Consistency of fat mass--fat-free mass relationship across ethnicity and sex groups.
The model developed by Forbes (1987) of how body fat mass (FM) and fat-free mass (FFM) change during periods of weight loss or gain (Δ body weight (BW)) assumed that they change in relationship to a constant C = 10·4, where ΔFFM/ΔBW = 10·4/(10·4+FM). Forbes derived C based on aggregated, cross-sectional data from a small sample of women. The objective of the present study was to reanalyse the relationship described by Forbes and to explore whether this relationship is consistent across ethnicity and sex groups using cross-sectional data from a large sample of white and African-American men and women. Baseline data from white and African-American men and women aged 18-60 years, who participated in a clinical study at the Pennington Biomedical Research Center since 2001 and who underwent dual-energy X-ray absorptiometry scans, were available for analysis. To overcome differences in BMI distributions among the ethnicity-by-sex groups, a stratified random sample of participants was selected within each group such that numbers in each BMI category ( < 25, 25-29·9, 30-34·9, 35-39·9, 40+ kg/m2) were proportional to those within the group with the smallest sample size, yielding a sample of 1953 individuals. Linear regression models assessed the FM-FFM relationship across the four ethnicity-by-sex groups. The FM-FFM relationship varied little by ethnicity (P = 0·57) or by sex (P = 0·26). The constant describing the FM-FFM relationship was estimated to be 9·7 (95 % CI 9·0, 10·3). In conclusion, results from our large, biethnic sample of men and women found a FM-FFM relationship very close to that originally described by Forbes, absent of significant variability by ethnicity or sex.


Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis.
Earlier four monoclonal antibodies (MAbs) against surface glycoproteins Gn and Gc of puumala virus (PUUV, genus Orthohantavirus, family Hantaviridae, order Bunyavirales) were generated and for three MAbs with neutralizing capacity the localization of binding epitopes was predicted using pepscan and phage-display techniques. In this work, we produced vesicular stomatitis virus (VSV) particles pseudotyped with the Gn and Gc glycoproteins of PUUV and applied site-directed mutagenesis to dissect the structure of neutralizing epitopes. Replacement of cysteine amino acid (aa) residues with alanines resulted in pseudotype particles with diminished (16 to 18 %) neut-titres; double Cys→Ala mutants, as well as mutants with bulky aromatic and charged residues replaced with alanines, have shown even stronger reduction in neut-titres (from 25 % to the escape phenotype). In silico modelling of the neut-epitopes supported the hypothesis that these critical residues are located on the surface of viral glycoprotein molecules and thus can be recognized by the antibodies indeed. A similar pattern was observed in experiments with mutant pseudotypes and sera collected from patients suggesting that these neut-epitopes are utilized in a course of human PUUV infection. These data will help understanding the mechanisms of hantavirus neutralization and assist construction of vaccine candidates.


[Fiber in the treatment of obesity and its comorbidities].
A considerable part of the health-care significance of obesity lies in its co-morbidity. Obesity is associated with high blood pressure, type 2 diabetes mellitus and dyslipidaemia, representing both individually and when taken together risk factors for cardiovascular disease, the main cause of death in industrialized countries. The influence of fibre consumption on body weight, the risk of type 2 diabetes and cardiovascular disease has been shown in important epidemiological surveys, but the mechanisms whereby fibre exercises this protective effect have not been definitively clarified. For the most part, the ability of fibre to slow down the process of absorption of nutrients by modifying the metabolic response to intake, its ability to increase the excretion of biliary acid and the metabolic effects of the short-chain fatty acids produced in the bacterial fermentation of fibre have all focussed the attention of the working hypotheses analyzed in the studies published in the last few years. This review is intended to identify the importance of fibre for the prevention and treatment of obesity and its comorbidities on the basis of the available evidence at present.


[Comparison of long-chain polyunsaturated fatty acids in plasma and erythrocyte phospholipids for biological monitoring].
Previous data have indicated that the erythrocyte membrane may be the preferred sample type for assessing long-chain polyunsaturated fatty acid (LCPUFA) contents in cardiac and cerebral membranes. In this epidemiological study, we examined whether plasma phospholipids can be used for accurate biological monitoring of the LCPUFA state or whether analysis of erythrocyte membrane phospholipids is indispensable. (1) The analysis of LCPUFA contents in erythrocyte membrane phospholipids was conducted at baseline and after 1 and 3 days at 4°C, and 21 days at -40°C, after blood drawing, and the changes in LCPUFA content were examined. (2) The LCPUFA compositions of plasma and erythrocyte phospholipids in 133 young women (18-30 years old) were examined and the relationships between the sample type and the levels of LCPUFAs were determined. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and DHA/arachidonic acid (AA) and (EPA+DHA)/AA ratios in erythrocyte membrane phospholipids after 21 days of blood drawing significantly decreased compared with the corresponding baseline data. Regarding AA, EPA and DHA, a significant positive correlation was shown between levels of erythrocyte membrane phospholipids and plasma phospholipids (AA, r=0.364; EPA, r=0.709; DHA, r=0.653). The predictive value of plasma phospholipids for determining the highest concentration quartile in erythrocyte phospholipids was better in EPA (70%) than in DHA (55%) and AA (42%). The measurement of LCPUFA content in erythrocyte membrane phospholipids is necessary for accurate biological monitoring. We also found that LCPUFA in erythrocyte membrane phospholipids is stable in cold storage (4°C) for 3 days after blood drawing.


Stroop interference depends also on the level of automaticity of the to-be-interfered process.
The size of the Stroop effect is usually taken as dependent on the level of practice of the more automatized of two competing processes (e.g., reading in the standard Stroop task), possibly modulated in children by the age-dependent ability to inhibit nonrelevant information. However, this conclusion stems from experimental settings where the automaticity of the second process (e.g., color naming) is hard to assess and manipulate. The musical Stroop task, in which a note name is written inside a note on a staff, overcomes this limit. In the present experiment, children engaged in musical education were asked to read the written note names while ignoring the notes on the staff, or conversely, to name the notes while ignoring the written names. Both a Stroop-like effect and its reverse were observed, but, unexpectedly, the two effects did not evolve in parallel even though both musical and reading abilities improved during practice. Introducing the level of immunity to interference of the to-be-interfered process as a predictor of Stroop interference, in addition to the strength of the interfering process, appears as the best way to account for the interactive pattern.


The development of electrically conductive polycaprolactone fumarate-polypyrrole composite materials for nerve regeneration.
Electrically conductive polymer composites composed of polycaprolactone fumarate and polypyrrole (PCLF-PPy) have been developed for nerve regeneration applications. Here we report the synthesis and characterization of PCLF-PPy and in vitro studies showing PCLF-PPy materials support both PC12 cell and dorsal root ganglia (DRG) neurite extension. PCLF-PPy composite materials were synthesized by polymerizing pyrrole in preformed PCLF scaffolds (M(n) 7,000 or 18,000 g mol(-1)) resulting in interpenetrating networks of PCLF-PPy. Chemical compositions and thermal properties were characterized by ATR-FTIR, XPS, DSC, and TGA. PCLF-PPy materials were synthesized with five different anions (naphthalene-2-sulfonic acid sodium salt (NSA), dodecylbenzenesulfonic acid sodium salt (DBSA), dioctyl sulfosuccinate sodium salt (DOSS), potassium iodide (I), and lysine) to investigate effects on electrical conductivity and to optimize chemical composition for cellular compatibility. PCLF-PPy materials have variable electrical conductivity up to 6 mS cm(-1) with bulk compositions ranging from 5 to 13.5 percent polypyrrole. AFM and SEM characterization show microstructures with a root mean squared (RMS) roughness of 1195 nm and nanostructures with RMS roughness of 8 nm. In vitro studies using PC12 cells and DRG show PCLF-PPy materials synthesized with NSA or DBSA support cell attachment, proliferation, neurite extension, and are promising materials for future studies involving electrical stimulation.


Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: a candidate gene approach.
Experimental evidence shows that telomere shortening induces mitochondrial damage but so far studies in humans are scarce. Here, we investigated the association between leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in elderly and explored possible intermediate mechanisms by determining the gene expression profile of candidate genes in the telomere-mitochondrial axis of ageing. Among 166 non-smoking elderly, LTL, leukocyte mtDNA content and expression of candidate genes: sirtuin1 (SIRT1), tumor protein p53 (TP53), peroxisome proliferator-activated receptor γ-coactivator1α (PGC-1α), peroxisome proliferator-activated receptor γ-coactivator1β (PGC-1β), nuclear respiratory factor 1 (NRF1) and nuclear factor, erythroid 2 like 2 (NRF2), using a quantitave real time polymerase chain assay (qPCR). Statistical mediation analysis was used to study intermediate mechanisms of the telomere-mitochondrial axis of ageing. LTL correlated with leukocyte mtDNA content in our studied elderly (r = 0.23, p = 0.0047). SIRT1 gene expression correlated positively with LTL (r = 0.26, p = 0.0094) and leukocyte mtDNA content (r = 0.43, p < 0.0001). The other studied candidates showed significant correlations in the telomere-mitochondrial interactome but not independent from SIRT1. SIRT1 gene expression was estimated to mediate 40% of the positive association between LTL and leukocyte mtDNA content. The key finding of our study was that SIRT1 expression plays a pivotal role in the telomere-mitochondrial interactome.


Four-Corner Concept: CT-Based Assessment of Fracture Patterns in Distal Radius.
Operative treatment using plate fixation is an important adjunct in the treatment of distal radius fractures, although the evidence for its superiority over other modalities remains limited. We propose a new concept for fractures of the distal radius, based on the three-column model of the distal radius, and on the expanding knowledge about the different fracture patterns obtained by evaluation of the distal radius by computed tomographic (CT) scan. All fracture types can be characterized by subdividing the wrist joint into four corners, each with its own characteristics in terms of mobility, stability, and transfer of forces in the intact distal radius. Recognition of the specific fracture types based on this four-corner concept enables a tailored approach to treatment.


