Exploration of ligands to the Qi site semiquinone in the bc1 complex using high-resolution EPR.
Pulsed EPR spectroscopy was used to explore the structural neighborhood of the semiquinone (SQ) stabilized at the Qi site of the bc1 complex of Rhodobacter sphaeroides (EC 126.96.36.199) and to demonstrate that the nitrogen atom of a histidine imidazole group donates an H-bond to the SQ. Crystallographic structures show two different configurations for the binding of ubiquinone at the Qi site of mitochondrial bc1 complexes in which histidine (His-201 in bovine sequence) is either a direct H-bond donor or separated by a bridging water. The paramagnetic properties of the SQ formed at the site provide an independent method for studying the liganding of this intermediate species. The antimycin-sensitive SQ formed at the Qi site by either equilibrium redox titration, reduction of the oxidized complex by ascorbate, or addition of decylubihydroquinone to the oxidized complex in the presence of myxothiazol all showed similar properties. The electron spin echo envelope modulation spectra in the 14N region were dominated by lines with frequencies at 1.7 and 3.1 MHz. Hyperfine sublevel correlation spectroscopy spectra showed that these were contributed by a single nitrogen. Further analysis showed that the 14N nucleus was characterized by an isotropic hyperfine coupling of approximately 0.8 MHz and a quadrupole coupling constant of approximately 0.35 MHz. The nitrogen was identified as the N-epsilon or N-delta imidazole nitrogen of a histidine (it is likely to be His-217, or His-201 in bovine sequence). A distance of 2.5-3.1 A for the O-N distance between the carbonyl of SQ and the nitrogen was estimated. The mechanistic significance is discussed in the context of a dynamic role for the movement of His-217 in proton transfer to the site.


Determination of the threshold odor concentration of main odorants in essential oils using gas chromatography-olfactometry incremental dilution technique.
An essential oil, obtained by steam distillation of Clinopodium tomentosum (Kunth) Govaerts (Lamiaceae), collected in Ecuador, was analyzed by gas chromatography-olfactometry (GC-O) and GC-MS techniques. To our knowledge, the composition of this essential oil is described here for the first time, both from the chemical and olfactometric viewpoints. A preliminary analysis by GC-MS and using Kovats' retention indexes, lead to characterize and quantify the oil constituents, while GC-O was then applied for the identification of the main odorants. By the incremental dilution method (AEDA, CHARM Analysis), applied to the GC-O technique, the flavor dilution (FD) chromatogram was obtained. In order to calculate the TOC values of the main odorants, the relationship between the odorant concentration at the sniffing port and that one in the injected solution was established. This relationship was calculated by comparing the injected amount with the TOC value of a reference compound (limonene), obtained by dynamic dilution olfactometry. A good agreement was found between calculated and measured TOC values of few odorants.


The quest for ordinariness: transition experienced by midlife women living with chronic illness.
This paper reports the findings of research that aimed to elucidate the meaning of midlife women's experiences of living with chronic illness. A lack of awareness by health professionals of the context in which women must live with chronic illness often results in women feeling overwhelmed, alienated and without voice within the delivery of health care. This inquiry privileged women's voices. The construct of 'transition' in chronic illness experience evolved from this collaborative and participatory research with midlife women living with adult onset chronic illness. Over a 1-year timeframe, 81 women were asked to tell their stories of living with a chronic illness. These correspondence data were thematically analysed to provide storied accounts. Guided by feminist principles, women were empowered through research processes and have actively participated in the development of the transition construct. The research revealed that when women are first confronted with a chronic illness they appear to move through a complex trajectory that involves an 'extraordinary' phase of turmoil and distress; however, they may then make the transition toward an 'ordinary' phase that involves incorporating chronic illness into their lives. Transitions in chronic illness experience involve movement from extraordinariness to ordinariness and sometimes back again and were found to be processes that are nonlinear, sometimes cyclical and potentially recurring throughout a woman's life. Four major constructs emerged from women's narratives: How quickly life changes; extraordinariness: confronting life with illness; The illness experience as transforming and ordinariness: reconstructing life with illness. Nurses are in a position where they may make a difference to women who live with chronic illness. Understanding illness transitions offers a framework that will enable nurses to move beyond the bio-medically orientated concepts of nursing practice, towards a holistic approach to the provision of nursing care.


The impact of caring for family members with mental illnesses on the caregiver: a scoping review.
A large number of multidisciplinary, qualitative and quantitative research suggests that providing care for family members with mental health illnesses can have both positive and negative effects on the carers' wellbeing. However, to date a comprehensive overview and synthesis of literature that compares and contrasts positive and negative effects of family-caregiving on the carer is missing. To address this gap, this scoping review examines the effects of family-caregiving on carers' wellbeing. A Boolean search generated a total of 92 relevant articles that were included in the analysis. The results suggest that, to understand the effects of family-caregiving on the carer's mental and physical wellbeing, it is necessary to take a combination of situational and sociodemographic characteristics into consideration. Elderly, female, spousal-carers and primary-carers may be a group that is at risk of suffering from a lack of positive mental and physical wellbeing as a result of caring. However, the negative effects of caregiving can be balanced by extraversion, social support and religious or spiritual beliefs. Therefore, future interventions that aim to promote family caregivers' wellbeing may need to take personality, particular circumstances as well as cultural and personal beliefs into consideration.


'Tear-drop' fractures of the cervical spine - radiological features.
Severe flexion and compression forces applied to the cervical spine may result in a 'tear-drop' fracture of the vertebral body. These are serious injuries because of the high incidence of associated spinal cord involvement and ligamentous damage which renders the spine potentially unstable. The radiological features of these fractures are described and compared with less serious vertebral body 'burst' and compression fractures.


Regulation of host cell recognition in Streptococcus pyogenes.
Protein F, a fibronectin-binding protein, and the M protein of Streptococcus pyogenes both play important roles in directing adherence to different populations of host cells in the skin. Expression of both proteins is regulated in response to alterations in atmosphere. Transcriptional control of mry, a positive-acting regulator of expression of the gene which encodes the M protein (emm) in response, to elevated levels of CO2, is a mechanism for control of emm expression in response to atmosphere. Expression of protein F is controlled at the level of transcription in response to the concentration of O2, and its expression is stimulated in the presence of superoxide. Further support for a role of superoxide in regulation of prtF expression comes from the observation that an S. pyogenes mutant which contains an insertionally inactivated gene for superoxide dismutase (sod) becomes hypersensitive to superoxide and will express prtF constitutively. A second strain also demonstrates constitutive expression of prtF but contains a functional sod. Complementation analyses in this strain using a prtF allele cloned from a regulating host and a novel method for shuttle mutagenesis which utilized the transposon mini-gamma delta have been used to identify rofA, a positive-acting regulator of prtF expression. A model for the role of the surface proteins, F and M and their regulatory genes mry and rofA in streptococcal infections of the skin will be discussed.


A Core Genome Multilocus Sequence Typing Scheme for Enterococcus faecalis.
Among enterococci, Enterococcus faecalis occurs ubiquitously, with the highest incidence of human and animal infections. The high genetic plasticity of E. faecalis complicates both molecular investigations and phylogenetic analyses. Whole-genome sequencing (WGS) enables unraveling of epidemiological linkages and putative transmission events between humans, animals, and food. Core genome multilocus sequence typing (cgMLST) aims to combine the discriminatory power of classical multilocus sequence typing (MLST) with the extensive genetic data obtained by WGS. By sequencing a representative collection of 146 E. faecalis strains isolated from hospital outbreaks, food, animals, and colonization of healthy human individuals, we established a novel cgMLST scheme with 1,972 gene targets within the Ridom SeqSphere+ software. To test the E. faecalis cgMLST scheme and assess the typing performance, different collections comprising environmental and bacteremia isolates, as well as all publicly available genome sequences from the NCBI and SRA databases, were analyzed. In more than 98.6% of the tested genomes, >95% good cgMLST target genes were detected (mean, 99.2% target genes). Our genotyping results not only corroborate the known epidemiological background of the isolates but exceed previous typing resolution. In conclusion, we have created a powerful typing scheme, hence providing an international standardized nomenclature that is suitable for surveillance approaches in various sectors, linking public health, veterinary public health, and food safety in a true One Health fashion.


Extension of historical range of Betylobraconinae (Hymenoptera: Braconidae) into Palaearctic Region based on a Baltic amber fossil, and description of a new species of Mesocentrus Szépligeti from Papua New Guinea.
Two new species of the parasitic wasp genus Mesocentrus Szépligeti (Betylobraconinae) are described. One based on a new species from Papua New Guinea, the other the first Palaearctic member of the subfamily based on a 30+ mya, species from Baltic amber. The second species is illustrated using synchrotron X-ray microtomography. Whereas the extant Betylobraconinae are restricted to Australia, New Guinea and New Caledonia, their ancestral distribution is now known to have extended considerably further. A key to the four species of Mesocentrus known from Papua New Guinea is provided. Both species possess some putatively plesiomorphic characters absent in other extant Mesocentrus spp. The new extant species differs in having a considerably larger number of antennal segments and a less laterally depressed frons, while the extinct one has the clypeus separated from the face dorsally and strongly developed hypoclypeal depression. Availability of sequence data for this species enabled further analysis of the relationships of the subfamily, which we present in a phylogenetic analysis additionally including the release of a number of new sequences of related taxa.


