Cngsc, a homologue of goosecoid, participates in the patterning of the head, and is expressed in the organizer region of Hydra.
We have isolated Cngsc, a hydra homologue of goosecoid gene. The homeodomain of Cngsc is identical to the vertebrate (65-72%) and Drosophila (70%) orthologues. When injected into the ventral side of an early Xenopus embryo, Cngsc induces a partial secondary axis. During head formation, Cngsc expression appears prior to, and directly above, the zone where the tentacles will emerge, but is not observed nearby when the single apical tentacle is formed. This observation indicates that the expression of the gene is not necessary for the formation of a tentacle per se. Rather, it may be involved in defining the border between the hypostome and the tentacle zone. When Cngsc(+) tip of an early bud is grafted into the body column, it induces a secondary axis, while the adjacent Cngsc(-) region has much weaker inductive capacities. Thus, Cngsc is expressed in a tissue that acts as an organizer. Cngsc is also expressed in the sensory neurons of the tip of the hypostome and in the epithelial endodermal cells of the upper part of the body column. The plausible roles of Cngsc in organizer function, head formation and anterior neuron differentiation are similar to roles goosecoid plays in vertebrates and Drosophila. It suggests widespread evolutionary conservation of the function of the gene.


White matter deficits in schizophrenia are global and don't progress with age.
Diffusion tensor imaging has revealed differences in all examined white matter tracts in schizophrenia, with a range of explanations for why this may be. The distribution and timing of differences may help explain their origin; however, results are usually dependent on the analytical method. We therefore sought to examine the extent of differences and their relationship with age using two different methods. A combined voxel-based whole-brain study and a tract-based spatial-statistics study of 104 patients with schizophrenia and 200 matched healthy controls, aged between 17 and 63 years. Fractional anisotropy was reduced throughout the brain in both analyses. The relationship of fractional anisotropy with age differed between patients and controls, with controls showing the gentle fractional anisotropy decline widely noted but patients showing an essentially flat relationship: younger patients had lower fractional anisotropy than controls, but the difference disappeared with age. Mean diffusivity was widely increased in patients. Reduction in fractional anisotropy and increase in mean diffusivity would be consistent with global disruption in myelination; the relationship with age would suggest this is present already at the onset of their illness, but does not progress.


[Phenotypic manifestation of mutations involving resistance to 2,6-diaminopurine (apt) in the genome of purine auxotrophs of Escherichia coli K-12].
Strains of Escherichia coli K-12 containing various combinations of pur (de novo synthesis of purines), pup (purine nucleoside phosphorylase), add (adenosine deaminase) and apt (adenine phosphoribosyl transferase) mutations have been constructed. The apt mutation blocks the ability of strains of pur add and pur add pup genotype to utilize both adenine and adenosine as sole purine sources. Exogenously supplied histidine (that blocks conversion of AMP to guanine nucleotides) does not reduce the growth rate of the strain of pur apt genotype on adenosine as the sole purine source. Adenine released into the cultural medium of bacteria containing simultaneously apt and pup mutations. This data suggest that cultures of E. coli are unable to phosphorylate adenosine to AMP and that they are capable to degrade adenosine to free adenine without participation of purine nucleoside phosphorylase (gene pup).


Probing Low-Copy-Number Proteins in a Single Living Cell.
Single-cell analysis techniques are essential for understanding the microheterogeneity and functions of cells. Low-copy-number proteins play important roles in cell functioning, but their measurement in single cells remains challenging. Herein, we report an approach, called plasmonic immunosandwich assay (PISA), for probing low-copy-number proteins in single cells. This approach combined in vivo immunoaffinity extraction and plasmon-enhanced Raman scattering (PERS). Target proteins were specifically extracted from the cells by microprobes modified with monoclonal antibody or molecularly-imprinted polymer (MIP), followed by labeling with Raman-active nanotags. The PERS detection, with Raman intensity enhanced by 9 orders of magnitude, provided ultrasensitive detection at the single-molecule level. Using this approach, we found that alkaline phosphatase and survivin were expressed in distinct levels in cancer and normal cells, and that extended culture passage resulted in reduced expression of survivin. We further developed acupuncture needle-based PISA for probing low-copy-number proteins in living bodies.


Diagnosis of pulmonary infections in immunocompromised patients by fiber-optic bronchoscopy with bronchoalveolar lavage and serology.
Fiber-optic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) were performed on 67 occasions in 57 immunocompromised patients with symptoms consistent with pulmonary infection. Diagnosis was achieved more often in renal transplant patients than in patients with hematological malignancies (85% versus 28%). Culture (bacteria, virus, fungi), staining and microscopy (bacteria, fungi, Pneumocystis carinii (PC)) and antigen detection by indirect immunofluorescence (cytomegalovirus (CMV), respiratory viruses, PC, Legionella) were used for diagnosis. On 20 occasions transbronchial biopsies with histopathologic examination were performed. In addition, serology comprising the herpes group (HHV-6) and respiratory viruses was done. A microbial diagnosis was obtained on 45% of occasions. The most common pathogens found were CMV (31%) and PC (25%). On 22 (33%) occasions a rapid diagnosis of 1 or more microbial agents was obtained within 24 h by conventional staining or indirect immunofluorescence. The clinical relevance of findings of CMV, HHV-6, and Epstein-Barr virus in BAL by polymerase chain detection on 18, 6 and 3 occasions is discussed. On 4 occasions pathogenic bacteria were found. It was not possible to relate findings of coagulase-negative staphylococci, alpha-streptococci and Candida albicans to the pulmonary infection.


Living kidney donation: outcomes, ethics, and uncertainty.
Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity.


Congenital complete heart block and successful vaginal delivery.
Congenital complete heart block is an uncommon fetal arrhythmia characterized by complete dissociation of the atrial and ventricular contractions. Two patients were diagnosed with isolated congenital complete heart block in the second trimester of pregnancy. Successful vaginal delivery was achieved by both. A monitoring protocol algorithm to be used by the clinician in managing term patients with isolated complete congenital heart block is presented. Vaginal delivery can be safely accomplished in patients with isolated congenital complete heart block, with the use of ultrasound and fetal scalp blood sampling to assess fetal well-being during labor and delivery.


Effect of Baduanjin Qigong on Sleep Quality and Hyperarousal State in Adults With Chronic Insomnia: Protocol for a Randomized Controlled Trial.
Chronic insomnia (CI) is a mind-body disease that is commonly defined as a state of having disturbed daytime activities due to poor nighttime sleep quality. Baduanjin qigong (BDJQG) is widely used for CI in China. However, there is little scientific evidence to evaluate its effects on the hyperarousal state, which is closely associated with improved sleep quality. The objective of the trial is to assess the therapeutic effects of BDJQG on sleep quality in patients with CI. A randomized controlled trial will be conducted on 86 patients, who will be divided into a BDJQG group and a cognitive behavioral therapy for insomnia group at a ratio of 1:1. Interventions in both groups will be given to the participants 7 times a week for 8 weeks, and the participants will be followed up for 4 weeks. The primary outcome is the change in the Pittsburgh Sleep Quality Index from baseline to week 8. The secondary outcomes are the changes in the Hyperarousal Scale, Insomnia Severity Index, Fatigue Scale-14, wrist actigraphy, salivary cortisol level, and functional magnetic resonance imaging from baseline to week 8. All main analyses will be carried out on the basis of the intention-to-treat principle. This study was funded from January 2023. As of the submission of the manuscript, there were 86 participants. Data collection began in April 2023 and will end in January 2024. Data analysis is expected to begin in January 2024, with the publication of results expected in February 2024. This study will present data concerning the clinical effects of BDJQG on CI. The results will help to demonstrate whether BDJQG is an effective therapy for improving sleep quality in association with a decreased hyperarousal level as a possible underlying mechanism. This study will provide much-needed knowledge for complementary and alternative therapy for patients with CI. China Clinical Registration Agency ChiCTR2300069241; https://chictr.org.cn/bin/project/ChiCTR2300069241. PRR1-10.2196/53501.


Systematic review of oral treatments for seborrheic dermatitis.
Seborrheic dermatitis (SD) is normally treated with topical corticosteroids and antifungals. Oral therapies can be prescribed in severe or unresponsive cases. This review aims to assess the quantity and quality of published reports on oral therapies for SD. MEDLINE and Embase databases and the reference listings of publications were searched for any publication using oral treatment for SD. The quality of the included publications was assessed using a modified 27 item checklist by Downs and Black. Twenty-one publications (randomized controlled trials, open trials and case reports) covering eight oral therapies (itraconazole, terbinafine, fluconazole, ketoconazole, pramiconazole, prednisone, isotretinoin and homeopathic mineral therapy) were identified. Most of the publications investigated oral antifungals and the quality of the evidence was generally low. The clinical efficacy outcome reported varied considerably between the studies, preventing statistical analysis and direct comparison between treatments. However, ketoconazole therapy was associated with more relapses compared with other treatments. Itraconazole dosing regimen for SD was generally 200 mg/day for the first week of the month followed by 200 mg/day for the first 2 days for 2-11 months. Terbinafine was prescribed at 250 mg/day either as a continuous (4-6 weeks) or as an intermittent regimen (12 days per month) for 3 months. Fluconazole has administered daily (50 mg/day for 2 weeks) or weekly (200-300 mg) for 2-4 weeks. Ketoconazole dosing regimen was 200 mg daily for 4 weeks. Finally, a single 200 mg dose of pramiconazole was administered to patients. This review also highlights key areas for consideration when designing future studies.


