The requirement for a 5' stem-loop structure in brome mosaic virus replication supports a new model for viral positive-strand RNA initiation.
Sequences with strong similarity to internal control regions 1 and 2 (ICR1 and -2; A and B boxes) of tRNA genes are found at the 5' termini of the genomic RNAs of brome mosaic virus (BMV) and other plant viruses. The functionality of these motifs was studied by introducing point mutations into the ICR2-like sequence of pRNA-2 M/S, a BMV RNA-2 deletion mutant that replicates in the presence of RNAs-1 and -2 but does not encode a functional viral protein. The accumulation of positive-strand progeny from pRNAs bearing single and double base substitutions was 70 to 91% lower than that of the wild type, while the addition of single bases at position 8 of this motif reduced replication by 80%. These dramatic decreases in positive-strand synthesis paralleled decreases in transcription seen (C. Traboni, G. Ciliberto, and R. Cortese, Cell 36:179-187, 1984) from a tRNAPro gene containing similar mutations, suggesting comparable functions for the ICR regions in protein factor binding and demonstrating that a wild-type composition of the virus ICR2-like motif is required for proper RNA replication. Substitutions introduced at bases surrounding the ICR2 motif yielded levels of pRNA replication that differed, depending on the maintenance of a putative 5' stem-loop structure in the positive strand of the viral genome. Mutations disrupting this positive-strand stem-loop while maintaining the integrity of the complementary negative-strand structure reduced pRNA replication by 85 to 97%. In contrast, disruption of the negative-strand structure while maintaining the positive-strand stem-loop did not reduce pRNA replication. Similar positive-strand structures can be predicted to form from 5' sequences of cucumber mosaic virus (strain Q) and cowpea chlorotic mottle virus RNAs-1 and -2, supporting the concept that such structures comprise an integral part of virus genomic positive-strand promoters. The requirement of a stem-loop structure present on the positive-strand provided the basis for a new model describing how these sequence and structural elements act in the production of virus positive-strand RNA.


Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin.
Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and the novel intravenous antithrombotic agent AR-C69931MX act at the level of the platelet P2Y12 receptor, which is known to amplify platelet activation, aggregation and other responses induced by numerous platelet agonists. We studied the effects of clopidogrel and aspirin on ADP-induced platelet-leukocyte conjugate formation and P-selectin expression in healthy volunteers. The effects of clopidogrel and AR-C69931MX administered to patients with ischaemic heart disease were also assessed. AR-C69931MX and aspirin were also studied in vitro. Clopidogrel and AR-C69931MX suppressed ADP-induced platelet aggregation, P-selectin expression and platelet-leukocyte conjugate formation whereas aspirin had no inhibitory effect. These effects of clopidogrel and AR-C69931MX may confer therapeutic benefits in the management of acute coronary syndromes.


Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance.
An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.


Degradation of metribuzin in two soil types of Lebanon.
The degradation of metribuzin [4-amino-6-tert-butyl-3-methylthio-1,2,4-triazin-5(4H)-one] as influenced by soil type, temperature, humidity, organic fertilizers, soil sterilization, and ultra-violet radiation was studied in two soil types of Lebanon under laboratory conditions. The two soil types were sandy loam and clay. Deamination of metribuzin in the sandy loam soil to its deaminometribuzin (DA) derivative was basically a result of biological activity. In the clay soil the first metabolite diketometribuzin (DK) was a result of oxidative desulfuration, while diketo-deaminometribuzin (DADK) was the product of reductive deamination. The two soils represented major differences in the pesticide transformation processes. Photodecomposition on the soil surface and in aqueous media was also an important process in the degradation of metribuzin. Furthermore, the increase in soil organic matter enhanced degradation.


[Communications difficulties during the medical interview].
The aims of medical interview are to obtain diagnostic information, to obtain an empathetic communication with the patient, to educate him about his disease and to establish a personal link allowing a lasting relationship. We analyze some features of communication with patients. Individualized communication, recognizing his identity and personal aspects, "looking from the patient". Context, a shared but not mentioned value, part of the world of emotions and ideas. An analog and digital language, the former precise in words and the latter more diffuse, with gestures, not verbal. Coherence, as the similitude between what we think, feel and say. If there is no coherence, communication is impaired. Emotions, always present, rending communication more valid and real. We need to recognize, express and respond to emotions. An emotionless patient becomes a distant and impersonal object, an "it". When emotions are incorporated the patient is a "him" with whom I share and dialog. Empathy is an emotional comprehension, a personal bond. It improves relationships and creates links. Compassion is a variation of empathy that includes spiritual aspects and values. Negative emotions as rage, frustration and aggression creates communicational difficulties. We must recognize, express and clarify them to improve the situation. Difficult patients with whom communication is difficult such as confuse, agitated, terminal, elder, manipulating or hypochondriac subjects. The idea of transference and counter transference in these complicated situations is analyzed.


OKT3 for the treatment of steroid-resistant acute renal allograft rejection.
OKT3 (Orthoclone) was first used in this unit on February 25, 1987. Up until March 31, 1996, 153 patients had a total of 163 transplants. Fifty of these patients who received 53 transplants (28 male, mean age 37.5 years, 48 cadaveric donors), were treated with OKT3 for steroid-resistant acute rejection. Forty-nine graft biopsies were undertaken and 47 showed acute rejection. In the other 4 episodes a clear-cut clinical and laboratory diagnosis of severe rejection was made. OKT3 (5 mg i.v.) was started at a median of 19 days following transplantation and was successful in reversing 43 of 51 (84%) episodes of steroid-resistant acute rejection. Of those treated, the patient and graft survival at 1 year was 86 and 69%, at 3 years 82 and 64% and at 5 years 79 and 61%, respectively. Adverse effects were common. Four patients died from sepsis within the first 3 months after transplantation. OKT3 was effective in reversing 84% of steroid-resistant acute rejection episodes.


Occurrence of Na(+)-Ca2+ exchange in the ciliate Euplotes crassus and its role in Ca2+ homeostasis.
Ciliates possess diverse Ca2+ homeostasis systems, but little is known about the occurrence of a Na(+)-Ca2+ exchanger. We studied Na(+)-Ca2+ exchange in the ciliate Euplotes crassus by digital imaging. Cells were loaded with fura-2/AM or SBF1/AM for fluorescence measurements of cytosolic Ca2+ and Na+ respectively. Ouabain pre-treatment and Na+o substitution in fura-2/AM-loaded cells elicited a bepridil-sensitive [Ca2+]i rise followed by partial recovery, indicating the occurrence of Na(+)-Ca2+ exchanger working in reverse mode. In experiments on prolonged effects, ouabain, Na+o substitution, and bepridil all caused Ca2+o-dependent [Ca2+]i increase, showing a role for Na(+)-Ca2+ exchange in Ca2+ homeostasis. In addition, by comparing the effect of orthovanadate (affecting not only Ca2+ ATPase, but also Na(+)-K+ ATPase and, hence, Na(+)-Ca2+ exchange) to that of bepridil on [Ca2+]i, it was shown that Na(+)-Ca2+ exchange contributes to Ca2+ homeostasis. In electrophysiological experiments, no membrane potential variation was observed after bepridil treatment suggesting compensatory mechanisms for ion effects on cell membrane voltage, which also agrees with membrane potential stability after ouabain treatment. In conclusion, data indicate the presence of a Na(+)-Ca2+ exchanger in the plasma membrane of E. crassus, which is essential for Ca2+ homeostasis, but could also promote Ca2+ entry under specific conditions.


Complex slow potential generators in a simplified attention paradigm.
We have recently obtained evidence for complex multifocal, individually variable generators of slow cortical potentials, elicited during performance of visual tasks involving expecting attention, comparison and memory [Basile, L.F.H., Ballester, G., Castro, C.C., and Gattaz, W.F., 2002. Multifocal slow potential generators revealed by high-resolution EEG and current density reconstruction. Int. J. Psychophysiol., 45 (3), 227-240; Basile, L.F.H, Baldo, M.V., Castro, C.C., and Gattaz, W.F. 2003. The generators of slow potentials obtained during verbal, pictorial and spatial tasks. Int. J. Psychophysiol., 48, 55-65]. The cue-target aspect of traditional paradigms for attention studies is equivalent to 'warning S1'-'imperative S2' in slow potential designs. We simplified Posner's spatial cueing task [Posner, M.I. 1980. Orienting of attention.Q. J. Exp. Psychol. Feb;32 (1), 3-25; Posner, M.I., Snyder, C.R., Davidson, B.J. 1980. Attention and the detection of signals. J Exp Psychol. Jun; 109 (2), 160-174] to temporal cuing only, by using visual cues to indicate the mere presence, on a known central position, of the eventual target (17 ms duration, +/-0.3 degrees grey circle). We recorded slow potentials on 12 healthy subjects, by 124-channel EEG system (Neuroscan Inc.), and modeled their generators using current density reconstruction (CDR) by L(p) 1.2 norm minimization ("Curry V4.6", Neurosoft Inc.) applied to the target onset time. MRIs were obtained for each subject for constraining source models to individual brain anatomy. Average slow potentials were computed from above 60 artifact-free EEG-epochs (ISI=1.6 s, average ITI=2.5 s). We tabulated individual cortical current distributions by cytoarchitectonic area of Brodmann, after scaling into negligible, low, moderate and strong local density, based on percentile bands with respect to absolute maximum current. Despite the task's simplicity, the main result was individual variability and complexity in both scalp voltage and cortical current distributions. As observed in our previous studies, there was strong intersubject variability in the exact distribution of task-related cortical activity. Only parietal area 7 bilaterally was non-negligibly active in all subjects (currents above 10% maximum). As opposed to drawing conclusions based on group averaged data, we propose that activity by cytoarchitectonic area be ranked and statistically analysed only after being scaled on each individual. Based on the present results, the concept of a universal attention-related set of cortical areas if restricted to common areas across subjects is challenged, since even area 7 may no longer be common when the sample size becomes larger. We discuss the fact that group averaging may de-emphasize weakly but consistently active areas, and emphasize strongly but inconsistently active ones.


