpha-catenin, beta-catenin, plakoglobin, and p120(ctn). Ultrastructurally, it is formed between two or three neighboring cells. For pragmatic reasons, we suggest the name "meningeal junction" for this new structure.


Murine Corneal Epithelial Wound Modeling.
A murine model of corneal epithelial wounding can be performed using simple injury and imaging methods. Here, we describe the creation of a central corneal epithelial defect using mechanical debridement under ophthalmic microscopic visualization. Subsequent monitoring with vital dye application and slit-lamp bio microscopy (slit-lamp) is described in detail.


Stability of the pBR322 plasmid as affected by the promoter region of the tetracycline-resistance gene.
A region affecting the pBR322 plasmid maintenance has been located within the region of the TcR gene promoter. On the basis of stability analysis of pBR322 derivatives comprising the modified region of the TcR gene, we deduced that it is the nucleotide sequence localized in the region of the HindIII site that causes destabilization of the plasmid and not the TcR gene product or active transcription of this region. The destabilizing effect is manifested both in cis and in trans.


Opportunistic Breast Density Assessment in Women Receiving Low-dose Chest Computed Tomography Screening.
Low-dose chest computed tomography (LDCT), increasingly being used for screening of lung cancer, may also be used to measure breast density, which is proven as a risk factor for breast cancer. In this study, we developed a segmentation method to measure quantitative breast density on CT images and correlated with magnetic resonance density. Forty healthy women receiving both LDCT and breast magnetic resonance imaging (MRI) were studied. A semiautomatic method was applied to quantify the breast density on LDCT images. The intra- and interoperator reproducibility was evaluated. The volumetric density on MRI was obtained by using a well-established automatic template-based segmentation method. The breast volume (BV), fibroglandular tissue volume (FV), and percent breast density (PD) measured on LDCT and MRI were compared. The measurements of BV, FV, and PD on LDCT images yield highly consistent results, with the intraclass correlation coefficient of 0.999 for BV, 0.977 for FV, and 0.966 for PD for intraoperator reproducibility, and intraclass correlation coefficient of 0.953 for BV, 0.974 for FV, and 0.973 for PD for interoperator reproducibility. The BV, FV, and PD measured on LDCT and MRI were well correlated (all r ≥ 0.90). Bland-Altman plots showed that a larger BV and FV were measured on LDCT than on MRI. The preliminary results showed that quantitative breast density can be measured from LDCT, and that our segmentation method could yield a high reproducibility on the measured volume and PD. The results measured on LDCT and MRI were highly correlated. Our results showed that LDCT may provide valuable information about breast density for evaluating breast cancer risk.


Identifying meaningful subpopulation segments among older public assistance recipients: a mixed methods study to develop tailor-made health and welfare interventions.
Public assistance recipients have diverse and complex needs for health and social support in addition to financial support. Segmentation, which means dividing the population into subgroups (segments) with similar sociodemographic characteristics, is a useful approach for allocating support resources to the targeted segments. Clustering is a commonly used statistical method of segmentation in a data-driven marketing approach. This explanatory sequential mixed methods study applied a clustering technique, aiming to identify segments among older public assistance recipients quantitatively, and assess the meaningfulness of the identified segments in consultation and support activities for older recipients qualitatively. We identified the segments of older recipients in two municipalities using probabilistic latent semantic analysis, a machine learning-based soft clustering method. Semi-structured interviews were subsequently conducted with caseworkers to ask whether the identified segments could be meaningful for them in practice and to provide a reason if they could not think of any older recipients from the segment. A total of 3,165 older people on public assistance were included in the analysis. Five distinct segments of older recipients were identified for each sex from 1,483 men and 1,682 women. The qualitative findings suggested most of identified segments reflected older recipients in practice, especially two of them: female Cluster 1 (facility residents aged over 85 years with disability/psychiatric disorder), and female Cluster 2 (workers). Some caseworkers, however, did not recall older recipients in practice when working with certain segments. A clustering technique can be useful to identify the meaningful segments among older recipients and can potentially discover previously unrecognized segments that may not emerge through regular consultation practices followed by caseworkers. Future research should investigate whether tailored support interventions for these identified segments are effective.


Effects of pituitary adenylate cyclase activating polypeptide27 on cyclic AMP efflux and atrial dynamics in perfused beating atria.
Although pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to increase cardiac force of contraction and to change the heart rate, the effect of PACAP on cyclic (c) AMP production in the atrium still has to be defined. In the present experiments, a simple protocol was developed for the evaluation of cAMP production in real-time base in the perfused beating left atria. The PACAP27-induced cAMP efflux in the atrial perfusate reflected changes in the production of cAMP in the atrial tissue. cAMP efflux was measured as an indicator of cAMP production in beating perfused rabbit atria. PACAP27 increased cAMP production in a dose- and time-dependent manner with a minor effect on atrial dynamics. These results suggest that PACAP27 has other roles besides control of force of contraction through cAMP production in the atrium.