Survial of fasted rats exposed to altitude.
Rats fasted for 48-96h before exposure were shown to have a longer survival time at groups 33,500 ft (1 ft = 0.305 m) simulated altitude than nonfasted controls. Although both become hypothermic at 33500 ft, colonic temperatures of the fasted rats were not sufficiently lower than those of nonfasted animals to explain the difference in survival time. The injection of glucose and insulin before exposure almost completely eliminated the protection afforded by fasting, whereas glucose alone had no effect on survival. It is therefore suggested that an alteration in carbohydrate metabolism, possibly in combination with other starvation-induced changes, allowed fasted rats to survive at 33500 ft until declining body temperature reduced metabolic rate to a level compatible with oxygen supply.


Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany.
In 2021, three encephalitis cases due to the Borna disease virus 1 (BoDV-1) were diagnosed in the north and east of Germany. The patients were from the states of Thuringia, Saxony-Anhalt, and Lower Saxony. All were residents of known endemic areas for animal Borna disease but without prior diagnosed human cases. Except for one recently detected case in the state of Brandenburg, all >30 notified cases had occurred in, or were linked to, the southern state of Bavaria. Of the three detected cases described here, two infections were acute, while one infection was diagnosed retrospectively from archived brain autopsy tissue samples. One of the acute cases survived, but is permanently disabled. The cases were diagnosed by various techniques (serology, molecular assays, and immunohistology) following a validated testing scheme and adhering to a proposed case definition. Two cases were classified as confirmed BoDV-1 encephalitis, while one case was a probable infection with positive serology and typical brain magnetic resonance imaging, but without molecular confirmation. Of the three cases, one full virus genome sequence could be recovered. Our report highlights the need for awareness of a BoDV-1 etiology in cryptic encephalitis cases in all areas with known animal Borna disease endemicity in Europe, including virus-endemic regions in Austria, Liechtenstein, and Switzerland. BoDV-1 should be actively tested for in acute encephalitis cases with residence or rural exposure history in known Borna disease-endemic areas.


Phase formation and stability of Ag-60 at%Cu alloy nanoparticles synthesized by chemical routes in aqueous media.
The present work reports the nature of the evolution of an array of nanoparticles during the synthesis of alloy nanoparticles of Ag-60 at%Cu by the co-reduction of metal salt precursors using NaBH4 in an aqueous medium. This was achieved by studying samples extracted at different intervals of time from the reaction bath. The microstructural characterization reveals that at the initial stage of synthesis, a single-phase solid solution of alloy nanoparticles of very small sizes was formed; however, as the reaction time increases, a network of chains of nanoparticles evolves containing particles rich in either Ag or Cu. Keeping the particles in the reaction bath for a longer time, the chemistry of the network changes further with the chain containing an Ag-rich core and Cu2O as the shell. In the present study, we tried to rationalize the evolution of the phases from the observed results.


[Effect of eating habits on morbidity in 645 patients at a specialized clinic].
Among 645 obese patients examined at an out-patient clinic for obese patients by physical examination and a computerized questionnaire, two subgroups of patients could be identified according to their nutritional preferences: 177 patients preferred carbohydrates exclusively (group A) and 73 patients fat exclusively (group B). No definite preferences were formulated by the other patients. Among patients under 25 years, only 3 belonged to group B and 49 to group A, while in older patients no significant differences were found. Among patients with BMI less than 30, there were significantly fewer patients from group B than from group A (p = 0.006), while in patients with BMI greater than 30 no significant difference was observed. There were significantly more men in group B than in group A. 57% of the patients of group B complained of physical symptoms related to their obesity, compared to 37% in group A (p = 0.006). 26% of group B suffered from joints and muscles compared to 13% of group A (p = 0.003). Hyperglycemia (greater than 5,6 mmol/l) was found in 21% of group A and in 40% of group B (p less than 0.005). Hypercholesterolemia (greater than 6.5 mmol/l) was found in 20% of group A and in 32% of group B (p less than 0.05). In conclusion, obese patients who prefer fat have more general symptoms related to obesity, more abnormal physical signs, and more frequently have hyperglycemia and hypercholesterolemia than patients who prefer carbohydrates.


Image correlates of crowding in natural scenes.
Visual crowding is the inability to identify visible features when they are surrounded by other structure in the peripheral field. Since natural environments are replete with structure and most of our visual field is peripheral, crowding represents the primary limit on vision in the real world. However, little is known about the characteristics of crowding under natural conditions. Here we examine where crowding occurs in natural images. Observers were required to identify which of four locations contained a patch of "dead leaves'' (synthetic, naturalistic contour structure) embedded into natural images. Threshold size for the dead leaves patch scaled with eccentricity in a manner consistent with crowding. Reverse correlation at multiple scales was used to determine local image statistics that correlated with task performance. Stepwise model selection revealed that local RMS contrast and edge density at the site of the dead leaves patch were of primary importance in predicting the occurrence of crowding once patch size and eccentricity had been considered. The absolute magnitudes of the regression weights for RMS contrast at different spatial scales varied in a manner consistent with receptive field sizes measured in striate cortex of primate brains. Our results are consistent with crowding models that are based on spatial averaging of features in the early stages of the visual system, and allow the prediction of where crowding is likely to occur in natural images.


Sporobolomyces yunnanensis sp. nov., a Q-10(H2)-containing yeast species with a close phylogenetic relationship to Erythrobasidium hasegawianum.
A ballistoconidia-forming yeast strain, CH 2.141T, isolated from a semi-dried leaf sample collected in Yunnan, China, was found to have Q-10(H2) as its major ubiquinone. Molecular phylogenetic analysis based on the nucleotide sequences of small subunit (18S) rDNA and the internal transcribed spacer region (including 5.8S rDNA) indicated that the strain was closely related to the two described Q-10(H2)-containing yeast species, Erythrobasidium hasegawianum and Sporobolomyces elongatus, with a closer relationship to the former. A DNA-DNA reassociation experiment showed that strain CH 2.141T represents a new yeast species, for which the name Sporobolomyces yunnanensis sp. nov. is proposed.


An Interplanetary Dust Particle Linked Directly to Type CM Meteorites and an Asteroidal Origin.
Tochilinite, an ordered mixed-layer mineral containing Mg, Al, Fe, Ni, S, and O, has been identified in an interplanetary dust particle (IDP). This mineral is found in only one other class of meteoritic materials, type CM carbonaceous chondrites. The presence of tochilinite in an IDP provides a direct petrogenetic link between a member of the layer-silicate subset of IDPs and a specific class of meteorites and thus establishes that some IDPs collected in the stratosphere have an asteroidal origin. The scarcity of this IDP type suggests that materials with CM mineralogy are not abundant among the dust-producing asteroids.


A new classification of heritable human enamel defects and a discussion of dentin defects.
rude paradigms for both nonsyndromic human heritable primary enamel defects and heritable primary dentin defects have been presented. Since such classifications are merely attempts to identify biologic patterns, their accuracy only can be determined mathematically, and thus must wait for pertinent quantifiable data.


[Frequency and affecting factors of metabolic syndrome in women older than 20 years of age].
Metabolic syndrome (MetS) is a major cause of morbidity and mortality affecting increasing number of people. This was a cross-sectional study aiming to identify the prevalence of MS and risk factors in women aged 20 years and older. Study's universe consisted of women aged 20 years and older living in Gölbaşi Ali Soydan Health Centre's territory. Eight hundred fifty women were accessed among them. Data were collected by a questionnaire. Measurements were done in the health centre following fasting 12 hours. One way ANOVA, correlation and logistic regression analyses were used for statistical analysis. The mean age was 39.4 years, 62% have primary school education. Prevalence of MetS was found 39.1%; low high-density lipoprotein (HDL) and abdominal obesity were the most common MetS components. On the contrary, education and age had negative correlation with HDL and positive correlation with other MetS components. Age (OR=1.091; 95%CI = 1.071-1.110; p=0.0001), and education lower than middle school (literate OR=2.491; 95%CI = 1.334-2.855; p=0.007; primary school OR=1.841; 95%CI 1.281-2.855; p=0.006) were found to increase MetS risk. Even more than half of our study group who has urban life style has two or more MetS components. Because of older age, accelerant factor for MetS, improving of healthy lifestyle behaviors in study group with genetic and environmental risk factors should be primary goal in terms of prevention of cardiovascular diseases and diabetes.


First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement.
RNA interference (RNAi) is a potent and specific mechanism for regulating gene expression. Harnessing RNAi to silence genes involved in disease holds promise for the development of a new class of therapeutics. Delivery is key to realizing the potential of RNAi, and lipid nanoparticles (LNP) have proved effective in delivery of siRNAs to the liver and to tumors in animals. To examine the activity and safety of LNP-formulated siRNAs in humans, we initiated a trial of ALN-VSP, an LNP formulation of siRNAs targeting VEGF and kinesin spindle protein (KSP), in patients with cancer. Here, we show detection of drug in tumor biopsies, siRNA-mediated mRNA cleavage in the liver, pharmacodynamics suggestive of target downregulation, and antitumor activity, including complete regression of liver metastases in endometrial cancer. In addition, we show that biweekly intravenous administration of ALN-VSP was safe and well tolerated. These data provide proof-of-concept for RNAi therapeutics in humans and form the basis for further development in cancer. The fi ndings in this report show safety, pharmacokinetics, RNAi mechanism of action, and clinical activity with a novel fi rst-in-class LNP-formulated RNAi therapeutic in patients with cancer. The ability to harness RNAi to facilitate specifi c multitargeting, as well as increase the number of druggable targets, has important implications for future drug development in oncology.


