Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels.
Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential. An understudied yet promising hypothesis is that maternal mood affects infant mood via maternal prenatal inflammatory mechanisms, but this has not been prospectively examined in humans. Using data from a pilot study of women followed from the second trimester of pregnancy through six months postpartum (N = 68) our goal was to initiate a prospective study as to whether maternal inflammatory cytokines mediate the association between maternal depressive symptoms and infant offspring negative affect. The study sample was designed to examine a broad range of likely self-regulation and mood-regulation problems in offspring; to that end we over-selected women with a family history or their own history of elevated symptoms of attention-deficit/hyperactivity disorder. Results supported the hypothesis: maternal pro-inflammatory cytokines during the third trimester (indexed using a latent variable that included plasma interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations as indicators) mediated the effect, such that higher maternal depressive symptoms were associated with higher maternal inflammation, and this mediated the effect on maternal report of infant negative affect (controlling for maternal affect during the infant period). This is the first human study to demonstrate that maternal inflammatory cytokines mediate the association between prenatal depression and infant outcomes, and the first to demonstrate a biological mechanism through which depressive symptoms impact infant temperament.


Assessment of acid neutralizing capacity in cola-based drinks and energy beverages by artificial saliva.
To assess the pH of regular and light cola-based drinks and energy drinks, and examine the acid neutralizing capacity by the addition of artificial saliva. Ten packages of each product purchased locally at different stores were evaluated. The pH was measured by a pH-electrode calibrated in standard buffer solutions. To assess the pH neutralizing capacity, 1 ml/min of artificial saliva was added until a pH of 5.5 set as a cutoff point was reached in the tested solution. The data were subjected to analysis of variance (ANOVA), at the 0.05 significance level. The surveyed beverages had an initial acidic pH, ranging between 2.3 and 3.4. The average amount of saliva required to raise the pH of the cola-based drinks above 5.5 ranged between 6.0 and 6.8 ml. Energy drinks used volumes between 11.3 and 12.5 ml; however, it was not possible to achieve a pH of 5.5. According to the methodology used, it was concluded that: (1) All beverages analyzed showed an initial acidic pH. (2) There was no statistical difference between the initial pH level and acid neutralization by the addition of artificial saliva in both regular and light drinks. It was not possible to reach the appropriate pH, set as the cutoff point, for the energy drinks.


A Sigmoid Functional Response Emerges When Cytotoxic T Lymphocytes Start Killing Fresh Target Cells.
Cytotoxic T lymphocyte (CTL)-mediated killing involves the formation of a synapse with a target cell, followed by delivery of perforin and granzymes. Previously, we derived a general functional response for CTL killing while considering that CTLs form stable synapses (i.e., single-stage) and that the number of conjugates remains at steady state. However, the killing of target cells sometimes requires multiple engagements (i.e., multistage). To study how multistage killing and a lack of steady state influence the functional response, we here analyze a set of differential equations as well as simulations employing the cellular Potts model, in both cases describing CTLs that kill target cells. We find that at steady state the total killing rate (i.e., the number of target cells killed by all CTLs) is well described by the previously derived double saturation function. Compared to single-stage killing, the total killing rate during multistage killing saturates at higher CTL and target cell densities. Importantly, when the killing is measured before the steady state is approached, a qualitatively different functional response emerges for two reasons: First, the killing signal of each CTL gets diluted over several targets and because this dilution effect is strongest at high target cell densities; this can result in a peak in the dependence of the total killing rate on the target cell density. Second, the total killing rate exhibits a sigmoid dependence on the CTL density when killing is a multistage process, because it takes typically more than one CTL to kill a target. In conclusion, a sigmoid dependence of the killing rate on the CTLs during initial phases of killing may be indicative of a multistage killing process. Observation of a sigmoid functional response may thus arise from a dilution effect and is not necessarily due to cooperative behavior of the CTLs.


Autoimmune regulator expression in thymomas with or without autoimmune disease.
The autoimmune regulator (AIRE) regulates autoimmunity and self-antigen expression, such as acetylcholine receptor (AchR), in the thymus. Regulatory T cells (Tregs) can down-regulate autoimmunity, but also promote tumor growth. The objective of this study was to examine the levels of AIRE, AchR, and Foxp3 expression in thymomas. The relative levels of AIRE, AchR, and Foxp3 mRNA transcripts and the frequency of AIRE+, AchR+, and Foxp3+ cells were determined by quantitative RT-PCR and immunohistochemistry in 79 thymoma tissue samples from 21 patients with simple thymoma (the Tm group), 39 patients with myasthenia gravis (the MG group) and 19 patients with myasthenia gravis and one other autoimmune disease (the AD group). The numbers of peripheral blood CD4+CD25+Foxp3+ Tregs were determined by flow cytometry analysis. The relative levels of AIRE and AchR mRNA transcripts in the MG group were significantly lower than that in the Tm group (p=0.04, p=0.03), but higher than that in the AD group (p=0.03, p=0.04). The relative levels of Foxp3 mRNA transcripts in the Tm group were significantly higher than that in the MG and AD groups (p=0.03 for both). A similar pattern of the percentages of AIRE+, AchR+, and Foxp3+ cells in the thymoma tissues and the numbers of peripheral blood Tregs were detected in these patients. The levels of AIRE mRNA transcripts were correlated positively with that of the AchR and Foxp3 in this population. The levels of AIRE and AchR mRNA transcripts in the A/AB/B1 types of thymomas were significantly higher than that in the B2/B3/C types of thymomas in this population. Significantly lower levels of AIRE, AchR, and Foxp3 expression are associated with the development of thymoma-related autoimmune diseases.


Does an interaction exist between ketamine hydrochloride and Becton Dickinson syringes?
An international alert from Becton Dickinson (BD) has noted the possibility of interaction between several molecules and some syringes. The Centralized IntraVenous Additives Service of the institution was using 3 mL BD syringes to store ketamine HCl. This study evaluated the interaction between ketamine and these syringes. A batch of BD syringes produced in Europe and left in quarantine from the day of the international alert has been tested at 22, 29, 36, 43 and 50 days of storage at room temperature. At each time, the pH of the solutions was measured. The solutions were inspected visually and by microscope, and spectrophotometric measurements were performed. The concentrations were measured by a validated ultra-high-performance liquid chromatography-diode array detector. Neither physical change nor pH modification was observed during the study. According to a lower limit of the 95% unilateral CI on the mean >90% of the theoretical concentration, the solutions remain stable for at least 50 days. In our study conditions, ketamine can be stored for at least 50 days without risk of sorption with syringes.


Sex does not have an impact on perioperative transfemoral carotid artery stenting outcomes among octogenarians.
Transfemoral carotid artery stenting (CAS) has been validated as an acceptable alternative to carotid endarterectomy in patients at high risk for open surgery. There are variable sex- and age-based differences in transfemoral CAS outcomes of published randomized controlled trials. The aim of our study was to evaluate sex-based differences in perioperative outcomes after transfemoral CAS performed in octogenarians. The National Surgical Quality Improvement Program targeted vascular module was queried for all patients ≥80 years of age who underwent transfemoral CAS between 2011 and 2017. Symptomatic status was defined as a history of prior ipsilateral stroke, transient ischemic attack, or amaurosis fugax. The primary outcome was a composite outcome of perioperative (30-day) stroke or death. Outcomes were compared for male vs female patients and stratified by symptomatic status using univariate and multivariable logistic regression analyses adjusting for emergent status, symptomatic status, comorbidities, and use of an embolic protection device. Overall, there were 143 patients ≥80 years of age who underwent transfemoral CAS during the study period, including 95 men (66.4%) and 48 women (33.6%). Race (white, 88.0% vs 85.4%), symptomatic status (30.9% vs 29.2%), and degree of stenosis (severe, 71.6% vs 62.5%) were not significantly different for men vs women (P ≥ .27). Periprocedural stroke/death occurred in six men (6.4%) vs two women (4.2%; P = .59) and did not significantly differ when stratified according to symptomatic (6.9% vs 7.1%; P = .98) and asymptomatic (6.2% vs 2.9%; P = .49) status. Based on multivariable analysis, independent factors associated with the composite end point included emergent vs elective status (adjusted odds ratio OR [aOR], 20.3; 95% confidence interval [CI], 2.25-183) and failure to use an embolic protection device (aOR, 2.86; 95% CI, 1.59-50.0). Sex was not significantly associated with the primary outcome after risk adjustment (aOR, 0.81; 95% CI, 0.28-3.28). We found no sex-based differences in risk of perioperative stroke/death among patients ≥80 years of age undergoing transfemoral CAS. Our study validates previous studies showing a high rate of perioperative complications after transfemoral CAS in octogenarians and suggests that the decision to use this technology in older patients should be determined by patients' anatomic and medical risk factors irrespective of sex.


Medical examinations at entry to treatment for drug abuse as an opportunity to initiate care for hepatitis C virus infection.
Over the course of addiction, a substantial proportion of drug users enter drug abuse treatment programs. Data from a cross-sectional survey of drug abuse treatment programs in the United States were analyzed to describe the scope of the medical examination performed at admission to such programs. All of the methadone programs (n=95) and 50% of drug-free programs (80 of 161) required a medical examination at entry. Most examinations included screening for signs and symptoms of liver disease and liver function testing. Nearly all methadone programs (97%) provided referral to medical care or support for patients with test results positive for antibody to hepatitis C virus (HCV), compared with 75% of drug-free programs (P<.01). Drug-free programs requiring medical examinations provided education about HCV and testing for HCV to a larger proportion of their patients (P<.05). With high dropout rates in the early stages of treatment for drug addiction, these medical visits may be an important opportunity for further monitoring and care for HCV infection and other conditions.