Synergy of microRNA and stem cell: a novel therapeutic approach for diabetes mellitus and cardiovascular diseases.
MicroRNAs ( miRNAs) are highly conserved, 19-23 nucleotide long, non-coding, endogenous RNA, which are transcribed from either intergenic, intronic or polycistronic regions and modulate gene expression through mRNA degradation or translational repression. They are fine tuners of biological processes and have recently emerged as biomarkers and therapeutic targets of cardiovascular diseases. Several miRNAs regulate stem cell for differentiation, proliferation and degeneration. Stem cells are pluripotent, self-renewing and clonogenic cells having tremendous potential for regenerative therapy. The current therapeutic approach is unable to cope up with rapidly increasing rates of diabetes and cardiovascular diseases. The empirical and clinical evidences revealed that transplantation of exogenous stem cells can regenerate beta cells in diabetic patients and myocardium in patients with myocardial infarction. Nevertheless, the major limitation of stem cell therapy is unpredictable behavior of exogenous stem cells that incur few reports of teratoma and cancer after transplantation. Therefore, understanding the regulation of newly transplanted stem cells into the foreign body is a major challenge to translational research / clinical trail. Since miRNA plays pivotal role in the fine regulation of proliferation and differentiation of stem cells, investigations on the regulation of miRNA in transplanted stem cells in a specific micro-environment that houses the stem cell is indispensable. Additionally, the inhibition or over expression of specific miRNAs in the niche surrounding the stem cell will be crucial for maintaining the specific lineage of exogenous stem cells. This review embodies major advancement in the field of miRNA biogenesis and its regulatory mechanisms, role of different miRNAs and stem cells as a therapeutic target for diabetes and cardiovascular diseases. It also provides insights into the novel future therapy, where synergistic approach for manipulating miRNAs and stem cells will emerged as a potential treatment for diabetes and cardiovascular diseases.


Clinical Reasoning: Pediatric Seizures of Unknown Cause.
We describe a neonate and a 14-month-old child presenting with seizures that were not (completely) controlled with antiepileptic medications. There were no signs of infection, and electrolytes and neuroimaging were normal. In the neonate, pyridoxine was administered followed by cessation of seizures, and a diagnosis of pyridoxine-dependent epilepsy (PDE-ALDH7A1, a neurometabolic disorder of lysine metabolism) was genetically confirmed. The 14-month-old child received a genetic diagnosis of PDE-ALDH7A1 after abnormalities in the metabolic investigations. Both children were treated with pyridoxine and adjunct lysine reduction therapy (LRT). Seizures were controlled completely, but both children are developmentally delayed. During her second pregnancy, the mother of the neonate was started on pyridoxine treatment because of the risk of PDE-ALDH7A1. After delivery, pyridoxine treatment was continued in the neonate, who did not show any clinical symptoms. Molecular analysis identified the familial variants consistent with the diagnosis of PDE-ALDH7A1. Adjunct LRT was initiated. This child has never experienced seizures, and development has been completely normal thus far (age 2.9 years), despite the shared genotype with their sibling with developmental delays (DDs). In conclusion, in neonates, infants, and children presenting with seizures of unknown origin with partial or no response to common antiepileptic medications, the diagnosis of PDE-ALDH7A1 or other pyridoxine-responsive genetic epilepsies should be considered, prompting a trial of pyridoxine as "diagnostic therapeuticum." The digital application Treatable-ID (treatable-id.org) can support clinicians in the early diagnosis of treatable conditions in patients presenting with DD/intellectual disability of unknown cause.


Normal and abnormal retinal projections following the crush of one optic nerve in goldfish (Carassius auratus).
Optic nerve regeneration was examined with [3H]proline radioautography in fish that had one nerve crushed. Fibers had not yet grown beyond the crush site at 2 days post-crush (PC) and were at the optic chiasm by 4-5 days PC. By 6 days PC the fibers had reinnervated the rostral pole of the contralateral tectum, the lateral geniculate nucleus and area pretectalis dorsalis and ventralis. Area preopticus, nucleus opticus dorsolateralis and nucleus opticus commissurae posterior were partially reinnervated by 8 days PC. At this time numerous abnormal targets were labeled, including nucleus rotundus, nucleus isthmi, cerebellum, pituitary gland and ipsilateral optic tectum. Optic fibers also entered the posterior, intertectal and horizontal commissures, as well as tractus rotundus, the tectocerebellar, tectobulbar and mesencephalocerebellar tracts. In addition, fibers with the contralateral optic tectum were not restricted to their usual laminae. They were distributed from the superficial edge of the tectum to the ventricle. At 32 days PC only the normal retinal projections were evident, and all of the anomalous projections had disappeared. The anomalous projections may have either retracted or degenerated or become undetectable with radioautography.


Prevalence of Trichinella nativa in lynx (Felis lynx) from Alaska, 1988-1993.
Lynx (Felis lynx) carcasses were collected during the 1989 to 1990 through 1992 to 1993 trapping seasons in Alaska (USA). Seven areas were represented. Tongue samples were removed from 1,065 carcasses. Specimens were examined for the presence of Trichinella nativa larvae by means of enzymatic digestion. Overall prevalence was 21%. Both prevalence and number of larvae per gram of host tissue were directly related to age of the host. Age-specific prevalence ranged from 4% for kittens up to 59% for lynx 5 yr of age and older. For infected lynx, intensity ranged from 0.27 larvae per gram of host tissue for kittens up to 2.35 larvae per gram for lynx 3 yr of age and older. Location-specific prevalence ranged from 19% to 27%. Year-specific prevalence ranged from 13% to 26%. Prevalence in both males and females was 21%.


Ultrastructural localization of the neurotrophin receptor (TrkA) in cultured rat pheochromocytoma PC12 Cells: three-dimensional image analysis by high voltage electron microscopy.
Nerve growth factor (NGF) is a well-known neurotrophic factor and the NGF signaling through the receptor, TrkA, plays important roles in regulating neuronal differentiation and survival. A recent study has demonstrated that the TrkAs expressed in undifferentiated PC12 cells were associated with caveolae, which were invaginated small pits on the plasma membrane. Caveolae are frequently seen in many cell types such as endothelial cells, fibroblasts and hepatocytes, but few in neurons. In the present study, we performed immunocytochemistry of TrkA in differentiated PC12 cells and analyzed the ultrastructural localization of TrkA by conventional electron microscopy and high-voltage electron microscopic (HVEM) tomography. The TrkA immunoreactivities were mainly associated with the cytoplasmic vesicles (10-30 nm in diameter) and a part of the plasma membrane. The HVEM tomography showed that the TrkA immunoreactivities were often assembled into ring-like structures (400-800 nm in diameter) near the plasma membrane, unlike typical flask-shaped invaginations of caveolae (50-100 nm in diameter). These results suggest that TrkA are not localized in the caveolae, at least in differentiated PC12 cells, but other invaginations are involved in a novel process of internalization of ligand-bound TrkA.


The Buffering Effect of Hope on Clinicians' Behavior: A Test in Pediatric Primary Care.
Although trait hope is thought to motivate goal directed actions in the face of impediments, few studies have examined directly hope's role in overcoming obstacles, and none have done so while accounting for related goal constructs. We describe a study of 127 pediatric primary care providers who over the course of a year were asked to identify new cases of asthma and confirm previously diagnosed active disease by completing for each of their patients a brief survey validated for this purpose. These clinicians also completed measures of hope, self-efficacy, conscientiousness, and perceived obstacles to implementing a pediatric asthma management program. As predicted by hope theory, the agency component of hope buffered clinicians from perceived obstacles by facilitating the identification of asthma cases among high hope clinicians in the face of obstacles. This buffering effect remained after controlling for self-efficacy and conscientiousness. We discuss the study findings in terms of current theories of goal directed behavior and implications for delivering hope-related interventions, and we offer a testable hypothesis regarding when agency and pathways thinking facilitate goal-related behavior.


Absolute exponential stability of a class of continuous-time recurrent neural networks.
This paper presents a new result on absolute exponential stability (AEST) of a class of continuous-time recurrent neural networks with locally Lipschitz continuous and monotone nondecreasing activation functions. The additively diagonally stable connection weight matrices are proven to be able to guarantee AEST of the neural networks. The AEST result extends and improves the existing absolute stability and AEST ones in the literature.


Hyperactive boys and their brothers. A 25-year follow-up study.
Twenty men, who had conformed to diagnostic criteria for the hyperactive child syndrome 20 to 25 years ago, and their brothers were interviewed. A large majority of men who were hyperactive had completed high school, and each was steadily employed and self-supporting. Half of the men who were hyperactive continued to show a number of symptoms of hyperactivity. Nearly half had problems of a psychiatric nature and despite normal intelligence quota scores and levels of education, these men had not achieved a socioeconomic status equal to that of their brothers or their fathers. Our findings suggest that emotional problems in everyday living may result from the persistance of symptoms of hyperactivity and that most social and psychiatric consequences of the disorder relate to its presence in childhood as well as to its persistance in adulthood.


Are the perceptual effects of spectral smearing influenced by speaker gender?
The purpose of this study was to determine whether the effect of loss of spectral detail on speech perception is influenced by the gender of the speaker. Spectral smearing was carried out by multiplying the speech signal by a series of low-passed white noise samples, causing tonal components in the signal to be replaced by noise. Smearing bandwidths of 0 Hz (no smearing), 250 Hz, 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz, 8,000 Hz and full bandwidth were used. Smearing was applied to 15 isophonemic lists, each with 10 one-syllable CVC Hebrew words. The words were recorded using two speakers, a male and a female, both native speakers of Hebrew. A total of 23 subjects participated in the study: eight listened to the male speaker and 15 to the female. The results show no significant differences in the effect of speaker on recognition of words, phonemes, vowels and consonants at the different smearing bandwidths. The results also show that regardless of the speaker's gender, vowels were adversely affected by spectral smearing, as compared to consonants. Interpolation of the results shows that smearing bandwidths of 1,080 Hz, 1,950 Hz, 1,590 Hz and 2,150 Hz are required to reduce word, phoneme, vowel and consonant recognition to 50%, respectively. Several tentative explanations are offered for the fact that the results were independent of gender: all smearing bandwidths were larger than the average interharmonic spacing for both speakers, and the difference between male and female formant frequencies is typically smaller then the difference in formant frequencies of the different vowels.