Transumbilical endoscopic cholecystectomy in a porcine model.
Natural orifice transluminal endoscopic surgery (NOTES) is a new technique. This study describes our initial experience of NOTES and investigates the feasibility of transumbilical endoscopic cholecystectomy (TUEC). Eight domestic pigs were submitted to TUEC. After establishment of pneumoperitoneum, a bi-channel endoscope was placed through an infra-umbilical trocar. The gallbladder fundus was lifted by a grasper. The cystic duct and artery was dissected with a flexible hook and clipped by a clip fixing device. The specimen was extracted through the infra-umbilical trocar. The mean operation time was 114 minutes, ranging from 75 to 155 minutes. All the gallbladders were removed successfully. There was one case of subtotal resection, two cases of bleeding and three cases of bile leakage. Transumbilical endoscopic cholecystectomy is feasible although it needs more support of experiments and techniques before being applied on human subjects.


Color-coded pattern suppresses visual evoked cortical potentials and electroretinograms.
We developed a new visual stimulating system for recording visual evoked cortical potentials and electroretinograms. The stimulus was a color checkerboard, in which each check kept its chromaticity but changed its luminance with its corresponding check. Color-coded pattern stimuli using red and green checks did not produce visual evoked cortical potentials, while yellow checks produced clear responses in a normal subject. Moreover, five color stairs from red and green to yellow showed only that the more colors are different, the smaller the visual evoked cortical potentials become. In addition electroretinogram recordings indicated that color-coded patterns behave in the same way as in visual evoked cortical potentials. The mechanism that causes the small color visual evoked cortical potentials may already be present in the retina. Color perception may be able to induce a suppression of responses for luminance contrast that appears to be formed already in the retina. Retinal responses were affected whether the stimulus field was color coded or not. Pattern electroretinograms appear to be more than the sum of local on and off responses.


Cetirizine release from cyclodextrin formulated compressed chewing gum.
Beside the efficient effect on masking cetirizine bitter taste, the cyclodextrins (CDs) as well could have influence on the release from the formulation. In vitro release profiles of cetirizine from compressed chewing gums containing α-, β- and γ-CD were investigated using a three cell chewing apparatus. Different cetirizine/CD formulations were produced and analysed with respect to type of CD (α-, β- and γ-CD), the molar ratio between cetirizine and CD and the formulation of cetirizine (complex or physical mixture). Release experiments from all compressed chewing gum formulations gave similar release patterns, but with variations in the total amount released. Chewing gum formulated with cetirizine alone, demonstrated a release of 75% after 8 min of chewing. The presence of CDs resulted in increased cetirizine release. The analysis of variance (ANOVA) demonstrated that parameters with the most important influence on the release were the molar ratio of cetirizine/CD (P < 0.05) and the formulation of cetirizine/CD (complex or physical mixture) (P < 0.05). The compressed chewing gum formulations with 1:5 molar ratio of cetirizine/CD in complexed form demonstrated the highest release. Even though the statistical analysis (ANOVA) demonstrated significance in the release (P < 0.05) for the complex/physical mixture factor, this difference was negligible compared to the release from chewing gums containing cetirizine without CD. This makes physical mixtures suitable for use in cetirizine/CD formulations instead the complexes with respect to release yield. Thus unnecessary expenses for the complex preformulation may be avoided.


Microbiota of table olive fermentations and criteria of selection for their use as starters.
Fermentation is one of the oldest methods for preserving of olives applied worldwide for thousands of years. However, olive processing is a speculative area where whether olives are fermented products or pickled products produced by organic acids and salt. Although lactobacilli and yeasts play a major role in the process, literature survey indicates that lactobacilli are less relevant at least in some types of natural green olives during fermentation. There have been significant advances recently in understanding the process to produce olives, especially the role of lactic acid bacteria and yeasts including biofilm formation on olive surfaces by these organisms. The purpose of this paper is to review the latest developments regarding the microbiota of olives on the basis of olive types, their role on the fermentation process, the interaction between both group of microorganisms and the olive surface, the possibility to use starter cultures and the criteria to select appropriate cultures.


A Cross-Lagged Analysis of Emotion Regulation, Peer Problems, and Emotional Problems in Children With and Without Early Language Difficulties: Evidence From the Millennium Cohort Study.
Purpose Adolescents with a history of language difficulties are at risk for increased social and emotional difficulties; however, the pathways involved are unclear. We examine the contribution of poor emotion regulation by comparing longitudinal data from children at risk of developmental language disorder (rDLD) and the general population. Method Data from the Millennium Cohort Study were analyzed at ages 3, 5, 7, 11, and 14 years. The rDLD group (children with parent-reported difficulties and/or a score of -1.5 SDs on the Naming Vocabulary subtest at age 5 years) was compared to a general population group on parent reports of emotion regulation, peer problems, and emotional problems. Results In line with the established literature, increased socioemotional problems in individuals with language difficulties were reported. Poor emotion regulation consistently predicted subsequent peer and emotional problems throughout development in both groups. Stronger cross-lag effects were found in the rDLD group for poor emotion regulation at age 3 years predicting age 5 years emotional problems and age 5 years emotional problems predicting age 7 years emotion regulation difficulties. Stronger reciprocal cross-lag effects were also observed in the rDLD group between peer and emotional problems at ages 3 and 5 years. No significant group differences were found in adolescence. Conclusions Poor emotion regulation makes a small but significant contribution to later peer and emotional difficulties, and this relationship is stronger in children at rDLD. Early reciprocal peer and emotional difficulties are also stronger in the rDLD group, but these effects dissipate in midchildhood. Nevertheless, the consistent relationship between early emotion regulation difficulties and socioemotional problems throughout development warrants further investigation in individuals with lower language skills. Supplemental Material https://doi.org/10.23641/asha.12142059.


Monocyte-derived dendritic cells display a highly activated phenotype and altered function in patients with familial Mediterranean fever.
Dendritic cells (DCs) are sentinels of the immune system that bridge innate and adaptive immunity. By capturing antigens in peripheral tissue, processing and presenting them with concurrent expression of co-stimulatory molecules and cytokine secretion they control and modulate immune reactions. Through pattern recognition receptors, DCs sense molecules that are associated with infection or tissue damage, frequently resulting in the formation of inflammasomes upon intracellular stimulation. The inherited autoinflammatory familial Mediterranean fever (FMF) is associated with deregulated activity of the pyrin inflammasome leading to acute inflammatory episodes. However, differentiation and function of DCs in this disease are as yet unclear. Therefore, we first determined DC subpopulation frequency in peripheral blood of a cohort of FMF patients. Joint evaluation without classification according to specific patient characteristics, such as mutational status, did not disclose significant differences compared to healthy controls. For the further examination of phenotype and function, we used immature and mature monocyte-derived DCs (imMo-DCs, mMo-DCs) that were generated in vitro from FMF patients. Immunophenotypical analysis of imMo-DCs revealed a significantly elevated expression of CD83, CD86 and human leukocyte antigen D-related (HLA-DR) as well as a significant down-regulation of CD206, CD209 and glycoprotein NMB (GPNMB) in our FMF patient group. Furthermore, FMF imMo-DCs presented a significantly higher capacity to migrate and to stimulate the proliferation of unmatched allogeneic T cells. Finally, the transition towards a more mature, and therefore activated, phenotype was additionally reinforced by the fact that peripheral blood DC populations in FMF patients exhibited significantly increased expression of the co-stimulatory molecule CD86.


Interchannel coupling effects in the valence photoionization of SF6.
The complex Kohn and polyatomic Schwinger variational techniques have been employed to illustrate the interchannel coupling correlation effects in the valence photoionization dynamics of SF6. Partial photoionization cross sections and asymmetry parameters of six valence subshells (1t1g, 5t1u, 1t2u, 3eg, 1t2g, 4t1u) are discussed in the framework of several theoretical and experimental studies. The complex Kohn results are in rather good agreement with experimental results, indicative of the fact that the interchannel coupling effects alter the photoionization dynamics significantly. We find that the dominant effect of interchannel coupling is to reduce the magnitude of shape resonant cross sections near the threshold and to induce resonant features in other channels to which resonances are coupled. The long-standing issue concerning ordering of the valence orbitals is addressed and confirmed 4t1u (6)1t2g (6)3eg (4)(5t1u (6)+1t2u (6)) 1t1g (6) as the most likely ordering.


An assessment of effectiveness of PLATO basic medical science lessons.
The present study investigated the effectiveness of PLATO basic medical science lessons. Evidence was found that users of the PLATO lessons earned higher mean scores than non-users on subtests of basic science examinations. The findings offer encouragement that PLATO materials may be viable educational tools within a first-year basic science program.


A solution concentration dependent transition from self-stratification to lateral phase separation in spin-cast PS:d-PMMA thin films.
Thin films with a rich variety of different nano-scale morphologies have been produced by spin casting solutions of various concentrations of PS:d-PMMA blends from toluene solutions. During the spin casting process specular reflectivity and off-specular scattering data were recorded and ex situ optical and atomic force microscopy, neutron reflectivity and ellipsometry have all been used to characterise the film morphologies. We show that it is possible to selectively control the film morphology by altering the solution concentration used. Low polymer concentration solutions favour the formation of flat in-plane phase-separated bi-layers, with a d-PMMA-rich layer underneath a PS-rich layer. At intermediate concentrations the films formed consist of an in-plane phase-separated bi-layer with an undulating interface and also have some secondary phase-separated pockets rich in d-PMMA in the PS-rich layer and vice versa. Using high concentration solutions results in laterally phase-separated regions with sharp interfaces. As with the intermediate concentrations, secondary phase separation was also observed, especially at the top surface.