Differential effects of amygdala lesions on early and late plastic components of auditory cortex spike trains during fear conditioning.
In auditory fear conditioning, pairing of a neutral acoustic conditioned stimulus (CS) with an aversive unconditioned stimulus (US) results in an enhancement of neural responses to the CS in the amygdala and auditory cortex. It is not clear, however, whether cortical plasticity governs neural changes in the amygdala or vice versa, or whether learning in these two structures is determined by independent processes. We examined this issue by recording single-cell activity in the auditory cortex (areas Te1, Te1v, and Te3) of freely behaving, amygdalectomized rats using a movable bundle of microwires. Amygdala damage did not affect short-latency (0-50 msec) tone responses, nor did it interfere with conditioning-induced increases of these onset responses. In contrast, lesions of the amygdala interfered with the development of late (500-1500 msec) conditioned tone responses that were not present before conditioning. Furthermore, whereas onset conditioned responses in the control group remained elevated after 30 extinction trials (presentation of CS alone), onset responses in lesioned animals returned to their preconditioning firing level after approximately 10 extinction trials. These results suggest that the amygdala enables the development of long-latency (US anticipatory) responses and prevents the extinction of short-latency onset responses to threatening stimuli. The findings further suggest that auditory cortex cells may participate differently in explicit and implicit memory networks.


The inhibitory effect of tongxieyaofang on rats with post infectious irritable bowel syndrome through regulating colonic par-2 receptor.
The aims of this study were to evaluate the effect and mechanism of a traditional Chinese medicine formula: Tongxieyaofang (TXYF) on Rats with Post Infectious Irritable Bowel Syndrome (PI-IBS). SD male rats in adult were used to model PI-IBS and treated with TXYF at three dosage for 14 consecutive days, and then visceral sensation and the frequency of stool in PI-IBS rats were investigated. In addition, the contents of SP, TNF- α and IL-6 in colonic mucosal were analyzed by ELISA. Moreover faecal serine protease activity and PAR-2 mRNA expression were measured by ultraviolet spectrophotometry and RT-PCR, respectively. Our study showed that TXYF attenuated visceral hyperalgesia and inhibited stool frequency in Campylobacter-stimulated Post Infectious Irritable Bowel Syndrome (PI-IBS) rats. Furthermore, TXYF decreased the colonic SP, TNF- α and IL-6 content in PI-IBS rats. In addition, the up-regulated colonic mucosa PAR-2 mRNA expression in PI-IBS rats was significantly suppressed by orally TXYF. TXYF attenuated PI-IBS symptom by attenuating behavioral hyperalgesia and anti-diarrhea, the underlying mechanism was mediated by inhibiting PAR-2 receptor expression, reducing the levels of SP, TNF- α and IL-6 in colonic mucosa and decreasing faecal serine protease activity.


Characterization of inactive renin ("prorenin") from renin-secreting tumors of nonrenal origin. Similarity to inactive renin from kidney and normal plasma.
Inactive renin comprises well over half the total renin in normal human plasma. There is a direct relationship between active and inactive renin levels in normal and hypertensive populations, but the proportion of inactive renin varies inversely with the active renin level; as much as 98% of plasma renin is inactive in patients with low renin, whereas the proportion is consistently lower (usually 20-60%) in high-renin states. Two hypertensive patients with proven renin-secreting carcinomas of non-renal origin (pancreas and ovary) had high plasma active renin (119 and 138 ng/h per ml) and the highest inactive renin levels we have ever observed (5,200 and 14,300 ng/h per ml; normal range 3-50). The proportion of inactive renin (98-99%) far exceeded that found in other patients with high active renin levels. A third hypertensive patient with a probable renin-secreting ovarian carcinoma exhibited a similar pattern. Inactive renins isolated from plasma and tumors of these patients were biochemically similar to semipurified inactive renins from normal plasma or cadaver kidney. All were bound by Cibacron Blue-agarose, were not retained by pepstatin-Sepharose, and had greater apparent molecular weights (Mr) than the corresponding active forms. Plasma and tumor inactive renins from the three patients were similar in size (Mr 52,000-54,000), whereas normal plasma inactive renin had a slightly larger Mr than that from kidney (56,000 vs. 50,000). Inactive renin from each source was activated irreversibly by trypsin and reversibly by dialysis to pH 3.3 at 4 degrees C; the reversal process followed the kinetics of a first-order reaction in each instance. The trypsin-activated inactive renins were all identical to semipurified active renal renin in terms of pH optimum (pH 5.5-6.0) and kinetics with homologous angiotensinogen (Michaelis constants, 0.8-1.3 microM) and inhibition by pepstatin or by serial dilutions of renin-specific antibody. These results indicate that a markedly elevated plasma inactive renin level distinguishes patients with ectopic renin production from other high-renin hypertensive states. The co-production of inactive and active renin by extrarenal neoplasms provides strong presumptive evidence that inactive renin is a biosynthetic precursor of active renin. The unusually high proportion of inactive renin in plasma and tumor extracts from such patients is consistent with ineffective precursor processing by neoplastic tissue, suggesting that if activation of "prorenin" is involved in the normal regulation of active renin levels it more likely occurs in the tissue of origin (e.g., kidney) than in the circulation.


Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography-ion mobility-mass spectrometry.
The elastin degradation products, desmosine (DES) and isodesmosine (IDES) are highly stable, cross-linking amino-acids that are unique to mature elastin. The excretion of DES/IDES in urine, in the free form and with associated peptide fragments, provides an indicator of lung damage in chronic obstructive pulmonary disease (COPD). A quantitative ion mobility-mass spectrometry (IM-MS) method has been developed for the analysis of free DES/IDES in urine with deuterated IDES as an internal standard. Resolution of DES/IDES isomers was achieved in less than five minutes using ultra performance liquid chromatography (UPLC) combined with ion pairing. The optimized UPLC-IM-MS method provided a linear dynamic range of 10-300 ng/mL and a limit of quantitation of 0.028 ng/mL for IDES and 0.03 ng/mL for DES (0.55 ng and 0.61 ng on column respectively). The method reproducibility (%RSD) was <4% for DES and IDES. The UPLC-IM-MS method was applied to the analysis of urine samples obtained from healthy volunteers and COPD patients. The DES/IDES concentrations in healthy and COPD urine showed an increase in DES (79%) and IDES (74%) in the COPD samples, relative to healthy controls. The incorporation of an IM separation prior to m/z measurement by MS was shown to reduce non-target ion responses from the bio-fluid matrix.


Rates and predictive factors of return to the emergency department following an initial release by the emergency department for acute heart failure.
Following release by emergency department (ED) for acute heart failure (AHF), returns to ED represent important adverse health outcomes. The objective of this study was to document relapse events and factors associated with return to ED in the 14-day period following release by ED for patients with AHF. The primary outcome was the number of return to ED for patients who were release by ED after the initial visit, for any related medical problem within 14 days of this initial ED visit. Return visits to the EDs occurred in 166 (20%) patients. Of all patients who returned to ED within the 14-day period, 77 (47%) were secondarily admitted to the hospital. The following factors were associated with return visits to ED: past medical history of percutaneous coronary intervention or coronary artery bypass graft (aOR=1.51; 95% CIs [1.01-2.24]), current use of antiarrhythmics medications (1.96 [1.05-3.55]), heart rate above 80 /min (1.89 [1.28-2.80]), systolic blood pressure below 140 mm Hg (1.67[1.14-2.47]), oxygen saturation (SaO2) above 96% (1.58 [1.08-2.31]), troponin above the upper reference limit of normal (1.68 [1.15-2.45]), and chest X-ray with pleural effusion (1.52 [1.04-2.23]). Many heart failure patients (i.e. 1 in 5 patients) are released from the ED and then suffer return to ED. Patients with multiple medical comorbidities, and those with abnormal initial vital signs are at increased risk for return to ED and should be identified.


Incidence and modes of onset of early reinitiation of atrial fibrillation after successful internal cardioversion, and its prevention by intravenous sotalol.
To study the incidence and mode of onset of early reinitiation of atrial fibrillation (ERAF) following successful internal cardioversion of chronic atrial fibrillation, and to determine the effects of sotalol in the prevention of ERAF. The incidence and modes of onset of ERAF and the acute effects of intravenous sotalol in the prevention of ERAF were studied retrospectively. Electrophysiology laboratory at a university teaching hospital. 64 patients, mean (SD) age 62 (10) years, who underwent internal cardioversion of chronic atrial fibrillation (mean duration of atrial fibrillation 31 (39) months). ECGs and intracardiac electrograms recorded during the internal cardioversion of atrial fibrillation using 3/3 ms biphasic, R wave synchronised shocks. 52 patients (81%) had successful electrical cardioversion, and 20 (31%) of these had ERAF during the procedure. There was no clinical predictor for the occurrence of ERAF. Fifty eight episodes of ERAF were observed. Five ERAF episodes (9%) had preceding bradycardia and 53 (91%) of these were triggered by atrial premature beats with normal preceding heart rate. Atrial premature beats that reinitiated atrial fibrillation had a shorter coupling interval (333 (43) ms v 396 (100), p < 0.001) and a lower prematurity index (0.44 (0.11) v 0. 55 (0.14), p < 0.001) than those that did not reinitiate atrial fibrillation. Repeated shock delivery and increasing the defibrillation energy did not prevent ERAF. Intravenous sotalol infusion decreased the numbers of atrial premature beats and prolonged their coupling interval, and prevented ERAF after repeated defibrillation in 83% of patients with ERAF. ERAF is a significant clinical problem after successful internal cardioversion of chronic atrial fibrillation, and was observed in up to 31% of patients. In most episodes, ERAF was triggered by short coupling atrial premature beats with preceding normal heart rate. Intravenous sotalol was effective in preventing ERAF in most cases.