Seven genes on the short arm of human chromosome 3 map to two regions on Macropus eugenii (tammar wallaby) chromosome 2.
Seven genes were mapped by in situ hybridization to metaphase chromosomes of the marsupial species Macropus eugenii, using a series of human-derived cloned probes (six cosmids and one cDNA). The genes were located in two widely separated clusters on the long arm of M. eugenii chromosome 2, in contrast to their location in a single cluster on the distal half of the short arm of human chromosome 3. Multiple rearrangements had to be involved in the evolutionary divergence of these chromosome segments from the unknown arrangement in the common ancestor.


Addressing Educational Needs in Managing Complex Pain in Cancer Populations: Evaluation of APAM: An Online Educational Intervention for Nurses.
Cancer-related pain is associated with significant suffering and is one of the most challenging symptoms to manage. Studies indicate that front-line clinicians often lack the knowledge on best practices in cancer pain management. The current project, a quality improvement (QI) initiative, evaluated the outcome of an online educational intervention for nurses on complex cancer pain management. An online 7-module educational intervention, Advanced Pain Assessment and Management, was offered from 2012 to 2017. Pre-post course evaluations included self-reported knowledge and confidence across cancer pain management domains. In-course competency assessments included knowledge examination, online discussion forum participation, opioid dosage calculation assignment, and small-group-based case study. A mixed-model statistical analysis was used to assess pre-post course change in pain management confidence level. In all, 306 nurses from 89 hospitals in Ontario, Canada, were enrolled in the course; 81.4% returned the precourse survey and 71.9% successfully completed the course. The average confidence level on pain management was low at baseline (57.5%) but improved significantly post-course. In-course competency assessments ranged from 81% to 89%. Mixed-model results showed post-course improvements in confidence levels, independent of sociodemographic background, clinical role, and professional educational level. Nurses with longer years of practice and more cancer cases reported greater confidence. A facilitator-led online educational intervention focusing on complex cancer pain management can significantly improve nurses' knowledge, confidence, and skills. Low baseline knowledge among nurses highlights the pressing need for health-care organizations to implement cancer pain management training as an integral part of health-care QI initiative.


Inhibition of azoxymethane-induced aberrant crypt foci in rat by diphenylmethyl selenocyanate through downregulation of COX-2 and modulation of glutathione-S-transferase and lipid peroxidation.
Preventive intervention of colorectal cancer has become essential, as a major portion of the population could develop the disease at some point during their lives. An inverse association between dietary intake of selenium, an important biological trace element, and colorectal cancer risk has been observed through epidemiological and experimental studies. Inhibitory activity of an organoselenocyanate, diphenylmethylselenocyanate, was tested on azoxymethane (15 mg/kg body wt) induced colon carcinogenesis in Sprague-Dawley rats. Pretreatment and concomitant treatment, at a dose of 2 mg/kg body wt, was carried out and the effect was observed on aberrant crypt foci, the preneoplastic lesion. To investigate the mechanism of action of the compound, lipid peroxidation level and glutathione-S-transferase (GST) activities were assessed in the liver as well as in the colon. Expression of cyclooxygenase-2 protein, inducible during colon carcinogenesis, was also analyzed in the colon. Inhibitory activity of the compound was shown by the reduced incidences of aberrant crypt foci in the treated groups (by 63.3%, p=0.00044 in the pretreated group, and by 44%, p=0.0067 in the concomitant treatment group). Significant induction of GST activities and significant reduction in lipid peroxidation level both in the liver as well as in the colon and suppression of cyclooxygenase-2 expression in the colon of the treated groups suggest that the compound could exert its preventive effect at different levels of the carcinogenic process. The preventive effect was better in the pretreatment group than in the concomitant treatment group, suggesting some added protection to the target tissue resulting from preadministration of the compound.


[Midterm toxicity of nitrates: experimental evaluation of the effects on reproductive functions in the female rabbit].
Chronic exposure to low levels of nitrate are associated with detrimental effects on reproduction in animals. In order to determine this relationship, an experiment was conducted: female rabbits were given nitrate doses of 0, 250 or 500 mg/l in drinking water for several months. After 2 successive gestations, no detrimental effect was observed on fertility, litter size or weight at birth and weaning, or on plasma oestradiol and progesterone concentration. Hemoglobin level was slightly decreased in dams given 500 mg/l.


The interactive effect of anger and disgust on moral outrage and judgments.
The two studies reported here demonstrated that a combination of anger and disgust predicts moral outrage. In Study 1, anger toward moral transgressions (sexual assault, funeral picketing) predicted moral outrage only when it co-occurred with at least moderate disgust, and disgust predicted moral outrage only when it co-occurred with at least moderate anger. In Study 2, a mock-jury paradigm that included emotionally disturbing photographs of a murder victim revealed that, compared to anger, disgust was a more consistent predictor of moral outrage (i.e., it predicted moral outrage at all levels of anger). Furthermore, moral outrage mediated the effect of participants' anger on their confidence in a guilty verdict--but only when anger co-occurred with at least a moderate level of disgust--whereas moral outrage mediated the effect of participants' disgust on their verdict confidence at all levels of anger. The interactive effect of anger and disgust has important implications for theoretical explanations of moral outrage, moral judgments in general, and legal decision making.