Cardiopulmonary resuscitation in COVID-19 patients.
COVID-19 is extremely transmissible. Cardiopulmonary resuscitation (CPR) is associated with multiple aerosol-generating procedures including chest compression, positive pressure ventilation, and airway manipulation. Healthcare providers who perform CPR are at high risk of contracting COVID-19. CPR in patients with suspected or proven COVID-19 must be performed without compromising the safety of healthcare providers. An overview of special considerations.


[Suffering and pleasure in the process of forming multidisciplinary health residents].
to identify situations of pleasure and suffering in the process of training multidisciplinary health resident. qualitative research, developed in the Multiprofessional Residence Program in Health at a university from the south of Brazil. Data was collected in 2013 through focus groups with nine residents, and analyzed according to a thematic analysis. The situations of suffering were stimulated by negative situations undergone by the health workers such as difficulties in participating in other professional training activities, excessive number of activities the residents commit to as health workers, lack of knowledge and hindered integration in the areas of Residency. The situations of pleasure were a result of the multiprofessional activities developed and the resident's larning possibility. The situations of pleasure and suffering identified can help in the planning of institutional actions that contribute to a professional training process and the overall wellbeing of the residents.


An alternative method for serum protein depletion/enrichment by precipitation at mildly acidic pH values and low ionic strength.
Serum proteome analysis is severely hampered by the extreme dynamic range of protein concentrations, but tools for the specific depletion of highly abundant serum proteins lack for most farm and companion animals. A well-established alternative strategy to reduce the dynamic range of plasma protein concentrations, treatment with combinatorial peptide ligand libraries (CPLL), is generally applicable but requires large amounts of sample. Therefore, additional depletion/enrichment protocols for plasma and serum samples from animals are desirable. In this respect, we have tested a protein precipitate that formed after withdrawal of salt from human, bovine, or porcine serum at pH 4.2. The bovine sample was composed of over 300 proteins making it a potential source for biomarker discovery. Precipitation was highly reproducible and the concentrations of albumin and other highly abundant serum proteins were strongly reduced. In comparison to the CPLL treatment, precipitation did not introduce any selection bias based on hydrophathy or pI. However, the composition of both preparations was partially complementary. Salt withdrawal at pH 4.2 is suggested as additional depletion/enrichment strategy for serum samples. Also, we point out that the removal of precipitates from serum samples under the described conditions bears the risk of losing a valuable protein fraction.


The effects of deep abdominal muscle strengthening exercises on respiratory function and lumbar stability.
[Purpose] The purpose of this study was to examine the effects of deep abdominal muscle strengthening exercises on respiratory function and lumbar stability. [Subjects] From among 120 male and female students, 22 whose thoraxes opened no more than 5 cm during inspiration and expiration and whose forced expiratory flow rates were around 300 m/L were recruited. The subjects were randomly divided into an experimental group of eleven, who performed deep abdominal muscle strengthening exercises, and a control group of eleven, who received no particular intervention. [Methods] The subjects were instructed to perform normal breathing in the hook-lying position. They were then directed to hold their breath for ten seconds at the end of inspiration. Ten repetitions of this breathing comprised a set of respiratory training, and a total of five sets were performed by the subjects. [Results] Deep abdominal muscle training was effective at enhancing respiratory function and lumbar stabilization. [Conclusion] The clinical application of deep abdominal muscle strengthening exercises along with lumbar stabilization exercises should be effective for lower back pain patients in need of lumbar stabilization.


Preconception stress, birth weight, and birth weight disparities among US women.
We examined the impact of preconception acute and chronic stressors on offspring birth weight and racial/ethnic birth weight disparities. We included birth weights for singleton live first (n = 3512) and second (n = 1901) births to White, Mexican-origin Latina, other-origin Latina, and Black women reported at wave IV of the National Longitudinal Study of Adolescent Health (2007-2008; ages 24-32 years). We generated factor scores for preconception acute and chronic stressors from wave I (1994-1995; ages 11-19 years) or wave III (2001-2002; ages 18-26 years) for the same cohort of women. Linear regression models indicated that chronic stressors, but not acute stressors, were inversely associated with birth weight for both first and second births (b = -192; 95% confidence interval = -270, -113; and b = -180; 95% confidence interval = -315, -45, respectively), and partially explained the disparities in birth weight between the minority racial/ethnic groups and Whites. Preconception chronic stressors contribute to restricted birth weight and to racial/ethnic birth weight disparities.


Receptor-mediated changes at the myristoylated amino terminus of Galpha(il) proteins.
G protein-coupled receptors (GPCRs) catalyze nucleotide release in heterotrimeric G proteins, the slow step in G protein activation. G i/o family proteins are permanently, cotranslationally myristoylated at the extreme amino terminus. While myristoylation of the amino terminus has long been known to aid in anchoring G i proteins to the membrane, the role of myristoylation with regard to interaction with activated receptors is not known. Previous studies have characterized activation-dependent changes in the amino terminus of Galpha proteins in solution [Medkova, M. (2002) Biochemistry 41, 9963-9972; Preininger, A. M. (2003) Biochemistry 42, 7931-7941], but changes in the environment of specific residues within the Galpha i1 amino terminus during receptor-mediated G i activation have not been reported. Using site-specific fluorescence labeling of individual residues along a stretch of the Galpha il amino terminus, we found specific changes in the environment of these residues upon interaction with the activated receptor and following GTPgammaS binding. These changes map to a distinct surface of the amino-terminal helix opposite the Gbetagamma binding interface. The receptor-dependent fluorescence changes are consistent with a myristoylated amino terminus in the proximity of the membrane and/or receptor. Myristoylation affects both the rate and intensity of receptor activation-dependent changes detected at several residues along the amino terminus (with no significant effect on the rate of receptor-mediated GTPgammaS binding). This work demonstrates that the myristoylated amino terminus of Galpha il proteins undergoes receptor-mediated changes during the dynamic process of G protein signaling.


Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects.
Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.


Compartmentation of alpha 2-adrenergic receptors in human erythroleukemia (HEL) cells.
We have identified alpha 2-adrenergic receptors on human erythroleukemia (HEL) cells, a suspension-grown cell line related to human platelets. properties of receptors were assessed in intact cells by binding of the antagonist [3H]yohimbine and by inhibition of cAMP accumulation. [3H]Yohimbine labeled 5900 +/- 2100 receptors/cell with a Kd of 3.6 +/- 0.9 nM (n = 7). alpha 2-Adrenergic receptors were potently coupled to inhibition of adenylate cyclase, with EC50 values for epinephrine, UK-14,304, and p-aminoclonidine in the low nM range. Treatment of cells with pertussis toxin abolished this response. In radioligand binding studies with membrane preparations [3H]yohimbine and [3H]UK-14,304 bound to the same number of sites (71 versus 69 fmol/mg of protein), and epinephrine competed for [3H]yohimbine binding in a biphasic manner. After addition of GTP, no high affinity [3H]UK-14,304 binding was detected, and epinephrine competed for [3H]yohimbine binding with lower affinity at both 4 degrees and 37 degrees. In studies with intact cells, we detected no specific binding of [3H]UK-14,304 at either 37 degrees or 4 degrees. At 37 degrees, epinephrine competed for all [3H]yohimbine binding sites with a low apparent affinity (Ki = 21 microM), whereas at 4 degrees epinephrine (up to 1 mM) was able to compete for only 59 +/- 13% of [3H]yohimbine-binding sites. The potency of epinephrine in competing for [3H]yohimbine sites in intact cells at 4 degrees was greater than at 37 degrees (Ki = 1 microM) and was similar to that observed with membranes in the presence of GTP. We hypothesize that sites not detectable by epinephrine at 4 degrees are sequestered within the cell. Treatment of HEL cells with pertussis toxin reduced the proportion of receptors on the surface from 51 +/- 12% to 23 +/- 7% (n = 3, p less than 0.05) of the total sites. Treatment of HEL cells with epinephrine (100 microM, 1 hr) reduced the cell surface component to 25 +/- 8% (n = 3) of the total sites. This treatment was not accompanied by significant desensitization of the ability of epinephrine to inhibit cAMP accumulation. We conclude that alpha 2-adrenergic receptors exist in more than one compartment in HEL cells and that interaction of receptors with a guanine nucleotide-binding protein or with agonist may regulate this compartmentation. These cells provide a new model system for the study of expression and metabolism of alpha 2-adrenergic receptors.


Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die.
Apoptosis after growth factor withdrawal or drug treatment is associated with mitochondrial cytochrome c release and activation of Apaf-1 and caspase-9. To determine whether loss of Apaf-1, caspase-2, and caspase-9 prevented death of factor-starved cells, allowing them to proliferate when growth factor was returned, we generated IL-3-dependent myeloid lines from gene-deleted mice. Long after growth factor removal, cells lacking Apaf-1, caspase-9 or both caspase-9 and caspase-2 appeared healthy, retained intact plasma membranes, and did not expose phosphatidylserine. However, release of cytochrome c still occurred, and they failed to form clones when IL-3 was restored. Cells lacking caspase-2 alone had no survival advantage. Therefore, Apaf-1, caspase-2, and caspase-9 are not required for programmed cell death of factor-dependent cells, but merely affect its rate. In contrast, transfection with Bcl-2 provided long-term, clonogenic protection, and could act independently of the apoptosome. Unlike expression of Bcl-2, loss of Apaf-1, caspase-2, or caspase-9 would therefore be unlikely to enhance the survival of cancer cells.