An olive oil-rich diet reduces scavenger receptor mRNA in murine macrophages.
During atherogenesis, a pathological accumulation of lipids occurs within aortic intimal macrophages through uptake of oxidised LDL via scavenger receptors. Here we investigated whether some of the anti-atherosclerotic effects ascribed to an olive oil rich-diet are mediated through effects on macrophage scavenger receptors (MSR). Male C57 Bl6 mice aged 6 weeks were fed for 12 weeks on a low-fat diet (containing 25 g corn oil/kg) or on high-fat diets containing 200 g coconut oil, olive oil or safflower oil/kg. Thioglycollate-elicited peritoneal macrophages were analysed for fatty acid composition by GC and the levels of mRNA coding for three MSR (MSRA type I, MSRA type II and CD36) were measured by reverse-transcription polymerase chain reaction. Feeding mice diets enriched with different fats resulted in significant differences in the fatty acid profile of macrophages, which reflected the fatty acid compositions of the diets. These differences were accompanied by a lower level of mRNA for MSRA type I, MSRA type II and CD36 in macrophages from mice fed an olive-oil-enriched diet compared with the mice fed on the low-fat diet. These data suggest that part of the protective effect of olive oil against atherosclerosis might be via reducing macrophage uptake of oxidised LDL. Whether this effect is due to the downregulation of gene transcription directly by unsaturated fatty acids or is the result of the effect of monounsaturated fatty acids or other components of olive oil on LDL composition and oxidation remains to be ascertained.


U1 small nuclear ribonucleoproteins are required early during spliceosome assembly.
U1 small nuclear ribonucleoproteins (snRNPs) are required for in vitro splicing of pre-mRNA. Sequences within U1 RNA hybridize to, and thus recognize, 5' splice junctions. We have investigated the mechanism of association of U1 snRNPs with the spliceosome. U1-specific antibodies detected U1 association with precursor RNA early during assembly. Removal of the 5' terminal sequences of U1 RNA by oligo-directed cleavage or removal of U1 snRNPs by immunoprecipitation prior to the addition of precursor RNA depressed the association of all snRNPs with precursor RNA as detected by immunoprecipitation of splicing complexes by either Sm or U1-specific antibodies. Assembly of the spliceosome as monitored by gel electrophoresis was also depressed after cleavage of U1 RNA. The dependency of Sm precipitability of precursor RNA upon the presence of U1 snRNPs suggests that U1 snRNPs participate in the early recognition of substrate RNAs by U2 to U6 snRNPs. Although removal of the 5'-terminal sequences of U1 depressed U1 snRNP association with precursor RNA, it did not eliminate it, suggesting semistable association of U1 snRNPs with the assembling spliceosome in the absence of U1 RNA hybridization. This association was not dependent upon 5' splice junction sequences but was dependent upon 3' intronic sequences, indicating that U1 snRNPs interact with factors recognizing 3' intronic sequences. Mutual dependence of 5' and 3' recognition factors suggests significant snRNP-snRNP communication during early assembly.


Model for aging in the basal forebrain cholinergic system.
A key component of the cognitive deficits associated with aging is the loss of function of cholinergic neurons in the basal forebrain due to neuronal losses and decreased cholinergic function of spared neurons. A model to mimic one aspect of this phenomenon is to kill cholinergic neurons selectively in the basal forebrain via administration of the immunotoxin IgG-192-saporin. Here we discuss apoptotic regulators, such as nerve growth factor, in age-associated changes present in the cholinergic system and the role of the NF-kappaB signaling system in cellular commitment to apoptosis. We also examine the age-associated decline in intrinsic response mechanisms, which may account for the age-associated reduction in recovery from both acute and chronic insults to the central nervous system.


Shedding light on pediatric diseases: multispectral optoacoustic tomography at the doorway to clinical applications.
Optoacoustic imaging (OAI), or photoacoustic imaging (PAI), has fundamentally influenced basic science by providing high-resolution visualization of biological mechanisms. With the introduction of multispectral optoacoustic tomography (MSOT), these technologies have now moved closer to clinical applications. MSOT utilizes short-pulsed near-infrared laser light to induce thermoelastic expansion in targeted tissues. This results in acoustic pressure waves, which are used to resolve specific endo- and exogenous chromophores. Especially in the pediatric population, this non-invasive imaging approach might hold fundamental advantages compared to conventional cross-sectional imaging modalities. As this technology allows the visualization of quantitative molecular tissue composition at high spatial resolution non-invasively in sufficient penetration depth, it paves the way to personalized medicine in pediatric diseases.


Does sampling saliva increase detection of SARS-CoV-2 by RT-PCR? Comparing saliva with oro-nasopharyngeal swabs.
The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in the nasopharyngeal sample by RT-PCR. Recently, saliva samples have been suggested as an alternative sample. In the present study, we aimed to compare RT-PCR results in nasopharyngeal, oro-nasopharyngeal and saliva samples of COVID-19 patients. 98 of 200 patients were positive in RT-PCR analysis performed before the hospitalization. On day 0, at least one sample was positive in 67 % of 98 patients. The positivity rate was 83 % for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63 % for saliva samples (p < 0.001). On day 5, RT-PCR was performed in 59 patients, 34 % had at least one positive result. The positivity rate was 55 % for both saliva and nasopharyngeal samples, while it was 60 % for oro-nasopharyngeal samples. Our study shows that the sampling saliva does not increase the sensitivity of RT-PCR tests at the early stages of infection. However, on the 5th day, viral RNA detection rates in saliva were similar to nasopharyngeal and oro-nasopharyngeal samples. In conclusion, we suggest that, in patients receiving treatment, RT-PCR in saliva, in addition to the standard samples, is important to determine the isolation period and control transmission.


Oncogenic TRK fusions are amenable to inhibition in hematologic malignancies.
Rearrangements involving the neurotrophic receptor kinase genes (NTRK1, NTRK2, and NTRK3; hereafter referred to as TRK) produce oncogenic fusions in a wide variety of cancers in adults and children. Although TRK fusions occur in fewer than 1% of all solid tumors, inhibition of TRK results in profound therapeutic responses, resulting in Breakthrough Therapy FDA approval of the TRK inhibitor larotrectinib for adult and pediatric patients with solid tumors, regardless of histology. In contrast to solid tumors, the frequency of TRK fusions and the clinical effects of targeting TRK in hematologic malignancies are unknown. Here, through an evaluation for TRK fusions across more than 7,000 patients with hematologic malignancies, we identified TRK fusions in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), histiocytosis, multiple myeloma, and dendritic cell neoplasms. Although TRK fusions occurred in only 0.1% of patients (8 of 7,311 patients), they conferred responsiveness to TRK inhibition in vitro and in vivo in a patient-derived xenograft and a corresponding AML patient with ETV6-NTRK2 fusion. These data identify that despite their individual rarity, collectively, TRK fusions are present in a wide variety of hematologic malignancies and predict clinically significant therapeutic responses to TRK inhibition.


The association between fetal and postnatal growth status and serum levels of uric acid in children at 3 years of age.
Recent studies suggest that uric acid plays a causal role in the development of hypertension in relation to birth weight. The aim of the study was to elucidate the effect of prenatal and/or postnatal growth status on serum uric acid levels in children at 3 years of age. A total of 178 children from the birth cohort at Ewha Womans University Hospital were followed. Anthropometric characteristics, blood pressure, and serum uric acid were measured at 3 years of age. The level of serum uric acid was significantly higher in hypertensive children (3.8 mg/dl) than in nonhypertensive children (3.4 mg/dl). Preterm birth and lower placental weight were the preterm factors significantly associated with increased serum uric acid in early childhood. In addition, current weight, body mass index, and change-in-weight s.d. score from birth to current were also associated with serum uric acid level. Both the first- and fourth-quartile groups for weight and weight gain presented higher levels of serum uric acid. We found that the highest uric acid level belonged to the group of preterm or low birth weight (LBW) and higher change in weight s.d. score. Children who were born at full term or with a normal birth weight and lower change in weight s.d. score had the lowest serum uric acid levels. Preterm birth and a subsequent high rate of postnatal weight gain are risk factors for increased serum uric acid levels in early childhood.


Alterations of intravascular volume: influence on renal susceptibility to ischemic injury.
The purpose of this investigation was to test whether alterations of intravascular volume change renal susceptibility to ischemic injury. Acute volume depletion (2% body weight; by furosemide injection or by hemorrhage) or volume expansion (10% body weight; by saline infusion) was induced in Sprague-Dawley rats. The effects of these interventions on renal blood flow (RBF), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), and renal adenine nucleotide content were assessed by comparison with values observed in euvolemic control rats. Volume-depleted, volume-expanded, and euvolemic control rats were also subjected to 25 minutes of bilateral renal artery occlusion (RAO). The severity of ischemic injury was assessed 24 hours later (by determination of GFR, blood urea nitrogen, creatinine, and histology). Before RAO, the volume-depleted rats had significant reductions in GFR (33%), MAP (20% to 45%), and RBF (52% to 72%), but renal adenosine triphosphate (ATP) content was totally preserved. Both groups of volume-depleted rats had normal susceptibility to RAO, compared with the euvolemic controls. Before RAO, volume expansion had no significant effect on GFR, MAP, or RBF, but it decreased renal ATP content by 21%. In addition, volume expansion significantly exacerbated the ATP depletion that occurred both during and after RAO. Nevertheless, the volume-expanded rats were almost totally protected against ischemia. It is concluded that the kidney can tolerate severe volume depletion without apparent deterioration in tubular cell energetics or a change in renal susceptibility to superimposed ischemic injury. Acute volume expansion can protect against ischemic injury, despite lowering renal ATP content.


