Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Adjunctive Lamotrigine Treatment on the Plasma Concentrations of Clozapine, Risperidone and Olanzapine in Patients With Schizophrenia or Bipolar Disorder

The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxy-risperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 ± 7 ng/mL at baseline, 32 ± 7 ng/mL at week 6, and 36 ± 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance.
Transcription Factor IIB (TFIIB)-Related Protein (pBrp), a Plant-Specific Member of the TFIIB-Related Protein Family

ABSTRACT Although it is now well documented that metazoans have evolved general transcription factor (GTF) variants to regulate their complex patterns of gene expression, there is so far no information regarding the existence of specific GTFs in plants. Here we report the characterization of a ubiquitously expressed gene that encodes a bona fide novel transcription factor IIB (TFIIB)-related protein in Arabidopsis thaliana. We have shown that this protein is the founding member of a plant-specific TFIIB-related protein family named pBrp (for plant-specific TFIIB-related protein). Surprisingly, in contrast to common GTFs that are localized in the nucleus, the bulk of pBrp proteins are bound to the cytoplasmic face of the plastid envelope, suggesting an organelle-specific function for this novel class of TFIIB-related protein. We show that pBrp proteins harbor conditional proteolytic signals that can target these proteins for rapid turnover by the proteasome-mediated protein degradation pathway. Interestingly, under conditions of proteasome inhibition, pBrp proteins accumulate in the nucleus. Together, our results suggest a possible involvement of these proteins in an intracellular signaling pathway between plastids and the nucleus. Our data provide the first evidence for an organelle-related evolution of the eukaryotic general transcription machinery.
Neonatal hearing screening model: An Italian regional experience

Objective. To produce a model for routine centralized hearing screening including all aspects of the screening, from diagnosis to psychological counseling and early rehabilitation. Methods. A prospective observational study on a geographically defined pediatric population (Liguria region, northwestern Italy) and data collection in a data bank. The model proposed was created for the audiological screening of all newborns of the Liguria region. The model includes four phases: (1) preliminary identification of contractual, administrative, legal aspects; (2) screening for identification of congenital hearing impairment; (3) therapy and rehabilitation of identified subjects and genetic analysis; (4) epidemiology, data management, and workload management. To test the feasibility of the model proposed and to establish the workload required according to the resources available in the regional health plan, we performed a pilot study on all infants born in four of the 13 regional birth centers of Liguria region from 1 April 2001 to 30 September 2001. Results. Out of the 3268 newborns enrolled during the 6-month pilot study, 3238 (99.1%) were screened with otoacoustic emissions (OAE), while screening was refused in 30 newborns (0.9%). OAE resulted in a ‘pass’ for 3180 newborns (98.2%) and a ‘refer’ in 58 (1.8%). The standard auditory brainstem response (ABR) test was performed in 156 newborns, 58 of them as a result of the ‘refer’ at the second OAE and 98 others at audiological risk. Results were positive or uncertain at first ABR in 45 patients. Workload was calculated on the basis of the data obtained in the pilot study to allocate financial and organizational resources. Conclusions. The results of the pilot study allowed project planning. We think that the screening model proposed is an example of how a regional organization can deliver improved quality care through a rationalization and optimization process.
Effect of Variations in Basal Plasma Glucose Concentration on Glucose Utilization (M) and Metabolic Clearance (MCR) Rates During Insulin Clamp Studies in Patients with Non-insulin-dependent Diabetes Mellitus

Two insulin clamp studies were performed at different steady-state plasma glucose concentrations in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM). Steady-state plasma insulin concentrations were comparable, with mean ± SEM levels of 94 ± 3 and 95 ± 4 μU/ml being achieved during the two studies. Glucose utilization rate (M) varied directly with plasma glucose concentration in each subject. Thus, the mean ± SEM value of M was 4.92 ± 0.73 mg/kg/min when patients were studied at a mean ± SEM plasma glucose concentration of 226 ± 15 mg/dl, and M was 2.71 mg/kg/min when the same subjects were studied at a glucose concentration of 118 ± 6 mg/dl. In contrast, the values for glucose metabolic clearance rate (MCR), which were 2.35 ± 0.50 and 2.49 ± 0.47 ml/kg/min, respectively, during the two studies, did not vary significantly with plasma glucose concentration. These data indicate that the glucose metabolic clearance rate (MCR), but not glucose utilization rate (M), can be used to compare in vivo insulin action when insulin clamp studies are performed in subjects with different basal plasma glucose concentrations.
Cholesterol and F‐actin are required for clustering of recycling synaptic vesicle proteins in the presynaptic plasma membrane