Dedifferentiated liposarcoma of the retro-peritoneum: histologically low-grade type.
A dedifferentiated liposarcoma of the retro-peritoneum of a 45-year-old female is described in this case report. It showed dedifferentiation into a histological low-grade type and thus defies the traditional definition of dedifferentiated liposarcoma. The excised specimen was a huge, multi-nodular encapsulated mass surrounding the kidney and infiltrating into it. The mass showed a dedifferentiated focus different in color from the surrounding tumor and containing areas of necrosis and hemorrhage. The sections from the dedifferentiated part of the tumor appeared predominantly as benign spindle cell component on histology but the tumor was infiltrating into the kidney. Hence, a close and long-term follow-up is expected in such cases though they look benign. In the retro-peritoneum, a lipoma-like well-differentiated liposarcoma with spindle cell component, like the present tumor, which shows dedifferentiation, should not be overlooked.


Effective impedance of rough porous ground surfaces
Laboratory measurements at grazing angles of the impedance of sand surfaces containing artificial two-dimensional (2D) roughness are compared with predictions of an extended boss theory, which allows for incoherent scatter, randomness, and finite impedance effects. The data and predictions are found to be in reasonable agreement. The rough surface impedance model may be used, as an alternative to layering, to explain measurements where the reactance exceeds the resistance at low frequencies. The model also explains instances where the measured ground impedance tends to zero at higher frequencies. In addition, the model is found to predict features of measurements made with an elevated source and vertically separated receivers at a range of 30 m over cultivated ground surfaces.


[Diagnosis and treatment of the cruciate ligament injury of knee joint].
During 1959 to 1986, 62 Cases with cruciate ligament injury of the knee joint were treated in our hospital. Thirty of these cases were anterior cruciate ligament injuries and 32 cases were posterior The diagnosis of the cruciate ligament injuries was made by stability tests of the cruciate ligament. When the knee was greatly swollen with multiple ligament injuries, a series of X-ray films should be taken to test the knee stability under local or nerve block anesthesia. Fresh tear of the cruciate ligament (33 cases) was treated with immediate surgical repair except in one. Old ligament injuries (28 cases) were treated by conservative method (10 cases) or surgical reconstruction (18 cases). All patients were followed for 2 to 18 years (mean 6 years). The results showed that the fresh tear of the cruciate ligament treated surgically had excellent and good rates in 87.9% (29/33). In the conservative treatment group, only 27.3% (3/11) obtained good result, and most of them were complicated with meniscal lesions and osteoarthritis. Eighteen cases treated by ligament reconstruction gave 34.5% (8/18) good result.


The Association of Physical Activity Level with Micronutrient and Health Status of Austrian Bank Employees.
Favorable health benefits of an active lifestyle have been clearly documented within the context of occupational health. However, a knowledge gap exists regarding the monitoring and comparison of micronutrient status across varying levels of physical activity (PA). This study aimed to investigate the association of PA level with micronutrient status and the associated health biomarkers among a cohort of Austrian bank employees. Using a cross-sectional design, this study involved the participation of bank employees (n = 123; average age: 43 years; 49% males) from the federal state of Tyrol, located in the western part of Austria. To assess PA levels and sedentary behavior, the Global Physical Activity Questionnaire (GPAQ; developed by the WHO) was administered. Accordingly, participants were categorized into three groups: low PA, moderate PA, and high PA. Participants' blood samples were obtained to measure blood levels of micronutrients, homocysteine, and CoQ10. The values of vitamins and minerals in whole-blood were compared to sex-specific reference ranges and grouped into three categories: below, within, or exceeding the reference range. The prevalence of a high PA level was 61%, while 18% of participants had a low PA level. Overweight/obesity was significantly less prevalent among participants with high PA levels (22%) compared to those with moderate (50%) and low (50%) PA levels (p = 0.045). No significant differences between PA levels were found for sex, age, diet type, homocysteine, or CoQ10 markers (p > 0.05). There was no significant PA-based difference in blood concentrations of most vitamins and minerals (p > 0.05), except for vitamin D (p = 0.001) among females, as well as selenium (p = 0.040) and vitamin B12 (p = 0.048) among males. The present findings offer initial insights into the link between PA behaviors, micronutrient status, and health, highlighting potential implications in occupational health and lifestyle, specifically in developing tailored approaches based on PA levels.


Comparative Transcriptome Analysis of Acne vulgaris, Rosacea, and Hidradenitis Suppurativa Supports High Dose Dietary Zinc as a Therapeutic Agent.
Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. We also identified high dose dietary zinc as a potential therapeutic agent and validated its efficacy in an acne mouse model.


Potential of Pseudomonas chlororaphis subsp. aurantiaca Strain Pcho10 as a Biocontrol Agent Against Fusarium graminearum.
To develop an effective biocontrol strategy for management of Fusarium head blight on wheat caused by Fusarium graminearum, the bacterial biocontrol agent Pcho10 was selected from more than 1,476 wheat-head-associated bacterial strains according to its antagonistic activity in vitro. This strain was subsequently characterized as Pseudomonas chlororaphis subsp. aurantiaca based on 16S ribosomal DNA sequence analysis, assays of the BIOLOG microbial identification system, and unique pigment production. The major antifungal metabolite produced by Pcho10 was further identified as phenazine-1-carboxamide (PCN) on the basis of nuclear magnetic resonance data. The core PCN biosynthesis gene cluster in Pcho10 was cloned and sequenced. PCN showed strong inhibitory activity against F. graminearum conidial germination, mycelial growth, and deoxynivalenol production. Tests both under growth chamber conditions and in field trials showed that Pcho10 well colonized on the wheat head and effectively controlled the disease caused by F. graminearum. Results of this study indicate that P. chlororaphis subsp. aurantiaca Pcho10 has high potential to be developed as a biocontrol agent against F. graminearum. To our knowledge, this is the first report of the use of P. chlororaphis for the management of Fusarium head blight.


Induction of segmentation in polyps of Aurelia aurita (Scyphozoa, Cnidaria) into medusae and formation of mirror-image medusa anlagen.
Polyps of Aurelia aurita can transform into several medusae (jellyfish) in a process of sequential subdivision. During this transformation, two processes take place which are well known to play a key role in the formation of various higher metazoa: segmentation and metamorphosis. In order to compare these processes in bilaterians and cnidarians we studied the control and the kinetics of these processes in Aurelia aurita. Segmentation and metamorphosis visibly start at the polyp's head and proceed down the body column but do not reach the basal disc. The small piece of polyp which remains will develop into a new polyp. The commitment to the medusa stage moves down the body column and precedes the visible onset of segmentation by about one day. Segmentation and metamorphosis can start at the cut surface of transversely cut body columns, leading to a mirror-image pattern of sequentially developing medusae.


[Surgical treatment of ulcerous pyloroduodenal stenosis].
From 1990 to 2001 531 patients underwent surgery for ulcerous pyloroduodenal stenosis, from 1990 to 1995 312 operations were performed with lethality 0.9%, from 1996 to 2001--312 surgeries with one lethal outcome (0.4%). Surgical policy is based on a differential approach to choice of surgical method with consideration of stage of stenosis and level of gastric secretion, and also surgical risk. Organ-saving operations including laparoscopic vagotomy were performed in forming and compensated stenosis. At late stages (sub- and decompensated stenosis) resections (chiefly with vagotomy) were performed. In long-term period excellent and good results were achieved in 91.4% patients.


Surgeon-related factors and outcome in rectal cancer.
To determine whether surgical subspecialty training in colorectal surgery or frequency of rectal cancer resection by the surgeon are independent prognostic factors for local recurrence (LR) and survival. Variation in patient outcome in rectal cancer has been shown among centers and among individual surgeons. However, the prognostic importance of surgeon-related factors is largely unknown. All patients undergoing potentially curative low anterior resection or abdominoperineal resection for primary adenocarcinoma of the rectum between 1983 and 1990 at the five Edmonton general hospitals were reviewed in a historic-prospective study design. Preoperative, intraoperative, pathologic, adjuvant therapy, and outcome variables were obtained. Outcomes of interest included LR and disease-specific survival (DSS). To determine survival rates and to control both confounding and interaction, multivariate analysis was performed using Cox proportional hazards regression. The study included 683 patients involving 52 surgeons, with > 5-year follow-up obtained on 663 (97%) patients. There were five colorectal-trained surgeons who performed 109 (16%) of the operations. Independent of surgeon training, 323 operations (47%) were done by surgeons performing < 21 rectal cancer resections over the study period. Multivariate analysis showed that the risk of LR was increased in patients of both noncolorectal trained surgeons (hazard ratio (HR) = 2.5, p = 0.001) and those of surgeons performing < 21 resections (HR = 1.8, p < 0.001). Stage (p < 0.001), use of adjuvant therapy (p = 0.002), rectal perforation or tumor spill (p < 0.001), and vascular/neural invasion (p = 0.002) also were significant prognostic factors for LR. Similarly, decreased disease-specific survival was found to be independently associated with noncolorectal-trained surgeons (HR = 1.5, p = 0.03) and surgeons performing < 21 resections (HR = 1.4, p = 0.005). Stage (p < 0.001), grade (p = 0.02), age (p = 0.02), rectal perforation or tumor spill (p < 0.001), and vascular or neural invasion (p < 0.001) were other significant prognostic factors for DSS. Outcome is improved with both colorectal surgical subspecialty training and a higher frequency of rectal cancer surgery. Therefore, the surgical treatment of rectal cancer patients should rely exclusively on surgeons with such training or surgeons with more experience.


Three cases of akathisia and "acting out".
Three cases of akathisia are described in which the manifestations of motor restlessness were subtle enough to be easily missed, but in which the resultant propensities to behavioral "action" nonetheless contributed to significant difficulties for the patients. Appropriate medication adjustments, including adequate treatment with antiparkinsonian agents or suitable lowering of neuroleptic dosage, were beneficial. Subtle manifestations of akathisia of this sort may occur more frequently than is commonly recognized.