Stacking interaction of guanine with netropsin in the minor groove of d(CGTATATACG)2.
We present the structure of the decanucleotide d(CGTATATACG) determined by single crystal X-ray diffraction at 1.58 A resolution. A netropsin drug is found in the minor groove with guanine stacked on a pyrrole ring of the drug, a feature described here for the first time. The stacked guanine is an extra-helical base coming from the end of a neighbour oligonucleotide. This observation may open the way to the development of minor groove binding drugs with a higher sequence selectivity. The oligonucleotide is in the B-conformation, but the terminal base-pairs are disrupted: the cytosine residues are disordered while the guanine residues penetrate into the minor groove of neighbouring duplexes. Four hydrated Ni ions with octahedral co-ordination are found associated with the N7 atoms of each guanine. The high affinity of these ions with guanine suggests that they may be used as probes for specific guanine residues.


Weekly near-peer tutoring sessions improve students' performance on basic medical sciences and USMLE Step1 examinations.
This study examined the relationship between attendance at weekly near-peer tutoring (NPT) sessions offered in the second year of medical school and academic performance on basic science and USMLE Step 1 examinations. Twenty-four weekly NPT sessions were delivered across all modules in the second year of medical school. Attendance of the sessions was recorded and students were divided into three groups: high (16-24 sessions), moderate (7-15 sessions), and low-no (0-6 sessions) attendance groups. Pearson product-moment correlation coefficient was computed to determine the relationship between students' frequency of attendance and their performance on overall basic sciences, two NBME CBSEs, and USMLE Step 1 examinations. Students' academic performance was also analyzed using ANOVA and Bonferroni post hoc test (p < 0.05) to compare differences between the three groups. Pearson correlation analyses revealed that attending peer tutoring sessions was significantly correlated with students' performance in overall basic sciences, CBSE mid-year, CBSE final, and USMLE Step 1 examinations. The high attendance groups significantly outperformed the low-no attendance groups on overall basic sciences (p = 0.007), CBSE mid-year (p < 0.001), CBSE final (p < 0.018), and USMLE Step 1 (p = 0.048) examinations. Attending NPT sessions are significantly correlated with students' performance on basic sciences and on USMLE Step1 examinations. Attendance of weekly NPT sessions is a valuable experience for M2 students.


The influence of host factors on the natural history of chronic hepatitis C viral infections.
The natural history of hepatitis C is variable, with some patients progressing rapidly to cirrhosis and others showing no significant fibrosis over many decades. A number of studies have examined the factors that influence disease progression. Age at time of infection, gender, alcohol abuse and, perhaps, route of transmission, appear to have the greatest influence on the natural history of the hepatitis C virus with the possible exception of alcohol, the mechanism whereby these factors influence disease progression has yet to be determined.


The role of experiential avoidance in posttraumatic stress symptoms and symptoms of depression, anxiety, and somatization.
This study examined the relationships between experiential avoidance in general (and thought suppression in particular), posttraumatic stress symptom severity, and symptoms of depression, anxiety, and somatization among a sample of individuals exposed to multiple potentially traumatic events. Although experiential avoidance was not associated with severity of posttraumatic stress symptoms beyond their shared relationship with general psychiatric symptom severity, it was associated with symptoms of depression, anxiety, and somatization when controlling for posttraumatic stress symptom severity. Thought suppression, on the other hand, was associated with severity of posttraumatic stress symptoms when controlling for their shared relationship with general psychiatric symptom severity. No significant relationships were found between thought suppression and the presence of depression, anxiety, and somatization symptoms when controlling for posttraumatic stress symptom severity. Results suggest the importance of separately examining the influence of different forms of experiential avoidance on posttraumatic psychopathology.


Controlling the regiospecific oxidation of aromatics via active site engineering of toluene para-monooxygenase of Ralstonia pickettii PKO1.
A primary goal of protein engineering is to control catalytic activity. Here we show that through mutagenesis of three active site residues, the catalytic activity of a multicomponent monooxygenase is altered so that it hydroxylates all three positions of toluene as well as both positions of naphthalene. Hence, for the first time, an enzyme has been engineered so that its regiospecific oxidation of a substrate can be controlled. Through the A107G mutation in the alpha-subunit of toluene para-monooxygenase, a variant was formed that hydroxylated toluene primarily at the ortho-position while converting naphthalene to 1-naphthol. Conversely, the A107T variant produced >98% p-cresol and p-nitrophenol from toluene and nitrobenzene, respectively, as well as produced 2-naphthol from naphthalene. The mutation I100S/G103S produced a toluene para-monooxygenase variant that formed 75% m-cresol from toluene and 100% m-nitrophenol from nitrobenzene; thus, for the first time a true meta-hydroxylating toluene monooxygenase was created.


Enhancement of IgE production in B cells by neutrophils via galectin-3 in IgE-associated atopic eczema/dermatitis syndrome.
Spontaneous IgE production by B cells from patients with IgE-associated atopic eczema/dermatitis syndrome (AEDS) is enhanced by polymorphonuclear leukocytes (PMN) from patients with AEDS, but not by PMN from non-atopic controls. The enhancement is abolished by preincubation of PMN with lactose, but not with glucose. Anti-galectin-3 serum, but not control rabbit serum, blocked the enhancement. These results indicate that AEDS PMN can enhance IgE production via galectin-3.


Five-year changes in dietary intake and body composition in adolescents with severe obesity undergoing laparoscopic Roux-en-Y gastric bypass surgery.
Information is scarce on long-term changes in energy intake (EI), dietary energy density (DED), and body composition in adolescents undergoing laparoscopic Roux-en-Y gastric bypass (RYGB). To investigate long-term changes in EI, DED, and body composition in adolescents after LRYGB. University hospitals, multicenter study, Sweden. Eighty-five adolescents (67% girls; mean ± standard deviation, age 16.0 ± 1.2 yr, body mass index 45.5 ± 6.1 kg/m2) were assessed preoperatively (baseline) and 1, 2, and 5 years after LRYGB with diet history interviews and dual-energy x-ray absorptiometry. Matched obese adolescent controls receiving nonsurgical treatment were assessed only at 5 years. Weight decreased 31%, 33%, and 28% at 1, 2, and 5 years after LRYGB (P < .001) while controls gained 13% over 5 years (P < .001). Dietary assessments were completed in 98%, 93%, 87%, and 75% at baseline and 1, 2, and 5 years, respectively, and in 65% of controls. Baseline EI (2558 kcal/d), decreased by 34%, 22%, and 10% after 1, 2, and 5 years (P < .05). DED decreased at 1 year (P = .03). Macronutrient distribution was not different from controls at 5 years, but EI and DED were 31% and 14% lower (P < .015). Fat, fat-free, and muscle mass decreased through 5 years after LRYGB (P < .001). Boys preserved muscle mass more than girls (P < .01). Adequate protein intake was associated with preservation of muscle mass (P = .003). In adolescents undergoing LRYGB EI remained 10% lower 5 years after surgery. Decreased EI and DED, rather than macronutrient distribution, are important factors in weight loss after surgery. Higher protein intake may facilitate preservation of muscle mass.


Bil2 Is a Novel Inhibitor of the Yeast Formin Bnr1 Required for Proper Actin Cable Organization and Polarized Secretion.
Cell growth in budding yeast depends on rapid and on-going assembly and turnover of polarized actin cables, which direct intracellular transport of post-Golgi vesicles to the bud tip. Saccharomyces cerevisiae actin cables are polymerized by two formins, Bni1 and Bnr1. Bni1 assembles cables in the bud, while Bnr1 is anchored to the bud neck and assembles cables that specifically extend filling the mother cell. Here, we report a formin regulatory role for YGL015c, a previously uncharacterized open reading frame, which we have named Bud6 Interacting Ligand 2 (BIL2). bil2Δ cells display defects in actin cable architecture and partially-impaired secretory vesicle transport. Bil2 inhibits Bnr1-mediated actin filament nucleation in vitro, yet has no effect on the rate of Bnr1-mediated filament elongation. This activity profile for Bil2 resembles that of another yeast formin regulator, the F-BAR protein Hof1, and we find that bil2Δ with hof1Δ are synthetic lethal. Unlike Hof1, which localizes exclusively to the bud neck, GFP-Bil2 localizes to the cytosol, secretory vesicles, and sites of polarized cell growth. Further, we provide evidence that Hof1 and Bil2 inhibitory effects on Bnr1 are overcome by distinct mechanisms. Together, our results suggest that Bil2 and Hof1 perform distinct yet genetically complementary roles in inhibiting the actin nucleation activity of Bnr1 to control actin cable assembly and polarized secretion.


Designing nanoparticle translocation through membranes by computer simulations.
Nanoparticle penetration into cells is an important process in drug/gene delivery. Here, we successfully design one type of novel nanoparticles with ligands decorating its surface by dynamic bonds and find that the nanoparticle can spontaneously penetrate through membranes by using dissipative particle dynamics simulations. Moreover, the physical parameters of both ligands (for example, ligand type and density) and nanoparticles (such as size and shape) have significant effects on penetration efficiency and translocation time. Especially for nanoparticles with anisotropic shapes or asymmetric surface decoration, the penetration efficiency may reach about 80%. We also provide insights into the interaction between nanoparticles and asymmetric membranes and find that the membrane asymmetry can even increase the penetration efficiency to above 90%. The present study suggests a potential way to translocate novel nanoparticles through membranes, which may provide new ideas for future experimental nanoparticle design and drug delivery.


Effects of renal neutral endopeptidase inhibition on sodium excretion, renal hemodynamics and neurohormonal activation in patients with congestive heart failure.
We investigated the effects of inhibiting endogenous atrial natriuretic factor (ANF) metabolism on renal hemodynamics, sodium excretion and neurohormones in 12 patients with New York Heart Association functional class II congestive heart failure (CHF) due to left ventricular systolic dysfunction. In a randomized, placebo-controlled, double-blinded fashion, 8 patients received a single oral dose of candoxatril, an inhibitor of renal neutral endopeptidase, and 4 patients received placebo. Candoxatril treatment increased plasma ANF by 70 +/- 71 pg/ml (p < 0.015 vs. placebo) and plasma cGMP by 7.9 +/- 2.7 pmol/ml (p < 0.001 vs. placebo), with maximal effects at 3.5 h. Urinary cGMP more than doubled (p = 0.025 vs. placebo). Candoxatril increased urinary sodium by 2.7 +/- 2.0 mEq/h (p < 0.05 vs. placebo) and significantly elevated filtration fraction with no significant effect on glomerular filtration rate, renal plasma flow or lithium clearance. A significant reduction in aldosterone concentration with a similar trend in plasma renin activity was noted in candoxatril-treated patients. Thus in patients with moderate heart failure, renal neutral endopeptidase inhibition increases urinary sodium excretion. The lack of an effect on renal hemodynamics suggests that this natriuresis results from ANF-mediated inhibition of tubular sodium reabsorption. These findings justify additional investigation into potential clinical benefit of endopeptidase inhibition in patients with CHF.