Congenital pouch colon in girls: Genitourinary abnormalities and their management.
To discuss the assessment and management of genitourinary (GU) tract abnormalities in 21 girls with Types I-III congenital pouch colon (CPC), studied over a period of 10 years. Assessment included clinical and radiological assessment, examination under anesthesia (EUA), endoscopy of the lower GU tract, and evaluation of the surgical findings, operative procedures for the GU anomalies, and the results of management. Initial examination of the external genitalia showed a "clover-leaf" appearance (n = 6) and a single perineal opening (n = 6). In 9 patients, the openings of the urethra and double vagina were seen, of which a vestibular fistula was seen in 5 and an anterior perineal fistula in 1. Seventeen patients (81%) had urinary incontinence (UI) - partial in 10, and complete in 7. Renal function tests, X-ray sacrum, and abdominal US were normal in all patients. Micturating cystourethrogram (n = 9) showed a wide, bladder neck incompetence (BNI) with reduced bladder capacity in seven patients. EUA and endoscopy revealed a septate vagina in all patients and the urethral opening at a "high" position (n = 14) or at a relatively normal or "low" position (n = 7). In 8 patients, the intervaginal septum was thick and fleshy. Endoscopy showed a short, wide urethra, an open incompetent bladder neck, poorly developed trigone, and reduced bladder capacity in the patients with UI. The fistula from the colonic pouch opened in the proximal urethra (n = 4), high in the vestibule (n = 3), low in the vestibule (n = 8), perineum just posterior to the vestibule (n = 1), and undetermined (n = 5). Vaginoscopy (n = 8) showed normal cervices in all and cervical mucus in 4 patients. The subtypes of CPC were Type I CPC (n = 4), Type II CPC (n = 16), and Type III CPC (n = 1). All 21 patients had uterus didelphys. In four patients with UI, during tubular colorraphy, a segment of the colonic pouch was preserved for later bladder augmentation if required. A Young-Dees bladder-neck repair (BNR) was performed in four older girls for treatment of UI, with marked improvement in urinary continence in two girls, some improvement in one girl with complete urinary incontinence, and minimal improvement in one child. Division of the intervaginal septum was performed in three girls. GU abnormalities in girls with CPC need to be assessed and managed by a tailored protocol. UI is frequent, and its correction may require BNR. A segment of the colonic pouch can be preserved for possible future bladder augmentation. All girls have a septate vagina, often widely separated, and uterus didelphys. Gynecologic assessment and monitoring is required throughout adult life. Considering the wide opening of the vestibule, surgical management of the urogenital component by division of the intervaginal septum and if required, the vagino-fistula septum on each side results in a normal or a hypospadiac urethral opening and an adequate vaginal inlet.


Targeted integration and removal of transgenes in hybrid aspen (Populus tremula L. x P. tremuloides Michx.) using site-specific recombination systems.
Two site-specific recombination systems, Cre/lox and FLP/FRT, were tested for marker gene removal and targeted gene transfer in a model tree system. A hybrid aspen clone (Populus tremula x Populus tremuloides) was co-transformed with plasmids containing either the FLP or the Cre recombinase, both under control of a heat-inducible promoter (HSP, Gmhsp17.5-E from soybean) flanked by the two recognition sites (FRT or lox). Molecular investigations of heat-shock treated Cre or FLP transgenic lines indicate excision of inserts between the two recognition sites. Further, a site-specific recombination at the FRT sites leading to targeted integration of a fragment could be demonstrated for the FLP/FRT system. Transgenic aspen carrying two constructs (each with different genes between the FRT sites) revealed (i) excision of both fragments between the FRT sites, and (ii) targeted integration of the fragment from the second construct exactly at the former position of the fragment in the first construct. These results indicate the usefulness of the two site-specific recombination systems in the tree species Populus. Combining both site-specific recombination systems, a strategy is suggested for targeted transgene transfer and removal of antibiotic marker genes.


Moderators of effects of motivational enhancements to cognitive behavioral therapy.
Patient treatment matching hypotheses were tested for substance users randomly assigned to a group cognitive behavioral therapy (CBT; n= 114) or a group motivational intervention (GMI; n= 116). Treatment was scheduled twice weekly for 10 weeks. Using a patient attribute by treatment interaction design with a 15-week follow-up, the study predicted that alexithymia, antisocial personality disorder (ASPD), and network support for alcohol and drug use would be associated with less substance use for CBT subjects and that hostility and lower treatment motivation would be associated with less substance use for GMI subjects. Three of the hypothesized moderators were empirically supported: alexithymia, network support for alcohol, and ASPD. Results indicate the use of assessing specific patient attributes to better inform treatment recommendations.


Positive correlation of CTG expansion and pharyngoesophageal alterations in myotonic dystrophy patients.
Alteration of the pharyngoesophageal musculature is a common finding in patients with myotonic dystrophy (MD), regardless of the presence of dysphagia. The aim of the present study was to determine whether a specific pattern of swallowing abnormalities could be identified in MD patients, and the possible correlation with the size of CTG repeats. Fifteen MD patients, 8 of whom were asymptomatic for dysphagia, underwent a videofluoroscopic study of swallowing. Alterations of the pharyngoesophageal phase of swallowing were detected in 12 of 15 patients, 6 without clinical evidence of dysphagia. Incomplete relaxation of the upper esophageal sphincter (UES) and esophageal hypotonia were the most common alterations. We found a significant correlation between the number of radiological alterations and the size of CTG repeats. A typical radiological pattern of swallowing has also been identified. The role of videofluoroscopy in evaluation of MD patients is briefly discussed.


Auto-immune hemolytic anemia in two horses.
Two cases of Auto-immune hemolytic anemia (AHA) in the horse are described. The pathogenesis of AHA in man is related to the findings in the horses. Besides from routine hematological and biochemical investigations specific data were obtained from the erythrocyte osmotic fragility test, the Coombs test, the serum haptoglobulin level and the cold agglutinin test. The first patient, a six month old Dutch standardbred colt, probably suffered from an acute attack of cold-induced hemoglobinuria with severe anemia and acronecrosis of the tops of both ears and of several parts of the skin that had been in close contact with the cold floor. The second patient, a nine years old Friesian mare, showed a type of AHA resembling the acute hemolyte type of cold agglutinin disease in man. This patient had a clear septicemic picture, extensive bacteriological examination, however, was negative.


Chemical Reduction of Nitrate by Zero-Valent Iron: Shrinking-Core versus Surface Kinetics Models.
Zero valent iron (ZVI) is being used in permeable reactive barriers (PRB) for the removal of oxidant contaminants, from nitrate to chlorinated organics. A sound design of these barriers requires a good understanding of kinetics. Here we present a study of the kinetics of nitrate reduction under relatively low values of pH, from 2 to 4.5. We use a particle size of 0.42 mm, which is within the recommended size for PRBs (0.2 mm to 2.0 mm). In order to avoid possible mass-transfer limitations, a well-stirred reactor coupled with a fluidized bed reactor was used. The experiments were performed at constant pH values using a pH controller that allows to accurately track the amount of acid added. Since the reduction of H + to H 2 by the oxidation of ZVI will always be present for these pH values, blank experiments (without nitrate) were performed and the rate of this H + reduction obtained. This rate of reduction was studied using three kinetic models: a regular empirical one, the Shrinking-Core Model (SCM), and the Surface Kinetics Model (SKM). The best performance was obtained from the SKM model. Therefore, this model was also used to study the results for the nitrate reduction, also with satisfactory results. In both cases, some assumptions are introduced to maintain a moderate number of fitting parameters.


General Strategy for the Design of DNA Coding Sequences Applied to Nanoparticle Assembly.
The DNA-directed assembly of nano-objects has been the subject of many recent studies as a means to construct advanced nanomaterial architectures. Although much experimental in silico work has been presented and discussed, there has been no in-depth consideration of the proper design of single-strand sticky termination of DNA sequences, noted as ssST, which is important in avoiding self-folding within one DNA strand, unwanted strand-to-strand interaction, and mismatching. In this work, a new comprehensive and computationally efficient optimization algorithm is presented for the construction of all possible DNA sequences that specifically prevents these issues. This optimization procedure is also effective when a spacer section is used, typically repeated sequences of thymine or adenine placed between the ssST and the nano-object, to address the most conventional experimental protocols. We systematically discuss the fundamental statistics of DNA sequences considering complementarities limited to two (or three) adjacent pairs to avoid self-folding and hybridization of identical strands due to unwanted complements and mismatching. The optimized DNA sequences can reach maximum lengths of 9 to 34 bases depending on the level of applied constraints. The thermodynamic properties of the allowed sequences are used to develop a ranking for each design. For instance, we show that the maximum melting temperature saturates with 14 bases under typical solvation and concentration conditions. Thus, DNA ssST with optimized sequences are developed for segments ranging from 4 to 40 bases, providing a very useful guide for all technological protocols. An experimental test is presented and discussed using the aggregation of Al and CuO nanoparticles and is shown to validate and illustrate the importance of the proposed DNA coding sequence optimization.