A brief overview of some physical studies on the relaxation dynamics and Förster resonance energy transfer of semiconductor quantum dots.
This article highlights some physical studies on the relaxation dynamics and Förster resonance energy transfer (FRET) of semiconductor quantum dots (QDs) and the way these phenomena change with size, shape, and composition of the QDs. The understanding of the excited-state dynamics of photoexcited QDs is essential for technological applications such as efficient solar energy conversion, light-emitting diodes, and photovoltaic cells. Here, our emphasis is directed at describing the influence of size, shape, and composition of the QDs on their different relaxation processes, that is, radiative relaxation rate, nonradiative relaxation rate, and number of trap states. A stochastic model of carrier relaxation dynamics in semiconductor QDs was proposed to correlate with the experimental results. Many recent studies reveal that the energy transfer between the QDs and a dye is a FRET process, as established from 1/d(6) distance dependence. QD-based energy-transfer processes have been used in applications such as luminescence tagging, imaging, sensors, and light harvesting. Thus, the understanding of the interaction between the excited state of the QD and the dye molecule and quantitative estimation of the number of dye molecules attached to the surface of the QD by using a kinetic model is important. Here, we highlight the influence of size, shape, and composition of QDs on the kinetics of energy transfer. Interesting findings reveal that QD-based energy-transfer processes offer exciting opportunities for future applications. Finally, a tentative outlook on future developments in this research field is given.


microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.
Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.


BK viral enhancer element and a human cellular homolog.
Comparison of two closely related primate papovaviruses, simian virus 40 (SV40) and human BK virus (BKV), reveals that the only region of extensive divergence, the tandem sequences adjacent to the origins of DNA replication, is responsible in SV40 for enhancing early gene expression. This study demonstrates a similar enhancer function for the analogous repeated region in BKV. The dissimilarity in sequence of the BKV and SV40 enhancer elements suggests that they may have been acquired since SV40 and BKV diverged. A locus cloned from the human genome homologous to the BKV tandem repeats has been shown to function as low level enhancer element in mammalian cells. These data support the hypothesis that viral enhancer sequences may be evolutionarily related to host cell sequences.


Hodgkin's disease in children: correlation of clinical characteristics, staging procedures, and treatment at the University of Minnesota.
The cases of 63 children treated for Hodgkin's disease were retrospectively evaluated according to clinical and laboratory characteristics at initial appearance, clinical and pathologic staging, and treatment for their effects on survival and disease-free survival. An initial erythrocyte sedimentation rate over 50 mm/h was common in patients who ultimately had a relapse. There was no correlation between the size of the mediastinal mass at diagnosis and occurrence of relapse. A residual mediastinal mass was found in 22% of patients after 1 year of treatment regardless of its size at initial appearance. With a median follow-up time of 10.5 years, the overall survival rate is 89%, and disease-free survival rate is 71%. The disease-free survival rates for patients with stages I-IV disease are 92, 81, 78, and 40%, respectively. Relapses occurred in 7 of 22 (36%) patients with positive staging laparotomy despite radiotherapy for three with stage IA and IIA disease, chemotherapy alone for two with stage IIIB disease, or chemotherapy for one with stage IIIB and one with stage IVB disease. Of patients who had no evidence of abdominal Hodgkin's disease at a staging laparotomy, 6 of 34 (19%) had a relapse. These included one with stage IA and five stage IIA disease, all treated with radiotherapy alone. Treatment of stage III and IV disease with regimens including CCNU (lomustine) or cyclophosphamide, plus vinblastine sulfate or vincristine sulfate, prednisone, and procarbazine hydrochloride with or without radiation therapy yielded poor results, with 6/7 having a relapse.


SIGffRid: a tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics.
Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (sigma) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations. We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of Streptomyces coelicolor and Streptomyces avermitilis. Cross-check with the well-defined SFBSs of the SigR regulon in S. coelicolor is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these sigma factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. Escherichia coli/Salmonella typhimurium and Bacillus subtilis/Bacillus licheniformis pairs). Motifs of house-keeping sigma factors were found as well as other SFBSs such as that of SigW in Bacillus strains. We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs. The method versatility authorizes the recognition of other kinds of two-box regulatory sites.


[Effect of 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl)thiazole chloride on nystatin-created K(+)-current across bilayer lipid membrane].
The application of 0.1 mM of vitamin B1 (thiamine) structural analogue, 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl)thiazole chloride (DMHT) from the cis-side of cholesterol-containing phospholipid bilayer membrane in symmetric solution of 100 mM KCl reversibly reduced the conductance of nystatin channels, reconstituted from the same side of membrane, by 67 +/- 3%. The conductance of nystatin channels applied to the cis-side of bilayer membrane remained unaffected, when DMHT was introduced separately to the opposite trans-side of modified membrane. The kinetics of nystatin channels inhibition with DMHT showed no cooperativity allowing to expect that negatively charged ionogenic groups of these channels formed one DMHT binding site per channel. Relatively high pK of binding with nystatin channels (5,17) suggests that this site provides specific interaction with DMHT.


Effectiveness of psychosocial interventions for reducing parental substance misuse.
Parental substance use is a substantial public health and safeguarding concern. There have been a number of trials of interventions relating to substance-using parents that have sought to address this risk factor, with potential outcomes for parent and child. To assess the effectiveness of psychosocial interventions in reducing parental substance use (alcohol and/or illicit drugs, excluding tobacco). We searched the following databases from their inception to July 2020: the Cochrane Drugs and Alcohol Group Specialised Register; CENTRAL; MEDLINE; Embase; PsycINFO; CINAHL; Applied Social Science (ASSIA); Sociological Abstracts; Social Science Citation Index (SSCI), Scopus, ClinicalTrials.gov, WHO ICTRP, and TRoPHI. We also searched key journals and the reference lists of included papers and contacted authors publishing in the field. We included data from trials of complex psychosocial interventions targeting substance use in parents of children under the age of 21 years. Studies were only included if they had a minimum follow-up period of six months from the start of the intervention and compared psychosocial interventions to comparison conditions. The primary outcome of this review was a reduction in the frequency of parental substance use. We used standard methodological procedures expected by Cochrane. We included 22 unique studies with a total of 2274 participants (mean age of parents ranged from 26.3 to 40.9 years), examining 24 experimental interventions. The majority of studies intervened with mothers only (n = 16; 73%). Heroin, cocaine, and alcohol were the most commonly reported substances used by participants. The interventions targeted either parenting only (n = 13; 59%); drug and alcohol use only (n = 5; 23%); or integrated interventions which addressed both (n = 6; 27%). Half of the studies (n = 11; 50%) compared the experimental intervention to usual treatment. Other comparison groups were minimal intervention, attention controls, and alternative intervention. Eight of the included studies reported data relating to our primary outcome at 6- and/or 12-month follow-up and were included in a meta-analysis. We investigated intervention effectiveness separately for alcohol and drugs. Studies were found to be mostly at low or unclear risk for all 'Risk of bias' domains except blinding of participants and personnel and outcome assessment. We found moderate-quality evidence that psychosocial interventions are probably more effective at reducing the frequency of parental alcohol misuse than comparison conditions at 6-month (mean difference (MD) -0.32, 95% confidence interval (CI) -0.51 to -0.13; 6 studies, 475 participants) and 12-month follow-up (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.03; 4 studies, 366 participants). We found a significant reduction in frequency of use at 12 months only (SMD -0.21, 95% CI -0.41 to -0.01; 6 studies, 514 participants, moderate-quality evidence). We examined the effect of the intervention type. We found low-quality evidence that psychosocial interventions targeting substance use only may not reduce the frequency of alcohol (6 months: SMD -0.35, 95% CI -0.86 to 0.16; 2 studies, 89 participants and 12 months: SMD -0.09, 95% CI -0.86 to 0.61; 1 study, 34 participants) or drug use (6 months: SMD 0.01, 95% CI -0.42 to 0.44; 2 studies; 87 participants and 12 months: SMD -0.08, 95% CI -0.81 to 0.65; 1 study, 32 participants). A parenting intervention only, without an adjunctive substance use component, may not reduce frequency of alcohol misuse (6 months: SMD -0.21, 95% CI -0.46 to 0.04, 3 studies; 273 participants, low-quality evidence and 12 months: SMD -0.11, 95% CI -0.64 to 0.41; 2 studies; 219 participants, very low-quality evidence) or frequency of drug use (6 months: SMD 0.10, 95% CI -0.11 to 0.30; 4 studies; 407 participants, moderate-quality evidence and 12 months: SMD -0.13, 95% CI -0.52 to 0.26; 3 studies; 351 participants, very low-quality evidence). Parents receiving integrated interventions which combined both parenting- and substance use-targeted components may reduce alcohol misuse with a small effect size (6 months: SMD -0.56, 95% CI -0.96 to -0.16 and 12 months: SMD -0.42, 95% CI -0.82 to -0.03; 2 studies, 113 participants) and drug use (6 months: SMD -0.39, 95% CI -0.75 to -0.03 and 12 months: SMD -0.43, 95% CI -0.80 to -0.07; 2 studies, 131 participants). However, this evidence was of low quality. Psychosocial interventions in which the child was present in the sessions were not effective in reducing the frequency of parental alcohol or drug use, whilst interventions that did not involve children in any of the sessions were found to reduce frequency of alcohol misuse (6 months: SMD -0.47, 95% CI -0.76 to -0.18; 3 studies, 202 participants and 12 months: SMD -0.34, 95% CI -0.69 to 0.00; 2 studies, 147 participants) and drug use at 12-month follow-up (SMD -0.34, 95% CI -0.69 to 0.01; 2 studies, 141 participants). The quality of this evidence was low. Interventions appeared to be more often beneficial for fathers than for mothers. We found low- to very low-quality evidence of a reduction in frequency of alcohol misuse for mothers at six months only (SMD -0.27, 95% CI -0.50 to -0.04; 4 studies, 328 participants), whilst in fathers there was a reduction in frequency of alcohol misuse (6 months: SMD -0.43, 95% CI -0.78 to -0.09; 2 studies, 147 participants and 12 months: SMD -0.34, 95% CI -0.69 to 0.00; 2 studies, 147 participants) and drug use (6 months: SMD -0.31, 95% CI -0.66 to 0.04; 2 studies, 141 participants and 12 months: SMD -0.34, 95% CI -0.69 to 0.01; 2 studies, 141 participants). We found moderate-quality evidence that psychosocial interventions probably reduce the frequency at which parents use alcohol and drugs. Integrated psychosocial interventions which combine parenting skills interventions with a substance use component may show the most promise. Whilst it appears that mothers may benefit less than fathers from intervention, caution is advised in the interpretation of this evidence, as the interventions provided to mothers alone typically did not address their substance use and other related needs. We found low-quality evidence from few studies that interventions involving children are not beneficial.