Identification of an increased short-term blood pressure variability on ambulatory blood pressure monitoring as a coronary risk factor in diabetic hypertensives.
We examined risk factors for coronary heart disease (CHD) by ambulatory blood pressure (BP) monitoring in 72 diabetic hypertensives who were hospitalized for the educational program. The patients were divided into two groups (CHD group, 19 subjects; and non-CHD group, 53 subjects) along with or without co-existing CHD. On ambulatory BP monitoring, no significant differences were found between the groups regarding BP values through the day. However, the CHD group had a significantly greater BP variability than non-CHD group. The result of logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CHD.


Preperitoneal mesh-plug herniorraphy during radical retropubic prostatectomy.
The treatment of localized prostate cancer has increased over the past decade in large part due to enhanced screening efforts with prostate specific antigen (PSA) and has resulted in a dramatic increase in the number of radical retropubic prostatectomies being performed in recent years. It is estimated that between 5% and 10% of men who are candidates for radical surgical treatment for localized prostate cancer will have concomitant inguinal hernia. Given the well described complications of untreated inguinal hernias we propose that simultaneous repair be undertaken along with radical retropubic prostatectomy for preoperatively defined hernias and those incidentally discovered at the time of surgery. We concomitantly performed a novel inguinal hernia repair using a Marlex mesh plug in 15 patients who presented to our center for radical prostatectomy. There were no intra or post operative complications related to the repair. At a median follow up time of 18 months there were no developed recurrences or post operative orchalgia. Preperitoneal mesh-plug herniorraphy is a safe and effective technique used to repair inguinal hernias that present concomitantly with prostate cancer in patients undergoing radical retropubic prostatectomy.


Late life attachment in context: patterns of relating among men and women from seven ethnic groups.
The purpose of the present study was to develop the later life attachment literature by providing data contrasting patterns of attachment among 616 older men and women (aged 50 to 70) from seven ethnic groups in the United States: African Americans, English-speaking Caribbeans, Haitians, Dominicans, Puerto Ricans, Eastern Europeans, and European Americans. A multivariate analysis of the variance with ethnicity, gender, and income as factors predicting four dimensional styles of attachment (secure, dismissive, preoccupied, and fearful avoidant) revealed numerous ethnic differences in attachment styles. Most notably, Haitians reported greater dismissiveness than all other groups, with Eastern Europeans reporting more than Dominicans, Puerto Ricans, European Americans and African Americans. Haitians also reported lower fearful avoidance than all other groups. Dominicans and Puerto Ricans reported greater preoccupation than Haitians, African Americans, and English-speaking Caribbeans. The most notable interactions with gender and income revealed that although preoccupation was lower among African American, English-speaking Caribbean, Haitian, and European American women versus men, it was greater among Dominican, Puerto Rican, and Eastern European women, and that whereas security was generally high among European Americans notwithstanding income, income strongly impacted attachment security in other groups. These differences are interpreted in light of ethnic differences in historical, familial, and religious contexts. This study provides a glimpse into the ethnic and cultural diversity in the ways in which older adults relate to significant others.


Concomitant increase by peroxisome proliferators of fatty acid-binding protein, peroxisomal beta-oxidation and cytosolic acyl-CoA hydrolase in liver.
Inductions of FABP in hepatic cytosol by administration of tiadenol and clofibric acid were studied in rats, mice and guinea-pigs. In rats and mice, [1-14C]oleic acid-binding capacity of hepatic cytosol was increased, in association with induction of peroxisomal beta-oxidation, by the administration of either the two peroxisome proliferators. The increase in [1-14C]oleic acid binding capacity was responsible for the increase in the content of FABP in livers. The peroxisome proliferators caused an induction of acyl-CoA hydrolase of lower-molecular-weight form alone in hepatic cytosol of mice, although inductions of two long-chain acyl-CoA hydrolases (higher- and lower-molecular-weight form) were brought about in hepatic cytosol of rats. Guinea-pigs lacked the peroxisome proliferator-caused inductions of FABP, peroxisomal beta-oxidation and acyl-CoA hydrolase. There was no essential difference in the inductions of FABP, acyl-CoA hydrolases and peroxisomal beta-oxidation between tiadenol and clofibric acid, despite a marked difference in their chemical structures. These results suggest that the induction of FABP is correlated with the inductions of both peroxisomal beta-oxidation and cytosolic long-chain acyl-CoA hydrolase of lower-molecular-weight form.


Dynamic thermal/acoustic response for human bone materials at different energy levels: A diagnosis approach.
The non-invasive diagnostic approaches have gained high attention in recent years, utilizing high technology sensor systems, including infrared, microwave devices, acoustic transducers, etc. The patient safety, high resolution images, and reliability are among the driving forces toward high technology approaches. The thermal and acoustic responses of the materials may reflect the important research parameters such as penetration depth, power consumption, and temperature change used for the practical models of the system. This paper emphasizes the approach for orthopedic application where the bone densities were considered in simulation to designate the type of human bones. Thermal energy pulses were applied in order to study the penetration depth, the maximum temperature change; spatially and dynamically, and the acoustic pressure distribution over the bone thickness. The study was performed to optimize the amount of energy introduced into the materials that generate the temperature value for high resolution beyond the noise level. Three different energy pulses were used; 1 J, 3 J and 5 J. The thermal energy applied to the four bone materials, cancellous bone, cortical bone, red bone marrow, and yellow bone marrow were producing relative changes in temperature. The maximum change ranges from 0.5 K to 2 K for the applied pulses. The acoustic pressure also ranges from 210 to 220 dB among the various types of bones. The results obtained from simulation suggest that a practical model utilizing infra-red scanning probe and piezoelectric devices may serve for the orthopedic diagnostic approach. The simulations for multiple layers such as skin interfaced with bone will be reserved for future considerations.


[Mitochondrial cytopathies].
Mitochondrial cytopathies are diseases due to a defect of mitochondrial respiratory chain and are characterized by the presence of morphological abnormalities of mitochondria (ragged red fibers). The clinical manifestations can be polymorphic as various organs may be involved; but in general, these disorders affect either muscle alone (progressive external ophtalmoplegia, myopathy with weakness) or muscle and brain (encephalomyopathies). Some of these diseases may be due to alterations of the mitochondrial genome. Diagnosis can be achieved through the following steps: measurement of lactate, pyruvate and ketone bodies after fasting followed by a carbohydrate rich meal and/or exercise; histological examination and biochemical investigation of a skeletal muscle biopsy; study of possible mitochondrial genome alterations.


Development of a confrontation naming test for Spanish-speakers: the Cordoba Naming Test.
To date, a psychometrically sound standardized Spanish-language test of confrontation naming has not been developed for clinical use. Because of the shortcomings of adapting tests developed in other cultures, it was decided to develop a confrontation naming test suitable for Spanish-speakers. For the validity study the performance on the test of 26 control subjects between 70 and 87 years old and 23 subjects with a mild to moderate degree of dementia of the Alzheimer type was compared. Stability of the test was assessed with a test-retest design (n = 80). Norms were developed using a regression-based method. Four hundred and fifty-six Spanish-speaking subjects of both sexes were recruited for the normative sample. Subjects were between 14 and 94 years old, and three educational levels were represented. Mean differences between the control and dementia groups were significant, yielding a large effect size (η(2) = .25). The test-retest correlation coefficient was r = .90. Education, age, and gender significantly influenced test scores. The validity study confirmed that the test discriminates between individuals with and without anomia. The magnitude of the reliability coefficient of this test can be considered as "very high". Norms were developed considering the influence of three demographic variables: gender, age, and education.


Retinal toxicity in human immunodeficiency virus-infected children treated with 2',3'-dideoxyinosine.
To assess the safety and antiretroviral activity of 2',3'-dideoxyinosine, we enrolled 43 children with symptomatic (Centers for Disease Control class P-2) human immunodeficiency virus infection in a Phase I-II study and monitored them prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. Follow-up ranged from 12 to 103 weeks with a median follow-up of 71 weeks. Three of 43 children (7.0%) developed peripheral atrophy of the retinal pigment epithelium during treatment with 2',3'-dideoxyinosine. The two children with the most severe retinal atrophy were enrolled in the study at the highest dosage studied (540 mg/m2/day). In contrast to findings in children, no retinal atrophy in HIV-infected adults treated with 2',3'-dideoxyinosine has been evident to date.


Evidence that the catechol 3,4-Dihydroxytamoxifen is a proximate intermediate to the reactive species binding covalently to proteins.
Metabolism of tamoxifen by rat and human hepatic microsomal cytochrome P450s (CYPs) forms a reactive intermediate that irreversibly binds to microsomal proteins (C. Mani and D. Kupfer, Cancer Res., 51: 6052-6058, 1991.). The current study examines the nature of the tamoxifen metabolite that is proximate to the reactive intermediate(s). The rate of covalent binding of tamoxifen metabolites, tamoxifen N-oxide, N-desmethyltamoxifen, and tamoxifen N-oxide-epoxide was approximately equal to or less than that of tamoxifen. By contrast, covalent binding of 4-hydroxytamoxifen (4-OH-tam) was 3-5-fold higher than that of tamoxifen, indicating that among the metabolites examined, 4-OH-tam or its metabolite(s) is most proximate to the reactive intermediate(s). Incubation of 4-OH-tam with liver microsomes from PCN-treated rat yielded three detectable metabolites. One was identified as 4-OH-tam N-oxide via its facile reduction back to 4-OH-tam by titanium(III) chloride. Another metabolite of 4-OH-tam, assumed to be 3,4-dihydroxytamoxifen (3,4-di-OH-tam) catechol, was demonstrated by its monomethylation with [3H]S-adenosyl-L-methionine ([3H]SAM) in presence of endogenous catechol-O-methyltransferase. Monomethylated catechol from 4-OH-tam was formed at a 3-4-fold higher rate than from tamoxifen. It was reasoned that if the catechol is most proximate metabolite to the reactive intermediate, then its methylation would reduce the formation of the reactive intermediate and result in lower rate of covalent binding. In fact, addition of radioinert SAM to incubations of tamoxifen inhibited covalent binding by 17-23%. By contrast, inclusion of 1.0 mM S-adenosyl-L-homocysteine, a potent inhibitor of catechol-O-methyltransferase-mediated methylation of 3,4-di-OH-tam, essentially overcame the inhibition of the covalent binding by SAM. Additionally, ascorbic acid and glutathione, inhibitors of covalent binding of tamoxifen, produced an elevation of methylated catechol. These findings collectively indicate that 3,4-di-OH-tam is proximate to the ultimate reactive intermediate that results in covalent binding to microsomal proteins.