Structural and optical properties of sol-gel synthesised Zn(1-x)Mg(x)O nanocrystals.
Zn(1-x)Mg(x)O nanocrystals with various compositions (x = 0-0.1) were synthesised by sol-gel process using tri ethanol amine (TEA) as a capping agent. The structural properties of the prepared materials were studied by X-ray diffraction analysis. Un-agglomerated nanocrystals with spherical morphology were observed by scanning electron microscope (SEM). The presence of Mg in the Zn(1-x)Mg(x)O was confirmed by X-ray photoelectron spectroscopy (XPS). Moreover, the Mg composition relatively increases in the synthesised nanocrystals as it increases in the precursor solution. The optical absorption studies of the Zn(1-x)Mg(x)O samples show the blue shift from the pure ZnO due to the incorporation of Mg in ZnO lattice. The photoluminescence studies demonstrated that the intensity of defect related deep level emission increases drastically with increasing the x value from 0.02 to 0.08 and decreases sharply on further increase of Mg from 0.08 to 0.1. The mechanism for the enhanced green emission was explained based on the structural properties of the Zn(1-x)Mg(x)O samples.


[Antimalarial 6-aminoquinolines. VIII. 2- and 4-amino derivatives (author's transl)].
Ten 2- or 4-amino derivatives 10b-I of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline were synthesised with the aim of studying the influence of these substituents on antimalarial activity and toxicity of the 6-aminoquinolines. The 4-dialkylamino derivatives 10c-h were less active against P. vinckei (mouse) than 4-alkoxy derivatives. The 4-amino derivative 10b was inactive.


Sorghum-cowpea composite porridge as a functional food, Part II: Antioxidant properties as affected by simulated in vitro gastrointestinal digestion.
The effect of compositing red non-tannin sorghum with brownish-cream cowpea and in vitro gastrointestinal digestion on total phenolic and flavonoid contents and antioxidant properties of a sorghum-cowpea composite porridge was studied. Maize-soybean composite porridge was used as a reference sample. Antioxidant properties were studied using radical scavenging activities against the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), peroxyl and NO radicals as well as inhibition of low density lipoprotein (LDL) oxidation and oxidative damage of vector DNA. Hydroperoxide content of the samples was also measured. All the samples demonstrated radical scavenging activity. Simulated duodenal digests of the porridges had hydroperoxides and therefore caused LDL oxidation. The undigested porridges and simulated gastric digests inhibited LDL oxidation. Compositing the cereals with legumes increased total phenolic and flavonoid contents and NO scavenging activity of their porridges. In vitro gastrointestinal digestion of the porridges increased their total phenolic and flavonoid contents, radical scavenging activities and LDL oxidation inhibitory activity.


Discriminating multiplexed GFP reporters in primary articular chondrocyte cultures using image cytometry.
Flow cytometry has become a standard tool for defining a heterogeneous cell population based on surface expressed epitopes or GFP reporters that reflect cell types or cellular differentiation. The introduction of image cytometry raised the possibility of adaptation to discriminate GFP reporters used to appreciate cell heterogeneity within the skeletal lineages. The optical filters and LEDs were optimized for the reporters used in transgenic mice expressing various fluorescent proteins. In addition, the need for compensation between eGFP and surrounding reporters due to optical cross-talk was eliminated by selecting the appropriate excitation and emission filters. Bone marrow or articular cartilage cell cultures from GFP and RFP reporter mouse lines were established to demonstrate the equivalency in functionalities of image to flow cytometry analysis. To examine the ability for monitoring primary cell differentiation, articular chondrocyte cell cultures were established from mice that were single or doubly transgenic (Dkk3eGFP and Col2A1GFPcyan), which identify the progression of superficial small articular cell to a mature chondrocyte. The instrument was able to rapidly and accurately discriminate cells that were Dkk3eGFP only, Dkk3eGFP/Col2A1GFPcyan, and Col2A1GFP, which provides a useful tool for studying the impact of culture conditions on lineage expansion and differentiation.


First trimester diagnosis of cystinosis using intact chorionic villi.
Cystinosis was diagnosed in the first trimester of pregnancy by studies of uptake and retention of [35S]-cystine by intact biopsy samples of chorionic villi. The diagnosis was confirmed by similar studies on cell cultures of villi and fetal skin fibroblasts.


Convergent community structure of algal-bacterial consortia and its effects on advanced wastewater treatment and biomass production.
Microalgal-bacterial consortium is an effective way to meet increasingly stringent standards in wastewater treatment. However, the mechanism of wastewater removal effect has not been properly explained in community structure by phycosphere. And little is known about that the concept of macroecology was introduced into phycosphere to explain the phenomenon. In the study, the algal-bacterial consortia with different ratios of algae and sludge were cultured in same aerobic wastewater within 48 h in photobioreactors (PSBRs). Community structure at start and end was texted by metagenomic analysis. Bray-Curtis similarities analysis based on microbial community showed that there was obvious convergent succession in all consortia, which is well known as "convergence" in macroecology. The result showed that Bray-Curtis similarities at End (overall above 0.88) were higher than these at Start (almost less than 0.66). In terms of community structure, the consortium with 5:1 ratio at Start are the more similar with the consortia at End by which the maximum removal of total dissolved nitrogen (TDN, 73.69%), total dissolved phosphorus (TDP, 94.40%) and NH3-N (93.26%) in wastewater treatment process and biomass production (98.2%) higher than other consortia, according with climax community in macroecology with the highest resource utilization than other communities. Therefore, the macroecology can be introduced into phycosphere to explain the consortium for advanced wastewater treatment and optimization community structure. And the study revealed a novel insight into treatment effect and community structure of algal-bacterial consortia for advanced wastewater treatment, a new idea for to shortening the culture time of consortium and optimize predicting their ecological community structure and predicting ecological community.