Keloids: a prospective study of 57 cases.
Of the total 57 cases of keloids, 8 cases of massive keloids were treated by diathermy excision and immediate skin grafting; 35 keloids of ear lobule by intramarginal excision and post-operative local hydrocostisone; 7 presternal keloids by local corticoids alone and a miscellaneous group of 7 cases of keloids were treated by combination therapy. It is concluded that massive keloids with or without sinuses and keloidal contractures require surgery to improve appearance and function respectively. Ear lobule keloids are best treated by intramarginal excision and post-operative local hydrocortisone. Presternal keloids and small keloids elsewhere should be treated by intralesional injection of corticoids alone. Initial results of intramarginal excision with or without local corticoids were satisfactory. However it is too early to claim best result with this regimen, in the absence of long term follow up.


Blunt rupture of the heart in a child.
The spectrum of blunt cardiac trauma ranges from injuries with no actual cellular damage (myocardial concussion) to cardiac chamber rupture. Although blunt injuries to the heart are common and potentially lethal, rupture of a cardiac chamber is rare. This injury should be suspected in any patient who presents with cardiac tamponade after blunt trauma. A child who sustained blunt rupture of the right atrium is presented, and the pathophysiology, diagnosis, and treatment of these injuries are discussed.


Too many, too few, too concentrated? A review of the pediatric subspecialty workforce literature.
To summarize recent pediatric subspecialty workforce analyses and to highlight similarities and differences across studies. By using MEDLINE, we conducted a systematic search of the literature published from January 1, 1992, through December 31, 2002. We included research articles and task force reports, and abstracted author, year of publication, specialty, sample size, analytic perspective (eg, physician or academic department), inclusion of data on nonclinical activities, inclusion of an objective measure of demand, and workforce-related conclusions. We identified 41 relevant articles. Physician surveys provided data for most (n = 24) of these studies. Only 8 studies attempted to make future workforce projections; of these 8 studies, 1 explicitly accounted for nonclinical activities in its projections. An additional 16 studies presented data on involvement in nonclinical activities. While some studies suggest that additional pediatric subspecialists are not needed, these studies did not include objective assessments of demand in geographic areas where pediatric subspecialty physicians are not available. Of those studies that took a market perspective and attempted to account for demand, workforce recommendations varied considerably across specialties. We know little about the distribution of the pediatric subspecialty workforce relative to the demand for their services. Given concerns about the adequacy of the pediatric subspecialty workforce, future research should assess the availability of these physicians relative to need for their services and account for nonclinical activities in workforce projections.


Effect of vitamin E supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials.
C-reactive protein (CRP), a marker of chronic inflammation, has a major role in the etiology of chronic disease. Vitamin E may have anti-inflammatory effects. However, there is no consensus on the effects of vitamin E supplementation on CRP levels in clinical trials. The aim of this study was to systematically review randomized controlled trials (RCTs) that report on the effects of vitamin E supplementation (α- and γ-tocopherols) on CRP levels. A systematic search of RCTs was conducted on Medline and EMBASE through PubMed, Scopus, Ovid and Science Direct, and completed by a manual review of the literature up to May 2014. Pooled effects were estimated by using random-effects models and heterogeneity was assessed by Cochran's Q and I(2) tests. Subgroup analyses and meta-regression analyses were also performed according to intervention duration, dose of supplementation and baseline level of CRP. Of 4734 potentially relevant studies, only 12 trials met the inclusion criteria with 246 participants in the intervention arms and 249 participants in control arms. Pooled analysis showed a significant reduction in CRP levels of 0.62 mg/l (95% confidence interval = -0.92, -0.31; P < 0.001) in vitamin E-treated individuals, with the evidence of heterogeneity across studies. This significant effect was maintained in all subgroups, although the univariate meta-regression analysis showed that the vitamin E supplementation dose, baseline level of CRP and duration of intervention were not the sources of the observed heterogeneity. The results of this meta-analysis suggest that supplementation with vitamin E in the form of either α-tocopherol or γ-tocopherol would reduce serum CRP levels.


High-resolution structure of eukaryotic Fibrillarin interacting with Nop56 amino-terminal domain.
Ribosomal RNA (rRNA) carries extensive 2'-O-methyl marks at functionally important sites. This simple chemical modification is thought to confer stability, promote RNA folding, and contribute to generate a heterogenous ribosome population with a yet-uncharacterized function. 2'-O-methylation occurs both in archaea and eukaryotes and is accomplished by the Box C/D RNP enzyme in an RNA-guided manner. Extensive and partially conflicting structural information exists for the archaeal enzyme, while no structural data is available for the eukaryotic enzyme. The yeast Box C/D RNP consists of a guide RNA, the RNA-primary binding protein Snu13, the two scaffold proteins Nop56 and Nop58, and the enzymatic module Nop1. Here we present the high-resolution structure of the eukaryotic Box C/D methyltransferase Nop1 from Saccharomyces cerevisiae bound to the amino-terminal domain of Nop56. We discuss similarities and differences between the interaction modes of the two proteins in archaea and eukaryotes and demonstrate that eukaryotic Nop56 recruits the methyltransferase to the Box C/D RNP through a protein-protein interface that differs substantially from the archaeal orthologs. This study represents a first achievement in understanding the evolution of the structure and function of these proteins from archaea to eukaryotes.


Is indexed preoperative superior vena cava blood flow a risk factor in patients undergoing bidirectional cavopulmonary shunt?
This study evaluated the effect of a new measurement-superior vena cava (SVC) flow-and anatomic factors on postoperative arterial oxygen saturation and clinical outcome in patients who underwent bidirectional cavopulmonary shunt (BCPS). We reviewed 19 patients who underwent a BCPS between January 2009 and May 2011 who also had SVC blood flow measurements. Median age was 6 months (range, 2 to 29 months). Body weight was 7.0 ± 1.7 kg. Bilateral SVCs were present in 4. SVC flow was measured at the time of BCPS by a Transonic flow probe (Transonic Systems Inc, Ithaca, NY). SVC flow, preoperative hemodynamics, pulmonary artery size, and clinical outcome were analyzed to determine risk for morbidity and death. Mean absolute and indexed pre-BCPS SVC flow was 0.65 ± 0.23 L/min and 1.63 ± 0.55 L/min/m(2) or 91.1 ± 30.8 mL/kg/min, respectively. In all but 1 patient, the SVC flow was increased after BCPS from 1.63 ± 0.55 to 1.99 ± 0.57 L/min/m(2) (p = 0.005). There was a significant positive correlation between pre-BCPS and post-BCPS SVC flow (r = 0.627, p = 0.029). Pulmonary artery size correlated with post-BCPS SVC flow (r = 0.560, p = 0.016). Two patients with preoperative SVC flow of below 1.0 L/min/m(2) died or required BCPS takedown. SVC size did not correlate with BCPS flow (r = 0.231, p = 0.356). Univariate analysis indicated pre-BCPS pulmonary artery pressure was a risk factor for low arterial oxygen saturation (≤ 75%) immediately after BCPS (p = 0.042) and at discharge (p = 0.030). A new indicator-low SVC flow, may be a marker for BCPS failure or death, suggesting that the SVC flow vs size is more important in predicting successful BCPS.


A multicenter application and evaluation of the oxford classification of IgA nephropathy in adult chinese patients.
The Oxford classification of immunoglobulin A (IgA) nephropathy (IgAN) provides a histopathologic grading system that is associated with kidney disease outcomes independent of clinical features. We evaluated the Oxford IgAN classification in a large cohort of patients from China. Retrospective study. 1,026 adults with IgAN from 18 referral centers in China. Inclusion criteria and statistical analysis were similar to the Oxford study. Histologic findings of mesangial hypercellularity score, endocapillary proliferation, segmental sclerosis or adhesion, crescents, necrosis, and tubular atrophy/interstitial fibrosis. Clinical features, blood pressure, estimated glomerular filtration rate (eGFR), proteinuria, and treatment modalities. Time to a 50% reduction in eGFR or end-stage renal disease (the combined event); the rate of eGFR decline (slope of eGFR); proteinuria during follow-up. Compared with the Oxford cohort, the Chinese cohort had a lower proportion of patients with mesangial hypercellularity (43%) and endocapillary proliferation (11%), higher proportion with segmental sclerosis or adhesion (83%) and necrosis (15%), and similar proportion with crescents (48%) and tubular atrophy/interstitial fibrosis (moderate, 24%; severe, 3.3%). During a median follow-up of 53 (25th-75th percentile, 36-67) months, 159 (15.5%) patients reached the combined event. Our study showed that patients with a mesangial hypercellularity score higher than 0.5 were associated with a 2.0-fold (95% CI, 1.5-2.8; P<0.001) higher risk of the combined event than patients with a score of 0.5 or lower. Patients with tubular atrophy/interstitial fibrosis of 25%-50% and >50% versus <25% were associated with a 3.7-fold (95% CI, 2.6-5.1; P<0.001) and 15.1-fold (95% CI, 9.5-24.2; P<0.001) higher risk of the combined event, respectively. Endocapillary proliferation, glomerular crescents, and necrosis were not significant. Retrospective study; the therapeutic interventions were miscellaneous. We confirmed the associations of mesangial hypercellularity and tubular atrophy/interstitial fibrosis with kidney disease outcomes.


We-talk, communal coping, and cessation success in a couple-focused intervention for health-compromised smokers.
We investigated first-person plural pronoun use (we-talk) by health-compromised smokers and their spouses as a possible implicit marker of adaptive, problem-resolving communal processes. Twenty couples in which one or both partners used tobacco despite one of them having a heart or lung problem participated in up to 10 sessions of a smoking cessation intervention designed to promote communal coping, where partners define smoking as "our" problem, rather than "your" problem or "my" problem, and take collaborative action to solve it. We used the Linguistic Inquiry Word Count automatic text analysis program to tabulate first-person pronoun use by both partners from transcripts of a pretreatment marital interaction task and later intervention sessions. Results indicated that pretreatment we-talk by the patient's spouse predicted whether the patient remained abstinent 12 months after quitting, and residualized change in we-talk by both partners during the course of intervention (controlling for baseline levels) predicted cessation outcomes as well. These findings add to evidence regarding the prognostic significance of partner we-talk for patient health and provide preliminary documentation of communal coping as a possible mechanism of change in couple-focused intervention.