Post-Inflammatory Hyperpigmentation: A Review of Treatment Strategies.
Post-inflammatory hyperpigmentation (PIH) is a reactive process resulting from increased melanin or abnormal distribution of melanin secondary to inflammatory skin conditions, dermatologic therapies, and external stimuli. Because PIH is a common condition that has a substantial effect on the quality of life, an understanding of its treatment modalities is essential. Though there are many therapeutic strategies for hyperpigmentary conditions such as melasma that are described in the literature, fewer studies focus on PIH. This article aims to provide a comprehensive literature review of therapies specifically used to treat PIH, such as topical combinations, chemical peels, and lasers. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4887.


One-Dimensional Programmable Polymeric Microfiber Waveguide with Optically Reconfigurable Photonic Functions.
Programmable materials and reconfigurable photonic components, which can change their physicochemical properties and functionalities upon external stimuli, are a major topic of interest in modern science. However, most conventional reconfigurable photonic components rely heavily on mechanical deformation, restricting their application. Herein, a novel strategy based on a dynamically tunable fluorescence resonance energy transfer process to design and fabricate programmable fluorescent micropatterns within single polymer microfiber is proposed. A set of reconfigurable photonic components (including optical switchable waveguide systems, photonic analogies of diodes and transistors, as well as one-dimensional (1D) optical encoding) can be achieved within a single polymeric waveguide microfiber straightforwardly, in which such photonic components can be written, erased, and rewritten as 1D binary patterns with tailored external optical stimuli. These results might be of great fundamental value for the rational design of novel reconfigurable photonic devices with numerous potential applications in highly integrated optical communication components and optical computing devices.


[From rings to segregation. Mexico City, 1950-1987].
The author discusses different methods of urban analysis, using the example of Mexico City, Mexico. "In this work two outlines are used: a concentric one that reflects the city's expansion and a segregated one that sees the 'different cities' within. We analyze the commercial occupation of central areas and the growth due to the expansion of the periphery from 1950 to 1986. In both processes, the massive expulsion of the inhabitants appears, firstly as an effect and secondly as a cause. This fact serves as an argument to explore certain proposals in a prospective dimension. In the technical [spatial] analysis we generally avoid the design of the city itself. Here we approach some design ideas without forgetting their social dimension." (SUMMARY IN ENG)


Push-out strength of hydroxyapatite coated by sputtering technique in bone.
Hydroxyapatite was coated with 1 microm thickness on titanium columns of a length of 10 mm, an outer diameter of 4.0 mm by radio frequency magnetron sputtering. The hydroxyapatite coating titanium columns were implanted in the diaphysis of femora of 3 adult dogs, and push-out test was carried out after 2, 4 and 12 weeks of implantation using a testing machine. The interface of bone/column was observed histologically after the test. At 12 weeks the push-out strengths of coating and non-coating columns were 3.5 and 1 MPa, respectively. Histological observation indicated a formation of thin connective tissue with 5-30 microm thickness at the interface of the bone/column. No inflammation was observed during the implantation periods.


Right pulmonary artery obstruction is a long-term complication of aortopulmonary window repair.
The early outcomes of transaortic patch repair closure for aortopulmonary window are satisfactory, but the lifelong fate of the aorta and pulmonary artery remains unknown. We describe a 40-year-old patient with right pulmonary artery occlusion accompanied by aneurysmal dilation of the ascending aorta 38 years after transaortic repair of an aortopulmonary window. Operative findings revealed patch shrinkage and thrombotic occlusion of the right pulmonary artery. The dilated ascending aorta firmly adhered to the right pulmonary artery. After pulmonary artery thrombectomy, the right pulmonary artery was reconstructed and the dilated ascending aorta was replaced.


[The recent research progress in nutritional assessment and intervention treatment of liver failure in patients].
Malnutrition can reduce the body's immune function, and significantly increased higher incidence of infection, related complications, leading to higher hospitalization days, hospitalization expenses and mortality. At present, the nutrition assessment not only has been widely used in tumor disease; kidney disease; geriatric disease and other disciplines, but also concentrated in the patients with chronic liver disease. However, the clinic application of nutrition assessment in liver failure is limited. In the clinical practice work, malnutrition commonly comes with the course of patients with liver failure, and need to treatment. Therefore, the early judgment on their nutritional status, and follow the nutrition characteristics of individualized has gradually become an important part of the treatment of liver failure patients.


Belonging and Inclusivity Make a Resilient Future for All: A Cross-Sectional Analysis of Post-Flood Social Capital in a Diverse Australian Rural Community.
In 2017, marginalised groups were disproportionately impacted by extensive flooding in a rural community in Northern New South Wales, Australia, with greater risk of home inundation, displacement and poor mental health. While social capital has been linked with good health and wellbeing, there has been limited investigation into its potential benefits in post-disaster contexts, particularly for marginalised groups. Six months post-flood, a cross-sectional survey was conducted to quantify associations between flood impact, individual social capital and psychological distress (including probable post-traumatic stress disorder). We adopted a community-academic partnership approach and purposive recruitment to increase participation from socio-economically marginalised groups (Aboriginal people and people in financial hardship). These groups reported lower levels of social capital (informal social connectedness, feelings of belonging, trust and optimism) compared to general community participants. Despite this, informal social connectedness and belonging were important factors for all participant groups, associated with reduced risk of psychological distress. In this flood-prone, rural community, there is a pressing need to build social capital collectively through co-designed strategies that simultaneously address the social, cultural and economic needs of marginalised groups. Multiple benefits will ensue for the whole community: reduced inequities; strengthened resilience; improved preparedness and lessened risk of long-term distress from disaster events.


Depression and anxiety in cancer patients before and during the SARS-CoV-2 pandemic: association with treatment delays.
Pandemics can be associated with anxiety and depression in cancer patients who are undergoing treatment. In the present study, we aimed to perform a comparative evaluation of the conditions of cancer patients before and during the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) to detect the impact of the pandemic on treatment delays that are associated with anxiety and depression in cancer patients. In addition, the effect of public transport use on treatment delays was examined. BDI and BAI were administered to 595 breast, ovarian, colon and gastric cancer patients before and during the pandemic. The questionnaires were administered by the physician blindly, who was unaware of the delay of the patients. The number of days by which the patients delayed their treatment due to the fear of contamination were recorded retrospectively. Correlation analyses were performed between the obtained scores and treatment delays. The depression and anxiety levels in cancer patients were found to increase during the pandemic (p = 0.000), and this increase was positively correlated with the disruption of their treatment (p = 0.000, r = 0.81). Depression and anxiety levels and treatment delays were higher in elderly patients (p = 0.021). Depression and anxiety were more pronounced in female patients (p = 0.000). Moreover, treatment delays were more common in patients who had to use public transportation (p = 0.038). SARS-CoV-2 pandemic may increase anxiety and depression in cancer patients. This can cause patients to experience treatment delays due to concerns about becoming infected. At this point, if necessary, assistance should be obtained from psychiatric and public health experts.


Pharmacology of endothelin-1 in vivo in humans.
Endothelin-1 (ET-1) is a potent vasoconstrictor and pressor agent with a prolonged action in animal preparations. We have investigated the vascular pharmacology of ET-1 in healthy human volunteers. In arterial studies, blood flow was measured in both forearms and the left brachial artery cannulated for infusion of drugs and vehicle. Local blood flow was reduced in a dose-dependent manner by ET-1. At 5 pmol/min, the response was maximal by 60 min, and flow returned to baseline only after a further 120 min. ET-1 and angiotensin II, both at 5 pmol/min, reduced flow by 40% at 60 min. These responses were reversed to a similar degree by the dihydropyridine calcium antagonist nicardipine (0.3-10 micrograms/min). At 1 pmol/min, ET-1 did not affect sympathetic vasoconstriction to arterial norepinephrine or lower body negative pressure. In venous studies, the internal diameter of a dorsal hand vein was measured during local infusion of drugs and vehicle. ET-1 (5 pmol/min) produced local venoconstriction, with a maximal reduction in vein size of 83 +/- 12% at 60 min. Reversal of responses was slow, and unaffected by nicardipine (1.5 micrograms/min). We have shown that ET-1 is a potent vasconstrictor producing prolonged effects in resistance and capacitance vessels in humans. Low-dose ET-1 does not appear to affect sympathetically mediated vasoconstriction. Studies with nicardipine do not provide support for the hypothesis that ET-1 is an endogenous ligand of the dihydropyridine-sensitive calcium channel.


Variability in lateral positioning of surface EMG electrodes.
The positions of EMG electrodes over the knee extensor muscles were examined in 19 healthy men using MR images; electrodes were placed according to the SENIAM (surface electromyography for non-invasive assessment of muscles) guidelines. From axial images, the medial and lateral borders of the muscles were identified, and the are length of the muscle surface was measured. The electrode location was expressed as a percentage value from the muscle's medial border. EMGs were recorded during isometric maximal contraction, squat jumps, and countermovement jumps and analyzed for cross-correlation. The results showed that variations in lateral positioning were greatest in vastus medialis (47% SD 11) and rectus femoris (68% SD 15). In vastus lateralis, the electrode was usually placed close to the rectus femoris (19% SD 6). The peak cross-correlation coefficient varied between 0.15 and 0.68, but was not associated with electrode location. It is recommended that careful consideration is given to the medial-lateral positioning of the vastus lateralis electrodes especially, so that the electrodes are positioned over the mid-muscle rather than in close proximity to rectus femoris.