Clinicopathological characteristics of erythroblast-rich RAEB and AML M6a in children.
The distinction between RAEB, RAEB-T and AML M6a is difficult when erythroblasts in the bone marrow (BM) exceed 50%. We analyzed 19 children (2 RAEB, 13 RAEB-T and 4 AML M6a) enrolled in a prospective pathological central review in Japan and divided them into two groups according to the myeloblasts percentage among non-erythroid cells in BM: group A (n = 8), 5-19% myeloblasts; group B (n = 11), 20% or more myeloblasts. Their characteristics were very similar except for the number of myeloblasts. The median WBC was in the range of 1.0-5.0 x 10(9) L(-1), the median Hb was around 7.5 g/dL, the median MCV was greater than 90 fL and both group had Auer rods at 60-65%. Severe multilineage dysplasia was observed in most of the patients in two groups. Six with group A and seven with group B treated with AML type chemotherapy achieved complete remission. Five with group A and seven with group B undergoing SCT are alive at a median of 3 years after diagnosis. Erythroblast-rich RAEB and AML M6a in children have similar characteristics and may belong to a single disease entity.


Glutamine supplementation does not prevent small bowel mucosal atrophy after total parenteral nutrition in the rat.
Glutamine supplementation to non-lipid parenteral nutrition has been demonstrated to attenuate villus atrophy and increase mucosal DNA content in the rat. This study was performed in order to determine the effects of glutamine supplementation to a balanced TPN mixture (including lipids) on epithelial cell kinetics using autoradiography. Male Sprague-Dawley rats were used. Group 1 (control) received food and an intravenous saline infusion. Group 2 received an intravenous TPN mixture including lipids but without glutamine. The same TPN mixture, glutamine replacing an isonitrogenous amount of non-essential amino acids, was given to Group 3. Animals were fed for 7 days, whereafter blood and intestinal samples were taken 1 h after injection of tritiated thymidine. Microscopy of specimens from proximal jejunum revealed a significant reduction in the number of cells in crypts and villi in both TPN groups (2 and 3) compared to orally fed animals (p < 0.001). Epithelial cell numbers were not significantly different in Group 2 and 3. Similarly, the labelling index (number of labelled cells/number of crypt cells) was not affected by glutamine administration. In plasma, glucagon concentrations in Group 2 (TPN without glutamine) seemed to decrease compared to Group 1 and 3 (p = 0.06). In this study, glutamine supplementation did not affect apithelial atrophy or cell proliferation. It is concluded, that the effects of glutamine on mucosal atrophy and renewal in jejunum may depend on the composition of the TPN mixture supplied during parenteral feeding.


Admissions Criteria as Predictors of Academic Performance in a Three-Year Pharmacy Program at a Historically Black Institution.
To determine the ability of University of Maryland Eastern Shore School of Pharmacy's admissions criteria to predict students' academic performance in a 3-year pharmacy program and to analyze transferability to African-American students. Statistical analyses were conducted on retrospective data for 174 students. Didactic and experiential scores were used as measures of academic performance. Pharmacy College Admission Test (PCAT), grade point average (GPA), interview, and observational scores combined with previous pharmacy experience and biochemistry coursework predicted the students' academic performance except second-year (P2) experiential performance. For African-American students, didactic performance positively correlated with PCAT writing subtests, while the experiential performance positively correlated with previous pharmacy experience and observational score. For nonAfrican-American students, didactic performance positively correlated with PCAT multiple-choice subtests, and experiential performance with interview score. The prerequisite GPA positively correlated with both of the student subgroups' didactic performance. Both PCAT and GPA were predictors of didactic performance, especially in nonAfrican-Americans. Pharmacy experience and observational scores were predictors of experiential performance, especially in African-Americans.


Neuronal ApoE4 stimulates C/EBPβ activation, promoting Alzheimer's disease pathology in a mouse model.
ApoE4 is a major genetic risk determinant for Alzheimer's disease (AD) and drives its pathogenesis via Aβ-dependent and -independent pathways. C/EBPβ, a proinflammatory cytokine-activated transcription factor, is upregulated in AD patients and increases cytokines and δ-secretase expression. Under physiological conditions, ApoE is mainly expressed in glial cells, but its neuronal expression is highly elevated under pathological stresses. However, how neuronal ApoE4 mediates AD pathologies remains incompletely understood. Here we show that ApoE4 activates C/EBPβ that subsequently regulates APP, Tau and BACE1 mRNA expression in mouse neurons, driving AD-like pathogenesis. To interrogate the pathological roles of both human ApoE4 and C/EBPβ elevation in neurons in the aged brain, we develop neuronal specific Thy1-ApoE4/C/EBPβ double transgenic mice. Neuronal ApoE4 strongly activates C/EBPβ and augmented δ-secretase subsequently cleaves increased mouse APP and Tau, promoting AD-like pathologies. Notably, Thy1-ApoE4/C/EBPβ mice develop amyloid deposits, Tau aggregates and neurodegeneration in an age-dependent manner, leading to synaptic dysfunction and cognitive disorders. Thus, our findings demonstrate that neuronal ApoE4 triggers AD pathogenesis via activating the crucial regulator C/EBPβ.