The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography.
This study sought to determine the accuracy of plaque pattern assessment by coronary computed tomography angiography (CCTA) to differentiate between early and advanced atherosclerotic lesions as defined by histology. A ringlike attenuation pattern of coronary atherosclerotic plaques termed as napkin-ring sign (NRS) was described in CCTA of patients who had acute coronary syndrome. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local ethics committees was obtained. We investigated 21 coronary arteries of 7 donor hearts. Overall, 611 histological sections were obtained and coregistered with CCTA images. The CCTA cross sections were read in random order for conventional plaque categories (noncalcified [NCP], mixed [MP], calcified [CP]) and plaque patterns (homogenous, heterogeneous with no napkin-ring sign [non-NRS], and heterogeneous with NRS). No plaque was detected in 134 (21.9%), NCP in 254 (41.6%), MP in 191 (31.3%), and CP in 32 (5.2%) CCTA cross sections. The NCP and MP were further classified into homogenous plaques (n = 207, 46.5%), non-NRS plaques (n = 200, 44.9%), and NRS plaques (n = 38, 8.6%). The specificities of NCP and MP to identify advanced lesions were moderate (57.9%, 95% confidence interval [CI]: 50.1% to 65.6%, and 72.1%, 95% CI: 64.7% to 79.4%, respectively), which were similar to the homogenous and heterogeneous plaques (62.6%, 95% CI: 54.8% to 70.3%, and 67.3%, 95% CI: 58.6% to 76.1%, respectively). In contrast, the specificity of the NRS to identify advanced lesions was excellent (98.9%, 95% CI: 97.6% to 100%). The diagnostic performance of the pattern-based scheme to identify advanced lesions was significantly better than that of the conventional plaque scheme (area under the curve: 0.761 vs. 0.678, respectively; p = 0.001). The assessment of the plaque pattern improves diagnostic accuracy of CCTA to identify advanced atherosclerotic lesions. The CCTA finding of NRS has a high specificity and high positive predictive value for the presence of advanced lesions.


Selenium distribution and speciation in waters of pristine alpine lakes from central-western Pyrenees (France-Spain).
The speciation of both redox reactive and volatile selenium (Se) compounds, barely reported in pristine aquatic environments, has never been investigated in remote alpine lakes, considered as sensitive ecosystems to detect the effect of global change. This work presents an integrated investigation on Se distribution and speciation conducted in 20 high altitude pristine lakes from the central-western Pyrenees. Five seasonal sampling campaigns were carried out after snowmelt (June/July) and in early fall (October) for the period 2017-2019. Concentrations of total dissolved Se (TDSe) ranged from 7 to 78 ng L-1, with selenate being ubiquitously observed in most cases (median of 61% of TDSe). Selenite was only occasionally detected up to 4 ng L-1, therefore a fraction of TDSe was presumably in the forms of elemental Se(0) and/or selenides. Depth profiles obtained in different lakes showed the occurrence of such Se(-II, 0) pools in bottom hypoxic to anoxic waters. The production of volatile Se compounds presented a low median total concentration (TVSe) of 33 pg L-1 (range 3-120 pg L-1), mainly in the form of dimethylselenide in subsurface samples (median of 82% of TVSe). The Se concentration in lake waters was significantly correlated with the sulphate concentration (ρ = 0.93, p < 0.0001), demonstrating that it is influenced by erosion and dissolution of Se and S-enriched parent bedrocks. In addition, for Se depleted alpine lake-bedrock systems, long-range transport and wet atmospheric depositions represent a major source of Se for lake waters.


Barriers, enablers and initiatives for uptake of advance care planning in general practice: a systematic review and critical interpretive synthesis.
How advance care planning (ACP) is conceptualised in Australia including when, where and how ACP is best initiated, is unclear. It has been suggested that healthcare delivered in general practice provides an optimal setting for initiation of ACP discussions but uptake remains low. This systematic review and critical interpretive synthesis sought to answer two questions: (1) What are the barriers and enablers to uptake of ACP in general practice? (2) What initiatives have been used to increase uptake of ACP in general practice? A systematic review and critical interpretive synthesis of the peer-reviewed literature was undertaken. A socioecological framework was used to interpret and map the literature across four contextual levels of influence including individual, interpersonal, provider and system levels within a general practice setting. Primary care general practice settings DATA SOURCES: Searches were undertaken from inception to July 2019 across Ovid Medline, Cumulative Index to Nursing and Allied Health Literature, Scopus, ProQuest and Cochrane Library of systematic reviews. The search yielded 4883 non-duplicate studies which were reduced to 54 studies for synthesis. Year of publication ranged from 1991 to 2019 and represented research from nine countries. Review findings identified a diverse and disaggregated body of ACP literature describing barriers and enablers to ACP in general practice, and interventions testing single or multiple mechanisms to improve ACP generally without explicit consideration for level of influence. There was a lack of cohesive guidance in shaping effective ACP interventions and some early indications of structured approaches emerging. Findings from this review present an opportunity to strategically apply the ACP research evidence across targeted levels of influence, and with an understanding of mediators and moderators to inform the design of new and enhanced ACP models of care in general practice. CRD42018088838.


Sentinel lymph node biopsy for gastric cancer: Where do we stand?
Development of sentinel node navigation surgery (SNNS) and advances in minimally invasive surgical techniques have greatly shaped the modern day approach to gastric cancer surgery. An extensive body of knowledge now exists on this type of clinical application but is principally composed of single institute studies. Certain dye tracers, such as isosulfan blue or patent blue violet, have been widely utilized with a notable amount of success; however, indocyanine green is gaining popularity. The double tracer method, a synchronized use of dye and radio-isotope tracers, appears to be superior to any of the dyes alone. In the meantime, the concepts of infrared ray electronic endoscopy, florescence imaging, nanoparticles and near-infrared technology are emerging as particularly promising alternative techniques. Hematoxylin and eosin staining remains the main method for the detection of sentinel lymph node (SLN) metastases. Several specialized centers have begun to employ immunohistochemical staining for this type of clinical analysis but the equipment costs involving the associated ultra-rapid processing systems is limiting its widespread application. Laparoscopic function-preserving resection of primary tumor from the stomach in conjunction with lymphatic basin dissection navigated by SLN identification represents the current paramount of SNNS for early gastric cancer. Patients with cT3 stage or higher still require standard D(2) dissection.


[Follow-up and long-term treatment of infections caused by human cytomegalovirus in 3 patients with AIDS].
We report the follow-up and treatment of HCMV infections in three patients with AIDS. The patients, affected by HCMV retinitis, have been followed 24, 12 and 6 months respectively. The antiviral treatment was based on the DHPG administration which was substituted in one case of resistance to DHPG with Foscarnet. In the follow-up period, virological tests have been performed to detect the presence of the HCMV antigenemia/viremia. The results show that, to avoid the progression of the retinitis, the antiviral treatment must not be stopped or discontinued. DHPG and Foscarnet were able to limit the infection to the eye and were well tolerated. In the HCMV-infected patients, the continuous monitoring of the antigenemia/viremia is of main importance to follow the clinical and therapeutical course of the disease.


Chromatin motion in interphase nuclei, its modulation and its potential role in gene expression.
Nuclear Rotation (NR) refers to the rotatory motion of nuclei in cells in vitro, a motion measured as the displacement of nucleoli over time. NR occurs in cycling cells; however, its observation in neurons indicates that mechanisms related to mitosis are not a prerequisite. We have shown that NR includes motion of chromatin domains in addition to those represented by nucleoli, that movements are saltatory, with periods of stationarity and reversal of direction. The observation that NR occurs independently of concurrent motion of juxtanuclear, cytoplasmic structures, leads to the concept of a stationary outer nuclear membrane. Although traditionally perceived as rotation in a two-dimensional plane, NR represents a complex, three-dimensional motion of chromatin within the interphase nucleus, with nucleoli and DAPI-stained, fluorescent chromatin domains describing curvilinear trajectories extending throughout the nucleus. Based upon evidence that the rate of this motion changes with metabolic demands, we have postulated that NR functions in gene expression, by transposing chromatin domains to be transcribed to specific nuclear compartments. In a test of this hypothesis, Nerve Growth Factor (NGF), which alters gene expression, increased NR at a time post-NGF coincident with increased activity of RNA polymerases, while GABA, also postulated to alter transcription, increased NR with near instantaneous shifts of nucleolar positions within the nuclear space. The calcium ionophore A23187 and the chelator EGTA, agents which redistribute calcium (Ca), also increased NR, while additional Ca, in presence of EGTA, returned NR to control rates. It is difficult to link NR with the action of agents which alter transcription or ion balance. Nevertheless, in support of our hypothesis, available evidence indicates that agents which alter gene expression, alter NR and that they do so, probably through calcium dependent mechanisms.


Goal attribution without agency cues: the perception of 'pure reason' in infancy.
The proper domain of naive psychological reasoning is human action and human mental states but such reasoning is frequently applied to non-human phenomena as well. The studies reported in this paper test the validity of the currently widespread belief that this tendency is rooted in the fact that naive psychological reasoning is initially restricted to, and triggered by, the perception of self-initiated movement of agents. We report three habituation experiments which examine the necessary conditions under which infants invoke a psychological principle, namely the principle of rational action, to interpret behaviour as goal directed action. Experiment 1 revealed that the principle of rational action already operates at 9 (but not yet at 6) months of age. Experiment 2 demonstrated that perceptual cues indicating agency, such as self-propulsion, are not necessary prerequisites for interpreting behaviour in terms of the principle of rational action. Experiment 3 confirmed that this effect cannot be attributed to generalisation of agentive properties from one object to another. These results suggest that the domain of naive psychology is initially defined only by the applicability of its core principles and its ontology is not restricted to (featurally identified) object kinds such as persons, animates, or agents. We argue that in its initial state naive psychological reasoning is not a cue-based but a principle-based theory.