Detection of hypoglycaemia by microdialysis measurements of glucose in subcutaneous adipose tissue.
The aim of the present investigation was to study how various fractional sampling times affect the detection of hypoglycaemia, using microdialysis of the adipose tissue. We therefore studied eight healthy subjects during a standardized hyperinsulinaemic hypoglycaemic clamp. The glucose concentration in the adipose tissue dialysate was determined in timed fractions of 15 min, 30 min and 60 min and compared to those in arterialized venous plasma. Before and after hypoglycaemia, the plasma and adipose tissue glucose concentrations were similar. However, during hypoglycaemia, the adipose tissue glucose nadir, as measured in 15-min fractions of the tissue dialysate, was significantly lower than that in plasma (2.1 +/- 0.1 vs. 2.4 +/- 0.1 mmol/l, p = 0.05) and during the increase in plasma glucose, the corresponding increase in adipose tissue glucose was delayed by approximately 20 min (p = 0.004). When the microdialysate was sampled over 30 or 60 min periods, there was a close agreement between the plasma and adipose tissue glucose nadirs. We conclude that there is a protracted fall in subcutaneous adipose tissue glucose levels in response to insulin-induced hypoglycaemia. While shorter microdialysis sampling periods improve the resolution of the hypoglycaemic event, 30-min fractions seem sufficient to detect hypoglycaemia in a clinically relevant way.


TGF-beta cooperates with TGF-alpha to induce the self-renewal of normal erythrocytic progenitors: evidence for an autocrine mechanism.
Simultaneous addition of both TGF-alpha and TGF-beta induces the sustained, long-term outgrowth of chicken erythrocytic progenitor cells, referred to as T2ECs from both chick bone marrow and 2-day-old chicken embryos. By analysis for differentiation antigens and gene expression, these cells were shown to represent very immature haematopoietic progenitors committed to the erythrocytic lineage. T2ECs differentiate into almost pure populations of fully mature erythrocytes within 6 days, when TGF-alpha and TGF-beta are withdrawn and the cells exposed to anaemic chicken serum plus insulin. Outgrowth of these cells from various sources invariably required both TGF-alpha and TGF-beta, as well as glucocorticoids. Proliferating, established T2ECs still require TGF-alpha, but are independent of exogenous TGF-beta. Using a TGF-beta-neutralizing antibody or expressing a dominant-negative TGF-beta receptor II, we demonstrate that T2ECs generate an autocrine loop involving TGF-beta during their establishment, which is required for sustained proliferation. Using specific inhibitors, we also show that signalling via Mek-1 is specifically required for induction and maintenance of cell proliferation driven by cooperation between the TGF-alpha and -beta receptors. These results establish a novel mechanism by which self-renewal of erythrocytic progenitors is induced and establish avian T2ECs as a new, quasi-optimal model system to study erythrocytic progenitors.


A multidimensional approach to modelling for workplace risk assessment.
This paper aims to help enhance the process of risk identification and assessment in small enterprises by facilitating the incorporation of insights from accident, human error and risk perception models. This effort takes place through grouping and classification models of all these aspects according to certain criteria, to fit the proper set of models to each situation. To further facilitate the process, the main guidelines of each model are presented. The whole approach is not a new theoretical model but a simplified presentation to help safety engineers in selecting the proper model for the workplace to better assess its risks. An example of the application of this approach is also presented.


Amino acid deprivation promotes tumor angiogenesis through the GCN2/ATF4 pathway.
As tumors continue to grow and exceed their blood supply, nutrients become limited leading to deficiencies in amino acids (AAD), glucose (GD), and oxygen (hypoxia). These alterations result in significant changes in gene expression. While tumors have been shown to overcome the stress associated with GD or hypoxia by stimulating vascular endothelial growth factor (VEGF)-mediated angiogenesis, the role of AAD in tumor angiogenesis remains to be elucidated. We found that in human tumors, the expression of the general control non-derepressible 2 (GCN2, an AAD sensor) kinase is elevated at both protein and mRNA levels. In vitro studies revealed that VEGF expression is universally induced by AAD treatment in all five cell lines tested (five of five). This is in contrast to two other angiogenesis mediators interleukin-6 (two of five) and fibroblast growth factor 2 (two of five) that have a more restricted expression. Suppressing GCN2 expression significantly decreased AAD-induced VEGF expression. Silencing activating transcription factor 4 (ATF4), a downstream transcription factor of the GCN2 signaling pathway, is also associated with strong inhibition of AAD-induced VEGF expression. PKR-like kinase, the key player in GD-induced unfolded protein response is not involved in this process. In vivo xenograft tumor studies in nonobese diabetic/severe combined immunodeficient mice confirmed that knockdown of GCN2 in tumor cells retards tumor growth and decreases tumor blood vessel density. Our results reveal that the GCN2/ATF4 pathway promotes tumor growth and angiogenesis through AAD-mediated VEGF expression and, thus, is a potential target in cancer therapy.


Summer workshop in metagenomics: one week plus eight students equals gigabases of cloned DNA.
We designed a week-long laboratory workshop in metagenomics for a cohort of undergraduate student researchers. During this course, students learned and utilized molecular biology and microbiology techniques to construct a metagenomic library from Puerto Rican soil. Pre-and postworkshop assessments indicated student learning gains in technical knowledge, skills, and confidence in a research environment. Postworkshop construction of additional libraries demonstrated retention of research techniques by the students.


[Causes of malnutrition in post-gastrectomy patient].
The stomach through its mechanical and chemical processes has an unique role in the food processing and bioavailability. Hence gastrectomy has predictable and modifiable nutritional consequences depending upon its knowledge and the post-surgery therapies. To point out the impact of gastrectomy on the nutritional status focusing on both mechanical and chemical actions of stomach on intaked foods. The protein-energy malnutrition and consequent body-weight loss follow reversely the remainer gastric volume and post-operatory length and have anorexy and intestinal malabsorption as their main causes. Lower food intake is probably due to either emotional factors or chemical mediators acting centrally on hypothalamus. The diarrhea may be due to either increased peristalsis or bacterial overgrowth both aggravated by exocrine-pancreas deficiency and gallbladder overflow. The intestinal malabsorption leading to fecal losses of fat and or nitrogen as well as lower utilization of dietary calcium and liposoluble vitamins. The gastrectomy-related anemia is consequent to lower secretion of both HCl and intrinsic factor leading to a decreased solubilization of iron and lower absorption of vitamin B12, respectively. Body-weight loss and anemia are the protein-energy malnutrition findings often found in these patients whose severity and lasting depend upon the type of surgery, post-surgery length and received nutritional care, being strongly recommended a supervisioned dietary care.


Bird v. Ross and Aphetow House Ltd., 18 December 1987.
The complainant charged her employer with discrimination on the basis of sex when she was dismissed after undergoing a legal abortion. The Saskatchewan Human Rights Board of Inquiry upheld the complaint. It ruled that, since legal abortions are performed only if continuance of the pregnancy is likely to endanger life or health of the mother, the complainant had a life- or health-threatening illness as a result of her pregnancy and was, thus, dismissed because of pregnancy, contrary to the Saskatchewan Human Rights Code. It awarded her damages for lost wages and humiliation.


Personal cleanser technology and clinical performance.
Cleansing is essential for health and hygiene. Personal cleansing agents, such as soap, one of the earliest to be developed, were initially expected to deliver only cleansing benefits, but consumer expectations came with time to encompass health and cosmetic benefits. This demand led to the development of an array of milder cleansing agents with a broader spectrum of application. Cleansing products are sold around the world in different forms such as bars (the most widely used), liquids, gels, and creams. The present paper discusses the chemistry, formulation, product attributes, and benefits of various types of personal wash products.


Enterococcus gallinarum carrying the vanA gene cluster: first report in Brazil.
In 2000, Enterococcus faecalis resistant to vancomycin was first reported at a tertiary hospital in Porto Alegre, southern Brazil. The resistance spread to other hospitals and surveillance programs were established by hospital infection committees to prevent the spread of vancomycin-resistant enterococci. In February 2002, an isolate initially identified at the genus level as Enterococcus was obtained by surveillance culture (rectal swab) from a patient admitted to a hospital for treatment of septic arthritis in the shoulder. The isolate proved to be resistant to vancomycin by the disc diffusion method and confirmed by an E-test resulting in a minimal inhibitory concentration of > or = 256 microg/ml. This isolate was sent to a reference laboratory (Laboratorio Especial de Bacteriologia e Epidemiologia Molecular, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, USP) for further study and proved to be an E. gallinarum by the polymerase chain reaction (PCR) using specific primers for the species. Due to the phenotype of unusually high vancomycin resistance, the isolate presumably had the resistance genes (vanA and vanB) and this was confirmed by PCR, which indicated the presence of the vanA gene. A 10.8-kb Tn1546-related transposon was also identified by long-PCR. Interspecies transfer of the vancomycin-resistance gene from the donor E. gallinarum was performed in a successful conjugation experiment in vitro, using E. faecium GE-1 and E. faecalis JH22 as receptors. This is the first report of the detection of a vanA determinant naturally acquired by E. gallinarum in Brazil, indicating the importance of characterizing VRE by both phenotype and genotype methods.


Corticosteroids in Patients Hospitalized With Community-Acquired Pneumonia: Systematic Review and Individual Patient Data Metaanalysis.
Our aim was to evaluate the benefits and harms of adjunctive corticosteroids in adults hospitalized with community-acquired pneumonia (CAP) using individual patient data from randomized, placebo-controlled trials and to explore subgroup differences. We systematically searched Medline, Embase, Cochrane Central, and trial registers (all through July 2017). Data from 1506 individual patients in 6 trials were analyzed using uniform outcome definitions. We investigated prespecified effect modifiers using multivariable hierarchical regression, adjusting for pneumonia severity, age, and clustering effects. Within 30 days of randomization, 37 of 748 patients (5.0%) assigned to corticosteroids and 45 of 758 patients (5.9%) assigned to placebo died (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], .46 to 1.21; P = .24). Time to clinical stability and length of hospital stay were reduced by approximately 1 day with corticosteroids (-1.03 days; 95% CI, -1.62 to -.43; P = .001 and -1.15 days; 95% CI, -1.75 to -.55; P < .001, respectively). More patients with corticosteroids had hyperglycemia (160 [22.1%] vs 88 [12.0%]; aOR, 2.15; 95% CI, 1.60 to 2.90; P < .001) and CAP-related rehospitalization (33 [5.0%] vs 18 [2.7%]; aOR, 1.85; 95% CI, 1.03 to 3.32; P = .04). We did not find significant effect modification by CAP severity or degree of inflammation. Adjunct corticosteroids for patients hospitalized with CAP reduce time to clinical stability and length of hospital stay by approximately 1 day without a significant effect on overall mortality but with an increased risk for CAP-related rehospitalization and hyperglycemia.