Mechanochemically Sulfidated Microscale Zero Valent Iron: Pathways, Kinetics, Mechanism, and Efficiency of Trichloroethylene Dechlorination.
In water treatment processes that involve contaminant reduction by zerovalent iron (ZVI), reduction of water to dihydrogen is a competing reaction that must be minimized to maximize the efficiency of electron utilization from the ZVI. Sulfidation has recently been shown to decrease H2 formation significantly, such that the overall electron efficiency of (or selectivity for) contaminant reduction can be greatly increased. To date, this work has focused on nanoscale ZVI (nZVI) and solution-phase sulfidation agents (e.g., bisulfide, dithionite or thiosulfate), both of which pose challenges for up-scaling the production of sulfidated ZVI for field applications. To overcome these challenges, we developed a process for sulfidation of microscale ZVI by ball milling ZVI with elemental sulfur. The resulting material (S-mZVIbm) exhibits reduced aggregation, relatively homogeneous distribution of Fe and S throughout the particle (not core-shell structure), enhanced reactivity with trichloroethylene (TCE), less H2 formation, and therefore greatly improved electron efficiency of TCE dechlorination (εe). Under ZVI-limited conditions (initial Fe0/TCE = 1.6 mol/mol), S-mZVIbm gave surface-area normalized reduction rate constants (k'SA) and εe that were ∼2- and 10-fold greater than the unsulfidated ball-milled control (mZVIbm). Under TCE-limited conditions (initial Fe0/TCE = 2000 mol/mol), sulfidation increased kSA and εe ≈ 5- and 50-fold, respectively. The major products from TCE degradation by S-mZVIbm were acetylene, ethene, and ethane, which is consistent with dechlorination by β-elimination, as is typical of ZVI, iron oxides, and/or sulfides. However, electrochemical characterization shows that the sulfidated material has redox properties intermediate between ZVI and Fe3O4, mostly likely significant coverage of the surface with FeS.


Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Antitumor Activity.
Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive to chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic thyroid cancer. Our previous study on the genomic landscape of HCCs identified a high incidence of disruptions of mTOR pathway effectors. Here, we report a detailed analysis of mTOR signaling in cell line and patient-derived xenograft mouse models of HCCs. We show that mTOR signaling is upregulated and that targeting mTOR signaling using mTOR inhibitors suppresses tumor growth in primary tumors and distant metastasis. Mechanistically, ablation of mTOR signaling impaired the expression of p-S6 and cyclin A2, resulting in the decrease of the S phase and blocking of cancer cell proliferation. Strikingly, mTOR inhibitor treatment significantly reduced lung metastatic lesions, with the decreased expression of Snail in xenograft tumors. Our data demonstrate that mTOR pathway blockade represents a novel treatment strategy for HCC.


Pd-catalysed mono- and dicarbonylation of aryl iodides: insights into the mechanism and the selectivity.
The mechanism of the experimentally reported phosphine-free palladium-catalysed carbonylation of aryl iodides with amines in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base was investigated at the DFT level. Paths were identified for both di- and monocarbonylation, and the calculated selectivity for three different substrates was in agreement with experiment. In dicarbonylation yielding α-ketoamides, formation of the second carbon-carbon bond occurs through reductive elimination in the Pd acyl amide intermediate after DBU-assisted nucleophilic attack of an amine at a terminal CO ligand. This path yields the major product with iodobenzene and the almost exclusive product with p-methoxyiodobenzene. Two different possible pathways yield the monocarbonylated amide product. In one of them, which affords the minor product for iodobenzene, base-assisted nucleophilic attack of the amine takes place on a Pd-bound acyl ligand. For substrates with electron-withdrawing substituents, such as p-cyanoiodobenzene, aryl migration to the CO ligand is disfavoured, and this allows base-assisted amine attack at a terminal CO ligand early in the catalytic cycle. From the resulting Pd amide aryl complex, the subsequent reductive elimination occurs easily, and monocarbonylation becomes favoured.


Disease severity, self-reported experience of workplace discrimination and employment loss during the course of chronic HIV disease: differences according to gender and education.
Evidence for the existence of a harmful effect of chronic disease on employment status has been provided. Although this effect of chronic illness on employment has been reported to be higher among the groups with the lowest position on the labour market, the mechanisms of such inequalities are poorly understood. The present study aimed at investigating social inequalities in the chances of maintaining employment during the course of HIV infection and at examining the correlates of such inequalities. The authors used data from a national representative sample of people living with HIV in France (ANRS-EN12-VESPA survey). Retrospective information on social trajectory and disease characteristics from the time of HIV diagnosis was available. The risk of employment loss associated with indicators of disease severity and HIV-related workplace discrimination was computed over time since HIV diagnosis according to sociodemographic and occupational factors, using Cox proportional hazards models. Among the 478 working-age participants diagnosed as being HIV-infected in the era of multitherapies and employed at the time of HIV diagnosis, 149 experienced employment loss. After adjusting for sociodemographic and occupational factors, disease severity and self-reported HIV-related discrimination at work were significantly associated with the risk of employment loss in a socially-differentiated manner: advancement in HIV disease was associated with an increased risk of employment loss among women (HR 4.45, 95% CI 2.10 to 9.43) but not among men; self-reported experience of HIV-related discrimination at work was associated with an increased risk of employment loss among individuals with a primary/secondary educational level (HR 8.85, 95% CI 3.68 to 21.30) but not among those more educated. Chronic HIV disease affects the chances of maintaining employment in a socially-differentiated manner, resulting in increasing inequalities regarding workforce participation. Disease severity and workplace HIV-related discrimination, particularly affecting the employment status of the most socioeconomically disadvantaged, may play a major role.


eGEMs' Early Adventures in Open Access Publishing.
In January 2013 AcademyHealth officially launched eGEMs (Generating Evidence and Methods to improve patient outcomes) to rapidly disseminate peer-reviewed approaches using electronic health data (EHD) to advance research and quality improvement (QI), with the overall goal of improving patient and community outcomes. Inspired by the publication of eGEMs 50(th) paper, Dr. Erin Holve, eGEMs editor-in-chief reviews the EDM Forum's early experiences with open access publishing. As of the end of September 2014 eGEMs has published 59 manuscripts and received nearly 150 submissions. These early findings demonstrate eGEMs is filling a need for dissemination outlets that bridge the gap between the health research and practice communities. Published papers are distributed across the EDM Forum's four thematic domains: governance (n=5), informatics (n=14), methods (n=13) and learning health systems (n=27). While system design issues are a consistent theme, papers addressing priority health topics such as diabetes, asthma, and obesity are frequently submitted. Authors include more than two hundred experts in the field representing nearly all of the EDM Forum's core stakeholder groups: research/QI, nonprofit/policy, healthcare delivery, government, industry, and patients/consumers. WHAT'S NEXT: With the help of our diverse community, eGEMs will continue to expand its depth and reach. Forthcoming special issues on community-level transformation using health IT, and ways to improve user-experience and system design will add to the journal's robust portfolio of work identifying and addressing shared challenges using EHD. The EDM Forum, working closely with our partners at the Agency for Healthcare Research and Quality, will work diligently to ensure eGEMs is accelerating the pace at which the community translates and disseminates key lessons, with the ultimate goal of helping transform knowledge into actions that can improve health and health care.


Multiple injuries of osteoma skin in the face: therapeutical least invasive in patients with acne sequela - case report.
Osteoma cutis is a bone formation in the dermis can to be primary or secondary forms. Only, multiples, many forms, occurring on either sex, they are a rare cutaneous disease. The pathogenesis and classification remains unclear. Our objective was the diagnostic and small invasive surgery treatment of the osteoma cutis multiple of the face, in patients as a sequel of acne. To remove the osteoma we used needle BD 0,70x25 22G1, without anesthetic topic or inject able site. The small wounds were exposed with scarring balsam. We got an excellent esthetic result after 15 days.


Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency.
Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delayed by many months, and most patients present with symptoms of acute adrenal insufficiency. Because PAI is rare, even medical specialists in this therapeutic area rarely manage more than a few patients. Currently, the procedures for diagnosis, treatment and follow-up of this rare disease vary greatly within Europe. The common autoimmune form of PAI is characterized by the presence of 21-hydroxylase autoantibodies; other causes should be sought if no autoantibodies are detected. Acute adrenal crisis is a life-threatening condition that requires immediate treatment. Standard replacement therapy consists of multiple daily doses of hydrocortisone or cortisone acetate combined with fludrocortisone. Annual follow-up by an endocrinologist is recommended with the focus on optimization of replacement therapy and detection of new autoimmune diseases. Patient education to enable self-adjustment of dosages of replacement therapy and crisis prevention is particularly important in this disease. The authors of this document have collaborated within an EU project (Euadrenal) to study the pathogenesis, describe the natural course and improve the treatment for Addison's disease. Based on a synthesis of this research, the available literature, and the views and experiences of the consortium's investigators and key experts, we now attempt to provide a European Expert Consensus Statement for diagnosis, treatment and follow-up.


Offering variety: a subtle manipulation to promote healthy food choice throughout the day.
Providing a variety of food generally increases consumption and enjoyment. This effect is typically associated with unhealthy behavior (e.g., overindulgence at a buffet) and studied during a single meal. Two studies tested whether this effect can be leveraged in a subtle, simple manipulation to promote healthy food choices over the course of a day. In Studies 1 and 2, 188 and 187 participants, respectively, chose between a sweet and a piece of fruit in the afternoon. The fruit was either the same as or different from fruit that was selected in the morning; choice was not given in the morning. Study 1 tested this effect in the domain of expressed preferences and Study 2 examined actual choice. In both studies, a second piece of fruit was more likely to be selected in the afternoon if it was different from fruit that was selected in the morning. These results illustrate how a robust effect that is typically associated with unhealthy outcomes can be harnessed to promote healthy food choices and underscore the importance of conceptualizing eating as a series of interrelated behavioral decisions. This work has implications for applied settings, such as cafeterias, and is distinguished from other simple structural manipulations by its focus on sustaining healthy food choice over the course of the day. (PsycINFO Database Record


Serum phosphate and mortality in patients with chronic kidney disease.
Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population. Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets. Mean (SD) eGFR was 32 (15) ml/min per 1.73 m(2), age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality. In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.


Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation.
The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+ T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors.


Peptide welding technology - A simple strategy for generating innovative ligands for G protein coupled receptors.
Based on their high selectivity of action and low toxicity, naturally occurring peptides have great potential in terms of drug development. However, the pharmacokinetic properties of peptides, in particular their half life, are poor. Among different strategies developed for reducing susceptibility to peptidases, and thus increasing the duration of action of peptides, the generation of branched peptides has been described. However, the synthesis and purification of branched peptides are extremely complicated thus limiting their druggability. Here we present a novel and facile synthesis of tetrabranched peptides acting as GPCR ligands and their in vitro and vivo pharmacological characterization. Tetrabranched derivatives of nociceptin/orphanin FQ (N/OFQ), N/OFQ related peptides, opioid peptides, tachykinins, and neuropeptide S were generated with the strategy named peptide welding technology (PWT) and characterized by high yield and purity of the desired final product. In general, PWT derivatives displayed a pharmacological profile similar to that of the natural sequence in terms of affinity, pharmacological activity, potency, and selectivity of action in vitro. More importantly, in vivo studies demonstrated that PWT peptides are characterized by increased potency associated with long lasting duration of action. In conclusion, PWT derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects.


Specific patterns of gene space organisation revealed in wheat by using the combination of barley and wheat genomic resources.
Because of its size, allohexaploid nature and high repeat content, the wheat genome has always been perceived as too complex for efficient molecular studies. We recently constructed the first physical map of a wheat chromosome (3B). However gene mapping is still laborious in wheat because of high redundancy between the three homoeologous genomes. In contrast, in the closely related diploid species, barley, numerous gene-based markers have been developed. This study aims at combining the unique genomic resources developed in wheat and barley to decipher the organisation of gene space on wheat chromosome 3B. Three dimensional pools of the minimal tiling path of wheat chromosome 3B physical map were hybridised to a barley Agilent 15K expression microarray. This led to the fine mapping of 738 barley orthologous genes on wheat chromosome 3B. In addition, comparative analyses revealed that 68% of the genes identified were syntenic between the wheat chromosome 3B and barley chromosome 3 H and 59% between wheat chromosome 3B and rice chromosome 1, together with some wheat-specific rearrangements. Finally, it indicated an increasing gradient of gene density from the centromere to the telomeres positively correlated with the number of genes clustered in islands on wheat chromosome 3B. Our study shows that novel structural genomics resources now available in wheat and barley can be combined efficiently to overcome specific problems of genetic anchoring of physical contigs in wheat and to perform high-resolution comparative analyses with rice for deciphering the organisation of the wheat gene space.


Assessment of inactive, active and mixed atherosclerotic plaques by 18F-FDG-PET; an age group-based correlation with cardiovascular risk factors.
The aim of this study was to assess the atherosclerotic plaques in a large asymptomatic population stratified based on age and sex. [18F]-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT of 100 men and 100 women, divided in four age groups were examined to assess FDG-accumulating active, calcified inactive and mixed atherosclerotic plaques in eight defined vessel segments. There was a high correlation between the total number of cardiovascular risk factors and the number of FDG-accumulating active plaques as well as the number of calcified inactive plaques. There was a significant difference in the number of plaques between all age-groups except for active plaques in age groups 60-70 and 80-90 years. There is a correlation between the number of cardiovascular risk factors and the number of FDG-accumulating atherosclerotic lesions in this patient material. Statin-treatment was associated with significantly lower numbers of active plaques.


Acquiring sub-efficient and efficient variants of novel means by integrating information from multiple social models in preschoolers.
Sub-efficient action routines often represent culture-specific conventional forms of actions that belong to the repertoire of cultural knowledge shared by a social group. Children readily acquire such sub-efficient routines from social demonstrations and often preserve them in their action repertoire despite encountering more efficient alternatives. This suggests that they can treat sub-efficient conventional forms and their efficient alternatives in a context-sensitive selective manner. We hypothesized that children may rely on their sensitivity to differentiate speakers of their own language versus a foreign language as an informative cue indicating whether the model belongs to their own cultural community and the action modeled represents shared cultural knowledge. We assessed preschoolers' imitation following two different demonstrations. The first model demonstrated a sub-efficient action sequence, whereas the second model presented a more efficient alternative to obtain the same goal. We varied whether the children had heard the models speak their own language or a foreign language before their nonverbal action demonstrations. We found that 4-year-olds adopted the second model's efficient alternative, but only when she spoke their own language. However, they disregarded the efficient alternative if it was presented by a foreign-language speaker and continued to perform the sub-efficient routine they initially acquired. Therefore, 4-year-olds employed the cue of shared language to optimize acquiring and maintaining culturally shared sub-efficient action routines by selectively updating their action repertoire relying on their language-based evaluation of the demonstrator's culture-specific competence. In contrast, 5- and 6-year-olds adopted the efficient alternative independently of the demonstrator's language. Possible reasons for this developmental trend are discussed.


Structure-function analysis of SUV39H1 reveals a dominant role in heterochromatin organization, chromosome segregation, and mitotic progression.
SUV39H1, a human homologue of the Drosophila position effect variegation modifier Su(var)3-9 and of the Schizosaccharomyces pombe silencing factor clr4, encodes a novel heterochromatic protein that transiently accumulates at centromeric positions during mitosis. Using a detailed structure-function analysis of SUV39H1 mutant proteins in transfected cells, we now show that deregulated SUV39H1 interferes at multiple levels with mammalian higher-order chromatin organization. First, forced expression of full-length SUV39H1 (412 amino acids) redistributes endogenous M31 (HP1beta) and induces abundant associations with inter- and metaphase chromatin. These properties depend on the C-terminal SET domain, although the major portion of the SUV39H1 protein (amino acids 89 to 412) does not display affinity for nuclear chromatin. By contrast, the M31 interaction surface, which was mapped to the first 44 N-terminal amino acids, together with the immediately adjacent chromo domain, directs specific accumulation at heterochromatin. Second, cells overexpressing full-length SUV39H1 display severe defects in mitotic progression and chromosome segregation. Surprisingly, whereas localization of centromere proteins is unaltered, the focal, G(2)-specific distribution of phosphorylated histone H3 at serine 10 (phosH3) is dispersed in these cells. This phosH3 shift is not observed with C-terminally truncated mutant SUV39H1 proteins or with deregulated M31. Together, our data reveal a dominant role(s) for the SET domain of SUV39H1 in the distribution of prominent heterochromatic proteins and suggest a possible link between a chromosomal SU(VAR) protein and histone H3.


Brain aging: impaired coding of novel environmental cues.
Studies of the spatial memory capacities of aged animals usually focus on performance during the learning of new environments. By contrast, efforts to characterize age-related alterations in spatial firing information processing by hippocampal neurons typically use an environment that is highly familiar to the animals. In the present study we compared the firing properties of hippocampal neurons in young adult and aged rats as they acquired spatial information about new environmental cues. Hippocampal complex spike cells were recorded while rats performed a radial arm maze task in a familiar environment and then recorded again after many of the spatial cues were changed. After the change in the environment, in aged rats 35-42% of place fields retained their original shape and location with respect to the maze center, although they usually rotated to another arm. By contrast, all place fields in young animals either disappeared or appeared in a new location. Some of the new place fields appeared in the new environment during the first 5 min of exploration, whereas others needed more than 30 min to develop fully. In the familiar environment spatial selectivity of place cells was similar in young and aged rats. By contrast, when rats were placed into a new environment, spatial selectivity decreased considerably in aged memory-impaired rats compared with that of young rats and aged rats with intact memory performance.


Regioselective 1,2-addition of allenamides with N-haloimides: synthesis of 2-halo allylic aminal derivatives.
A strategy for the synthesis of 2-halo allylic aminal derivatives through regioselective 1,2-addition of allenamides with N-haloimides is presented. This reaction was conducted under very mild conditions and gave up to 99% yield. Moreover, the obtained halides allow functional group diversification by palladium-catalyzed coupling reactions, which could act as potential intermediates for the synthesis of valuable compounds.


Discontinuation of Health Interventions Among Brazilian Older Adults During the Covid-19 Pandemic: REMOBILIZE Study.
The objective of this study was to analyze changes in access to health interventions during the pandemic among Brazilian older adults and to investigate the factors associated with social and health inequalities. We conducted an online survey with Brazilian adults aged 60 + years between May and June 2020. A multidimensional questionnaire was used to investigate access to health interventions during the pandemic and associated factors. Of 1482 participants, 56.5% reported health care before the pandemic, and 36.4% discontinued it during the pandemic. The discontinuation rate was 64.4% (95% CI 61.1-67.6). Participants with higher educational level (nine or more years of education: OR 0.34; 95% CI 0.17-0.70) and higher income (eight or more times the minimum wage: OR 0.54; 95% CI 0.36-0.81) were associated with less probability of discontinuation. Presenting multimorbidity (OR: 1.42; 95% CI 1.06-1.90) and polypharmacy (OR: 0.61; 95% CI 0.46-0.81) were associated with discontinuity in health interventions. Our study showed that structural health inequities in access to health care shaped the rates of discontinuation in health care interventions during the COVID-19 pandemic. Strategic actions should be set up to actively monitor socially vulnerable older adults and strengthen community-based services to mitigate the discontinuation of health care interventions.