Plasma timolol levels after oral and intravenous administration.
The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volume of distribution was 3.5 1/k. It is suggested that timolol is little affected by the 'first pass effect', even though there is marked interindividual variation in availability and peak plasma level.


Combining a matrix metalloproteinase inhibitor, a farnesyltransferase inhibitor, and a taxane improves survival in an anaplastic thyroid cancer model.
We previously showed that the in vivo anticancer effects of a combination of manumycin (a farnesyltransferase inhibitor) and paclitaxel (a microtubule inhibitor) against anaplastic thyroid carcinoma (ATC) were partially due to inhibition of angiogenesis. In this study, we investigated the effect of adding minocycline (a matrix metalloproteinase inhibitor) to manumycin and paclitaxel against human ATC cells xenografted in nude mice. The triple-drug combination resulted in the lowest average tumor growth rate, and it conferred significantly better survival than manumycin alone, paclitaxel alone, or manumycin plus paclitaxel. In conclusion, this novel combination deserves further investigation in the treatment of ATC.


Methodological quality and risk of bias of meta-analyses of pharmacy services: A systematic review.
A suboptimal meta-analysis with misleading conclusions, frequently published in the healthcare journals, can compromise decision making in clinical practice. To evaluate the reporting quality, methodological quality, and risk of bias of meta-analyses of pharmacy services. Systematic searches to identify all the meta-analyses reporting the effect of pharmacy services were performed in PubMed, Scopus, and Web of Science. The reporting quality, the methodological quality, and the risk of bias of the included meta-analyses were evaluated using PRISMA checklist, R-AMSTAR, and ROBIS, respectively. A total of 109 meta-analyses were eligible for the study. The heterogeneity, the quality of evidence, and the quality analyses were poorly reported on authors' conclusions (14.3%, 14.7%, and 17.4%, respectively). The median scores of PRISMA and R-AMSTAR tolls were 24 (IQR 21.75-25), and 30 (IQR 27-32.5), respectively. Additionally, most of the studies were considered as high risk of bias (n = 83, 76.1%). No association between the date of publication and guideline compliance exists. PRISMA score was higher in studies published in high impact factor journals (rho = 0.313; p = 0.002), in articles that reported the quality of evidence obtained (p = 0.018), and in those that stated the need for future studies in their conclusions (p = 0.011). R-AMSTAR score was higher in studies published in high impact factor journals (rho = 0.338; p = 0.001), in those which reported the quality of evidence (p = 0.002), and in articles that described the quality analyses in their conclusions (p = 0.046). An association between the risk of bias and the recognition of the need for further studies in their conclusions (p = 0.041) was also found. The rapid increase of the meta-analyses of pharmacy services was not associated with higher quality. Mechanistic meta-analyses with poor conclusions are commonly published. Quality of the analyses, strength of evidence, heterogeneity, and absence of confrontation with current guidelines are rarely considered when synthetizing evidence and making recommendations.


Trace metals in an urbanized estuarine sea turtle food web in San Diego Bay, CA.
San Diego Bay is an anthropogenically impacted waterway that is also a critical habitat for many sensitive species such as the green sea turtle (Chelonia mydas). In this study, we quantified trace metal concentrations in sediment and organisms composing the green sea turtle diet, and identified bioaccumulation patterns for a suite of trace metals. We found Ag, Cd, Cu, Mn, Se, and Zn exhibited the highest bioaccumulation levels in this food web. Cu and Mn concentrations in resident biota displayed a strong spatial gradient from the mouth to the head of the Bay, which was different from the patterns found in the sediment itself. Sediment median concentrations followed a general pattern across the bay of Al>Mn>Cu≈Zn>Pb>As>Cd>Ag>Se>Hg. In contrast, eelgrass displayed differential patterns in the mouth versus the back of the Bay (three front Bay sites: Al>Mn>Zn>Cu>Pb>Se>Cd≈Ag>As; five back Bay sites: Mn>Al>Zn>Cu>Pb≈Se>Cd>Ag>Hg>As) with the exception of Shelter Island where levels of Zn and Cu were elevated as a result of anti-fouling paint pollution. Observed differences between sediment and biota metal patterns are likely due to complex processes related to trace metals input and bioavailability, habitat characteristics and specific metabolic functioning of the trace metals for each member of the food web. These data highlight the fact that for the San Diego Bay ecosystem, the current use of toxicity reference values scaled up from sediment and invertebrate testing ex-situ is likely to be inaccurate when transposed to the green sea turtle. Here, we illustrate how identifying spatial variability in metal exposure can improve our understanding of habitat utilization by sea turtles in highly urbanized estuaries. Monitoring contaminants directly in food webs of sensitive vertebrates may greatly improve our understanding of their direct and indirect exposure to potentially deleterious contamination, and should be considered in the future to improve traditional risk assessment approaches.