Sequence variation of MicroRNAs and their binding sites in Arabidopsis.
Major differences exist between plants and animals both in the extent of microRNA (miRNA)-based gene regulation and the sequence complementarity requirements for miRNA-messenger RNA pairing. Whether these differences affect how these sites evolve at the molecular level is unknown. To determine the extent of sequence variation at miRNAs and their targets in a plant species, we resequenced 16 miRNA families (66 miRNAs in total) and all 52 of the characterized binding sites for these miRNAs in the plant model Arabidopsis (Arabidopsis thaliana), accounting for around 50% of the known miRNAs and binding sites in this species. As has been shown previously in humans, we find that both miRNAs and their target binding sites have very low nucleotide variation and divergence compared to their flanking sequences in Arabidopsis, indicating strong purifying selection on these sites in this species. Sequence data flanking the mature miRNAs, however, exhibit normal levels of polymorphism for the accessions in this study and, in some cases, nonneutral evolution or subtle effects on predicted pre-miRNA secondary structure, suggesting that there is raw material for the differential function of miRNA alleles. Overall, our results show that despite differences in the architecture of miRNA-based regulation, miRNAs and their targets are similarly constrained in both plants and animals.


Comparison of the recombinant Escherichia coli-produced protease domain of tissue-type plasminogen activator with alteplase, reteplase and streptokinase in a canine model of coronary artery thrombolysis.
Recent in vitro studies have shown that although recombinant Escherichia coli-produced protease domain of tissue-type plasminogen activator (t-PA) has no appreciable fibrin binding and less plasminforming activity compared to the wild-type, it is nevertheless an effective fibrinolytic agent in a dynamic in vitro plasma clot lysis system. The purpose of the present study was to evaluate the pharmacological profile of the protease in a canine model of coronary artery thrombosis. The effects of a single i.v. bolus injection of 1 mg/kg protease were compared with those of alteplase, reteplase and streptokinase at clinically relevant doses and dosing regimens in eight dogs per group. The protease rapidly restored coronary blood flow at 12 +/- 1 min in all treated dogs with a significantly higher maximal coronary blood flow than in the reference groups, but was associated with short cycles of reocclusion in 4/8 animals. Overall, the coronary blood flow quality of the protease was not significantly different from that of the reference thrombolytics. Although fibrinogen was nearly completely degraded during protease treatment, the bleeding time was not significantly more prolonged than in reference groups. In conclusion, the protease domain is a rapidly acting, effective, bolus-injectable thrombolytic agent associated with a systemic lytic state and does not appear to cause significantly more bleeding than the reference thrombolytic agents.


A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes.
Three independent pseudoautosomal loci are linked to sex determination at frequencies which define a gradient of linkage. The segregation patterns of these loci indicate that X/Y recombination results from a single obligatory meiotic crossing-over in the pseudoautosomal region. Recombination in male germ cells in the terminal regions of the short arms of the X and Y chromosomes in 10-fold greater than between the same regions of the X chromosomes in female germ cells.


[Protein concentration in the guinea-pig perilymph].
The protein concentration of the guinea pig perilymph was investigated systematically using a micro-modification of the method of Lowry et al. Perilymph of scala vestibuli and of scala tympani was obtained from living animals and immediately post mortem by various methods. In living animals it is especially difficult to obtain samples without blood contamination. Another problem in the obtaining of perilymph from living animals is the contamination of tympanic perilymph samples with cerebrospinal fluid. This contamination diminishes the protein concentration of perilymph to a high degree. When the subarachnoid space is opened suboccipitally before perilymph extraction, there is no significant difference between protein content in tympanic and vestibular perilymph. The mean protein concentration in both cochlea scales is about 150 mg/100 ml. When samples are extracted post mortem from animals perfused intra-arterially, mean values of protein are in the same range. Without perfusion of animals, the mean value of tympanic samples extracted post mortem is significantly higher. Causes of artefacts in perilymph investigations are discussed.


Granulocyte colony-stimulating factor (G-CSF) administration in individuals with sickle cell disease: time for a moratorium?
Granulocyte colony-stimulating factor (G-CSF) is used commonly in an attempt to reduce the duration of neutropenia and hospitalization in patients undergoing chemotherapy and to obtain hematopoietic stem cells (HSC) for transplantation applications. Despite the relative safety of administration of G-CSF in most individuals, including subjects with sickle cell trait, severe and life-threatening complications have been reported when used in individuals with sickle cell disease (SCD), including those who were asymptomatic and undiagnosed prior to administration. The administration of G-CSF has now been reported in a total of 11 individuals with SCD. Seven developed severe adverse events, including vaso-occlusive episodes, acute chest syndrome, multi-organ system failure and death. Precautions, including minimizing the peak white blood cell count, dividing or reducing the G-CSF dose and red blood cell transfusions to reduce sickle hemoglobin (HbS) levels, have been employed with no consistent benefit. These reported data indicate that administration of G-CSF in individuals with SCD should be undertaken only in the absence of alternatives and after full disclosure of the risks involved. Unless further data demonstrate safety, routine usage of G-CSF in individuals with SCD should be avoided.


Using Kendall's tau b correlations to improve variable selection methods in case-control studies.
In this manuscript we evaluate the performance of a variable selection procedure that could be used in case-control studies. This method is based on selection statistics computed from a matrix of Kendall tau b correlation coefficients. A simulation study was performed to compare the performance of this method to logistic regression, discriminant analysis, and the rank-transformed versions of these methods. For most of the situations studied the method based on Kendall tau b correlation coefficients correctly selected the variables that were related to case-control status more often than any of the other methods. We discuss the implications of the results of this study for epidemiologic research.


Cyanobacterial LPS potentiates cadmium toxicity in zebrafish (Danio rerio) embryos.
Cyanobacteria are prevalent in the freshwater environment, reaching critical mass in harmful algal blooms. These organisms produce a variety of toxins including endotoxins such as lipopolysaccharides (LPS), which have been previously shown to decrease glutathione-S-transferase (GST) activity in zebrafish (Danio rerio) embryos. GST plays a vital role in detoxification response during oxidative stress and provides a first line of defense after toxic heavy metal insult, before increased metallothionein expression. Although some attention has focused on cyanobacterial LPS, little research has focused on effects of concurrent exposures with other toxicants. Because cyanobacterial LPS can alter detoxification enzymes including GST, we hypothesized that cyanobacterial LPS could potentiate metal toxicity. This study investigated the effects of LPS from two cyanobacterial species, Lyngbya spp. and Microcystis aeruginosa, on cadmium toxicity in zebrafish embryos. Forty-eight-hour CdCl(2) LC(50) values showed that coexposure of cadmium and Lyngbya LPS or Microcystis LPS resulted in significantly increased cadmium toxicity in comparison with cadmium alone. However, increased cadmium toxicity was not due to decreased GST activity as initially hypothesized. In concurrent Microcystis LPS-cadmium exposures, GST activity was significantly increased in comparison with control embryos at all time points and cadmium concentrations sampled. Concurrent Lyngbya LPS-cadmium exposures also resulted in increased GST activity at most exposure concentrations. These results indicate that regardless of mechanism, cyanobacterial LPS can potentiate the toxic effects of heavy metals. This represents a significant risk for aquatic organisms exposed to combinations of LPS and metals in the environment.


Maternal dietary patterns during pregnancy in relation to offspring forearm fractures: prospective study from the Danish National Birth Cohort.
Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996-2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (< 16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01-1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dietary patterns showed no associations and neither did supplementary analyses of macro- and micronutrients or single food groups, except for the intake of artificially sweetened soft drinks, which was positively associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future research.


Expert evaluation of traffic signs: conventional vs. alternative designs.
Traffic sign comprehension is significantly affected by their compliance with ergonomics design principles. Despite the UN Convention, designs vary among countries. The goal of this study was to establish theoretical and methodological bases for evaluating the design of conventional and alternative signs. Thirty-one conventional signs and 1-3 alternatives for each conventional sign were evaluated for their compliance with three ergonomics guidelines for sign design: physical and conceptual compatibility, familiarity and standardisation. Twenty-seven human factors and ergonomics experts from 10 countries evaluated the signs relative to their compliance with the guidelines. Analysis of variance across alternatives revealed that for 19 of the 31 signs, an alternative design received a significantly higher rating in its ergonomics design than the conventional sign with the same meaning. We also found a very high correlation between the experts' ratings and comprehension from previous studies. In conclusion, many countries use signs for which better alternative designs exist, and therefore UN Convention signs should be re-examined, and ergonomics experts evaluation can serve as a good surrogate for road users' comprehension surveys. Practitioner summary: This study presents theoretical and methodological bases for evaluating the design of UN Conventional and alternative traffic signs. Human factors and ergonomics experts evaluated 31 conventional and 68 alternative road signs, based on ergonomics principles for sign design. Results indicated the need to re-examine poorly designed UN Convention signs.


Pediatric facial burns: Is facial transplantation the new reconstructive psychosurgery?
Current pediatric burn care has resulted in survival being the expectation for most children. Composite tissue allotransplantation in the form of face or hand transplantation may present opportunities for reconstructive surgery of patients with burns. The present paper addresses the question "Could facial transplantation be of therapeutic benefit in the treatment of pediatric burns associated with facial disfigurement?" Therapeutic benefit of facial transplantation was defined in terms of psychiatric adjustment and quality of life (QOL). To ascertain therapeutic benefit, studies of pediatric burn injury and associated psychiatric adjustment and QOL in children, adolescents and adults with pediatric burns, were reviewed. Pediatric burn injury is associated with anxiety disorders, including post-traumatic stress disorder and depressive disorders. Many patients with pediatric burns do not routinely access psychiatric care for these disorders, including those for psychiatric assessment of suicidal risk. A range of QOL outcomes were reported; four were predominantly satisfactory and one was predominantly unsatisfactory. Facial transplantation may reduce the risk of depressive and anxiety disorders other than post-traumatic stress disorder. Facial transplantation promises to be the new reconstructive psychosurgery, because it may be a surgical intervention with the potential to reduce the psychiatric suffering associated with pediatric burns. Furthermore, patients with pediatric burns may experience the stigma of disfigurement and psychiatric conditions. The potential for improved appearance with facial transplantation may reduce this 'dual stigmata'. Studies combining surgical and psychiatric research are warranted.