A method to correct the influence of carbon fiber couchtop and patient positioning device on image quality of cone beam CT.
To evaluate the influence of carbon fiber couchtop and patient positioning devices on cone beam CT (CBCT) image quality and develop an effective method to correct the influence. A standard CT phantom (Catphan 500) was used to evaluate the influence of iBeam evo carbon fiber couchtop on the quality of CBCT image obtained from an Elekta synergy machine. The evaluation indices were contrast-to-noise ratio (CNR), spatial resolution, image uniformity, and image noise. With using the Beer-Lambert law and the energy-response function of the flat-panel imager, a method was applied to deduct the image signal of the couchtop (and the positioning devices) from each projection image of a phantom/patient, and then used all corrected projection images to reconstruct a CBCT image. The performance of the correction method was evaluated using the CBCT images of a Catphan 500 phantom, a head-and-neck cancer patient, and a prostate cancer patient. In two phantom studies (the phantom to simulate a human head and neck and the one to simulate a human body), the CNR of the CBCT images obtained with the couchtop reduced 18.1% and 29.8%, respectively with respect to those obtained without the couchtop; meanwhile, the image uniformity reduced 16.4% and 24.1% due to the use of the carbon fiber couchtop. The couchtop also induced extra image noise (16.5% for the h&n phantom and 4.2% for the body phantom). However, CBCT imaging with the couchtop did not affect the spatial resolution. After applying the projection image correction, there was a significant improvement in CNR (by 19.5% and 25.8%), image uniformity (by 9.2% and 13.1%), and image noise (by 10.2% and 3.9%), with respect to CBCT images obtained with the couchtop. The presence of the carbon fiber couchtop and the patient positioning devices can significantly impair CBCT image quality in terms of the CNR, the image uniformity, and the image noise. By removing the influence of the couchtop and the patient-positioning devices from CB projection images, the correction method improves CBCT image quality and thus image guidance in radiotherapy.


4-Year Pulp Survival in a Randomized Trial on Direct Pulp Capping.
This study aimed to assess pulp survival in a randomized trial on pulp lavage in adult nonpainful posterior teeth with carious pulp exposure. The treatment included complete caries excavation, direct pulp capping with mineral trioxide aggregate, and immediate restoration with composite resin. Fluid was collected from the pulp wound to assess matrix metalloproteinase-9 (MMP-9) and total protein values. Before pulp capping, cavities were randomly (block randomization, n = 48) washed with a physiological saline or a sodium hypochlorite solution (2.5% NaOCl). Treatment outcome was assessed clinically (cold test) and radiographically after at least 1 year and again after at least 3 years. Painful failures were differentiated from nonpainful failures. Pulp survival was estimated using the Kaplan-Meier method including 95% confidence intervals (CIs) up to 1500 days. From the 96 patients originally enrolled, 73 individuals could be followed continuously. The clinical observations indicated a beneficial and sustained effect of pulp lavage with 2.5% NaOCl over a control treatment with physiological saline solution on estimated pulp survival 1500 days postintervention, with 7% (95% CI, 1%-40%) in the saline group versus 55% (95% CI, 30%-100%) in the NaOCl group. High MMP-9/total protein values in pulpal fluid collected from the exposed site indicated early and painful treatment failures yet were not associated with failures that occurred more than 250 days after intervention. The low 4-year success rates reported here challenge the concept of direct pulp capping in the cases that were included. NaOCl lavage did not only increase the survival of affected pulps substantially but also particularly diminished painful failures (33% in the NaOCl group vs 62% in the saline group). The lack of the predictive value of MMP-9 assessments beyond early treatment failures points to inflammatory states of the pulp tissue under deep caries, which are not related to neutrophil infiltration.


Disrupted resting brain graph measures in individuals at high risk for alcoholism.
Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors.


Self-engineering capabilities of bacteria.
Under natural growth conditions, bacteria can utilize intricate communication capabilities (e.g. quorum-sensing, chemotactic signalling and plasmid exchange) to cooperatively form (self-organize) complex colonies with elevated adaptability-the colonial pattern is collectively engineered according to the encountered environmental conditions. Bacteria do not genetically store all the information required for creating all possible patterns. Instead, additional information is cooperatively generated as required for the colonial self-organization to proceed. We describe how complex colonial forms (patterns) emerge through the communication-based singular interplay between individual bacteria and the colony. Each bacterium is, by itself, a biotic autonomous system with its own internal cellular informatics capabilities (storage, processing and assessment of information). These afford the cell plasticity to select its response to biochemical messages it receives, including self-alteration and the broadcasting of messages to initiate alterations in other bacteria. Hence, new features can collectively emerge during self-organization from the intracellular level to the whole colony. The cells thus assume newly co-generated traits and abilities that are not explicitly stored in the genetic information of the individuals.


"Then you raise them with Shirchoy or cookies": Understanding influences on delayed dietary diversity among children in Tajikistan.
Dietary diversity is a key component of infant and young child feeding (IYCF) as well as adult health. In Tajikistan, a predominantly rural, former Soviet country in Central Asia, we conducted formative research to identify barriers to dietary diversity and strategies for nutrition behaviour change. In Spring, 2016, mixed-methods data collection took place across 13 villages in all five regions, collecting collaborative mapping; structured assessments of stores and markets; home visits for dietary recalls; food storage, preparation, and meal observations; focus groups with pregnant women, mothers of young children, fathers, and mothers-in-law; and in-depth expert interviews with local nutrition and health influentials. Overall, maternal diet was adequate in terms of diversity (only 13% reported <5/10 food groups in the past 24 hr); however, only 42% of index children 6-24 months met WHO guidelines for diversity, and only 34% met minimum acceptable diet criteria. In addition to issues of poverty and food scarcity, qualitative data reveal many behavioural barriers to timely introduction of diverse complementary foods. Women's strategies focused on gradual introduction of household diet components, without regard for diversity or nutrition. Foods such as meat were seen as costly and thus inappropriate for IYCF, and food taboos (i.e., fresh vegetables) further reduced diversity. Infant food preparation methods such as grinding were seen as impractical, and many foods were withheld until children develop teeth. Possible nutrition education strategies include point-of-purchase campaigns to improve availability and appeal of IYCF-friendly foods, as well as influencing other key household members through mosques, schools, and health care providers.


Development of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE).
We describe the creation process of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE). Modeled after the existing minimum information specification for microarray data, we created a new specification for gene expression localization experiments, initially to facilitate data sharing within a consortium. After successful use within the consortium, the specification was circulated to members of the wider biomedical research community for comment and refinement. After a period of acquiring many new suggested requirements, it was necessary to enter a final phase of excluding those requirements that were deemed inappropriate as a minimum requirement for all experiments. The full specification will soon be published as a version 1.0 proposal to the community, upon which a more full discussion must take place so that the final specification may be achieved with the involvement of the whole community.


Comparative anatomical survey of Cyclamen L. (Primulaceae) taxa and their traditional medicinal uses in Turkey.
The genus Cyclamen is native to Turkey, where it is represented by 12 perennial tuberous geophytic taxa. In this study, a detailed anatomical description of all Cyclamen taxa found in Turkey is provided for the first time. Tuber, root, petiole, and leaf cross-sections were stained with Astra blue and safranin, and tuber slides were also stained with sartur. Tubers of these taxa used by local people as a treatment for infertility were separately investigated. Stomatal index values and epidermis cell features of the studied taxa were measured. Indumentum features of the leaves were described for the first time. Petiole and leaf anatomy and particularly stomatal density, size, and index, provided valuable evidence for species identification. Although the anatomical features of these taxa are not sufficient as diagnostic characters, they can be used together with morphological features.


The effect of hypothermia on neuronal viability following cardiopulmonary bypass and circulatory arrest in newborn piglets.
To determine the effect of recovery with mild hypothermia after cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on the activity of selected key proteins involved in initiation (Bax, Caspase-3) or inhibition of apoptotic injury (Bcl-2, increased ratio Bcl-2/Bax) in the brain of newborn piglets. The piglets were placed on CPB, cooled with pH-stat management to 18 degrees C, subjected to 30 min of DHCA followed by 1h of low flow at 20 ml/kg/min, rewarmed to 37 degrees C (normothermia) or to 33 degrees C (hypothermia), separated from CPB, and monitored for 6h. Expression of above proteins was measured in striatum, hippocampus and frontal cortex by Western blots. The results are mean for six experiments+/-SEM. There were no significant differences in Bcl-2 level between normothermic and hypothermic groups. The Bax levels in normothermic group in cortex, hippocampus and striatum were 94+/-9, 136+/-22 and 125+/-34 and decreased in the hypothermic group to 59+/-17 (p=0.028), 70+/-6 (p=0.002) and 48+/-8 (p=0.01). In cortex, hippocampus and striatum Bcl-2/Bax ratio increased from 1.23, 0.79 and 0.88 in normothermia to 1.96, 1.28 and 2.92 in hypothermia. Expression of Caspase-3 was 245+/-39, 202+/-74 and 244+/-31 in cortex, hippocampus and striatum in the normothermic group and this decreased to 146+/-24 (p=0.018), 44+/-16 (p=7 x 10(-7)) and 81+/-16 (p=0.01) in the hypothermic group. In neonatal piglet model of cardiopulmonary bypass with circulatory arrest, mild hypothermia during post bypass recovery provides significant protection from cellular apoptosis, as indicated by lower expression of Bax and Caspase-3 and an increased Bcl-2/Bax ratio. The biggest protection was observed in striatum probably by decreasing of neurotoxicity of striatal dopamine.