Effect of phenytoin on skeletal muscle from quarter horses with hyperkalaemic periodic paralysis.
The contractile activity, the threshold for calcium-induced calcium release in fractions of sarcoplasmic reticulum and the potassium concentration were determined in preparations of semimembranosus muscle from normal quarter horses and quarter horses with hyperkalaemic periodic paralysis before and after they were treated with phenytoin. Before the treatment there was no difference in caffeine contracture or electrically elicited twitch response between the two groups. For one week after the treatment, the time to peak tension of caffeine contractures was significantly (P < 0.005) reduced in the horses with hyperkalaemic periodic paralysis but unchanged in the normal horses. The variance but not the mean values for the threshold for Ca(2+)-induced Ca2+ release from the sarcoplasmic reticulum was greater for the horses with hyperkalaemic period paralysis before but not after the treatment with phenytoin.


Is montelukast as effective as N-acetylcysteine in hepatic injury due to acetaminophen intoxication in rats?
This study aims to investigate the acute protective effect of montelukast sodium in hepatic injury secondary to acetaminophen (APAP) intoxication. This study used 60 rats. The rats were grouped into 6 groups. The control group was administered oral distilled water 10 ml/kg, the APAP group oral APAP 1 g/kg, the montelukast sodium (MK) group oral MK 30 mg/kg, the acetaminophen+N-acetylcysteine (APAP+NAC) group oral APAP 1 g/kg, followed by a single dose of intraperitoneal NAC 1.5 g/kg three hours later, the acetaminophen+montelukast sodium (APAP+MK) group oral APAP 1 g/kg, followed by oral MK 30 mg/kg 3 h later, the acetaminophen+N-acetylcysteine+montelukast sodium (APAP+NAC+MK) group oral APAP 1 g/kg, followed by a single intraperitoneal NAC 1.5 g/kg plus oral MK 30 mg/kg 3 h later. Blood and liver tissue samples were taken 24h after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were studied from the blood samples. Liver tissue samples were used for histopathological examination. Compared with the control group, serum AST and ALT activities were higher in the APAP and APAP+NAC groups. APAP+NAC, APAP+MK, and APAP+NAC+MK groups had reduced serum ALT and AST activities than the group administered APAP alone. APAP+MK and APAP+NAC+MK groups had a lower serum ALP activity than the control group. Histopathologically, there was a difference between the group administered APAP alone and the APAP+MK and APAP+NAC+MK groups. MK is as protective as NAC in liver tissue in APAP intoxication in rats.


Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic.
Human exposure to environmental chemicals is most correctly characterized as exposure to mixtures of these agents. The metals/metalloids, lead (Pb), cadmium (Cd), and arsenic (As), are among the leading toxic agents detected in the environment. Exposure to these elements, particularly at chronic low dose levels, is still a major public health concern. Concurrent exposure to Pb, Cd, or As may produce additive or synergistic interactions or even new effects that are not seen in single component exposures. Evaluating these interactions on a mechanistic basis is essential for risk assessment and management of metal/metalloid mixtures. This paper will review a number of individual studies that addressed interactions of these metals/metalloids in both experimental and human exposure studies with particular emphasis on biomarkers. In general, co-exposure to metal/metalloid mixtures produced more severe effects at both relatively high dose and low dose levels in a biomarker-specific manner. These effects were found to be mediated by dose, duration of exposure and genetic factors. While traditional endpoints, such as morphological changes and biochemical parameters for target organ toxicity, were effective measures for evaluating the toxicity of high dose metal/metalloid mixtures, biomarkers for oxidative stress, altered heme biosynthesis parameters, and stress proteins showed clear responses in evaluating toxicity of low dose metal/metalloid mixtures. Metallothionein, heat shock proteins, and glutathione are involved in regulating interactive effects of metal/metalloid mixtures at low dose levels. These findings suggest that further studies on interactions of these metal/metalloid mixtures utilizing biomarker endpoints are highly warranted.


The impact of the COVID-19 pandemic on alloplastic breast reconstruction: An analysis of national outcomes.
Immediate alloplastic breast reconstruction shifted to the outpatient setting during the COVID-19 pandemic to conserve inpatient hospital beds while providing timely oncologic care. We examine the National Surgical Quality Improvement Program (NSQIP) database for trends in and safety of outpatient breast reconstruction during the pandemic. NSQIP data were filtered for immediate alloplastic breast reconstructions between April and December of 2019 (before-COVID) and 2020 (during-COVID); the proportion of outpatient procedures was compared. Thirty-day complications were compared for noninferiority between propensity-matched outpatients and inpatients utilizing a 1% risk difference margin. During COVID, immediate alloplastic breast reconstruction cases decreased (4083 vs. 4677) and were more frequently outpatient (31% vs. 10%, p < 0.001). Outpatients had lower rates of smoking (6.8% vs. 8.4%, p = 0.03) and obesity (26% vs. 33%, p < 0.001). Surgical complication rates of outpatient procedures were noninferior to propensity-matched inpatients (5.0% vs. 5.5%, p = 0.03 noninferiority). Reoperation rates were lower in propensity-matched outpatients (5.2% vs. 8.0%, p = 0.003). Immediate alloplastic breast reconstruction shifted towards outpatient procedures during the COVID-19 pandemic with noninferior complication rates. Therefore, a paradigm shift towards outpatient reconstruction for certain patients may be safe. However, decreased reoperations in outpatients may represent undiagnosed complications and warrant further investigation.