[Antibody reaction to immunization with different recombinant hepatitis B vaccine in primary school children].
To evaluate the safety and immunogenicity of local produced hepatitis B (HB) vaccine and to lay a basis for formulating an immunization strategy. Two batches of local produced and two batches of imported yeast derived recombinant HB vaccine (YDV), and four batches of local produced Chinese hamster ovary cell derived recombinant HB vaccine (CHOV) were administered to 550 children in primary schools to study their immunogenicity one year after immunization. No severe adverse reaction was found in all vaccinee. Positive seroconversion rate was more than 90 percent one month after completion of three-dose immunization with all kinds of HB vaccine mentioned above, and then declined slowly. Titer of antibody against hepatitis B surface antigen (anti-HBs) in those vaccinated with two batches of local produced YDV, except four groups, was significantly lower than that in those with imported YDV and local produced CHOV seven months after first-dose immunization, but no difference between local produced YDV and imported Merck vaccine and CHOV was found one year after immunization. Mean geometric titer (GMT) of anti-HBs reached the peak seven months after immunization in those vaccinated with all batches of HB vaccine except for the YDV imported from Amgen Co. There was no significant difference in positive seroconversion and GMT of anti-HBs between different batches of local produced YDV and CHOV. Safety and immnogenicity of local produced recombinant HB vaccine is as good as those of imported one in immunization for primary school children.


Green Synthesis of Cerium Oxide Nanoparticles (CeO2 NPs) and Their Antimicrobial Applications: A Review.
During the last decade green synthesized cerium oxide nanoparticles (CeO2 NPs) attracted remarkable interest in various fields of science and technology. This review, explores the vast array of biological resources such as plants, microbes, and other biological products being used in synthesis of CeO2 NPs. It also discusses their biosynthetic mechanism, current understandings, and trends in the green synthesis of CeO2 NPs. Novel therapies based on green synthesized CeO2 NPs are illustrated, in particular their antimicrobial potential along with attempts of their mechanistic elucidation. Overall, the main objective of this review is to provide a rational insight of the major accomplishments of CeO2 NPs as novel therapeutics agents for a wide range of microbial pathogens and combating other diseases.


Characteristics and development of leucine transport activity in the scutellum of germinating barley grain.
Scutella separated from grains of Himalaya barley after germination for 3 days rapidly took up l-leucine from aerated incubation media; with 1 millimolar leucine the rate varied between 4 and 14 micromoles per gram per hour and the pH optimum was at 3.5 to 5, both depending on buffer composition and prewashing time. The rate of the uptake increased with increasing concentration of leucine in a complex manner, which could be interpreted as multiphasic kinetics with apparent K(m) values of 3.4 and 15.5 millimolar below and above 3 millimolar leucine, respectively. The uptake took place against a concentration difference (highest estimated ratio 270: 1) and was strongly inhibited by dinitrophenol. Uptake was apparently due to active transport requiring metabolic energy.The development of the uptake activity during germination was studied using Pirkka barley. A low activity was present in the scutella of ungerminated grains. It began to increase after 6 hours imbibition, and the increase was biphasic, the major changes occurring during days 0 to 3 and 4 to 6. The total increase was about 20-fold.The regulation of the development was studied by allowing separated embryos to germinate on agar gel. The increase of uptake activity was strongly inhibited by inhibitors of RNA or protein synthesis. Increase did not require the presence of the embryo proper, and was not affected by gibberellic or abscisic acid. Removal of the endosperm greatly accelerated the increase of uptake activity, and the presence of 5 or 20 millimolar glutamine counteracted the removal of the endosperm. The results suggest that the availability of glutamine or amino acids in general in the endosperm may regulate the development or the activity of the transport system.


Malignant lymphomas with a follicular growth pattern.
Given the pivotal role of the B-cell follicle in B-cell proliferation, and the fact that the follicle centre has the highest proliferation fraction of any structure in the body, it would be reasonable to expect that the potential for the development of aberrant (neoplastic) growth within it would be relatively high, especially when compared to other lymphoid compartments. However, in all current lymphoma classifications only one entity, namely follicular lymphoma, is acknowledged as having any relation to the follicle. As knowledge of the immunophenotype and function of the normal follicle has increased, it has become evident that many lymphomas, including some examples of Hodgkin's disease, are related to the B-cell follicle and as a consequence manifest a follicular growth pattern. This has implications for the pathogenesis of these tumours and may point the way to novel therapeutic options.


Redefined hyponatremia as a marker to exclude the diagnosis of anastomotic leakage after colorectal cancer surgery.
Our objective was to investigate the association between anastomotic leakage (AL) and hyponatremia after colorectal cancer surgery. All anastomoses in colorectal cancer surgery performed in our hospital between January 2015 and December 2017 were retrospectively identified. According to the diagnostic criteria of AL, the patients were divided into an AL group and a no anastomotic leakage (NAL) group. We reviewed records of 498 consecutive colorectal cancer patients. The total incidence of AL was 5.4%. Postoperative serum sodium levels differed significantly: 137.63 ± 4.29 and 139.81 ± 3.41 mmol/L in the AL and NAL groups, respectively. By using area under the receiver-operating characteristic (auROC) curves, we determined the optimum postoperative serum sodium cut-off to be 139.5 mmol/L and redefined hyponatremia as postoperative serum sodium <139.5 mmol/L. Redefined hyponatremia had an auROC of 0.65, corresponding to a 97.2% negative predictive value. The negative predictive value reached 99.1% when serum sodium level was combined with leukocytosis. Multivariable analysis found that redefined hyponatremia (odds ratio, 1.176) was an independent predictive factor for AL. Redefined hyponatremia has good negative predictive value for AL diagnosis after colorectal cancer surgery and could be used as a marker to exclude the diagnosis.


The assessment and treatment of adult heterosexual men with self-perceived problematic pornography use: A review.
Self-Perceived Problematic Porn Use (SPPPU) refers to an individual who self-identifies as addicted to porn because they feel they are unable to regulate their porn consumption, and that use interferes with everyday life. Although porn addiction has not been formally classified as its own distinct behavioral addiction, therapists and clinicians are advised to educate themselves on the current state of literature pertaining to pornography consumption given the widespread availability and consumption of sexually explicit material online. This review article begins with a general overview of pornography and porn use so that therapists and researchers can discern between non-intrusive and problematic pornography consumption patterns within their practice and understand the common characteristics of those that most commonly present with SPPPU. Thereafter, an overview and examination of therapeutic interventions for SPPPU will be identified and analysed. Finally, the review concludes with recommendations for therapists, clinicians, and future research.


US depiction of partial-thickness tear of the rotator cuff.
To test previously defined ultrasound (US) criteria for identification of partial-thickness tears of the rotator cuff. Before shoulder arthroscopy, 52 patients with shoulder pain for more than 3 months were examined with a 7.5-MHz commercially available linear-array transducer and a standardized study protocol. The criteria used to detect partial-thickness tears were (a) a mixed hyper- and hypoechoic focus in the crucial zone of the supraspinatus tendon and (b) a hypoechoic lesion visualized in two orthogonal imaging planes with either articular or bursal extension. The US findings were reported as partial-thickness tears in 17 shoulders, of which three were false-positive findings. There was one false-negative finding. The sensitivity of US in depiction of partial-thickness tears was 93%, and specificity was 94%. The positive predictive value was 82%, and the negative predictive value was 98%. US can depict most partial-thickness tears with use of the criteria described.


The effect of fibrolytic enzymes sprayed onto forages and fed in a total mixed ratio to lactating dairy cows.
We investigated the effect of spraying different combinations of fibrolytic enzymes onto forages on their nutritive value for lactating cows. Holstein cows were fed a TMR consisting of 30% corn silage, 15% alfalfa hay, and 55% concentrate (dry matter basis). During a 12-wk treatment period, the forages were treated with no enzymes (control), cellulase D and sultanas B, or cellulase D and xylanase C. Enzymes were diluted in water and sprayed onto the forages while mixing. Both combinations of enzymes supplied similar amounts of fibrolytic activity based on classical enzyme assays conducted at 50 degrees C. Cows fed forages treated with cellulase D and xylanase B tended to produce more 3.5% FCM (+2.5 kg/d) than did cows fed the untreated forages. Dry matter intake, milk production, milk fat, and milk protein were unaffected by treatment. In vitro production of gas from forages treated with enzymes was greater than from untreated forage, but 96-h volatile fatty acid production was not different among treatments. With an alternative enzyme assay based on the depolymerization of dyed substrate at 40 degrees C, activity of xylanase C was greatest at a pH of 6.5 but was substantially reduced as the pH of the assay was decreased. In contrast, xylanase B showed highest activity at pH 5 and enzyme activity was twice that of xylanase B at pH 5.5 and 6. Overall, the results of this study provide more evidence that fibrolytic enzymes can be used to improve milk production in lactating cows.


Convolutional Neural Network-Based Shadow Detection in Images Using Visible Light Camera Sensor.
Recent developments in intelligence surveillance camera systems have enabled more research on the detection, tracking, and recognition of humans. Such systems typically use visible light cameras and images, in which shadows make it difficult to detect and recognize the exact human area. Near-infrared (NIR) light cameras and thermal cameras are used to mitigate this problem. However, such instruments require a separate NIR illuminator, or are prohibitively expensive. Existing research on shadow detection in images captured by visible light cameras have utilized object and shadow color features for detection. Unfortunately, various environmental factors such as illumination change and brightness of background cause detection to be a difficult task. To overcome this problem, we propose a convolutional neural network-based shadow detection method. Experimental results with a database built from various outdoor surveillance camera environments, and from the context-aware vision using image-based active recognition (CAVIAR) open database, show that our method outperforms previous works.