Intestinal blood loss during cow milk feeding in older infants: quantitative measurements.
To determine the response, in terms of fecal hemoglobin excretion and clinical symptoms, of normal 9 1/2-month-old infants to being fed cow milk. Longitudinal (before-after) trial in which each infant was fed formula for 1 month (baseline) followed by 3 months during which cow milk was fed. Healthy infants living in Iowa City, Iowa, a town with a population of about 60,000. Hemoglobin concentration in spot stools, 96-hour quantitative fecal hemoglobin excretion, stool characteristics, feeding-related behaviors, and iron nutritional status. Fecal hemoglobin concentration during formula feeding (baseline) was higher than previously observed in younger infants. Nine of 31 infants responded to cow milk feeding with increased fecal hemoglobin concentration. Fecal hemoglobin concentration (mean +/- SD) of the 9 responders rose from 1,395 +/- 856 microg/g of dry stool (baseline) to 2,711 +/- 1,732 microg/g of dry stool (P=.01). The response rate (29%) was similar to that in younger infants, but the intensity of the response was much less. Quantitative hemoglobin excretion was in general agreement with estimates based on spot stool hemoglobin concentrations. Cow milk feeding was not associated with recognizable changes in stool characteristics, nor were there clinical signs related to fecal blood loss. Iron status was similar, except that after 3 months of cow milk feeding responders showed lower (P= .047) ferritin concentrations than nonresponders. Cow milk-induced blood loss is present in 9 1/2-month-old infants but is of such low intensity that its clinical significance seems questionable. Nevertheless, infants without cow milk-induced blood loss were in better iron nutritional status than infants who showed blood loss.


The Idea of Volk and the Origins of Völkisch Research, 1800-1930s.
Völkisch research was a phenomenon in the social sciences and humanities that aimed to describe and cultivate the Volk, conceived broadly as a group united by some pre-existing or transcendental bond. Studies of this research complex have thus far been dominated by questions related to its close affiliation with the Nazi regime, but much remains unknown about how its longer-term development related to the transformation of science or to conceptual changes in the notion of Volk. This article addresses these questions by tracing the ways in which the idea of Volk transformed through accommodation with shifting scientific norms.


Neurotransmitter modulation of calcium channels in rat sympathetic neurons.
Adrenergic, cholinergic, and a variety of peptide neurotransmitters are known to modulate Ca currents in peripheral neurons. Using a protocol that allows for simultaneous assessment of effects on dihydropyridine (DHP)-sensitive and DHP-insensitive current components, we compared the actions of norepinephrine (NE), bethanechol (BeCh), and neuropeptide Y (NPY) on Ca currents in neonatal rat superior cervical ganglion neurons. Here, we show that these transmitters selectively depress the activity of DHP-insensitive Ca channels. Intracellular application of GTP-gamma-S, an activator of GTP-binding proteins, also exclusively affected the DHP-insensitive current, whereas 1,2-oleoylacetylglycerol (OAG), a protein kinase C (PKC) activator, depressed both the DHP-sensitive and DHP-insensitive currents. Pertussis toxin interrupted the coupling between NE and its effector, whereas three different inhibitors of PKC did not. Thus, we confirmed that the selective actions of the transmitters on Ca current appear to be mediated via GTP-binding proteins, but we found no evidence for direct involvement of PKC and conclude that the observed actions of OAG are distinct from those mediated by the neurotransmitters studied.


Habits and Reflective Processes in COVID-19 Transmission-reducing Behaviors: Examining Theoretical Predictions in a Representative Sample of the Population of Scotland.
Based on theory, COVID-19 transmission-reducing behaviors (TRBs) should become habitual because of their frequent performance. Habits have been hypothesized to develop through reflective processes and, to act in conjunction with them. We investigated the existence, development, and consequences of TRB habits, for physical distancing, handwashing, and wearing face coverings. A representative sample of the Scottish population (N = 1,003) was interviewed by a commercial polling company in August-October 2020 and half were re-interviewed later. Measures included adherence, habit, personal routine tendency, reflective processes, and action control for three TRBs. Data were analyzed using general linear modeling, regression, and mediation analyses. Handwashing was most habitual; only face covering became more habitual over time. Routine tendencies predicted TRB habits, and adherence to handwashing and physical distancing. Those reporting greater habits reported better adherence, for physical distancing and handwashing, and this remained true after controlling for previous adherence. Reflective and habit processes independently predicted adherence for physical distancing and handwashing; only reflective processes were independently predictive for face covering. The relationship between planning and forgetting and adherence was partly direct, and partly mediated by habit. The results confirm hypotheses from habit theory including the role of repetition and of personal routine tendency in developing habits. They are consistent with dual processing theory in finding that both reflective and habit processes predict adherence to TRBs. Action planning partly mediated the relation between reflective processes and adherence. The COVID-19 pandemic has enabled the testing and confirmation of several theoretical hypotheses about habit processes in the enactment of TRBs.


Detection of multiple cephalosporin-resistant Escherichia coli from a cattle fecal sample in Great Britain.
We describe the isolation of multiple cephalosporin-resistant Escherichia coli from cattle feces collected from animals at slaughter in Great Britain. Six E. coli strains were isolated with distinct XbaI pulsed-field gel electrophoresis (PFGE) profiles and different mechanisms of cephalosporin resistance from a single fecal sample. Two of these strains were found to contain conjugative plasmids conferring resistance to extended-spectrum cephalosporins that were indistinguishable from each other by restriction endonuclease digestion. Sequence analysis of the plasmid-encoded ampC showed that they were identical to bla(CMY-2), previously described in multiple-drug-resistant Salmonella and E. coli from animals in other parts of the world. DNA sequence analysis of the chromosomal ampC promoter regions for three cephalosporin-resistant strains lacking CMY-2 was determined. Several mutations were detected in the isolates tested including changes at positions -42 and -32, which are known to increase promoter strength. This report represents the first isolation of E. coli containing bla(CMY-2) from cattle in Great Britain, and, also to our knowledge, the first demonstration of multiple cephalosporin-resistant strains in a single animal.


A KDEL-tagged monoclonal antibody is efficiently retained in the endoplasmic reticulum in leaves, but is both partially secreted and sorted to protein storage vacuoles in seeds.
Transgenic plants are attractive biological systems for the large-scale production of pharmaceutical proteins. In particular, seeds offer special advantages, such as ease of handling and long-term stable storage. Nevertheless, most of the studies of the expression of antibodies in plants have been performed in leaves. We report the expression of a secreted (sec-Ab) or KDEL-tagged (Ab-KDEL) mutant of the 14D9 monoclonal antibody in transgenic tobacco leaves and seeds. Although the KDEL sequence has little effect on the accumulation of the antibody in leaves, it leads to a higher antibody yield in seeds. sec-Ab(Leaf) purified from leaf contains complex N-glycans, including Lewis(a) epitopes, as typically found in extracellular glycoproteins. In contrast, Ab-KDEL(Leaf) bears only high-mannose-type oligosaccharides (mostly Man 7 and 8) consistent with an efficient endoplasmic reticulum (ER) retention/cis-Golgi retrieval of the antibody. sec-Ab and Ab-KDEL gamma chains purified from seeds are cleaved by proteases and contain complex N-glycans indicating maturation in the late Golgi compartments. Consistent with glycosylation of the protein, Ab-KDEL(Seed) was partially secreted and sorted to protein storage vacuoles (PSVs) in seeds and not found in the ER. This dual targeting may be due to KDEL-mediated targeting to the PSV and to a partial saturation of the vacuolar sorting machinery. Taken together, our results reveal important differences in the ER retention and vacuolar sorting machinery between leaves and seeds. In addition, we demonstrate that a plant-made antibody with triantennary high-mannose-type N-glycans has similar Fab functionality to its counterpart with biantennary complex N-glycans, but the former antibody interacts with protein A in a stronger manner and is more immunogenic than the latter. Such differences could be related to a variable immunoglobulin G (IgG)-Fc folding that would depend on the size of the N-glycan.


THE EFFECT OF PHYSICAL TRAINING ON THE LOCOMOTOR APPARATUS IN ELDERLY PEOPLE.
Physiological changes taking place on the locomotive apparatus as a result of aging, such as muscular mass loss, body balance loss, reduced bone mass and osteoarthrosis cause limitations to the daily activities of elderly people, compromising their quality of life and making them weaker and dependent. Aged people who regularly practice physical activities have a higher level of functional independence and a better quality of life than the sedentary ones. This article addresses the key physiological changes with aging and provides a review of current literature about the effects of physical exercises on the locomotive apparatus of elderly individuals, specifying the best ways to prescribe physical exercises to this age group.


Sexuality and spinal cord injury: some psychosocial considerations.
Sexual functioning in patients with spinal cord injury has been the subject of considerable research interest in recent years. There have been numerous studies of both physiological and psychological aspects of sexual functioning, but only the physiological part of this literature has been organized in a systematic fashion. This paper reviews 33 articles that deal mainly or exclusively with psychosocial aspects of sexuality. It is observed that the psychosocial literature in this area is relatively diffuse, dealing with concepts that are inadequately specified and validated.


BETA-CAROTENE: THERMAL DEGRADATION.
Thermal treatment of crystalline beta-carotene (240 degrees C in a vacuum) results in the formation of a volatile fraction containing chiefly aromatic hydrocarbons such as toluene, m- and p-xylene, 2,6-dimethylnaphthalene, and ionene. These compounds have been identified by means of gas-liquid chromatography, infrared spectroscopy, and, in the case of ionene, by additional nuclear magnetic resonance and mass spectroscopy. The principal degradation product is a yellowish-brown, glutinous mass which can be separated by means of preparative thin-layer chromatography in a number of fractions different in molecular weight. The structure of these fractions is not yet clear.