Crambin in phospholipid vesicles: Circular dichroism analysis of crystal structure relevance.
Crambin, a hydrophobic plant seed protein that exhibits sequence homology to membrane-active plant toxins, was incorporated into phospholipid vesicles. Circular dichroism spectroscopy indicates that its structure in vesicles is nearly identical to its structure in 60% ethanol solution, the solvent from which the protein was crystallized. The secondary structure predicted from the circular dichroism data of the ethanol solution closely resembles that determined by x-ray diffraction of the crystals. This agreement suggests that the x-ray structure may form a useful basis for modeling the structure and behavior of lipophilic plant toxins. Finally, because the structure of crambin has been determined in an organic solvent medium, it provides a protein standard for examination of the effect of solvent dipole moment on the circular dichroism spectra of proteins, which may be important for interpretation of data for membrane proteins.


Formation of nanostructured porous Cu-Au surfaces: the influence of cationic sites on (electro)-catalysis.
The fabrication of nanostructured bimetallic materials through electrochemical routes offers the ability to control the composition and shape of the final material that can then be effectively applied as (electro)-catalysts. In this work a clean and transitory hydrogen bubble templating method is employed to generate porous Cu-Au materials with a highly anisotropic nanostructured interior. Significantly, the co-electrodeposition of copper and gold promotes the formation of a mixed bimetallic oxide surface which does not occur at the individually electrodeposited materials. Interestingly, the surface is dominated by Au(I) oxide species incorporated within a Cu(2)O matrix which is extremely effective for the industrially important (electro)-catalytic reduction of 4-nitrophenol. It is proposed that an aurophilic type of interaction takes place between both oxidized gold and copper species which stabilizes the surface against further oxidation and facilitates the binding of 4-nitrophenol to the surface and increases the rate of reaction. An added benefit is that very low gold loadings are required typically less than 2 wt% for a significant enhancement in performance to be observed. Therefore the ability to create a partially oxidized Cu-Au surface through a facile electrochemical route that uses a clean template consisting of only hydrogen bubbles should be of benefit for many more important reactions.


Comparable rates of gene loss and functional divergence after genome duplications early in vertebrate evolution.
Duplicated genes are an important source of new protein functions and novel developmental and physiological pathways. Whereas most models for fate of duplicated genes show that they tend to be rapidly lost, models for pathway evolution suggest that many duplicated genes rapidly acquire novel functions. Little empirical evidence is available, however, for the relative rates of gene loss vs. divergence to help resolve these contradictory expectations. Gene families resulting from genome duplications provide an opportunity to address this apparent contradiction. With genome duplication, the number of duplicated genes in a gene family is at most 2n, where n is the number of duplications. The size of each gene family, e.g., 1, 2, 3, ..., 2n, reflects the patterns of gene loss vs. functional divergence after duplication. We focused on gene families in humans and mice that arose from genome duplications in early vertebrate evolution and we analyzed the frequency distribution of gene family size, i.e., the number of families with two, three or four members. All the models that we evaluated showed that duplicated genes are almost as likely to acquire a new and essential function as to be lost through acquisition of mutations that compromise protein function. An explanation for the unexpectedly high rate of functional divergence is that duplication allows genes to accumulate more neutral than disadvantageous mutations, thereby providing more opportunities to acquire diversified functions and pathways.


Completeness and data validity for the Danish Fracture Database.
Fracture-related surgery is among the most common orthopaedic procedures. However, to our knowledge, register-based quality assessment of fracture-related surgery has not previously been conducted. The Danish Fracture Database (DFDB) has been developed for the purpose of web-based quality assessment, but its properties as a valid data source have not previously been explored. We therefore investigated: 1) the completeness of data in the DFDB, and 2) if the entered data are valid data sources for future quality assessment. We have developed the internet-based DFDB in which data entry is performed by the surgeon. Data collection includes primary fracture surgery and reoperations. After full implementation of the database at two orthopaedic departments, we assessed the completeness and validity of the entered data for 322 patients operated during a one-month period. Validity was calculated as observed agreement. We recorded 83% completeness for all types of data entry, with 88% completeness for primary fracture surgery and 77% for reoperations, respectively. Patient- and trauma-related data were 82-100% valid. Surgery-related data included method of osteosynthesis and was valid in 89-99% of the cases. The DFDB is an easy to use web-based database for registration of fracture-related surgery. Shortly after its implementation, we recorded satisfactory completeness and high data validity, which makes the DFDB a valuable tool with potential for nationwide quality assessment of fracture-related surgery.


Incidental endometrial adenocarcinoma in early pregnancy: a case report and review of the literature.
Endometrial cancer is the most common neoplasia of the female reproductive system, with the highest incidence among uterine malignancies, and is rarely associated with pregnancy. Thirty-five cases of pregnancy-associated endometrial cancer have been reported in literature, of which ours represents the 20th case diagnosed during the first trimester. A 39-year-old woman, gravida 4, para 2, was diagnosed with a focal, well- to moderately differentiated endometrial adenocarcinoma (International Federation of Gynecology and Obstetrics stage IA and grades G1 and G2) after dilatation and curettage (D&C) for a spontaneous abortion. The patient underwent progestational therapy and follow-up hysteroscopies and D&C to preserve fertility; she is alive and well 18 months after diagnosis. Recurrence of endometrial cancer coexisting with early pregnancy has not been reported in the literature. Conservative therapy for early endometrial cancer, diagnosed at the time of pregnancy, may be an option. Routine histologic examination after D&C performed for spontaneous abortion seems advisable.


Clinical implications of the competitive inhibition of the debrisoquin-metabolizing isozyme by quinidine.
Approximately 10% of western populations are genetically deficient in the enzyme that metabolizes the antihypertensive drug debrisoquin. These "poor metabolizers" process many common medications in an aberrant fashion, resulting in a variety of untoward consequences including exaggerated drug effect, subtherapeutic drug concentrations, or complex drug interactions. A variety of medications, including neuroleptics, antidepressants, beta-blockers, and certain antiarrhythmics, are subject to the influence of this metabolic polymorphism. Quinidine administration changes persons to poor metabolizers of debrisoquin for the duration of therapy. Thus, the use of quinidine with any of the other drugs metabolized by this isozyme may be expected to result in a drug interaction in which a person's response will mimic that of a poor metabolizer. Because no test is commonly available to determine directly the debrisoquin metabolic phenotype, clinicians should be alert to unusual drug reactions in patients receiving quinidine concurrently with the other medications.


Tunable Crosslinking, Reversible Phase Transition, and 3D Printing of Hyaluronic Acid Hydrogels via Dynamic Coordination of Innate Carboxyl Groups and Metallic Ions.
This article reports tunable crosslinking, reversible phase transition, and three-dimensional printing (3DP) of hyaluronic acid (HyA) hydrogels via dynamic coordination of Fe3+ ions with their innate carboxyl groups for the first time. The concentrations of Fe3+ and H+ ions and the reaction time determine the tunable ratios of mono-, bi-, and tridentate coordination, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. At the monodentate-dominant coordination, the liquid hydrogels have low crosslinking densities (HyA_L). At the mixed coordination of mono-, bi-, and tridentate bonding, the solid hydrogels have medium crosslinking densities (HyA_M). At the tridentate-dominant coordination, the solid hydrogels have high crosslinking densities (HyA_H). The reversible solid-liquid phase transitions among HyA_L, HyA_M, and HyA_H were achieved via controlling the concentrations of Fe3+ and H+ ions and reaction time. When the crosslinking densities are between HyA_L and HyA_M, the hydrogels become 3D printable (HyA_P). HyA_P hydrogels were 3D-printed successfully using cold-stage or direct writing methods, and the 3D constructs achieved better structural stability using the latter method. In the direct exposure culture with bone marrow-derived mesenchymal stem cells, the 3D-printed HyA_H (HyA_H_3D) and HyA_H hydrogels showed higher average cell adhesion densities than the HyA_M, HyA_P, and HyA_L hydrogel groups under both direct and indirect contact conditions. For all hydrogel groups, cell adhesion densities under direct contact conditions were statistically lower than the same groups under indirect contact conditions. In this article, we elucidated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3DP of HyA hydrogels without blending with other polymers or adding functional groups. This approach can be potentially adapted to crosslink and 3D print other polymeric hydrogels with carboxyl groups, which is promising for a wide range of applications.