Role of hypoxia and autophagy in MDA-MB-231 invasiveness.
Survival strategies adopted by tumor cells in response to a hypoxic stress include activation of hypoxia-inducible factor 1 (HIF-1) and autophagy. However, the importance and the function of each molecular response is not well defined. In the present study, we investigated invasiveness, migration, matrix metalloproteinases (MMPs) activity, and cell survival of MDA-MB-231 cells under normoxia, hypoxia, and hypoxia/reoxygenation (H/R). Moreover, to assess the importance of hypoxia and autophagy on the parameters studied, cells were either left untreated or treated with Chetomin (a selective inhibitor of HIF-1alpha) or trifluoperazine (TFP, an activator of autophagy). We found that hypoxia and H/R stimulated invasiveness and migration of MDA-MB-231 cells with an increased MMP-2 activity. Chetomin and TFP differently regulated the cellular behavior under the oxygenation conditions studied. In fact, Chetomin was most effective in inhibiting cell invasion, MMPs activity, and cell survival under hypoxia but not normoxia or H/R. By contrast, TFP inhibition of cell invasion, migration, and cell survival was independent from oxygenation conditions. TFP-induced autophagy was inhibited by light chain protein 3 (LC3) silencing or 3-methyladenine (3MA) treatment. In fact, LC3-silenced cells were able to invade in the presence of TFP without any GATE16 processing and p62 degradation. Immunofluorescence assay showed that LC3 silencing inhibited TFP-induced autophagosome formation. However, we also showed that both TPF treatment and LC3 silencing caused cytoskeleton impairments suggesting a possible interaction between LC3 and cytoskeleton components. In conclusion, our study shows that hypoxia and autophagy by acting on common (HIF-1alpha) or separate (MMPs, cytoskeleton) targets differently regulate cell invasion, MMPs activity, and survival.


Double-stranded DNA homology produces a physical signature.
DNA is found in the cell largely as a negatively supercoiled molecule. This high-energy form of the genetic material can engender sequence-dependent structures, such as cruciforms, Z-DNA, or H-DNA, even though they are not favored by conventional conditions in relaxed DNA. A key feature of DNA in living systems is the presence of homology. We have sought homology-dependent structural phenomena based on topological relaxation. Using two-dimensional electrophoresis, we demonstrate a structural transition in supercoiled plasmid molecules containing homologous segments. Atomic force microscopy (AFM) reveals a dumbbell structure in molecules whose linking difference is beyond the transition point. The position of the dumbbell shaft is a function of the site of homology, and its extent is proportional to the linking difference. Second-site-reversion electrophoresis data support the notion that the shaft contains PX-DNA. Predicted cross-linking patterns generated in vivo suggest that homology-dependent structures can occur within the cell.


Prognostic value of circulating proteins in patients undergoing surgery for pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Less than 20% of patients are diagnosed with resectable disease. Identifying truly resectable disease is challenging because 20%-40% of the patients subjected to resection are found to have advanced disease during surgery. The aim of our study was to identify panels of circulating proteins that could be used to distinguish patients with unresectable PDAC from patients with resectable PDAC and to identify prognostic signatures for both groups. We measured 92 circulating immuno-oncology-related proteins using the proximity extension assay from Olink Proteomics in 273 patients eligible for surgery for PDAC. Two bioinformaticians worked independently of one another on the same data. LASSO and Ridge regression were used in the statistical analyses. One protein index for determining resectability had an AUC value of 0.66. Several indices for prognosis had AUC values between 0.50 and 0.75 and were therefore not better than existing prognostic markers. Our study did not reveal any new high-performing protein panels that could be used to identify patients with inoperable PDAC before surgery. The panel of 92 proteins investigated has previously been found to be applicable for diagnostic use in patients with PDAC, but it does not seem to warrant further investigation regarding resectability in the subgroup of patients with PDAC referred to surgery.


Formation of surface-grafted polymeric amphiphilic coatings comprising ethylene glycol and fluorinated groups and their response to protein adsorption.
Amphiphilic polymer coatings were prepared by first generating surface-anchored polymer layers of poly(2-hydroxyethyl methacrylate) (PHEMA) on top of flat solid substrates followed by postpolymerization reaction on the hydroxyl terminus of HEMA's pendent group using three classes of fluorinating agents, including organosilanes, acylchlorides, and trifluoroacetic anhydride (TFAA). The distribution of the fluorinated groups inside the polymer brushes was assessed by means of a suite of analytical probes, including contact angle, ellipsometry, infrared spectroscopy, atomic force microscopy, and near-edge x-ray absorption fine structure spectroscopy. While organosilane modifiers were found to reside primarily close to the tip of the brush, acylchlorides penetrated deep inside PHEMA thus forming random copolymers P(HEMA-co-fHEMA). The reaction of TFAA with the PHEMA brush led to the formation of amphiphilic diblocks, PHEMA-b-P(HEMA-co-fHEMA), whose bottom block comprised unmodified PHEMA and the top block was made of P(HEMA-co-fHEMA) rich in the fluorinated segments. This distribution of the fluorinated groups endowed PHEMA-b-P(HEMA-co-fHEMA) with responsive properties; while in hydrophobic environment P(HEMA-co-fHEMA) segregated to the surface, when in contact with a hydrophilic medium, PHEMA partitioned at the brush surface. The surface activity of the amphiphilic coatings was tested by studying the adsorption of fibrinogen (FIB). While some FIB adsorption occurred on most coatings, the ones made by TFAA modification of PHEMA remained relatively free of FIB.


Effects of syllable frequency in speech production.
In the speech production model proposed by [Levelt, W. J. M., Roelofs, A., Meyer, A. S. (1999). A theory of lexical access in speech production. Behavioral and Brain Sciences, 22, pp. 1-75.], syllables play a crucial role at the interface of phonological and phonetic encoding. At this interface, abstract phonological syllables are translated into phonetic syllables. It is assumed that this translation process is mediated by a so-called Mental Syllabary. Rather than constructing the motor programs for each syllable on-line, the mental syllabary is hypothesized to provide pre-compiled gestural scores for the articulators. In order to find evidence for such a repository, we investigated syllable-frequency effects: If the mental syllabary consists of retrievable representations corresponding to syllables, then the retrieval process should be sensitive to frequency differences. In a series of experiments using a symbol-position association learning task, we tested whether high-frequency syllables are retrieved and produced faster compared to low-frequency syllables. We found significant syllable frequency effects with monosyllabic pseudo-words and disyllabic pseudo-words in which the first syllable bore the frequency manipulation; no effect was found when the frequency manipulation was on the second syllable. The implications of these results for the theory of word form encoding at the interface of phonological and phonetic encoding; especially with respect to the access mechanisms to the mental syllabary in the speech production model by (Levelt et al.) are discussed.


Association of Myopic Deformation of Optic Disc with Visual Field Progression in Paired Eyes with Open-Angle Glaucoma.
The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals. This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ≤ -2 diopter (D), and axial length ≥ 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch's membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis. The mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it. In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself.


Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD.
Differential cerebral metabolic effects of various hormone therapy formulations, and their associations with cognitive status, remain to be established. The principal aim of the current study was to assess relationships between regional cerebral metabolism and estrogen-based hormone therapies. Postmenopausal women (n=53) at elevated risk for Alzheimer's disease (AD) were on estrogen-containing hormone therapy for at least one year prior to enrollment in a prospective, randomized clinical trial. Subjects underwent an FDG-PET scan, along with neuropsychological, medical, and demographic assessments at time of enrollment, to be repeated one year following randomization to hormone therapy continuation versus discontinuation, and results from analyses of the baseline assessments are reported here. Across all subjects, years of endogenous estrogen exposure correlated most closely with metabolism in right superior frontal gyrus (p<0.0005). Women taking 17β-estradiol (E) performed three standard deviations higher in verbal memory than women taking conjugated equine estrogen (CEE), and their verbal memory performance positively correlated with metabolism in Wernicke's (p=0.003) and auditory association (p=0.002) areas. Women taking progesterone-plus-estrogen had lower metabolism than women taking unopposed estrogen within the mesial and inferior lateral temporal regions (p<0.0005) and the inferior frontal cortex, contralateral to Broca's area (p<0.0005). In conclusion, particular areas of relatively preserved metabolism were seen in women with more years of endogenous estrogen exposure, as well as in women taking estradiol-based formulations or estrogen therapies unopposed by progesterone, together suggesting regionally specific neuroprotective estrogenic effects.


Two Growth Mechanisms of Thiol-Capped Gold Nanoparticles Controlled by Ligand Chemistry.
Thiols play an important role in the synthesis of well-defined nanoparticles (NPs) with tailored properties, but their effects on the formation kinetics of NPs are still under investigation. Here, we used in situ small-angle X-ray scattering (SAXS)/UV-vis spectroscopy and time-dependent transmission electron microscopy (TEM) to elucidate the role of thiols in the formation process of gold NPs (AuNPs) by changing the adding sequence between thiol ligand and reducing agent. Through quantitative analysis of in situ SAXS/UV-vis and TEM, detailed information on size, size distribution, the number of particles, optical properties, and the size evolution was obtained. Two different growth mechanisms of monodisperse AuNPs controlled by thiol ligand are exhibited: (i) thiol plays a dual role as a digestive ripening etchant and as a stabilizing ligand in the presence of a weak phosphine ligand. The digestive ripening mechanism involving the dissolution of bigger particles and subsequent deposition of monomers onto existing small NPs is responsible for producing narrowly dispersed NPs. (ii) Thiol acts as a strong stabilizing agent; in this case, the formation rate constant is quite slow, thus limiting the growth rate of NPs. Therefore, diffusion-limited growth mechanism is proposed for obtaining narrowly dispersed NPs with a diameter of 5.6 nm (12%). Our findings demonstrate that the formation of nearly monodisperse AuNPs with controllable size distribution could be realized by different growth mechanisms in the presence of thiol ligand.