Impact of the COVID-19 pandemic on the physical and psychological health of female college students in Japan.
The spread of COVID-19 has dramatically changed our lives. This study aimed to examine the lifestyles of female college students, focusing on physical activity, sleep status, and anxiety status during the pandemic (while under a state of emergency) in Japan. A total of 184 female college students completed two questionnaires, anthropometric measurements, and daily activity logs and diet records, in groups of 115 and 69 participants recruited before and during the pandemic, respectively. Findings showed a significant decrease in physical activity: Physical activity levels fell from "normal" to "low" and the daily step counts decreased by nearly half, from 8671 to 4640. In addition, the results from the questionnaires revealed that half of the participants were at risk of having sleep disturbances, and their sleep cycles became more nocturnal, which may have caused higher anxiety states and lower sleep quality during the pandemic. Furthermore, anxiety states worsened, with 100% of the participants experiencing high anxiety during the pandemic. Monitoring lifestyle disturbances during the pandemic is needed for the development of interventions to improve health among young women.


Predictors of COVID-19 vaccination hesitancy in China: a meta-analysis.
This study aimed to examine predictors and moderators of COVID-19 vaccine hesitancy in Chinese cultural contexts. A meta-analysis and meta-regression analyses were conducted to examine the associations between predictors and vaccine hesitancy as well as moderators that may impact these associations. We searched relevant articles from January 1, 2020, to May 12, 2022, in the databases of Web of Science, PubMed, ProQuest, ProQuest Dissertations & Theses Global and CNKI. Weighted average effect sizes (e.g., odds ratio) and 95% confidence intervals were computed in Comprehensive Meta-Analysis 3.0 using random-effects models. Heterogeneity tests were conducted prior to moderation analyses. Results from 161 studies in 73 published articles (N = 705,957) were meta-analyzed. Perceived risk of COVID-19 infection, health status, medical workers' recommendation, recommendations from family and friends, and vaccine coverage among relatives and friends were significantly associated with COVID-19 vaccine hesitancy in Chinese cultural contexts. Participant age, operationalization of vaccine hesitancy, and the time of each study exerted significant moderation effects. Both individual and relational factors influence vaccine hesitancy in Chinese cultural contexts Future vaccine promotion initiatives should focus on risk perceptions as well as influence from medical professionals, family and friends.


Population based data on age related excretion of creatinine sodium and potassium in children of Southern Italy--the Cimitile study.
This is a population based study on urinary excretion of sodium, potassium and creatinine in children from Southern Italy aged 3-16 years. Mean urinary creatinine excretion was 33 +/- 10 mg/kg. Mean sodium excretion was of 3.91 +/- 1.52 mM/kg. Urinary sodium, potassium and creatinine correlated with age, body weight, body mass index (BMI) and height and no difference was found in the comparison among sexes. The data point to an excessive sodium intake in these children and additionally claim for a reconsideration of urinary creatinine excretion in this age group.


The protective effects of estrogen on hepatic ischemia-reperfusion injury in rats by downregulating the Ang II/AT1R pathway.
Hepatic ischemia/reperfusion (I/R) injury continued to be a significant clinical problem. The aim of this study was to examine whether the protective effects of 17-estradiol (E2) on hepatic ischemia/reperfusion (I/R) injury was associated with the downregulation of the angiotensin II (Ang II)/AT1R pathway. Forty male Sprague Dawley rats were randomized into five groups: Sham operation, ischemia/reperfusion (I/R), I/R + E2, I/R + E2+estrogen receptor antagonist ICI 182,780 (ICI), and I/R + E2+ Ang II subtype I receptor (AT1R) antagonist losartan (LOS) groups. A model of total hepatic I/R was established by portal pedicle clamping for 60 min followed by reperfusion. At onset of ischemia, rats were treated with vehicle, E2, or LOS. ICI was given 30 min before E2 administration. At 24 h after reperfusion, blood samples and liver tissues were collected and subjected to histological examination, biochemical assays, and Western blot assays. Compared with I/R group, the degree of hepatocyte damage, serum ALT and TNF-α levels, hepatic MDA level and MPO activity were decreased in I/R + E2 group (all p < 0.05). Moreover, the serum and liver Ang II levels and hepatic AT1R protein level in I/R + E2 group were also significantly reduced compared with I/R group (all p < 0.05). However, the protective effect of E2 could be abolished by ICI administration. In contrast, administration of LOS conferred similar, but not as effective as E2, protective effects on hepatic I/R injury, without affecting Ang II and AT1R levels. The salutary effects of E2 on hepatic I/R injury are mediated in part by downregulating the Ang II/AT1R pathway.


Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly : A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial.
Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia. To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations. Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583). Primary/community care in Australia and the United States. Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons). 100 mg of aspirin daily or placebo. Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset. 19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results. Hemoglobin was measured annually. No data were available on causes of anemia. Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin. National Institutes of Health and Australian National Health and Medical Research Council.