Prevalence and Risk Factors of Self-reported Vision Impairment among Native Hawaiians and Pacific Islanders in the United States.
Racial disparities in vision impairment have been reported among Black, Hispanic, and White Americans. However, there is a paucity of research on vision impairment among Native Hawaiians and Pacific Islanders (NHPIs). The objective of this study was to determine the prevalence of, and risk factors for, self-reported visual impairment in NHPI adults in the United States (US). Data from the NHPI and 2014 National Health Interview Surveys were analyzed using sample weights and variance estimates. Prevalence was calculated for vision impairment and blindness for the NHPI and overall US populations. Sociodemographic and clinical risk factors of vision impairment were explored using descriptive statistics, χ2 tests, and simple and multiple logistic regression. In total, 2 586 NHPIs and 36 673 individuals in the US were included. The prevalence of vision impairment was 8.8% among NHPIs and 9.1% for the overall US population, and the prevalence of blindness was 0.72% for NHPIs and 0.35% for the overall population. Independent risk factors associated with vision impairment were having a Charlson Comorbidity Index over 1 [OR: 2.89, 95% CI: (1.42-5.88)] and having a family income below $35 000 [OR: 2.03, 95% CI: (1.06-3.89)]. In summary, the rate of blindness is higher among NHPIs than the overall US population, especially for older and unemployed individuals with more comorbidities. Higher comorbidity burden, lower family income, and recent eye care were risk factors for vision impairment. More research is necessary to develop targeted and culturally sensitive interventions to promote NHPI eye health.


Hyperthermia in the treatment of recurrent abdominal desmoid tumor.
The most suitable management of recurrent abdominal desmoid tumor is still unclear. A case of recurrent huge abdominal desmoid tumor successfully treated by hyperthermia therapy is described. A 63-year-old man was operated upon for desmoid tumor in the retroperitoneum involving pancreas, posterior wall of the stomach and transverse mesocolon in 2007. In 2008, the tumor recurred and could not be resected because of the patient refused the operation. Several therapies using tamoxifen, anastrozole, imatinib mesylate and radiotherapy were all ineffective. The tumor grew bigger and bigger during a treatment period. Finally, hyperthermia treatment was applied to the tumor. The size of the recurrent desmoid tumor reduced 75% by hyperthermia treatment for 46-month. Base on this experience, we recommend hyperthermia as the treatment for patients with recurrent abdominal desmoid tumor that several therapeutic strategies did not achieve a remarkable response.


The ansa subclavia: a review of the literature.
The ansa subclavia, subclavian loop, Vieussens' ansa or Vieussens' loop is a nerve cord that connects the middle cervical and inferior cervical sympathetic ganglia, forming a loop around the subclavian artery. The structure of the ansa subclavia is evolutionarily conserved from rats, guinea pigs, the porcine species and dogs to humans. A common application in physiological studies is to electrically stimulate the ansa subclavia in animal models as a robust protocol to modulate stimulatory cardiac sympathetic input. Despite a large number of physiological studies utilizing the ansa subclavia, only very brief descriptions have been devoted to it in standard anatomy texts. An extensive search found only one report in the English language literature concerning the anatomy of the ansa subclavia. The aim of this report, therefore, was to provide a comprehensive review of the clinical anatomy of the ansa subclavia and to discuss its potential physiological functions.


A high-quality high-fidelity visualization of the September 11 attack on the World Trade Center.
In this application paper, we describe the efforts of a multidisciplinary team towards producing a visualization of the September 11 Attack on the North Tower of New York's World Trade Center. The visualization was designed to meet two requirements. First, the visualization had to depict the impact with high fidelity, by closely following the laws of physics. Second, the visualization had to be eloquent to a nonexpert user. This was achieved by first designing and computing a finite-element analysis (FEA) simulation of the impact between the aircraft and the top 20 stories of the building, and then by visualizing the FEA results with a state-of-the-art commercial animation system. The visualization was enabled by an automatic translator that converts the simulation data into an animation system 3D scene. We built upon a previously developed translator. The translator was substantially extended to enable and control visualization of fire and of disintegrating elements, to better scale with the number of nodes and number of states, to handle beam elements with complex profiles, and to handle smoothed particle hydrodynamics liquid representation. The resulting translator is a powerful automatic and scalable tool for high-quality visualization of FEA results.


Screen-printed poly(3,4-ethylenedioxythiophene) (PEDOT): A new electrochemical mediator for acetylcholinesterase-based biosensors.
This work describes the use of a PEDOT:PSS-based conductive polymer for designing AChE-based biosensors. The transducers were obtained directly by screen-printing a PEDOT:PSS suspension on the surface of thick film carbon electrodes. The obtained working electrodes showed a high conductivity when compared with electrodes modified with conventional mediators like cobalt phthalocyanine or tetracyanoquinodimethane. The PEDOT:PSS polymer was shown to be suitable for thiocholine oxidation, allowing the measurement of AChE activity at 100 mV vs Ag/AgCl. The high conductivity of PEDOT:PSS allowed the accurate detection of the organophosphate insecticide chlorpyrifos-oxon at concentrations as low as 4x10(-9)M, corresponding to an inhibition ratio of 5%.


Gene expression profile and immunological evaluation of unique hypothetical unknown proteins of Mycobacterium leprae by using quantitative real-time PCR.
The cell-mediated immunity (CMI)-based in vitro gamma interferon release assay (IGRA) of Mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of M. leprae infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential M. leprae-specific proteins called "hypothetical unknowns." Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the M. leprae-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in M. leprae. Fifteen of 26 selected antigen candidates were expressed and purified in Escherichia coli. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited M. leprae-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy.


The role of the blood-brain barrier during Venezuelan equine encephalitis virus infection.
Venezuelan equine encephalitis (VEE) virus is a mosquito-borne alphavirus associated with sporadic outbreaks in human and equid populations in the Western Hemisphere. After the bite of an infected mosquito, the virus initiates a biphasic disease: a peripheral phase with viral replication in lymphoid and myeloid tissues, followed by a neurotropic phase with infection of central nervous system (CNS) neurons, causing neuropathology and in some cases fatal encephalitis. The mechanisms allowing VEE virus to enter the CNS are currently poorly understood. Previous data have shown that the virus gains access to the CNS by infecting olfactory sensory neurons in the nasal mucosa of mice. However, at day 5 after inoculation, the infection of the brain is multifocal, indicating that virus particles are able to cross the blood-brain barrier (BBB). To better understand the role of the BBB during VEE virus infection, we used a well-characterized mouse model system. Using VEE virus replicon particles (VRP), we modeled the early events of neuroinvasion, showing that the replication of VRP in the nasal mucosa induced the opening of the BBB, allowing peripherally administered VRP to invade the brain. Peripheral VEE virus infection was characterized by a biphasic opening of the BBB. Further, inhibition of BBB opening resulted in a delayed viral neuroinvasion and pathogenesis. Overall, these results suggest that VEE virus initially enters the CNS through the olfactory pathways and initiates viral replication in the brain, which induces the opening of the BBB, allowing a second wave of invading virus from the periphery to enter the brain.


Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma.
Although most of the initial studies in angiogenesis were done on solid tumors, there is now data suggesting the importance of angiogenesis in hematologic malignancies. We estimated bone marrow microvessel density before autologous stem cell transplantation and at the time of response in 13 patients with myeloma (seven complete and six partial responders) using an immunohistochemical stain for factor VIII-related antigen (von Willebrand factor). Baseline microvessel density was significantly different between bone marrow samples from patients with myeloma and morphologically normal, staging marrows from patients with limited stage Hodgkin's disease, mean (+/- s.d.) 294 (+/-115)/mm2 vs 93 (+/-26/mm2, respectively, P = 0.001. After transplantation, microvessel density continued to be high in myeloma samples compared to samples from control patients with limited stage Hodgkin's disease, mean (+/- s.d.) 230 (+/-68)/mm2, P = 0.003. There was no difference in microvessel density at the time of complete or partial response compared to values prior to transplantation. This report confirms that increased angiogenesis is found in myeloma bone marrow prior to transplantation, and suggests that increased angiogenesis persists even after complete response.


Establishing a nursing student learning center for women's reproductive health in Nepal.
The goal of this paper is to describe the establishment of a self-sustaining Student Learning Center (SLC) employing humanistic anatomical models to aid in the teaching of family planning and reproductive health clinical skills to nursing students in Nepal. In response to a local needs assessment a plan was developed to implement more thorough training of nursing students in family planning clinical skills. Nepalese nursing leaders worked together with a U.S. Non-Governmental Organization (NGO) to implement this project. This paper details the need for the SLCs, the content and structure of the SLCs, and the process of establishing an SLC at Tribhuvan University, Maharjgunj Nursing Campus in Kathmandu, the largest of all nursing campuses in Nepal.


Evaluation of the virulence markers in the clinical isolates of citrobacter species: the first report from India.
Citrobacter, a gram negative bacillus, is emerging as one of the major pathogens in hospital settings, with a potential to cause serious infections. Virulence markers are the factors which enhance the survival ability of the micro-organisms. Among the gram negative bacilli, these have been extensively studied in Escherichia coli. To the best of our knowledge as per internet search, we report that this study has been done for the first time in India on Citrobacter. An investigation was done to determine the ability of Citrobacter in producing virulence markers like the ability to survive the serum bactericidal activity, the resistance to the intracellular killing in the Polymorphonuclear Leucocytes (PMNLs) and the Cell Surface Hydrophobicity (CSH). This prospective study was conducted in the Department of Microbiology of a tertiary care hospital in Aligarh, India, for a period of one year and six months. A total of 105 clinical isolates and 20 control isolates from healthy subjects were identified as having Citrobacter spp. by using standard biochemical tests and they were studied for the presence of virulence markers like the ability to survive the serum bactericidal activity, the resistance to the intracellular killing in the Polymorphonuclear Leucocytes (PMNLs) and the cell surface hydrophobicity. The statistical analysis which was used: The standard deviations and the p-values were calculated for comparison. Out of the 105 clinical isolates of Citrobacter which were studied, 86.6% isolates were resistant to 100% serum after 180 minutes of incubation and intracellular killing in PMNL was demonstrated in 17% strains. The Salt Aggregation Test (SAT) for the cell surface hydrophobicity was positive in 17.1% strains at different concentrations of ammonium sulphate. The presence of more than one virulence marker was present in 71.4% of the clinical isolates while in the control isolates. The presence of the virulence markers in Citrobacter demonstrated its pathogenic potential. Its invasiveness and ability to disseminate can be studied by identifying these markers.