Dose-dependent inhibitory effect of melatonin on carcinogenesis induced by benzo[a]pyrene in mice.
Three-month-old Swiss-derived SHR mice were subcutaneously injected with 2 mg of benzo[a]pyrene (BP) dissolved in 0.1 ml of olive oil. After the injections of the carcinogen two groups of mice were given melatonin with night drinking water at the doses of 2 mg/l or 20 mg/l and one group of mice was not treated with melatonin and served as a PB-control. At the 28th week after the carcinogen administration the experiment was stopped and animals were sacrificed. The results show that melatonin treatment inhibits BP-induced carcinogenesis, decreases the incidence of subcutaneous sarcomas, increases their latency and survival of mice. The malone dialdehyde (MDA) level in the serum of BP-induced tumor-bearing mice was increased by 2.6 times (p < 0.01) and in the tumors was increased by 11.1% (p < 0.01) as compared to intact control mice. Treatment with melatonin significantly decreased the MDA level both in the serum and tumor tissue. The activity of catalase in the serum of BP-induced tumor-bearing mice was increased by 12.1% as compared to the intact control mice (p < 0.01) and was unchanged in the tumor tissue. Treatment with melatonin at the dose of 2 mg/l significantly decreased activity of catalase in the serum (by 31.7%, p < 0.01) and in the tumor tissue (by 2.6 times, p < 0.01) as compared to the animals treated with BP alone. Thus, it wose shown for the first time an inhibitory effect of melatonina on malignancies of mesenchymal origin. Lower dose of melatonin appeared to be more effective in the inhibition of lipid peroxidation and tumorigenesis induced by chemical carcinogen than a higher one.


The fatigue experiences of older Taiwanese women with breast cancer.
This study explored the fatigue experiences in older Taiwanese women with breast cancer. Cancer is a common disease for older people, and breast cancer ranks second in occurrence among all cancers. Fatigue is the most frequently seen symptom, with more than 90% of cancer patients having such experiences. Fatigue may lead to functional dependence, affecting the care and quality of life for this older population. A qualitative design was used in this study. In-depth interviews were conducted with participants being treated at the oncology outpatient department in a teaching hospital in northern Taiwan. Data were collected from November 2006-March 2007. The study included 15 women, aged 65-82, with breast cancer. Analysis of the interviews revealed three themes: factors related to fatigue, interpretation of fatigue and ways to deal with fatigue. The factors related to fatigue arose from treatment, symptom distress and the impact of their emotions. Participants interpreted the fatigue as an inevitable normal reaction, and they were embarrassed to share its occurrence with others. Although fatigue made participants suffer, they found the ways to decrease the feeling of fatigue using psychological adjustments, practical changes and support systems. Facing the multilayered influences from treatments and ageing, older women with breast cancer considered fatigue as a physical and psychological expression. By raising the awareness of fatigue, nurses can help this older population manage or relieve fatigue by controlling symptoms, providing emotional support and making related resources available. The results of this study can enhance the sensitivity and evaluation abilities of nurses in dealing with the cancer-related fatigue in older women with breast cancer.


Genetic inference of the mating system of free-ranging domestic dogs.
Domestication has greatly changed the social and reproductive behavior of dogs relative to that of wild members of the genus Canis, which typically exhibit social monogamy and extended parental care. Unlike a typical gray wolf pack that consists of a single breeding pair and their offspring from multiple seasons, a group of free-ranging dogs (FRDs) can include multiple breeding individuals of both sexes. To understand the consequences of this shift in reproductive behavior, we reconstructed the genetic pedigree of an FRD population and assessed the kinship patterns in social groups, based on genome-wide single-nucleotide polymorphism genotypes. Consistent with behavioral observations, the mating system of the study population was characterized by polygynandry. Instead of the discreet family units observed in wolves, FRDs were linked by a network of kinship relationships that spread across packs. However, we also observed reproduction of the same male-female pairs in multiple seasons, retention of adult offspring in natal packs, and dispersal between neighboring packs-patterns in common with wolves. Although monogamy is the predominant mating system in wolves, polygyny and polyandry are occasionally observed in response to increased food availability. Thus, polygynandry of domestic dogs was likely influenced by the shift in ecological niche from an apex predator to a human commensal.


Hand-held computers in clinical audit: a comparison with established paper and pencil methods.
The performance of hand-held computer terminals was compared with that of paper and pencil data collection methods. The study was carried out on two wards, with a comparative study in the medical audit unit at Rampton Hospital, one of three special hospitals managed by the Special Hospitals Service Authority. These were analysed, focusing on time factors, error rates, ease of use and financial implications. Findings showed that the electronic system saved time, reduced staffing costs and errors and had unit-wide potential. The electronic data collection contributed to a cost-effective and flexible data-processing system for use in auditing.


Shaken, not stirred: mechanical stress testing of an IgG1 antibody.
Protein aggregation is known to occur under different stress conditions and displays a wide variety of morphologies. In this work, the aggregation behavior of a monoclonal antibody (IgG1) was investigated using two different mechanical stress methods namely stirring and shaking at two temperatures, various fill volumes and headspaces and different amounts of polysorbate present in the formulation. The detection of aggregates in terms of size and number was carried out using various analytical techniques including visible particle inspection, turbidity, sub-visible particle analysis, size exclusion chromatography and dynamic light scattering. The data showed that shaking and stirring resulted in different species of aggregates both qualitatively and quantitatively, where stirring was found more stressful than shaking on the IgG1 formulation. Mechanical stress testing performed at 5 and 25 degrees C only showed a difference on samples stressed by shaking and not by stirring. The headspace in the vials had great influence on the stability of the protein formulation when stressed by shaking. The presence of polysorbate had a protective effect on the antibody, however certain polysorbate concentrations even resulted in increased protein aggregation. An array of analytical methods was essential in order to cover the vast aggregate morphologies, which occurred during agitation.


Cultured Human Uveal Melanocytes Express/secrete CXCL1 and CXCL2 Constitutively and Increased by Lipopolysaccharide via Activation of Toll-like Receptor 4.
Purpose: Lipopolysaccharide (LPS) can activate Toll-like receptor 4 (TLR4) and increase the expression of CXCL1 and CXCL2, the potent neutrophils chemoattractants, in various cell types. These effects have not been previously reported in the uveal melanocytes. This study was designed to investigate the effects of LPS on the activation of TLR4 and expression of CXCL1/CXCL2 in cultured human uveal melanocytes and the relevant signal pathways.Methods: Effects of LPS on the expression of TLR4 were tested using real-time PCR, flow cytometry and fluorescence immunostaining. Effects of LPS-induced expression/secretion of CXCL1/CXCL2 were studied using real-time PCR in cell lysates and ELISA in conditioned media of cultured uveal melanocytes. Activated NF-κB and phosphorylated MAPK signals were tested in cells with and without LPS treatment using flow cytometry. Effects of various signal inhibitors on p38, ERK1/2, JNK1/2 and NF-κB on the secretion of CXCL1/CXCL2 were tested by ELISA. The effects of neutralized antibodies of CXCL1/CXCL2 on the severity of LPS-induced uveitis were tested in a mouse model.Results: LPS stimulation increased the expression of TLR4 mRNA and protein in culture uveal melanocytes. Constitutive secretion of CXCL1/CXCL2 was detected in uveal melanocytes and was significantly increased dose- and time-dependently by LPS stimulation. LPS mainly increased the activated NF-κB and phosphorylated JNK1/2. LPS-induced expression of CXCL1/CXCL2 was blocked by NF-κB and JNK1/2 inhibitors. The severity of LPS-induced uveitis was significantly inhibited by neutralizing antibody to CXCL1/CXCL2Conclusions: This is the first report on the LPS-induced expression of CXCL1 and CXCL2 by uveal melanocytes via the activation of TLR4. These results suggest that uveal melanocytes may play a role in the immune reaction that eliminates the invading pathogens. Conversely, an excessive LPS-induced inflammatory reaction may also lead to the development of inflammatory ocular disorders, such as non-infectious uveitis.


Pigmentation and melanocyte supply to the epidermis depend on type XVII collagen.
Genetic deficiency of type XVII collagen (C17), laminin-332 or type VII collagen causes epidermolysis bullosa (EB). Spontaneous correction of the deficiency, also known as revertant mosaicism, is caused by a second somatic mutation that restores protein expression resulting in clinically healthy (revertant) patches surrounded by fragile (mutant) skin. Interestingly, in some patients, patches of revertant skin show hyperpigmentation. To study the possible role of affected proteins in pigmentation and melanocyte distribution, we investigated clinical documentation and skin biopsy specimens of 13 revertant EB patients having correcting mutations in the COL17A1, LAMB3 or COL7A1 genes. Analysis revealed that lack of C17 led to decreased melanin intensity and melanocyte density in the epidermis when compared with the revertant patches. Reversions of LAMB3 and COL7A1 in keratinocytes did not influence clinical pigmentation or density of melanocytes. We conclude that in human skin, melanocyte supply to the epidermis depends on C17 expression in keratinocytes.


Fetal and Maternal Genetic Variants Influencing Neonatal Vitamin D Status.
Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.


Inactivation of soybean trypsin inhibitors and lipoxygenase by high-pressure processing.
Trypsin inhibitors (TIA), one of the antinutritional factors of soy milk, are usually inactivated by heat treatment. In the current study, high-pressure processing (HPP) was evaluated as an alternative for the inactivation of TIA in soy milk. Moreover, the effect of HPP on lipoxygenase (LOX) in whole soybeans and soy milk was studied. For complete LOX inactivation either very high pressures (800 MPa) or a combined temperature/pressure treatment (60 degrees C/600 MPa) was needed. Pressure inactivation of TIA was possible only in combination with elevated temperatures. For TIA inactivation, three process parameters, temperature, time, and pressure, were optimized using experimental design and response surface methodology. A 90% TIA inactivation with treatment times of <2 min can be reached at temperatures between 77 and 90 degrees C and pressures between 750 and 525 MPa.