Rendering SiO2/Si Surfaces Omniphobic by Carving Gas-Entrapping Microtextures Comprising Reentrant and Doubly Reentrant Cavities or Pillars.
We present microfabrication protocols for rendering intrinsically wetting materials repellent to liquids (omniphobic) by creating gas-entrapping microtextures (GEMs) on them comprising cavities and pillars with reentrant and doubly reentrant features. Specifically, we use SiO2/Si as the model system and share protocols for two-dimensional (2D) designing, photolithography, isotropic/anisotropic etching techniques, thermal oxide growth, piranha cleaning, and storage towards achieving those microtextures. Even though the conventional wisdom indicates that roughening intrinsically wetting surfaces (θo < 90°) renders them even more wetting (θr < θo < 90°), GEMs demonstrate liquid repellence despite the intrinsic wettability of the substrate. For instance, despite the intrinsic wettability of silica θo ≈ 40° for the water/air system, and θo ≈ 20° for the hexadecane/air system, GEMs comprising cavities entrap air robustly on immersion in those liquids, and the apparent contact angles for the droplets are θr > 90°. The reentrant and doubly reentrant features in the GEMs stabilize the intruding liquid meniscus thereby trapping the liquid-solid-vapor system in metastable air-filled states (Cassie states) and delaying wetting transitions to the thermodynamically-stable fully-filled state (Wenzel state) by, for instance, hours to months. Similarly, SiO2/Si surfaces with arrays of reentrant and doubly reentrant micropillars demonstrate extremely high contact angles (θr ≈ 150°-160°) and low contact angle hysteresis for the probe liquids, thus characterized as superomniphobic. However, on immersion in the same liquids, those surfaces dramatically lose their superomniphobicity and get fully-filled within <1 s. To address this challenge, we present protocols for hybrid designs that comprise arrays of doubly reentrant pillars surrounded by walls with doubly reentrant profiles. Indeed, hybrid microtextures entrap air on immersion in the probe liquids. To summarize, the protocols described here should enable the investigation of GEMs in the context of achieving omniphobicity without chemical coatings, such as perfluorocarbons, which might unlock the scope of inexpensive common materials for applications as omniphobic materials. Silica microtextures could also serve as templates for soft materials.


Environmental toxicants and human fertility.
Globally there is increasing concern that the environment is having a negative impact on human health. Hormone-like activity and endocrine toxicity of environmental toxicants have been documented in the contemporary literature raising concern that exposure to these chemicals could alter human reproductive function and affect fertility. In addition, epidemiological reports of an association between exposure to chemical toxicants in the workplace and adverse reproductive outcomes together with detection of environmental toxicant residues in serum and ovarian follicular fluid, has led to widespread concern that chemical contaminants may be a contributing factor in the pathobiology of idiopathic infertility in the general population. While the epidemiological evidence is equivocal, animal studies provide biological plausibility for a potential association between environmental toxicant exposures and altered reproductive function. Furthermore, cell and organ culture experiments illustrate potential mechanisms of toxicant action on the reproductive system. This review summarizes the evidence linking environmental toxicant exposure and infertility and examines the biological plausibility for this association.


[A case of prostate abscess with sepsis, infectious endocarditis and pyogenic spondylitis].
A 65-year-old man with diabetes mellitus (DM) presented with an indwelling urethral catheter placed for urinary retention by his previous doctor. Thereafter, he had fever, vomiting and general fatigue. His blood examination showed severe inflammatory findings. He was diagnosed with acute prostatitis and immediately admitted to our hospital. Pelvic computerized tomography (CT) showed a prostate abscess. We performed transrectal ultrasonographic-guided puncture of the prostate abscess for drainage and blood culture was tested. Methicillin-sensitive Staphylococcus aureus (MSSA) was cultured from the puncture fluid and blood. We administered antibiotics with strict control of DM. After the prostate abscess improved and the urethral catheter was removed, the patient was systematically examined for potential sepsis-related disease caused by MSSA septic infection. Magnetic resonance imaging (MRI) of the head indicated multiple cerebral infarction, abdominal CT indicated splenetic infarction, ultrasonography of the heart indicated vegetation on the mitral valve and aortic valve, and chest X-ray indicated pulmonary congestion. Furthermore, MRI of the lumbar spine showed a high intensity lesion at the 4th and 5th lumbar spine, indicating pyogenic spondylitis. We diagnosed prostate abscess with sepsis, infectious endocarditis, congestive heart failure and pyogenic spondylitis. Aortic valve replacement, mitral annuloplasty, tricuspid valvuloplasty and ovale hole closure surgeries were performed to treat these conditions.


Utilization of lung scans by clinicians.
To determine the effect of clinical assessments and lung scan results on the management of patients, we studied 566 consecutive patients referred for lung scans because of suspected pulmonary embolism. Prior to the lung scan, the clinician was asked to estimate the probability of pulmonary embolus. Two or three days later the physician was contacted to determine how the patient was managed. The results of the lung scan strongly influenced patient management. Patients with high probability lung scans were treated for pulmonary embolism regardless of the clinical pretest estimate. Low and intermediate probability lung scans resulted in most patients not being treated for pulmonary embolism and not referred for pulmonary angiography. Only 55 of the 566 patients were referred for pulmonary angiography, and approximately one-half of these patients had lung scans with an intermediate probability for pulmonary embolism.


[Sedation in neurointensive care unit].
The objectives for using sedation in neurointensive care unit (neuroICU) are somewhat different from those used for patients without severe brain injuries. One goal is to clinically reassess the neurological function following the initial brain insult in order to define subsequent strategies for diagnosis and treatment. Another goal is to prevent severely injured brain from additional aggravation of cerebral blood perfusion and intracranial pressure. Depending on these situations is the choice of sedatives and analgesics: short-term agents, e.g., remifentanil, if a timely neurological reassessment is required, long-term agents, e.g., midazolam and sufentanil, as part of the treatment for elevated intracranial pressure. In that situation, a multimodal monitoring is needed to overcome the lack of clinical monitoring, including repeated measurements of intracranial pressure, blood flow velocities (transcranial Doppler), cerebral oxygenation (brain tissue oxygen tension), and brain imaging. The ultimate stop of neurosedation can distinguish between no consciousness and an alteration of arousing in brain-injured patients. During this period, an elevation of intracranial pressure is usual, and should not always result in reintroducing the neurosedation.


Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability.
Decreased maternal nutrient availability during pregnancy induces compensatory fetal metabolic and endocrine responses. Knowledge of cellular changes involved is critical to understanding normal and abnormal development. Several studies in rodents and sheep report increased fetal plasma cortisol and associated increased gluconeogenesis in response to maternal nutrient reduction (MNR) but observations in primates are lacking. We determined MNR effects on fetal liver phosphoenolpyruvate carboxykinase 1 (protein, PEPCK1; gene, PCK1 orthologous/homologous human chromosomal region 20q13.31) at 0.9 gestation (G). Female baboon social groups were fed ad libitum (control, CTR) or 70% CTR (MNR) from 0.16 to 0.9G when fetuses were delivered by caesarean section under general anaesthesia. Plasma cortisol was elevated in fetuses of MNR mothers (P < 0.05). Immunoreactive PEPCK1 protein was located around the liver lobule central vein and was low in CTR fetuses but rose to 63% of adult levels in MNR fetuses. PCK1 mRNA measured by QRT-PCR increased in MNR (2.3-fold; P < 0.05) while the 25% rise in protein by Western blot analysis was not significant. PCK1 promoter methylation analysis using bisulfite sequencing was significantly reduced in six out of nine CpG-dinucleotides evaluated in MNR compared with CTR liver samples. In conclusion, these are the first data from a fetal non-human primate indicating hypomethylation of the PCK1 promoter in the liver following moderate maternal nutrient reduction.


Removal of dissolved copper(II) and zinc(II) by aerobic granular sludge.
This study investigated the adsorption kinetics of dissolved copper(II) and zinc(II) by aerobic granular sludge. Two series of batch experiments were conducted at different initial copper(II), zinc(II) concentrations (Co) and initial granule concentrations (Xo). Results showed that the biosorption kinetics of individual copper(II) and zinc(II) by aerobic granules were closely related to Co and Xo. The maximum biosorption capacity of individual copper(II) and zinc(II) by aerobic granules was 246.1 mg g(-1) and 180 mg g(-1), respectively. In order to theoretically interpret the results obtained, two kinetic models previously developed for biosorption were employed and compared in this study. It was found that the model proposed by Liu et al. (2003) could fit the experimental data very well, but the second-order model failed to fit the data in some cases. It appears that aerobic granules would be potential biosorbent with high efficiency for the removal of dissolved copper(II) and zinc(II) from wastewater.


[Falconer-Weddel's costoclavicular syndrome].
Analysed herein are the findings of examination and outcomes of surgical management of fifty-eight patients (25 men and 33 women) presenting with Falconer-Weddel's costoclavicular syndrome in which the subclavian artery and vein and the brachial plexus at the thoracic outlet appear to be compressed. Of the 58 patients,five subjects were found to have a rudimentary cervical rib and three more (5.3%) patients had trophic disorders on their digits fingers: dystrophy of the nail plates, their fragility, periodically opening trophic ulcers at the digital tips and one patient presented with gangrene of the inguinal phalanx of the middle finger. Three patients had hyperemia of the face. A further four patients had roughening, hyperkeratosis of the skin of the hands, cracks. The presence of the supernumerary ribs was determined roentgenologically. Haemodynamics was studied using Doppler ultrasonography making it possible to reveal disordered blood flow in the upper-limb arteries in the physiological position assumed, in the Adson test as well as with Raynaud syndrome, which was observed in 39 patients. The function of the nerves was studied using electroneuromyography (ENMG). All patients were operated on under endotracheal anaesthesia. Decompression-medical operations were carried outperformed in all 58 patients, with the following four types of interventions being performed: transaxillary resection of the first rib combined with sympathectomy carried out in 23 patients, resection of the first rib without sympathectomy in eighteen patients, resection of the first rib via a surpraclavicular approach in four patients, scalenotomy and selective cervicothoracic sympathectomy in 13 patients.