The length of lipoteichoic acid polymers controls Staphylococcus aureus cell size and envelope integrity.
The opportunistic pathogen Staphylococcus aureus is protected by a cell envelope that is crucial for viability. In addition to peptidoglycan, lipoteichoic acid (LTA) is an especially important component of the S. aureus cell envelope. LTA is an anionic polymer anchored to a glycolipid in the outer leaflet of the cell membrane. It was known that deleting the gene for UgtP, the enzyme that makes this glycolipid anchor, causes cell growth and division defects. In Bacillus subtilis, growth abnormalities from the loss of ugtP have been attributed to both the absence of the encoded protein and to the loss of its products. Here, we show that growth defects in S. aureus ugtP deletion mutants are due to the long, abnormal LTA polymer that is produced when the glycolipid anchor is missing from the outer leaflet of the membrane. Dysregulated cell growth leads to defective cell division, and these phenotypes are corrected by mutations in the LTA polymerase, ltaS, that reduce polymer length. We also show that S. aureus mutants with long LTA are sensitized to cell wall hydrolases, beta-lactam antibiotics, and compounds that target other cell envelope pathways. We conclude that control of LTA polymer length is important for S. aureus physiology and promotes survival under stressful conditions, including antibiotic stress.IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of community- and hospital-acquired infections and is responsible for a large fraction of deaths caused by antibiotic-resistant bacteria. S. aureus is surrounded by a complex cell envelope that protects it from antimicrobial compounds and other stresses. Here we show that controlling the length of an essential cell envelope polymer, lipoteichoic acid, is critical for controlling S. aureus cell size and cell envelope integrity. We also show that genes involved in LTA length regulation are required for resistance to beta-lactam antibiotics in MRSA. The proteins encoded by these genes may be targets for combination therapy with an appropriate beta-lactam.


[Morphological examinations of infected burn wounds].
Electron microscopical and electron radioautographic methods have been used for morphological examination. This allowed to raise sensitivity of the tests facilitating detection of living solitary bacterial cells (by intensive mark above them). Radioautography showed functional status of wound bacteria (the intensity of the metabolism and reproduction). It was determined that in living tissues, not damaged by the burn and unchanged morphologically bacteria do not penetrate. Especially massive accumulations of the microorganisms are found in necrotic tissues, under the scab, at the external border of demarcation protuberance, and they represent colonization of the wound. When modern methods of treatment and early necrectomy are used, morphological examination usually does not reveal pathogenic microorganisms. Only inflammatory reaction of the wound tissues could be seen: oedema, hyperemia, hemorrhages, cellular infiltrates. The development of granulation tissue indicated cessation of wound infection. Especially favourable feature, demonstrating healing of the wound, was appearance and reproduction of young cells of fat tissue (indusion of labelled thymidine). The results of the study have confirmed the advantage of new electronic methods for microscopy in infected burn wounds.


Erythrocyte membrane sodium transport in patients with treated and untreated essential hypertension.
Various parameters of erythrocyte membrane sodium transport were measured in patients with untreated essential hypertension, in the normotensive offspring of parents with hypertension, and in patients whose hypertension had been controlled by medication. Net sodium efflux, measured by an isotopic tracer technique, was 2.12 +/- 0.17 mM Na+/1 of red blood cells (RBCs)/hr in patients with untreated essential hypertension, compared with 1.55 +/- 0.12 mM Na/1 of RBCs/hr in a group of normotensive controls (p less than .025). Partitioning sodium efflux into ouabain-sensitive and ouabain-insensitive components revealed a significant elevation of both components of membrane sodium transport in the patients with untreated essential hypertension. Ouabain-sensitive sodium efflux was 1.38 +/- 0.09 mM Na/1 RBCs/hr in the patients, compared with 1.04 +/- 0.07 mM Na/1 RBCs/hr in the controls. Ouabain-insensitive sodium efflux was also increased from 0.51 +/- 0.05 mM Na/1 RBCs/hr in the controls to 0.74 +/- 0.09 mM Na/1 RBCs/hr in those with untreated hypertension. Despite these changes in sodium efflux, Na,K-ATPase activity in the erythrocyte membrane, measured at maximum velocity (Vmax), was normal, suggesting that the observed abnormalities in membrane sodium transport in patients with untreated essential hypertension resulted from a change in pump control mechanisms rather than a change in enzyme activity. With the techniques used in this study we were unable to identify changes in erythrocyte membrane transport in the normotensive offspring of hypertensive parents. Membrane sodium transport was also examined in hypertensive patients whose blood pressure had been controlled by medication. In this group it was found that erythrocyte sodium transport did not differ from that in our control group, which suggests that treatment of hypertension can modify fundamental pathophysiologic changes at the level of the cell membrane.


[Social costs of the most common inflammatory rheumatic diseases in Mexico from the patient's perspective].
To estimate the social costs of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout from the patient's perspective. We carried out a cross-sectional analysis of the cost and resource utilization of 690 RA, AS, and gout patients from 10 medical centers and private facilities in five cities of Mexico. The information was obtained from the baseline of a dynamic cohort. We estimated out-of-pocket expenses, institutional direct costs, and direct medical costs. The mean (SD) annual out-of-pocket expense (USD) was $610.0 ($302.2) for RA, $578.6 ($220.5) for AS, and $245.3 ($124.0) for gout. Figures correspond to 15%, 9.6%, and 2.5% of the family income. They also represented 26.1%, 25.3%, and 24.4% of the total annual cost per RA, AS, and gout patients, respectively. The expected direct institutional patient/year costs were 1,724.2 for RA, $1,710.8 for AS, and $760.7 for gout. The total patient annual costs were $2,334.3 for RA, $2,289.4 for AS, and $1,006.1 for gout. Most out-of-pocket expenses were used to purchase drugs, pay for laboratory tests, imaging studies, and alternative therapies. From the patient's perspective, the cost of RA, AS, and gout represents 25% of direct medical costs. The cost of RA is higher than that for AS and gout.


Overexpression of a Calcium-Dependent Protein Kinase Confers Salt and Drought Tolerance in Rice by Preventing Membrane Lipid Peroxidation.
The OsCPK4 gene is a member of the complex gene family of calcium-dependent protein kinases in rice (Oryza sativa). Here, we report that OsCPK4 expression is induced by high salinity, drought, and the phytohormone abscisic acid. Moreover, a plasma membrane localization of OsCPK4 was observed by transient expression assays of green fluorescent protein-tagged OsCPK4 in onion (Allium cepa) epidermal cells. Overexpression of OsCPK4 in rice plants significantly enhances tolerance to salt and drought stress. Knockdown rice plants, however, are severely impaired in growth and development. Compared with control plants, OsCPK4 overexpressor plants exhibit stronger water-holding capability and reduced levels of membrane lipid peroxidation and electrolyte leakage under drought or salt stress conditions. Also, salt-treated OsCPK4 seedlings accumulate less Na+ in their roots. We carried out microarray analysis of transgenic rice overexpressing OsCPK4 and found that overexpression of OsCPK4 has a low impact on the rice transcriptome. Moreover, no genes were found to be commonly regulated by OsCPK4 in roots and leaves of rice plants. A significant number of genes involved in lipid metabolism and protection against oxidative stress appear to be up-regulated by OsCPK4 in roots of overexpressor plants. Meanwhile, OsCPK4 overexpression has no effect on the expression of well-characterized abiotic stress-associated transcriptional regulatory networks (i.e. ORYZA SATIVA DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN1 and ORYZA SATIVA No Apical Meristem, Arabidopsis Transcription Activation Factor1-2, Cup-Shaped Cotyledon6 genes) and LATE EMBRYOGENESIS ABUNDANT genes in their roots. Taken together, our data show that OsCPK4 functions as a positive regulator of the salt and drought stress responses in rice via the protection of cellular membranes from stress-induced oxidative damage.


Parental Trust in School-Based Health Care: A Systematic Review.
Health care delivery in schools is a frequently adopted approach to reduce health care inequalities. Lack of parental trust has been identified as impacting participation in school-based health care programs (SBHPs). The aim of our systematic review is to outline themes related to parental trust in SBHPs. We searched MEDLINE, Embase, CINHAL, ERIC, PsycInfo, and Web of Science for articles published between 1969 and 2019. Eligible studies (1) were peer-reviewed primary research articles; (2) were school-based health interventions or screening programs; (3) included parental trust data; and (4) were carried out on schoolchildren from pre-K to grade 12. Study location, data collection date, number of participants, demographics, intervention type, study aim and methodology, and all trust themes mentioned, were extracted. Studies were critically appraised using the CASP checklist for qualitative research. We identified 9 themes related to parental trust in SBHPs: (1) safety; (2) effectiveness; (3) health professionals' training and credentials; (4) communication; (5) confidentiality; (6) providers; (7) government, authorities, and health service; (8) the pharmaceutical industry; and (9) research and data sharing. The themes identified provide a framework for examining trust in SBHPs, and may guide the development of interventions to increase trust and engagement in SBHPs.