Child Nutrition Outcomes and Maternal Nutrition-Related Knowledge in Rural Localities of Mbombela, South Africa.
Poor nutrition outcomes among children have become one of the major public health concerns in South Africa, attributed to poor feeding practices and maternal nutrition-related knowledge with conflicting data. In view of this, a cross-sectional study was conducted to determine the association of nutrition outcomes of children aged under two years with feeding practices and maternal nutrition-related knowledge in Mbombela, South Africa. Mothers' nutrition-related knowledge was estimated using an adapted structured questionnaire on colostrum, continued breastfeeding, diarrhea prevention and treatment using oral rehydration solution, immunization, and family planning, and scored as excellent (80-100), good (60-79), average (40-59), and fair (0-39). This was along with questions on socio-demographic factors and obstetric history, as well as anthropometric measurements. Child nutrition outcomes were estimated by WHO classification using z-scores for stunting (length-for-age (LAZ)), underweight (weight-for-age (WAZ)), and thinness (body mass index-for-age (BAZ)). Using STATA 17, 400 pairs of children (8 ± 6 months) and their mothers (29 ± 6 years) participated in the study and were living in a poor socio-economic status environment. Half of children were stunted (50%) and over half (54%) were obese, while mothers were underweight (39%) and overweight (34%). In addition to one third of mothers reporting obstetric complications, two thirds, initiated breastfeeding within one hour of delivery, 30% exclusively breastfed, 48% introduced early complementary feeding, and 70% practiced mixed feeding. Twenty-eight percent (28%) of mothers had fair nutrition-related knowledge, while 66% had average knowledge, 6% good knowledge, and none of the mothers had excellent knowledge. A chi-square test showed that mothers' nutrition-related knowledge was significantly associated with child stunting. The final hierarchical logistic regression showed significant associations of stunting with mothers' nutrition-related knowledge (average: AOR = 1.92, 95%CI: 1.12-3.29), child's age (6-11 months: AOR = 2.63, 95%CI: 1.53-4.53 and 12-23 months: AOR = 3.19, 95%CI: 1.41-7.25), and education (completing Grade 12: AOR = 0.36, 95%CI: 0.15-0.86). Contextual and intensified interventions on continued education for mothers to gain accurate information on nutrition-related knowledge and feeding practices could ultimately enhance child nutrition outcomes in poorer settings. Efforts should therefore be made to ensure that nutrition knowledge is appropriately provided based on the phases of child growth from 0 to 2 years, even beyond infancy into school age.


Nanostructured assemblies for dental application.
Millions of teeth are saved each year by root canal therapy. Although current treatment modalities offer high levels of success for many conditions, an ideal form of therapy might consist of regenerative approaches in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue to revitalize teeth. Melanocortin peptides (alpha-MSH) possess anti-inflammatory properties in many acute and chronic inflammatory models. Our recent studies have shown that alpha-MSH covalently coupled to poly-l-glutamic acid (PGA-alpha-MSH) retains anti-inflammatory properties on rat monocytes. This study aimed to define the effects of PGA-alpha-MSH on dental pulp fibroblasts. Lipopolysaccharide (LPS)-stimulated fibroblasts incubated with PGA-alpha-MSH showed an early time-dependent inhibition of TNF-alpha, a late induction of IL-10, and no effect on IL-8 secretion. However, in the absence of LPS, PGA-alpha-MSH induced IL-8 secretion and proliferation of pulp fibroblasts, whereas free alpha-MSH inhibited this proliferation. Thus, PGA-alpha-MSH has potential effects in promoting human pulp fibroblast adhesion and cell proliferation. It can also reduce the inflammatory state of LPS-stimulated pulp fibroblasts observed in gram-negative bacterial infections. These effects suggest a novel use of PGA-alpha-MSH as an anti-inflammatory agent in the treatment of endodontic lesions. To better understand these results, we have also used the multilayered polyelectrolyte films as a reservoir for PGA-alpha-MSH by using not only PLL (poly-l-lysine) but also the Dendri Graft poly-l-lysines (DGL(G4)) to be able to adsorb more PGA-alpha-MSH. Our results indicated clearly that, by using PGA-alpha-MSH, we increase not only the viability of cells but also the proliferation. We have also analyzed at the nanoscale by atomic force microscopy these nanostructured architectures and shown an increase of thickness and roughness in the presence of PGA-alpha-MSH incorporated into the multilayered film (PLL-PGA-alpha-MSH)(10) or (DGL(G4)-PGA-alpha-MSH)(10) in accordance with the increase of the proliferation of the cells growing on the surface of these architectures. We report here the first use of nanostructured and functionalized multilayered films containing alpha-MSH as a new active biomaterial for endodontic regeneration.


Direct measurement of tissue blood flow and metabolism with diffuse optics.
Diffuse optics has proven useful for quantitative assessment of tissue oxy- and deoxyhaemoglobin concentrations and, more recently, for measurement of microvascular blood flow. In this paper, we focus on the flow monitoring technique: diffuse correlation spectroscopy (DCS). Representative clinical and pre-clinical studies from our laboratory illustrate the potential of DCS. Validation of DCS blood flow indices in human brain and muscle is presented. Comparison of DCS with arterial spin-labelled MRI, xenon-CT and Doppler ultrasound shows good agreement (0.50<r<0.95) over a wide range of tissue types and source detector distances, corroborating the potential of the method to measure perfusion non-invasively and in vivo at the microvasculature level. All-optical measurements of cerebral oxygen metabolism in both rat brain, following middle cerebral artery occlusion, and human brain, during functional activation, are also described. In both situations, the use of combined DCS and diffuse optical spectroscopy/near-infrared spectroscopy to monitor changes in oxygen consumption by the tissue is demonstrated. Finally, recent results spanning from gene expression-induced angiogenic response to stroke care and cancer treatment monitoring are discussed. Collectively, the research illustrates the capability of DCS to quantitatively monitor perfusion from bench to bedside, providing results that match up both with literature findings and with similar experiments performed with other techniques.


Open Bose-Hubbard chain: Pseudoclassical approach.
We analyze the stationary current of bosonic carriers in the Bose-Hubbard chain of length L where the first and the last sites of the chain are attached to reservoirs of Bose particles acting as a particle source and sink, respectively. The analysis is carried out by using the pseudoclassical approach which reduces the original quantum problem to the classical problem for L coupled nonlinear oscillators. It is shown that an increase of oscillator nonlinearity (which is determined by the strength of interparticle interactions) results in a transition from the ballistic transport regime, where the stationary current is independent of the chain length, to the diffusive regime, where the current is inversely proportional to L.


A 3D approach to model the taper of irregular tree stems: making plots biomass estimates comparable in tropical forests.
In tropical forests, the high proportion of trees showing irregularities at the stem base complicates forest monitoring. For example, in the presence of buttresses, the height of the point of measurement (HPOM ) of the stem diameter (DPOM ) is raised from 1.3 m, the standard breast height, up to a regular part of the stem. While DPOM is the most important predictor for tree aboveground biomass (AGB) estimates, the lack of harmonized HPOM for irregular trees in forest inventory increases the uncertainty in plot-level AGB stock and stock change estimates. In this study, we gathered an original non-destructive three-dimensional (3D) data set collected with terrestrial laser scanning and close range terrestrial photogrammetry tools in three sites in central Africa. For the 228 irregularly shaped stems sampled, we developed a set of taper models to harmonize HPOM by predicting the equivalent diameter at breast height (DBH') from a DPOM measured at any height. We analyzed the effect of using DBH' on tree-level and plot-level AGB estimates. To do so, we used destructive AGB data for 140 trees and forest inventory data from eight 1-ha plots in the Republic of Congo. Our results showed that our best simple taper model predicts DBH' with a relative mean absolute error of 3.7% (R2 = 0.98) over a wide DPOM range of 17-249 cm. Based on destructive AGB data, we found that the AGB allometric model calibrated with harmonized HPOM data was more accurate than the conventional local and pantropical models. At the plot level, the comparison of AGB stock estimates with and without HPOM harmonization showed an increasing divergence with the increasing share of irregular stems (up to -15%). The harmonization procedure developed in this study could be implemented as a standard practice for AGB monitoring in tropical forests as no additional forest inventory measurements is required. This would probably lead to important revisions of the AGB stock estimates in regions having a large number of irregular tree stems and increase their carbon sink estimates. The growing use of three-dimensional (3D) data offers new opportunities to extend our approach and further develop general taper models in other tropical regions.


Perivenular Capillary Loss: An Early, Quantifiable Change in Macular Telangiectasia Type 2.
To evaluate differences in parafoveal vascular density surrounding arterioles and venules in type 2 macular telangiectasia (MacTel). Thirty-seven eyes (20 subjects) diagnosed with MacTel and 16 healthy eyes (10 subjects) were imaged with optical coherence tomography angiography between March 2016 and June 2019 in this single-center, observational, cross-sectional study. Arterioles and venules were manually identified, and perivascular density was generated using a custom MATLAB code. The primary outcome measure was the ratio of periarteriolar to perivenular vascular density (arteriovenous [A/V] capillary ratio) in the superficial and deep capillary plexuses across MacTel stages. The main secondary outcome measures were overall parafoveal vascular density (VD), periarteriolar VD, and perivenular VD. In the superficial capillary plexus (SCP), the A/V capillary ratio was significantly higher in MacTel subjects than controls (0.914 vs. 0.892; P = 0.0044). The greatest differences occurred between controls and nonproliferative MacTel subjects without optical coherence tomography evidence of disease (P = 0.0055). A/V capillary ratios progressed in a nonlinear fashion with MacTel severity, increasing from nonproliferative disease (0.912) to intraretinal proliferative disease (0.931), then decreasing in subretinal proliferative disease (0.905). Parafoveal VD in the SCP was lower in MacTel subjects than controls only in subretinal proliferative disease (P = 0.0130). The A/V capillary ratio of the SCP is a quantifiable metric of vascular pathology in MacTel that occurs earlier than decline in parafoveal VD. Elevated A/V capillary ratios in MacTel are consistent with an early, disproportionately perivenular disruption in the SCP. Findings inform MacTel pathogenesis through revealing early perivenular capillary loss and offer a new quantitative metric for earliest stage MacTel.