The Relationships between Plant Developmental Traits and Winter Field Survival in Rye (Secale cereale L.).
Overwintering cereals accumulate low temperature tolerance (LTT) during cold acclimation in the autumn. Simultaneously, the plants adjust to the colder season by making developmental changes at the shoot apical meristem. These processes lead to higher winter hardiness in winter rye varieties (Secale cereale L.) adapted to Northern latitudes as compared to other cereal crops. To dissect the winter-hardiness trait in rye, a panel of 96 genotypes of different origins and growth habits was assessed for winter field survival (WFS), LTT, and six developmental traits. Best Linear Unbiased Estimates for WFS determined from five field trials correlated strongly with LTT (r = 0.90, p < 0.001); thus, cold acclimation efficiency was the major contributor to WFS. WFS also correlated strongly (p < 0.001) with final leaf number (r = 0.80), prostrate growth habit (r = 0.61), plant height (r = 0.34), but showed weaker associations with top internode length (r = 0.30, p < 0.01) and days to anthesis (r = 0.25, p < 0.05). The heritability estimates (h2) for WFS-associated traits ranged from 0.45 (prostrate growth habit) to 0.81 (final leaf number) and were overall higher than for WFS (h2 = 0.48). All developmental traits associated with WFS and LTT are postulated to be regulated by phytohormone levels at shoot apical meristem.


Membrane-bound selenoproteins.
Selenoproteins employ selenium to supplement the chemistry available through the common 20 amino acids. These powerful enzymes are affiliated with redox biology, often in connection with the detection, management, and signaling of oxidative stress. Among them, membrane-bound selenoproteins play prominent roles in signaling pathways, Ca(2+) regulation, membrane complexes integrity, and biosynthesis of lipophilic molecules. The number of selenoproteins whose physiological roles, protein partners, expression, evolution, and biosynthesis are characterized is steadily increasing, thus offering a more nuanced view of this specialized family. This review focuses on human membrane selenoproteins, particularly the five least characterized ones: selenoproteins I, K, N, S, and T. Membrane-bound selenoproteins are the least understood, as it is challenging to provide the membrane-like environment required for their biochemical and biophysical characterization. Hence, their studies rely mostly on biological rather than structural and biochemical assays. Another aspect that has not received much attention is the particular role that their membrane association plays in their physiological function. Findings cited in this review show that it is possible to infer the structure and the membrane-binding mode of these lesser-studied selenoproteins and design experiments to examine the role of the rare amino acid selenocysteine.


Ezetimibe/simvastatin: a guide to its clinical use in hypercholesterolemia.
Ezetimibe/simvastatin therapy combines two lipid-lowering compounds with complementary mechanisms of action, thereby blocking the two sources of plasma cholesterol and improving lipid profiles. Ezetimibe/simvastatin is an effective and generally well tolerated adjunct to dietary therapy for markedly reducing low-density lipoprotein cholesterol (LDL-C) levels and improving other lipid parameters across diverse patient populations. Dual treatment with ezetimibe/simvastatin is more effective than monotherapy with an HMG-CoA reductase inhibitor (statin), and the addition of ezetimibe to current statin therapy is more effective than doubling the statin dose.


[Ego identity and self-concept problems in children of psychotic parents. Results of a qualitative cross-sectional study].
In contrast to previous high-risk studies of children of parents suffering from psychosis a new approach to the difficulties of affected children will be tested, using the linguistic and narrative tools of biography studies. The transcribed texts of biographical interviews of affected children will be analysed linguistically and hermeneutically through "close reading". The linguistic and interpretative study of these texts will demonstrate the children's specific problem of identity-formation and their construction of reality and biography through the order of language (as shown by their uses of metonymy and metaphor). By using the method of biographical research a) the creative potential of patients and their children is exposed, b) a qualified view of mental illnesses can be reached in the field of symbolic practice.


Ribozyme-mediated inhibition of caspase-3 protects cerebellar granule cells from apoptosis induced by serum-potassium deprivation.
Apoptosis is an important mechanism of physiological and pathological cell death. It is regulated by several gene products, including caspases and the bcl-2-like proteins, whose roles have been demonstrated in numerous systems. One of these is a model of cerebellar granule cells (CGCs) in which apoptosis is induced by acute removal of serum and depolarizing concentrations of potassium. Previous work by several authors showed that benzyloxycarbonyl-DEVD-fluoromethylketone, a somewhat selective caspase inhibitor, significantly protected CGCs from apoptosis; however, because this molecule targets multiple caspases, it is not known whether a single caspase is primarily responsible for effecting cell death in this model. We attempted to answer this question by cotransfecting CGCs with green fluorescent protein reporter and a hammerhead ribozyme directed against caspase-3 mRNA. Maximal protection by this ribozyme was observed after 24 hr of deprivation, at which time apoptosis was 18 +/- 0.7% compared with 32 +/- 2% in control cells. Significant protection was also observed with human inhibitor of apoptosis (IAP)-like protein-X-linked IAP, a specific inhibitor of caspase-3, -7, and -9, and with p35, a general caspase inhibitor. Overexpression of bcl-2 produced almost complete protection from apoptosis after 24 hr of serum-K(+) deprivation (5 +/- 2 vs 44 +/- 2% in control cells). These results confirm that caspases play an important role in CGC apoptosis and indicate that caspase-3 itself is a significant mediator of this process.


1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis.
Recent magnetic resonance imaging (MRI) and pathological studies have indicated that axonal loss is a major contributor to disease progression in multiple sclerosis. 1H magnetic resonance spectroscopy (MRS), through measurement of N-acetyl aspartate (NAA), a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis have few lesions on conventional MRI, suggesting that changes in normal appearing white matter (NAWM), such as axonal loss, may be particularly relevant to disease progression in this group. To test this hypothesis NAWM was studied with MRS, measuring the concentration of N-acetyl derived groups (NA, the sum of NAA and N-acetyl aspartyl glutamate). Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of metabolite to creatine concentration (Cr) were calculated in all subjects, and absolute concentrations were measured in 18 patients and all controls. NA/Cr (median 1.40, range 0.86-1.91) was significantly lower in NAWM in patients than in controls (median 1.70, range 1.27-2.14; P = 0.006), as was the absolute concentration of NA (patients, median 6.90 mM, range 4.62-10.38 mM; controls, median 7.77 mM, range 6.60-9.71 mM; P = 0.032). There was no significant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group.


Interactions between potential anti-tumour 2,5-bis(1-aziridinyl)-1,4-benzoquinone derivatives and glutathione: reductive activation, conjugation and DNA damage.
The interaction between glutathione and potential anti-tumour 3,6-disubstituted 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied using u.v. spectrophotometry and h.p.l.c. The formation of BABQ-glutathione adducts was demonstrated in vitro for the BABQ parent compound (TW13), triaziquone (2,3,5-tris(1-aziridinyl)-1,4-benzoquinone) and for BABQ derivatives containing halogen substituents. The clinically-used BABQ derivative diaziquone (AZQ; 2,5-bis(1-aziridinyl)-3,6-bis(ethoxycarbonylamino)-1,4-benzoquinon e) did not react with glutathione. TW13 and triaziquone markedly inactivated bacteriophage M13-DNA in the presence of glutathione. This inactivation is probably produced by reductive activation of the BABQ derivative to a DNA-alkylating semiquinone radical. However, formation of bulky glutathione adducts decreases reactivity to DNA. Halogen-substituted BABQ derivatives react rapidly with glutathione to form adducts. This appeared to prevent DNA alkylation by these compounds. Comparison of these results with in vivo and in vitro activity against tumour models (L1210) suggests that in vivo halogen-substituted BABQ derivatives are efficiently inactivated by glutathione conjugation. The differences between the halogen-substituted BABQ derivatives on the one hand and TW13 and triaziquone on the other hand are probably caused by a difference in reaction mechanism with glutathione. From the viewpoint of drug design, halogen-substituted BABQ derivatives are expected to be inactive anti-tumour agents, in spite of high reactivity and activity in tumour models in vitro.


Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells.
A case of acquired von Willebrand disease (AvWD) associated with an IgA lambda multiple myeloma is reported. No form of inhibitor could be detected. SDS-agarose gel electrophoresis patterns of von Willebrand factor (vWF) both in plasma and platelet lysates were normal but a decrease in all-sized multimers with a type IA pattern was seen. After 1-deamino-8-D arginine vasopressin (DDAVP) infusion, vWF multimers larger than those seen in the resting state appeared in patient plasma, which were progressively cleared. Indirect immunofluorescence studies with a monoclonal antibody to vWF showed that vWF was selectively absorbed into myelomatous cells. This is the first case of AvWD associated with multiple myeloma resulting from the selective absorption of vWF into abnormal plasma cells. This feature established a new pathophysiological mechanism of AvWD in multiple myeloma and probably in other lymphoproliferative diseases.


High level of CA 125 due to large endometrioma.
CA 125 is a tumor-associated antigen. Its high levels are usually associated with ovarian malignancies, whereas smaller increases in the levels were associated with benign gynecologic conditions. The authors report a high level of CA 125 in a case of large ovarian endometrioma. A 45-year-old nulliparous Thai woman, presented with an increase of her abdominal girth for 7 months. Transabdominal ultrasonogram demonstrated a large ovarian cyst and multiple small leiomyoma uteri, and serum CA 125 level was 1,006 U/ml. The preoperative diagnosis was ovarian cancer with leiomyoma uteri. Exploratory laparotomy was performed. There were a large right ovarian endometrioma, small left ovarian endometrioma and multiple small leiomyoma. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed and histopathology confirmed the diagnosis of endometrioma and leiomyoma. The serum CA 125 level declined to non-detectable at the 4th week. She was well at discharge and throughout her 4th week follow-up period Although a very high level of CA 125 is associated with a malignant process, it can also be found in benign conditions such as a large endometrioma. The case emphasizes the association of high levels of CA 125 with benign gynecologic conditions.