Methodological studies of orofacial aesthetics, orofacial function and oral health-related quality of life.
Among researchers and in the general population, awareness of the impact of health and health care on the quality of human life is increasing. An important medical and dental research area that addresses this issue is health measurement scales and psychometrics. Such instruments have numerous uses, such as to screen psychosocial aspects in individual patient care, assess perceived health or disease in population surveys, measure outcome in clinical trials, and gather data for cost-utility analyses. Assessing and improving oral health-related quality of life (OHRQoL), orofacial function, and orofacial aesthetics are three major goals in dental care. The overall aim of this thesis was to describe how three assessment tools were developed-using current scientific methodology-to measure these concepts in the Swedish culture. This thesis comprises five studies. In article I, recommended guidelines were used to translate the Oral Health Impact Profile (OHIP), an OHRQoL instrument, into Swedish. A group of 145 consecutive patients comprising five diagnostic groups participated in reliability and validity evaluations of OHIP-S, the Swedish OHIP version. Data supported excellent reliability and acceptable validity. In article II, the Jaw Functional Limitation Scale (JFLS) was developed, and reliability and validity were assessed in 132 consecutive patients from five diagnostic groups. An expert panel identified 52 functional limitation items. Rasch methodology reduced the number of items to 20 and assessed model fit. Three constructs were identified-mastication, vertical jaw mobility, and emotional and verbal expression-and good reliability and validity were found. The JFLS-20 is an organ-specific instrument for assessing functional status of the masticatory system while the shorter JFLS-8 assesses global functional limitation. Article III describes development of the Orofacial Aesthetic Scale (OAS), in particular its conceptual framework, measurement model, and method of questionnaire item generation. Interview and questionnaire data from 17 prosthodontic patients created an initial 28-item pool. After focus group reduction and pilot testing, a final 8-item instrument was generated. Exploratory factor analysis investigated OAS dimensionality, and item analysis was performed in 119 subjects. Forward and backward translations and reconciliation produced an English version of the instrument. Exploratory factor analysis supported OAS unidimensionality. In article IV, psychometric properties of the OAS were evaluated in 119 patients from four groups: aesthetically compromised, functional disability, and two age- and gender-matched control groups. Various methods of testing reliability and validity supported good score reliability and validity. In article V, the OAS was part of a mail survey to a national sample of 3000 persons and normative values were derived. Survey respondents totaled 1406, and missing data were analyzed. There was a significant difference in OAS for age, gender, self-reported oral health, and self-reported general health status groups. Subjects who reported extreme satisfaction (item score of 10) varied between 17% for "color of the teeth" and 30% for "appearance of face" and "profile". The OHIP, JFLS, and OAS are considered well suited for use in research and as clinical outcome measures in patients with functional and aesthetic concerns, such as prosthodontic patients.


Rat-bite fever as a cause of septic arthritis: a diagnostic dilemma.
Rat-bite fever results from an infection with the organism Streptobacillus moniliformis. Symptomatic patients often present with fever, malaise, cough, maculopapular rash, and occasional arthritis, and usually have a history of rodent exposure. This report describes a patient with rat-bite fever resulting in suppurative arthritis. The patient's diagnosis was made by culture of S moniliformis from his left wrist. The diagnosis was delayed, however, owing to the lack of an exposure history, atypical clinical presentation, and the unusual microbiologic characteristics shown by this organism.


Spectral relationships for atmospheric correction. II. Improving NASA's standard and MUMM near infra-red modeling schemes.
Spectral relationships, reflecting the spectral dependence of water-leaving reflectance, ρw(λ), can be easily implemented in current AC algorithms with the aim to improve ρw(λ) retrievals where the algorithms fail. The present study evaluates the potential of spectral relationships to improve the MUMM [Ruddick et al., 2006, Limnol. Oceanogr. 51, 1167-1179] and standard NASA [Bailey et al., 2010, Opt. Express 18, 7521-7527] near infra-red (NIR) modeling schemes included in the AC algorithm to account for non-zero ρw(λNIR), based on in situ coastal ρw(λ) and simulated Rayleigh corrected reflectance data. Two modified NIR-modeling schemes are investigated: (1) the standard NASA NIR-modeling scheme is forced with bounding relationships in the red spectral domain and with a NIR polynomial relationship and, (2) the constant NIR ρw(λ) ratio used in the MUMM NIR-modeling scheme is replaced by a NIR polynomial spectral relationship. Results suggest that the standard NASA NIR-modeling scheme performs better for all turbidity ranges and in particular in the blue spectral domain (percentage bias decreased by approximately 50%) when it is forced with the red and NIR spectral relationships. However, with these new constraints, more reflectance spectra are flagged due to non-physical Chlorophyll-a concentration estimations. The new polynomial-based MUMM NIR-modeling scheme yielded lower ρw(λ) retrieval errors and particularly in extremely turbid waters. However, including the polynomial NIR relationship significantly increased the sensitivity of the algorithm to errors on the selected aerosol model from nearby clear water pixels.


Two Arabidopsis thaliana dihydrodipicolinate synthases, DHDPS1 and DHDPS2, are unequally redundant.
In Arabidopsis thalinana (L.) Heynh., DHDPS1 and DHDPS2 encode orthologous dihydrodipicolinate synthases (DHDPS), the first enzyme of the lysine (Lys) biosynthesis pathway. A TDNA insertion mutant of dhdps2 was previously reported to be viable and to accumulate free threonine (Thr). Analysis of additional TDNA insertion lines showed that dhdps1 and dhdps2 mutants are both viable and that whereas dhdps2 mutants accumulate Thr, dhdps1 plants do not. Thr-accumulation was complemented by heterologous expression of Escherichia coli DapA, indicating that the phenotype is due to reduced DHDPS activity in dhdps2. DHDPS1 contributes ~30% towards the total DHDPS activity in leaves of young plants and DHDPS2 contributes 70%; therefore, the threshold of activity resulting in Thr accumulation lies within this narrow range. dhdps1-dhdps2 double mutants could not be isolated, even after exogenous feeding with Lys. Segregation analysis indicated that gametes lacking functional DHDPS genes are defective, as are embryos. Plants carrying only a single DHDPS2 gene do not accumulate Thr, but they show a gametophytic defect that is partially rescued by Lys application. Despite the accumulation of Thr, dhdps2 seedlings are no more sensitive than wild-type plants to growth inhibition by Lys or the Lys precursor diaminopimelate. They also are not rescued by methionine at growth-inhibitory Lys concentrations. Exogenous application of Lys and methionine to dhdps2 mutants did not reduce the accumulation of Thr.


Lack of association between glaucoma and macular choroidal thickness measured with enhanced depth-imaging optical coherence tomography.
To compare choroidal thickness measurements among normal eyes, eyes with normal tension glaucoma (NTG), and those with primary open-angle glaucoma (POAG), and to correlate choroidal thickness with demographic and clinical ocular parameters. Choroidal thickness was measured with enhanced depth-imaging (EDI) optical coherence tomography (OCT) in one eye of 38 normal, 20 NTG, and 56 POAG subjects and compared among groups. The mean age was 69.3 ± 13.6 years (60.1 ± 13.4 years for normal subjects and 73.8 ± 11.3 years for glaucoma subjects; P < 0.001). Measurements were made at the fovea and in the temporal and nasal choroid every 0.5 mm up to 3 mm away from the fovea. Univariate and multivariate linear regression analyses were performed to assess the association between choroidal thickness and demographic and ocular parameters. There were no differences in foveal, temporal, or nasal choroidal thickness between normal, NTG, and POAG subjects (all P > 0.05) after adjusting for age, axial length, and intraocular pressure. Similarly, glaucoma severity groups did not differ from each other in all choroidal thickness measurements (all P > 0.05). Age (β = -1.78; P < 0.001) was the most significant factor associated with subfoveal choroidal thickness in the entire group, followed by axial length (β = -11.8; P = 0.002). Choroidal thickness does not differ among normal, NTG, and POAG subjects, suggesting a lack of relationship between choroidal thickness and glaucoma based on EDI OCT measurements.


Negative effects of an exotic grass invasion on small-mammal communities.
Exotic invasive species can directly and indirectly influence natural ecological communities. Cheatgrass (Bromus tectorum) is non-native to the western United States and has invaded large areas of the Great Basin. Changes to the structure and composition of plant communities invaded by cheatgrass likely have effects at higher trophic levels. As a keystone guild in North American deserts, granivorous small mammals drive and maintain plant diversity. Our objective was to assess potential effects of invasion by cheatgrass on small-mammal communities. We sampled small-mammal and plant communities at 70 sites (Great Basin, Utah). We assessed abundance and diversity of the small-mammal community, diversity of the plant community, and the percentage of cheatgrass cover and shrub species. Abundance and diversity of the small-mammal community decreased with increasing abundance of cheatgrass. Similarly, cover of cheatgrass remained a significant predictor of small-mammal abundance even after accounting for the loss of the shrub layer and plant diversity, suggesting that there are direct and indirect effects of cheatgrass. The change in the small-mammal communities associated with invasion of cheatgrass likely has effects through higher and lower trophic levels and has the potential to cause major changes in ecosystem structure and function.


Measuring S100 protein and neurone specific enolase in melanocytic tumours using video image analysis.
Using a computed video image analysis system, the staining intensity for both neurone specific enolase (NSE) and S100 protein was measured in sections from 19 malignant melanomas and 16 benign melanocytic lesions. The results of this study confirm previous reports that NSE and S100 protein are useful markers for malignant melanoma. NSE staining intensity in the cases of malignant melanoma was significantly higher than that in benign naevi (p = 0.011). Intensity of staining for S100 protein was not significantly higher in the malignant melanomas. There was, however, a significant S100 gradient when comparing superficial and deep intradermal portions of these tumours (p = 0.003). This feature was not seen in benign naevi. The greatest intensity of S100 protein staining was found in the deeper portions of the malignant melanomas. This gradient difference was not seen with staining for NSE. Although it seems that the overall intensity of staining for NSE is more effective in differentiating between benign and malignant lesions, the difference in staining intensity between the superficial and deep portions of the tumour may be the better indicator of adverse behaviour in lesions in which the diagnosis of malignancy is uncertain.