Cholinergic projections in the telencephalo-habenulo-interpeduncular system of the goldfish.
Experiments were performed in order to see whether acetylcholine is a neurotransmitter in the telencephalo-habenulo-interpeduncular system of the goldfish. After telencephalic ablation choline acetyltransferase decreased by 53% in the habenular nuclei but was unchanged in the interpeduncular nucleus. After combined telencephalic and habenular lesions, the enzyme level dropped by 95% in the interpeduncular nucleus. These results suggest the existence of a telencephalo-habenular and a habenulo-interpeduncular cholinergic projection in the goldfish, as previously demonstrated in mammals. Acetylcholinesterase histochemistry additionally demonstrates some similarities between the habenulae and the interpeduncular nucleus in the goldfish and in mammals.


Area of residence and risk of cancer of the cervix uteri in Ireland.
A study of 85 women attending a national centre for treatment of invasive squamous cell carcinoma of the cervix uteri (SCC) and 85 age-matched female controls attending the same centre showed no significant difference for area of residence. A previously reported excess of rural women among cases was probably an artefact of sample selection. An increased risk for women resident in urban areas described in studies elsewhere is not apparent in the women studied and demographic features of the Irish population may influence this result.


Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non-severe pneumonia attended in the community: study protocol for a randomised controlled trial.
Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. In some Scandinavian countries, this infection is treated with penicillin V since the resistances of pneumococci to this antibiotic are low. Four reasons justify the undertaking of this study; firstly, the cut-off points which determine whether a pneumococcus is susceptible or resistant to penicillin have changed in 2008 and according to some studies published recently the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (minimum inhibitory concentration>2 μg/ml); secondly, there is no correlation between pneumococcal infection by a strain resistant to penicillin and therapeutic failure in pneumonia; thirdly, the use of narrow-spectrum antibiotics is urgently needed because of the dearth of new antimicrobials and the link observed between consumption of broad-spectrum antibiotics and emergence and spread of antibacterial resistance; and fourthly, no clinical study comparing amoxicillin and penicillin V in pneumonia in adults has been published. Our aim is to determine whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of uncomplicated community-acquired pneumonia. We will perform a parallel group, randomised, double-blind, trial in primary healthcare centres in Spain. Patients aged 18 to 65 without significant associated comorbidity attending the physician with signs and symptoms of lower respiratory tract infection and radiological confirmation of the diagnosis of pneumonia will be randomly assigned to either penicillin V 1.6 million units thrice-daily during 10 days or amoxicillin 1,000 mg thrice-daily during 10 days. The main outcome will be clinical cure at 14 days, defined as absence of fever, resolution or improvement of cough, improvement of general wellbeing and resolution or reduction of crackles indicating that no other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%. This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years. EudraCT number 2012-003511-63.


Transcranial sonography in movement disorders.
Over the past 15 years the use of transcranial B-mode sonography to assess brainstem and subcortical brain structures has become an important tool for the diagnosis and differential diagnosis of various movement disorders. The most widely recognised finding for movement disorders has been an increase in echogenicity of the substantia nigra, an area of the midbrain that is affected in idiopathic Parkinson's disease (PD). This finding has enabled the reliable diagnosis of PD with high predictive values. Other sonographic features, such as hypoechogenicity of the brainstem midline and hyperechogenicity of the lentiform nucleus, might help the differential diagnosis of PD and other movement disorders. This Review provides detailed information about the advantages and limitations of this novel neuroimaging method, including guidelines for the scanning procedure and considerations on the origin of ultrasound abnormalities. We discuss the use of transcranial sonography for early and preclinical diagnosis and for differential diagnosis of PD and other movement disorders, and we compare this method with other functional neuroimaging strategies. Transcranial B-mode sonography is a reliable, non-invasive, commonly available, easily applicable, and inexpensive method, which provides new information about the morphology of the brain to help the diagnosis of various movement disorders. Thus, this neuroimaging method could be recommended for general application in the diagnosis and differential diagnosis of PD.


Effects of taurine on vascular tone.
Taurine is widely distributed at high concentrations in mammalian tissues, and it plays an important role in a wide range of biological effects including modulation of cardiovascular functions. This review summarizes the role of taurine in vascular tone and blood pressure modulation based on experimental and human studies. It is well established that supplementation of taurine prevents development of hypertension in several animal models and p.o. taurine administration reduces blood pressure in hypertensive patients. Both central and peripheral actions of taurine may be involved in its hypotensive effects. In isolated animal arteries, taurine exerts vasodilation through endothelium-dependent and independent mechanisms. Several studies showed that taurine relaxed various animal arteries through opening potassium channels. We have recently shown that taurine relaxes human internal mammary and radial arteries by opening large conductance Ca2+-activated K+ channels. To date, the molecular mechanism(s) involved in the vascular effects of taurine are largely unknown and require further investigation. Clarifying the mechanisms in which taurine affects the vascular system may facilitate the development of therapeutic and/or diet-based strategies to reduce the burden of vascular diseases.


Percutaneously applied ureteral clips: treatment of vesicovaginal fistula.
Percutaneous techniques to manage urinary fistulas have had limited success. To overcome this, self-closing metallic clips were developed to occlude the ureter. The clips are applied through a percutaneously placed 30-F Teflon sheath. A case is reported in which the clips and new technique were successfully used.