Firearm-related injuries in Canada: issues for prevention.
We reviewed the available data on firearm-related injuries in Canada to suggest strategies for prevention in the context of the proposed amendments to the Criminal Code (Bill C-17) currently before Parliament. The risk of death from a firearm in Canada is equivalent to the risk of death from a motor vehicle crash. We discuss the risks associated with firearms with regard to suicides, homicides and "accidents." We also discuss the accessibility of firearms. This article builds upon a recently published update on the epidemiologic basis of the public health approach for the prevention of firearm-related injuries and deaths. The key to the etiologic approach to preventing such injuries and deaths is to view the incidents, regardless of their medicolegal circumstances, as having one factor in common: the discharge of a firearm.


[Concordance of two retinal mapping techniques to detect diabetic macular edema].
Optical coherence tomography quantifies retinal thickness, localizes diabetic macular edema (DME), and determines whether it implies visual risk. Evaluation is standardized by the macular mapping technique in two versions: 6 mm and 3.45 mm. The latter version measures with greater detail the zone adjacent to the central 1000 microm but does not evaluate the entire macula. Concordance between maps was evaluated in order to define which version better evaluated DME prospectively. The rate and 95% confidence intervals (95% CI) of eyes with DME, which had thickening adjacent to the central 1000 microm, was identified in fields of the 6-mm map and in the corresponding fields of the 3.45-mm map. The disparity between rates was identified using McNemar test, and concordance between fields was determined using kappa coefficient. The rate of thickening in the studied area ranged from 31.9 to 50% with overlapping 95% CI between corresponding fields. Although significant differences existed (p <0.05), there was good concordance for 3/8 comparisons and very good concordance in five. Information generated by the 6-mm macular mapping was as valid as that generated by the 3.45 mapping to identify thickening adjacent to the central 1000 microm. We recommend using the 6-mm mapping prior to surgery because it has the advantage of completely measuring the macula.


Mucins 1-shRNA inhibit the proliferation and HIF-1alpha protein expression on human cholangiocarcinoma cells.
To explore the effects of Mucins (MUC)1-shRNA on the proliferation and hypoxia inducible factor (HIF)-1alpha expression of human cholangiocarcinoma (CCA) QBC939 cells in vitro. MUC1-shRNA was constructed and transfected with Lipofectamine™ 2000 into cultured CCA cells. MUC1 mRNA and protein expression levels were determined by RT-PCR and Western blot, respectively. The cellular proliferation and HIF-1alpha expression of QBC939 cells were evaluated by the MTT assay and Western blot, respectively. After transfection, the expression levels of MUC1 mRNA and protein in the experimental group decreased significantly in QBC939 (P < 0.01). The proliferation of MUC1 shRNA-transfected group was 0.30 ± 0.05, 38.32 ± 1.43%, 15.18 ± 1.32%, and there were remarkable differences when compared with the control groups (P < 0.05). Significant inhibition of HIF-1alpha protein expression in MUC1 shRNA-transfected group was also discovered (P < 0.05). MUC1-shRNA could inhibit proliferation and significantly weaken HIF-1alpha protein expression of QBC939 cells, suggesting its potential as a therapeutic target of CCA.


In Vitro Effect on Plasmodium falciparum and In Vivo Effect on Plasmodium berghei of Annomaal, an Oily Fraction Obtained from the Seeds of Annona squamosa.
Malaria remains a life-threatening health problem and is responsible for the high rates of mortality and morbidity in the tropical and subtropical regions of the world. The increasing threat of drug resistance to available artemisinin-based therapy warrants an urgent need to develop new antimalarial drugs that are safer, more effective, and have a novel mode of action. Natural plants are an excellent source of inspiration in searching for a new antimalarial agent. This research reports a systematic investigation for determining the antimalarial potential of the seeds of A. squamosa. The study shows that the crude seed extract (CSE), protein, saponin, and the oily fractions of the seeds were nontoxic at a 2000 mg/kg body weight dose when tested in Wistar rats, thus revealing high safety is classified as class 5. The oily fraction, Annomaal, demonstrated pronounced antimalarial activity with low IC50 (1.25 ± 0.183 μg/mL) against P. falciparum in vitro. The CSE and Annomaal significantly inhibited the growth of P. berghei parasites in vivo with 58.47% and 61.11% chemo suppression, respectively, while the standard drug artemether showed chemo suppression of 66.75%. Furthermore, the study demonstrated that oral administration of Annomaal at a daily dose of 250 mg/kg/day for 3 days was adequate to provide a complete cure to the P. berghei-infected mice. Annomaal thus holds promise as being patient-compliant due to the shorter treatment schedule, eliminating the need for frequent dosing for extended time periods as required by several synthetic antimalarial drugs. Further studies are needed to determine the active compounds in the oily fraction responsible for antimalarial activity.


T cell receptor-mediated signaling is defective in T cells obtained from patients with primary intracranial tumors.
It has been well established that patients with malignant glioblastomas exhibit T cell anergy. In this report, we further investigate the nature of this T cell anergy. The results demonstrate that tumor size but not location correlates with decreased mitogen or anti-CD3 mAb responsiveness of T cells obtained from patients. Stimulation of the TCR/CD3 complex on these patients' T cells revealed defects in early transmembrane signaling. Both PHA and anti-CD3 mAb activated PBL and T cells obtained from patients exhibited a marked decrease in the tyrosine phosphorylation of a number of proteins. In particular, decreased phosphorylation of pp100 and phospholipase Cgamma1 (PLCgamma1) was observed. In addition, PLCgamma1 and p56(lck) protein levels were dramatically reduced in T cells obtained from patients harboring a glioma. In contrast, the protein levels of p59(fyn) were normal or only slightly reduced in T cells obtained from patients with gliomas. Quantitation of free intracellular calcium concentrations ([Ca2+]i) after mitogen (PHA) stimulation or ionomycin treatment of T cells obtained from patients revealed that they mobilize less calcium than do T cells obtained from normal subjects. Stimulation of T cells obtained from patients with PMA and ionomycin, which should bypass the requirement for PLCgamma1 activation as well as directly activate the p21(ras) signaling pathway, did not restore the proliferative capacity of these T cells to normal levels. These results indicate that the anergy observed in T cells obtained from these patients is a consequence of one or more defects in the early transmembrane signaling events associated with TCR/CD3 stimulation.


Increasing utilization of computed tomography in the adult emergency department, 2000-2005.
This study aims to characterize changes in computed tomography (CT) utilization in the adult emergency department (ED) over a 5-year period. CT scans ordered on adult ED patients from July 2000 to July 2005 were analyzed in five groups: head, cervical spine, chest, abdomen, and miscellaneous. ED patient volume and triage acuity scores were determined. Triage acuity scores are used to determine the severity of a patient's illness or injury and the need for immediate evaluation and treatment. There were 46,553 CT scans performed on 27,625 adult patients in the ED during the study period. During this same period, 194,622 adult patients were evaluated in the ED. From 2000 to 2005, the adult emergency department patient volume increased by 13% while triage acuity remained stable. During this same period, head CT increased by 51%, cervical spine CT by 463%, chest CT by 226%, abdominal CT by 72%, and miscellaneous CT by 132%. Although increases were generally greater for patients over age 40, the increase in those less than 40 years was also substantial. Of the 4,320 individual patients who underwent chest CT, 83 (2%) had chest CT on three or more separate ED visits. Of 10,960 patients undergoing abdominal CT, 406 (4%) had abdominal CT on three or more separate ED visits. ED CT utilization has increased at a rate far exceeding the growth in ED patient volume. This presumably reflects the improved utility of CT in diagnosing serious pathology, its increased availability, and a desire on the part of physicians for diagnostic certainty. Whether this increase in utilization results in improved patient outcomes is at present unclear and deserves additional study.


Inactivation of virulent Burkholderia pseudomallei by sunlight.
The goal of this study was to determine the sensitivity of virulent Burkholderia pseudomallei to natural sunlight. We describe solar dosimetry calibrated to integrate radiation between 295 and 305 nm and an exposure system that minimizes thermal effects on bacterial cells. Burkholderia pseudomallei cells were either exposed to sunlight in UV transparent dishes or maintained in the dark covered by opaque foil. The cells maintained in the dark remained at constant levels for the duration of all experiments. The exposed cells nearby were killed with a kinetic studied through 5 Log10 inactivation. We found that cells in stationary phase of growth were nearly two-fold more resistant to sunlight than cells in lag or exponential growth. A virulent strain of B. pseudomallei that produced mucoid colonies showed sensitivity to sunlight similar to both a virulent strain that produced nonmucoid colonies and a strain of B. thailandensis. The inactivation of B. pseudomallei by sunlight in different types of water of environmental relevance or inside amoebae was investigated. The sensitivity of virulent B. pseudomallei was calculated and its comparison with previous studies employing monochromatic germicidal light (254 nm) is discussed. This may be the first report in the open literature of the inactivation of a virulent biological threat agent by natural sunlight. These data should assist in estimating the risk for contracting melioidosis and in predicting the time period during which B. pseudomallei remains infectious after an accidental or intentional release in the environment.