Student engagement and attendance are central mechanisms interacting with inclusive and equitable quality education: Evidence from Afghanistan and Pakistan.
Despite considerable progress in the field of education science, there is currently no consensus on the components that define inclusive and equitable quality education, how they are articulated with one another, and what are the best interventions to foster inclusive and equitable quality education. Current research investigates separately components of what appears to be a complex dynamic system with feedback interactions. To characterize this system and identify structures that encompass inclusive and equitable quality education, we used a community-based system dynamics approach. This approach hypothesizes that community perceptions of the local school system is essential to define it. We therefore conducted 648 participatory Group Model Building workshops with school stakeholders (children, teachers, parents and members of school management committees) resulting in as many models in 99 schools of Afghanistan and Pakistan. To identify common components across models built by participants in two waves of schools' model building workshops, we applied techniques from multivariate analysis of ecological communities. Even across wide differences in participants' situations and roles in the educational process, their models expressed a common reinforcing feedback loop which connected child inclusive and equitable quality education to two other components: 1) child engagement in and motivation for education, and 2) child attendance. Increases in any of these three components were perceived to drive increases in the others. We also found that child focus on learning was commonly expressed as interacting with this generic structure. Any educational reform should simultaneously and primarily embrace learners' diversity, combine policy principles of ensuring easy equitable access to foster attendance, and promote student interest and engagement in learning through child centered pedagogy and non-discriminatory teaching practices while giving school communities power for implementation.


A new anti-inflammatory drug, proquazone, and ibuprofen in the treatment of degenerative joint disease of the knee (gonarthrosis). A double-blind comparative study.
The therapeutic effect and the tolerance of a new non-steriod anti-inflammatory compound, proquazone, were compared with those of ibuprofen in a double-blind, randomized study on patients with gonarthrosis. Totally 39 patients participated in the study: 19 patients in the proquazone group and 20 patients in the ibuprofen group. The two drugs were given in daily doses of 900 mg and 1200 mg respectively during 3 weeks. In both treatment groups a good result was achieved in more than 70% of the cases, but proquazone seemed to be more effective in reducing swelling and pain of knee. There were more side effects in the proquazone group than in the ibuprofen group, but they were generally mild and disappeared spontaneously. Only one patient in the proquazone group withdrew, because of epigastric discomfort.


Horseshoe lung associated with scimitar syndrome.
Horseshoe lung is a rare congenital anomaly and mostly accompanied by scimitar syndrome. Most aspects of this complex anomaly can be demonstrated via multidetector CT (MDCT). We present two baby girls who had horseshoe lung associated with right lung hypoplasia and scimitar vein. The chest roentgenograms showed displacement of the heart and mediastinum to the right with smaller right lung. Echocardiography revealed dextroposition, secundum atrial septal defect and bilateral slight peripheral pulmonary stenosis in the first case and dextroposition, severe pulmonary hypertension, secundum atrial septal defect and tricuspid regurgitation in the other one. On thoracic MDCT, the right lung and pulmonary artery were hypoplastic with cardiomediastinal shift to the right. There was an abnormal right pulmonary vein draining into the inferior vena cava on the lower zone of the right lung (scimitar vein). The posterobasal portions of the both lungs were fused through a midline isthmus behind the heart.


Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis.
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host's OS response.


[Neurobiology of neglect: implications for new therapeutic strategies].
Neglect is characterised by a clinically relevant impairment of spatial perception and awareness observed after focal brain damage. The neglect-specific deficit in responding to contralesional stimuli in various sensory modalities is most commonly explained by impairments of spatial attention, spatial working memory, impaired spatial reference frames and lateralised movement initiation. Many neglect interventions have been developed in the last decades to alleviate symptoms of neglect in stroke patients. However, hardly any of these methods has been proven to significantly ameliorate the patient's deficits in everyday activities. Thus, the identification of predictors for recovery of function and of the success of rehabilitative measures provides a major challenge for future research on neglect.


The Response of the Tongue Epithelial on Cigarette Smoke Exposure as a Risk Factor for Oral Cancer Development.
The aim of this study is to analyze the tongue epithelial response to cigarette smoke exposure on a number of macrophages, lymphocytes, plasma cells, and matrix metalloproteinase 9 (MMP-9) expression to determine the risk factor of oral cancer development. Thirty Rattus norvegicus will be exposed to two kinds of cigarette smoke by a smoking pump for 4 and 8 weeks. The tongues were collected to analyze the number of macrophages, lymphocytes, and plasma cells with hematoxylin-eosin. The MMP-9 expression was similarly analyzed with immunohistochemical staining and then compared with the control group. The number of macrophages, lymphocytes, and MMP-9 expression was higher in the 8-week cigarette smoke exposure compared to the 4-week cigarette smoke exposure and the control group (p < 0.000). The number of plasma cell did not differ in the 8-week cigarette smoke exposure from that of the control group (p > 0.05). The number of plasma cells in the tongue tissue during the 4-week cigarette smoke exposure was not determined. Cigarette smoke exposure induces the risk of oral cancer development as a result of an increase in the number of macrophages, lymphocytes, and MMP-9 expression in the tongue epithelial.


Reducing mask resistance among White evangelical Christians with value-consistent messages.
Public health experts have advocated for wearing protective face masks to combat the COVID-19 pandemic, yet some populations are resistant. Can certain messages shift attitudes toward masks? We investigate the effect of value-consistent messages within a mask-skeptical population: White evangelicals in the United States. An experiment within a national survey of White evangelicals (n = 1,212) assigned respondents to one of three conditions: One group was given a religious message equating mask use with loving your neighbor, another was given a message by Donald Trump saying mask use is patriotic, and a control group received no message. Those exposed to the religious message were more likely to see mask use as important and were more supportive of mask mandates. Republican evangelicals exposed to the patriotism message had similar responses. These findings show that messages that align with individuals' core values-in this case, religious tenets and patriotism-can shift certain views on mask use and government mask policies to combat COVID-19, even among a comparatively mask-resistant group.


Life versus disease in difficult diabetes care: conflicting perspectives disempower patients and professionals in problem solving.
Conflicts in problem solving are known from diabetes research on patients with good glycemic control but have rarely been studied in the care of patients with poor glycemic control. Equally, the different perspectives of health care providers and patients have not been a focus in previous studies. The authors studied the interactions between health care providers and 11 diabetes patients with poor glycemic control in a grounded theory study at a Danish university hospital. Keeping Life and Disease Apart was identified as a core category. It involved a pattern of conflicts both between and within patients and health professionals, which disempowered them in problem solving. Three approaches to problem solving were identified: A compliance-expecting approach kept the pattern unchanged, a failure-expecting approach deadlocked the pattern, and a mutuality-expecting approach appeared to neutralize the conflict.


Impact of non-respect of SYNTAX score II recommendation for surgery in patients with left main coronary artery disease treated by percutaneous coronary intervention: an EXCEL substudy.
The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease. The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years. SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51-3.24), P = 0.003; slope 0.67 (0.61-0.74), P < 0.001]. When the SSII-recommended treatment was CABG, randomized EXCEL patients treated with PCI had a trend towards higher mortality compared with those treated with CABG (14.1% vs 5.3%, P = 0.07) in the as-treat population. In the intention-to-treat population, patients randomized to PCI had higher mortality compared with those randomized to CABG (15.1% vs 4.1%, P = 0.02), when SSII recommended CABG. In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality.


Mineralocorticoid escape by the kidney but not the heart in experimental asymptomatic left ventricular dysfunction.
Unlike healthy subjects, overt congestive heart failure cannot "escape" the sodium- and water-retaining actions of mineralocorticoid excess. It is undefined whether escape occurs in asymptomatic left ventricular dysfunction (ALVD), which is characterized by preserved sodium homeostasis, natriuretic peptide activation, and normal circulating aldosterone. We hypothesized that, in ALVD, mineralocorticoid excess with exogenous deoxycorticosterone acetate (DOCA) would overwhelm renal compensatory mechanisms, resulting in sodium and water retention, and promote renal and cardiac collagen deposition. ALVD was induced in 2 groups (N=5 each) of dogs by tachypacing at 180 bpm. Urine was collected daily and blood drawn at baseline and days 2, 5, 8, and 11. One group served as control (ALVD), and the other received DOCA (ALVD+DOCA) starting at day 2 of pacing. Urine flow and sodium excretion were unchanged in the ALVD group. In ALVD+DOCA, urine flow and sodium excretion decreased on the first 2 days DOCA was given but normalized starting day 4. Urine flow and urinary cGMP excretion increased in ALVD+DOCA after DOCA escape. Plasma atrial natriuretic peptide, B-type natriuretic peptide, and cGMP increased equally in both groups. There were no differences in cardiorenal and hemodynamic parameters in an acute study on day 11. Although renal collagen area fraction was similar, left ventricular collagen area fraction in ALVD+DOCA was significantly higher than in ALVD (3.3+/-0.4% versus 2.0+/-0.2%; P=0.012). We conclude that ALVD can escape the sodium- and water-retaining effects of mineralocorticoid excess. Despite renal escape, increased left ventricular collagen deposition suggests that the heart but not the kidney failed to escape the tissue effects of DOCA.