Fos expression within vasopressin-containing neurons in the suprachiasmatic nucleus of diurnal rodents compared to nocturnal rodents.
The underlying neural causes of the differences between nocturnal and diurnal animals with respect to their patterns of rhythmicity have not yet been identified. These differences could be due to differences in some subpopulation of neurons within the suprachiasmatic nucleus (SCN) or to differences in responsiveness to signals emanating from the SCN. The experiments described in this article were designed to address the former hypothesis by examining Fos expression within vasopressin (VP) neurons in the SCN of nocturnal and diurnal rodents. Earlier work has shown that within the SCN of the diurnal rodent Arvicanthis niloticus, approximately 30% of VP-immunoreactive (IR) neurons express Fos during the day, whereas Fos rarely is expressed in VP-IR neurons in the SCN of nocturnal rats. However, in earlier studies, rats were housed in constant darkness and pulsed with light, whereas Arvicanthis were housed in a light:dark (LD) cycle. To provide data from rats that would permit comparisons with A. niloticus, the first experiment examined VP/Fos double labeling in the SCN of rats housed in a 12:12 LD cycle and perfused 4 h into the light phase or 4 h into the dark phase. Fos was significantly elevated in the SCN of animals sacrificed during the light compared to the dark phase, but virtually no Fos at either time was found in VP-IR neurons, confirming that the SCN of rats and diurnal Arvicanthis are significantly different in this regard. The authors also evaluated the relationship between this aspect of SCN function and diurnality by examining Fos-IR and VP-IR in diurnal and nocturnal forms of Arvicanthis. In this species, most individuals exhibit diurnal wheel-running rhythms, but some exhibit a distinctly different and relatively nocturnal pattern. The authors have bred their laboratory colony for this trait and used animals with both patterns in this experiment. They examined Fos expression within VP-IR neurons in the SCN of both nocturnal and diurnal A. niloticus kept on a 12:12 LD cycle and perfused 4 h into the light phase or 4 h into the dark phase, and brains were processed for immunohistochemical identification of Fos and VP. Both the total number of Fos-IR cells and the proportion of VP-IR neurons containing Fos (20%) were higher during the day than during the night. Neither of these parameters differed between nocturnal and diurnal animals. The implications of these findings are discussed.


Intermolecular interaction between CO or CO2 and ethylene oxide or ethylene sulfide in a complex, investigated by Fourier transform microwave spectroscopy and ab initio calculations.
The rotational spectra of the CO-ethylene oxide (EO), CO-ethylene sulfide (ES), CO(2)-EO, and CO(2)-ES complexes were measured by Fourier transform microwave spectroscopy in the frequency region from 4 up to 31 GHz. The isotopologues with a single (13)C atom in the EO or ES, (18)O in the EO, (34)S in the ES, and (13)C in the CO(2) moiety, respectively, were observed in natural abundance, and enriched samples, (13)CO or C(18)O in the CO-EO or CO-ES complex and C(18)OO and C(18)O(2) in the CO(2)-EO or CO(2)-ES complex, were employed to record respective rotational transitions. The rotational spectra observed for the CO-EO, CO-ES, CO(2)-EO, and CO(2)-ES complexes were analyzed by using an asymmetric-rotor S-reduced Hamiltonian to determine rotational and centrifugal distortion constants. The r(s) coordinates of the atoms in the four complexes, which were calculated from the observed rotational constants, led to a structure in which the CO or CO(2) moiety is located in a plane perpendicular to the EO or ES skeletal plane and bisecting the COC or CSC angle. We have also carried out ab initio molecular orbital calculations at the level of MP2 with basis sets 6-311++G(d,p) and aug-cc-pVDZ using the Gaussian 09 package. The MP2/6-311++G(d,p) calculations yield rotational constants in better agreement with the experimental values than with the other basis set; in other words, the molecular structures calculated using this basis set are close to those experimentally found for the ground state. The estimated dissociation energies of the complexes, including the zero-point vibrational energy corrections ΔZPV and the basis set superposition errors (BSSE) calculated with the counterpoise correction (CP), are in good agreement with the experimentally obtained binding energies E(B). We have applied an NBO analysis to the complexes to calculate the stabilization energy CT (=ΔE(σσ*)), which we found are closely correlated with the binding energies E(B). We have thus achieved a consistent overview on the intermolecular interaction in the complexes under consideration. It is to be noted that the spectral intensities of the inner OC(18)O-EO and OC(18)O-ES complexes were larger by a factor of 2 than those of the outer (18)OCO-EO/ES complexes. This observation was explained by the zero-point energy of the inner conformer being a little smaller than that of the outer one.


Antigenic characterization of a T-CLL with heteroantisera and monoclonal antibodies: evidence for the T cell lineage of an Ia-positive, Fc-IgG--positive, suppressor-cell subpopulation.
In a previous report, peripheral blood mononuclear T cells from a patient with T-chronic lymphocytic leukemia (T-CLL) were shown to bear receptors for the Fc portion of IgG (T gamma). Moreover, the ability of these cells to rosette with sheep erythrocytes was strongly inhibited by a preincubation of the cells with theophylline. These data indicated that they represent a highly purified subpopulation of Fc-IgG receptor-positive, low-affinity rosetting cells with in vitro suppressor activity on lectin-induced proliferation of normal lymphocytes. They also were reactive in antibody-dependent cell-mediated cytotoxicity but had no reactivity in natural killer cell assays. These cells were studied in this report with several heteroantisera and monoclonal antibodies. Results indicate that these T-CLL cells express a T cell antigenic pattern (OKT-3+) and the majority are Ia positive. They also react with the OKT-8 reagent (a reagent detecting the subset of T cells that contains the cytotoxic/suppressor cells), whereas they are negative with OKT-4 (which reacts with the subset of T cells that contains helper cells) and OKT-6 (thymocyte) antibodies. Heteroantisera also support the results obtained with monoclonal reagents. Despite some recent evidence showing that a high percentage of T gamma cells may belong to the monocyte-myeloid lineage, these T-CLL cells were negative with OKM-1, a monoclonal antibody reported to detect a monomyeloid antigen. These results suggest that a distinct subpopulation of suppressor T cells can be identified by membrane-marker phenotyping.


Biological correlates of HIV-1 heterosexual transmission.
To study the role of HIV-1 biological phenotype, viral load and neutralizing antibodies in male-to-female heterosexual transmission of HIV-1. Seven transmitting and seven non-transmitting HIV-1-seropositive heterosexual male index cases were included in the present study. All couples had engaged in unprotected sex for a period of over 1 year. Transmission was defined by the seroconversion of the female sexual partner. Virus isolates were tested in MT-2 cells for replication and syncytia induction. HIV-1 RNA plasma load was measured by the branched DNA technique. Serum neutralizing activity to primary HIV-1 isolates was tested by using peripheral blood mononuclear cells (PBMC) as target cells. Non-transmitting index cases had a lower HIV-1 RNA concentration in plasma than transmitting index cases. Non-transmitting index cases also tended to have serum neutralizing activity with broad specificity and to have viruses with low replicative capacity, as characterized by 50% infectious dose titres in PBMC and by the lack of MT-2 tropism. The results indicate that plasma viral-RNA load is a marker for transmission. Moreover, an interplay between the host immune response and viral replication may modulate the level of viral load and thereby influence HIV-1 transmission.


Molecular dynamics simulations of DNA in solutions with different counter-ions.
Molecular dynamics simulations of the [d(ATGCAGTCAG]2 fragment of DNA, in water and in the presence of three different counter-ions (Li+, Na+ and Cs+) are reported. Three-dimensional hydration structure and ion distribution have been calculated using spatial distribution functions for a detailed picture of local concentrations of ions and water molecules around DNA. According to the simulations, Cs+ ions bind directly to the bases in the minor groove, Na+ ions bind prevailing to the bases in the minor groove through one water molecule, whereas Li+ ions bind directly to the phosphate oxygens. The different behavior of the counter-ions is explained by specific hydration structures around the DNA and the ions. It is proposed how the observed differences in the ion binding to DNA may explain different conformational behavior of DNA. Calculated self-diffusion coefficients for the ions agree well with the available NMR data.


Structural and Luminescence Behavior of Nanocrystalline Orthophosphate KMeY(PO4)2: Eu3+ (Me = Ca, Sr) Synthesized by Hydrothermal Method.
KMeY(PO4)2:5% Eu3+ phosphates have been synthesized by a novel hydrothermal method. Spectroscopic, structural, and morphological properties of the obtained samples were investigated by X-ray, TEM, Raman, infrared, absorption, and luminescence studies. The microscopic analysis of the obtained samples showed that the mean diameter of synthesized crystals was about 15 nm. The KCaY(PO4)2 and KSrY(PO4)2 compounds were isostructural and they crystallized in a rhabdophane-type hexagonal structure with the unit-cell parameters a = b ≈ 6.90 Å, c ≈ 6.34 Å, and a = b ≈ 7.00 Å, c ≈ 6.42 Å for the Ca and Sr compound, respectively. Spectroscopic investigations showed intense 5D0 → 7F4 transitions connected with D2 site symmetry of Eu3+ ions. Furthermore, for the sample annealed at 500 °C, europium ions were located in two optical sites, on the surface of grains and in the bulk. Thermal treatment of powders at high temperature provided better grain crystallinity and only one position of dopant in the crystalline structure. The most intense emission was possessed by the KSrY(PO4)2:5% Eu3+ sample calcinated at 500 °C.


Identification of Protein Thiazolidination as a Novel Molecular Signature for Oxidative Stress and Formaldehyde Exposure.
Chemical modifications of proteins have been well-documented to play important roles in normal cell physiology such as cell signaling and protein functions. They have also been demonstrated to be one of the milestones in the pathophysiology of many human diseases such as cancer, age-related pathology, and neurodegenerative disorders. Here, we report the initial identification of a novel protein modification, cysteine thiazolidination, through reaction with endogenous and exogenous formaldehyde with cysteine residues in proteins. Using an isotope-dilution liquid chromatography-tandem mass spectrometric (LC-MS3) method, we initiated the study by quantitating thioproline in formaldehyde-treated Escherichia coli (E. coli) protein. The study was then extended to quantitate thioproline in protein obtained from formaldehyde- and oxidant-exposed E. coli. Furthermore, N6-formyllysine, a well-defined formylation product between formaldehyde and lysine, was exploited in a comparative study to evaluate the relative reactivity and amount of cysteine thiazolidination in the reaction of formaldehyde with proteins. It is anticipated that cysteine thiazolidination may serve as a novel biomarker for oxidative stress and formaldehyde exposure.