Contrast enhancement in cardiovascular MDCT: effect of body weight, height, body surface area, body mass index, and obesity.
The purpose of our study was to evaluate the effect of body weight, height, body surface area (BSA), body mass index (BMI), and obesity on aortic contrast enhancement in cardiac MDCT. Seventy-three consecutive patients underwent cardiac CT angiography on a 64-MDCT scanner. Seventy-five mL of contrast medium (350 mg I/mL) was injected at 4.5 mL/s, followed by a 40-mL saline flush at 4.5 mL/s. The scanning delay of CT was determined with a bolus tracking technique. Aortic attenuation was measured over the aortic-root lumen. BMI and BSA were calculated from the patient's body weight and height. The patients were divided into low-(BMI < 30) and high-(> or = 30) BMI groups. Associations of aortic attenuation with body weight, height, BMI, and BSA were evaluated with regression analysis and the Student's t test. Strong inverse correlations were seen between aortic attenuation and body weight (r = -0.73), height (r = -0.47), BMI (r = -0.63), and BSA (r = -0.74) (p < 0.001 for all). The regression formula of aortic attenuation versus body weight suggests that 1.0 mL/kg of contrast medium would yield a mean aortic attenuation of 355 H. The mean aortic attenuation was significantly higher in the low-BMI (352.6 +/- 59.1 H) than in the high-BMI (286.2 +/- 55.5 H) group. The regression formula for aortic attenuation on body weight was aortic attenuation = 586-3.1 body weight (p < 0.001) for the low-BMI group and aortic attenuation = 485-1.9 body weight (p < 0.001) for the high-BMI group, suggesting that the amount of contrast medium required with increased body weight is less in the high-BMI group. This group difference was less pronounced for the regression of aortic attenuation on BSA. To achieve a consistent contrast enhancement in cardiac CT angiography (CTA), contrast-medium dose should be adjusted with the body weight or the BSA (which accounts for both the body weight and height factors) to provide adjustment of iodine dose over a wide range of body sizes.


Assessment of the Perceived Acceptability of an Early Enrollment Strategy Using Advance Consent in Health Care-Associated Pneumonia.
Better treatment options are needed in life-threatening infections, including health care-associated pneumonia. Enrolling patients in antibacterial clinical trials before diagnosis may circumvent existing time-to-enrollment constraints. However, the acceptability of an early enrollment strategy using advance consent is unknown. To assess the perceived acceptability of an early enrollment strategy for enrolling patients in an antibacterial clinical trial before a pneumonia diagnosis. This qualitative, descriptive study used semistructured telephone interviews. Framed within a planned noninferiority pneumonia antibiotic trial, an early enrollment strategy was described and perceptions were assessed. Using this strategy, patients give consent to enroll before developing pneumonia, to be monitored by study staff, and to be randomly assigned a study antibiotic if pneumonia develops. All interviews were audiorecorded, transcribed verbatim, and analyzed using applied thematic analysis. Fifty-two key stakeholders from across the United States, including 18 patients at risk of pneumonia, 12 caregivers, 10 representatives of institutional review boards, 7 investigators, and 5 study coordinators, were interviewed from June 20 to August 19, 2016. Perceived acceptability of the early enrollment strategy. Among the 52 stakeholders interviewed (ages 29-75 years; 14 women), patients and caregivers expressed no concerns about patients being approached about participation before developing pneumonia; however, some patients may experience anxiety on learning about their risk for pneumonia. No concerns with study staff accessing patients' medical records were expressed. The clarity of consent information was important for understanding the study rather than having the condition under investigation. Among patients, caregivers, and institutional review board representatives, preferences varied regarding opt-out and precedent autonomy procedures. Nearly all patients would be willing to join a trial using the early enrollment strategy and caregivers would be willing to provide proxy consent. Institutional review board representatives were supportive of the strategy and made recommendations for the study protocol, primarily around informed consent. Investigators and study coordinators believed the strategy would not be burdensome and offered suggestions to ensure its feasibility. Results of the study suggest that the early enrollment strategy is acceptable. Future research should evaluate whether the strategy improves enrollment rates in registrational pneumonia trials and in trials of other acute infection syndromes with narrow enrollment windows and/or patients with transient decisional incapacity.


Paleomicrobiological study in dental calculus: Streptococcus mutans.
Morphological types of bacterial remains preserved in ancient tartar of teeth from extinct human groups, which included some communities of coastal gatherers, fishermen, hunters, and farmers, and those practicing a mixed economy, were analyzed. Previous studies have shown the presence of bacteria in ancient tartar. The aim of this work was to determine whether Streptococcus mutans was present in ancient populations (500-12,000 years old). Teeth samples were from ancient skulls obtained from different anthropological collections: the north and south of Chile (before the Spanish conquest), Palencia, Spain, and an eastern Mediterranean region (Levant). Optical microscopy showed Gram positive and Gram negative bacteria. Scanning electron microscopy identified morphological types of bacteria. Transmission electron microscopy enabled categorization of bacterial structures. Fluorescence microscopy helped label and identify S. mutans, using polyclonal antibodies. Bacterial morphotypes were related to different subsistence patterns. Hunters, fishermen, and gatherers had a less diverse flora with bacillary and coccal morphotypes. Agricultural groups showed greater diversity with additional filamentous and spiral morphotypes. The best preserved ultrastructural feature was the cell wall. The existence and colonization capacity of the mutans-like streptococci preserved in tartar was established for the ancient populations studied, with the exception of Cerro Sotta (south of Chile). Hence, their occurrence could not be related to diet or subsistence pattern.


Using the wax moth larva Galleria mellonella infection model to detect emerging bacterial pathogens.
Climate change, changing farming practices, social and demographic changes and rising levels of antibiotic resistance are likely to lead to future increases in opportunistic bacterial infections that are more difficult to treat. Uncovering the prevalence and identity of pathogenic bacteria in the environment is key to assessing transmission risks. We describe the first use of the Wax moth larva Galleria mellonella, a well-established model for the mammalian innate immune system, to selectively enrich and characterize pathogens from coastal environments in the South West of the UK. Whole-genome sequencing of highly virulent isolates revealed amongst others a Proteus mirabilis strain carrying the Salmonella SGI1 genomic island not reported from the UK before and the recently described species Vibrio injenensis hitherto only reported from human patients in Korea. Our novel method has the power to detect bacterial pathogens in the environment that potentially pose a serious risk to public health.


Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage.
A simple, reliable, and reproducible fluorometric method for measuring thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of TBARS was complete at pH 2.4-2.6, but extraction with n-butanol proved complete only at lower pH, i.e., 1.6-1.7. Analytical recoveries of MDA added to serum were 94%-101%; within- and between-run CVs were 2.4-3.6% and 4.6-5.5%; and the detection limit for TBARS in serum was 0.10 mumol/L. Optimized conditions included: (a) collection of either serum or heparinized plasma, (b) preservation from in vitro autoxidation by glutathione and EDTA, and (c) storage at -20 degrees C up to 35 days. The mean (+/- SD) TBARS concentration in 47 healthy adults was 1.01 (0.21) mumol/L; no sex-related difference was observed. Higher concentrations were measured in patients with renal insufficiency undergoing hemodialysis and in patients with insulin-dependent diabetes, chronic pancreatitis, or liver cirrhosis.


Cigarette smoke impairs elastin resynthesis in lungs of hamsters with elastase-induced emphysema.
The severity of pulmonary emphysema can be affected by exposure to cigarette smoke in several ways. Inactivation of alpha-1-antitrypsin and recruitment of leukocytes to lung airways shifts the protease-antiprotease balance towards increased elastolytic activity. The present study demonstrates an additional effect of cigarette smoke inhalation and retardation of the repair process and of the neosynthesis of cross-linked elastin. Hamsters with elastase-induced emphysema, exposed to cigarette smoke for 1 wk immediately after elastase administration, showed a 40% reduction of 14C-lysine incorporation into the elastin-specific cross-links, desmosine, and isodesmosine. Concomitantly, there was a decrease in the level of lung lysyl oxidase to that observed in uninjured control animals, in sharp contrast to the sevenfold increase in lysyl oxidase activity in hamsters with elastase-induced emphysema recovering under atmospheric conditions. These findings suggest that impairment of the production of lysyl oxidase and the resynthesis of cross-linked elastin by smoke inhalation exacerbates alveolar destruction.


Effects of twin pregnancy prevention strategies such as GnRH dose and drainage of the smaller follicle on ovulation in dairy cows with two follicles of pre-ovulatory size in the same ovary.
We examined the effects of a single or 2.5-fold dose of dephereline [a gonadotropin-releasing hormone (GnRH) analogue] as well as the drainage of the smaller follicle at the time of insemination on ovulation in dairy cows with two follicles of pre-ovulatory size in the same ovary. The three study groups included 220 monovular cows (control), 110 non-drained cows with two follicles, and 110 cows with two follicles, of which one was drained. In each group, cows treated with a single dose or 2.5-fold dose of dephereline showed similar results following treatment. Ovulation failure of the non-drained follicle occurred in 29.1% of the drained cows, whereas ovulation occurred in 96% of the non-drained and control cows. Twin pregnancy was recorded in 19.4% of the pregnant non-drained cows with two follicles. In conclusion, the increased dephereline dose did not improve the ovulation rate in any group. Follicular drainage, however, prevented twin pregnancy in cows with two follicles, but also resulted in an increase in the non-drained follicle's rate of ovulation failure.