Eimeria tenella: specific EtAMA1-binding peptides inhibit sporozoite entry into host cells.
Avian coccidiosis caused by Eimeria inflicts high economic losses to the poultry industry. Application of drugs and live vaccines presents particular challenges in pathogen resistance and cost, hence alternative anti-coccidial strategies are needed. In this study, peptides that specifically bind E. tenella AMA1 (EtAMA1) were screened from a phage display peptide library. The positive clones of target phages were characterized by ELISA after four rounds of biopanning. The binding capabilities with EtAMA1 and sporozoite proteins for the two selected peptides were detected by ELISA. The role of the two target peptides in inhibiting sporozoite invasion of MDBK cells was evaluated in vitro and the anti-coccidial effects of the two phages were assessed by an animal experiment. The three-dimensional (3D) structural model of EtAMA1 extracellular domain (EctoAMA1) protein was constructed based on the crystal template of TgAMA1 (PDB ID: 2 × 2Z), and the molecular docking between target peptides and EctoAMA1 model was analyzed. The results showed that two selected phages strongly interacted with EctoAMA1 and sporozoites protein. Two corresponding specific EtAMA1-binding peptide (named L and C) showed significant effects on inhibiting sporozoite invasion of MDBK cells. Chickens orally fed the two target phages showed partial protection against homologous challenge. Homology modeling analysis showed an apical hydrophobic groove was shaped on the top of the EctoAMA1 model. Molecular docking indicated the interaction between the EctoAMA1 protein and the two peptides, which was mainly reflected by the hydrophobic interaction and formation of intermolecular hydrogen bond. The above results suggest that the peptides L and C, especially L peptide, competed with E. tenella rhotry neck protein 2 (EtRON2) for binding to EtAMA1 located on the surface of sporozoites, and therefore inhibited the parasite invasion into cells.


Necker cube: stimulus-related (low-level) and percept-related (high-level) EEG signatures early in occipital cortex.
During observation of an ambiguous Necker cube, our percept changes spontaneously although the external stimulus does not. An EEG paradigm allowing time-resolved EEG measurement during endogenous perceptual reversals recently revealed a chain of ERP correlates beginning with an early occipital positivity at around 130 ms (Reversal Positivity, "RP"). In order to better understand the functional role of this RP, we investigated its relation to the P100, which is spatiotemporally close, typically occurring 100 ms after onset of a visual stimulus at occipital electrodes. We compared the relation of the ERP amplitudes to varying sizes of ambiguous Necker cubes. The main results are: (1) The P100 amplitude increases monotonically with stimulus size but is independent of the participants' percept. (2) The RP, in contrast, is percept-related and largely unaffected by stimulus size. (3) A similar pattern to RP was found for reaction times: They depend on the percept but not on stimulus size. We speculate that the P100 reflects processing of elementary visual features, while the RP is related to a processing conflict during 3D interpretation that precedes a reversal. The present results indicate that low-level visual processing (related to stimulus size) and (relative) high-level processing (related to perceptual reversal) occur in close spatial and temporal vicinity.


[Fever in children; a guide to treatment].
An exaggerated fear exists on behalf of parents of young children, aged 0 to 3, and sanitary professionals regarding fever and its complications; this fear is the origin of many mistaken beliefs and attitudes on how to handle and treat fever. For this reason, a Guide to Treatment has been developed by means of systematic reviews, from other clinical practice guides, and original documents over the past ten years related to handling young children who have fever. This Guide exclusively summarizes those nursing practices in handling young children having fever which are contemplated in scientific literature and which provide sufficient rigor to be taken into consideration in our nursing work.


Risk factors for computed tomography angiography spot sign in deep and lobar intracerebral hemorrhage are shared.
Patients with intracerebral hemorrhage (ICH) who present with a spot sign on computed tomography angiography are at increased risk of hematoma expansion and poor outcome. Because primary ICH is the acute manifestation of chronic cerebral small vessel disease, we investigated whether different clinical or imaging characteristics predict spot sign presence, using ICH location as a surrogate for arteriolosclerosis- and cerebral amyloid angiopathy-related ICH. Patients with primary ICH and available computed tomography angiography at presentation were included. Predictors of spot sign were assessed using uni- and multivariable regression, stratified by ICH location. Seven hundred forty-one patients were eligible, 335 (45%) deep and 406 (55%) lobar ICH. At least one spot sign was present in 76 (23%) deep and 102 (25%) lobar ICH patients. In multivariable regression, warfarin (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.01-5.71; P=0.04), baseline ICH volume (OR, 1.20; 95% CI, 1.09-1.33, per 10 mL increase; P<0.001), and time from symptom onset to computed tomography angiography (OR, 0.89; 95% CI, 0.80-0.96, per hour; P=0.009) were associated with the spot sign in deep ICH. Predictors of spot sign in lobar ICH were warfarin (OR, 3.95; 95% CI, 1.87-8.51; P<0.001) and baseline ICH volume (OR, 1.20; 95% CI, 1.10-1.31, per 10 mL increase; P<0.001). The most potent associations with spot sign are shared between deep and lobar ICH, suggesting that the acute bleeding process that arises in the setting of different chronic small vessel diseases shares commonalities.


Effect of the vertical position of the canine on the frictional/orthodontic force ratio of Ni-Ti archwires during the levelling phase of orthodontic treatment.
This study investigated the effect of the vertical position of the canine on changes in the frictional/orthodontic (F/O) force ratio of nickel-titanium (Ni-Ti) archwires during the initial levelling phase of orthodontic treatment. Frictional and orthodontic forces were measured by using low-friction brackets and Ni-Ti archwires with three different cross-sectional sizes and force types. To simulate canine malocclusion (first premolar extraction case), the upper right canine was displaced gingivally by 1 to 3 mm and the inter-bracket distance between the upper right lateral incisor and second premolar was set at 15 mm or 20 mm. A three-point bending test was performed to measure the orthodontic force of each Ni-Ti archwire. Frictional forces were measured with a universal testing machine and dental arch models by pulling parallel to the end of the archwire at a crosshead speed of 0.5 mm/min. F/O force ratio was calculated and analysed statistically. At a displacement of 3 mm, few archwires had F/O force ratios of less than 1.0, at which orthodontic force overcame frictional force, thus ensuring extrusion of the canine. For effective tooth movement, orthodontists should use Ni-Ti archwires with an F/O force ratio of less than 1.0.


Sexual minority men want provider behavior consistent with attitudes and norms during patient-provider interactions regarding HIV prevention.
HIV is a health problem for sexual minority men in the United States. One factor among many that contributes to this HIV disparity is poor patient-provider interactions. We focused on specific provider behavior preferred by sexual minority men during patient-provider interactions about HIV prevention. We interviewed 20 HIV-negative sexual minority men who endorsed 1+ psychosocial HIV risk factor. We used follow up interviews and conventional content analysis. Among our sample, 55% identified as White; 50% as bisexual, (Mage = 28.45). Findings suggested even some providers knowledgeable about sexual minority health provided unhelpful care to sexual minority men (knowledge-behavior discrepancy). Some knowledgeable providers engaged in affirmative, tailored treatment (knowledge-behavior consistency). Specific behaviors of preferred patient-provider interactions regarding HIV prevention are reported. Our recommendations are based on patient perceptions, which is a limit and strength. We identified an important type of unhelpful patient-provider interaction for HIV-negative sexual minority men beyond discriminatory experiences. Patient-provider interaction efforts need to go beyond education to help providers practice skills. With increased focus on cultural competency for sexual minority patients, more providers may advertise their practice as affirmative, yet interactions will likely vary, may require lifelong practice of cultural humility, and impact HIV prevention.


Medication administration hassles for Mexican American family caregivers of older adults.
In order to take their medications at home, elders rely increasingly on their family, but little is known about the factors influencing this task. This study explored the effects of acculturation and social exchange on the hassles that Mexican American (MA) family caregivers face in administering medication to their elders. A descriptive, correlational design, with a convenience sample of 239 MA adult caregivers of elders who were on a daily prescription that was recruited in Dallas, Texas and San Diego, California, USA, was used. The caregivers' scores on the medication administration hassles scale were significantly affected by acculturation and social exchange factors that explained 36% of the variance in the scores; the social exchange block had a larger influence than did the acculturation block. Caregiving might be an outcome of dynamic family exchange relationships between the caregiving dyad. The results can help healthcare professionals to detect potentially at-risk MA families and provide them with culturally appropriate nursing interventions.


Electron transfer oxidation of DNA radicals by paranitroacetophenone.
The reaction of a typical electron-affinic sensitizer, paranitroacetophenone (PNAP) with the model compounds thymine, thymidine, thymidylic acid, deoxyribose and single and double-stranded DNA has been investigated by pulse radiolysis. Radicals formed by one-electron reduction of the bases and of DNA react rapidly and efficiently with PNAP by electron transfer. A small yield of transfer (less than 10 per cent) is also observed arising from oxidation of the radicals formed by the small proportion of OH which react at the sugar moieties in DNA. In contrast, electron transfer oxidation by PNAP of radicals formed by the addition of OH to the base moieties, e.g. thymine, is not an efficient process. Further, addition of the sensitizer to the thymine OH-adduct proceeds at a rate that is too low to measure by pulse radiolysis. We conclude that, since the major sites of OH reaction with DNA are the heterocyclic bases (greater than 80 per cent), oxidation of the resultant radicals is unlikely to be a major step in the mechanism of sensitization by this typical hypoxic-cell sensitizer.


Transformation of murine pre-B-lymphocytes by v-erb-B: progression to growth factor independence and tumorigenicity.
v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leukemia virus and containing a chimeric gag-v-erb-B gene, to determine the murine hematopoietic cells transformed by v-erb-B. Infection of day 16.5 murine embryonal cells in liquid culture with this virus resulted in the outgrowth of foci of loosely to non-adherent hematopoietic cells which grew in close association with an adherent monolayer. After several weeks in culture a clonal population of transformed pre-B-lymphocytes emerged from this transformation initiated, though still growth factor dependent, population. These transformed cells were growth factor independent, and were tumorigenic in syngeneic mice. The results indicate that although v-erb-B can initiate transformation of murine hematopoietic cells, additional events are required for establishment of the fully transformed growth factor independent, tumorigenic phenotype. This v-erb-B induced progression from growth factor dependence to independence provides an in vitro model system for analysing events involved in the initiation and maintenance of leukemia.