Extraction of cholesterol from synaptic vesicles trapped on the presynaptic plasma membrane causes synaptic vesicle proteins to disperse after exocytosis. Vesicular cholesterol regulates both presynaptic phosphatidylinositol (4,5)‐bisphosphate levels and actin distribution during synaptic vesicle recycling. Inhibition of actin polymerization results in the dispersal of proteins from trapped synaptic vesicles and impairs synaptic vesicle recycling. Vesicular cholesterol and actin together confine synaptic vesicle proteins on the presynaptic plasma membrane during synaptic vesicle recycling. Alteration of membrane or synaptic vesicle lipids might therefore affect the ability of synapses to undergo sustained exocytosis and endocytosis by compromising the recycling of synaptic vesicle proteins.
The diurnal pattern of salivary IL-1β in healthy young adults

Abstract Disruption in circadian rhythm affects the production of inflammatory cytokines. Understanding how it behaves in diseased conditions is essential. Despite the role of the interleukin-1β (IL-1β), a potent inflammatory cytokine, in human diseases, little is known about the steady-state circadian rhythm of IL-1β in healthy individuals. This short study investigates the diurnal pattern of salivary IL-1β throughout the day in healthy young adults. Twelve participants provided saliva samples at various times throughout the day. Salivary IL-1β were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Salivary IL-1β levels were highest at 0430 h and lowest at 0000 h and shared a similar diurnal pattern to that of salivary IL-6. Western blot analysis showed that these levels correspond to the mature form of IL-1β. Our findings are important as it established the diurnal pattern of salivary IL-1β is fluctuating normally throughout the day. The findings also open an incredible opportunity for developing research conducted in the field with saliva as the diagnostic tool.
The Mediator Complex MED 15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED 1 Transcription Factor 1 [ OPEN ]

The Mediator complex is known to be a master coordinator of transcription by RNA polymerase II, and this complex is recruited by transcription factors (TFs) to target promoters for gene activation or repression. The plant-specific TF WRINKLED1 (WRI1) activates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. However, no Mediator subunit has yet been identified that mediates WRI1 transcriptional activity. Promoter-b-glucuronidase fusion experiments showed that MEDIATOR15 (MED15) is expressed in the same cells in the embryo as WRI1. We found that the Arabidopsis (Arabidopsis thaliana) MED15 subunit of the Mediator complex interacts directly with WRI1 in the nucleus. Overexpression of MED15 or WRI1 increased transcript levels of WRI1 target genes involved in glycolysis and fatty acid biosynthesis; these genes were downregulated in wild-type or WRI1-overexpressing plants by silencing of MED15. However, overexpression of MED15 in the wri1 mutant also increased transcript levels of WRI1 target genes, suggesting that MED15 also may act with other TFs to activate downstream lipid-related genes. Chromatin immunoprecipitation assays confirmed the association of MED15 with six WRI1 target gene promoters. Additionally, silencing of MED15 resulted in reduced fatty acid content in seedlings and mature seeds, whereas MED15 overexpression increased fatty acid content in both developmental stages. Similar results were found in wri1 mutant andWRI1 overexpression lines. Together, our results indicate that the WRI1/MED15 complex transcriptionally regulates glycolysis-related and fatty acid biosynthetic genes during embryogenesis.
Time‐varying spectral analysis revealing differential effects of sevoflurane anaesthesia: non‐rhythmic‐to‐rhythmic ratio

Heart rate variability (HRV) may reflect various physiological dynamics. In particular, variation of R‐R peak interval (RRI) of electrocardiography appears regularly oscillatory in deeper levels of anaesthesia and less regular in lighter levels of anaesthesia. We proposed a new index, non‐rhythmic‐to‐rhythmic ratio (NRR), to quantify this feature and investigated its potential to estimate depth of anaesthesia.
Changes in Anterior Fontanel Pressure in Preterm Neonates Receiving Isoflurane, Halothane, Fentanyl, or Ketamine

The effects of anesthetics on intmcranial pressure (ICP) may be different in preterm neonates than in adults because the neonate's cranial sutures are not yet fused. The authors monitored changes in anterior fontanel pressure (AFP), a noninvasive indicator of ICP, during anesthesia in 44 preterm neonates without neurologic disease. Atropine, 0.02 mg/kg, and pancuronium, 0.1 mg/kg, were given intravenously to all patients, who were ventilated with oxygen and air. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic blood pressure (SAP) and mean blood pressure (MAP) were recorded at 1-min intervals. After a 5-min control period of stable AFP, each of the four groups of 11 patients then received either 0.75% isoflurane, 0.5% halothane, 20 μg/kg fentanyl, or 2 mg/kg ketamine. Anterior fontanel pressure decreased 11% during isoflurane administration, 9% during halothane administration, 10% after fentanyl, and 10% after ketamine. These changes were statistically significant, but clinically mild, and AFP remained within the normal range. Statistically significant decreases in SAP and MAP occurred during isoflurane and halothane administration, but not after fentanyl or ketamine. The authors conclude that indirectly measured ICP decreases slightly in preterm neonates without neurologic disease after administration of the anesthetics studied. The difference between these results and those of studies of ICP in adults is presumably due to the compliance of the neonate's open-sutured cranium.
Detection of msj‐1 gene expression in the frog, Rana esculenta testis, brain, and spinal cord

MSJ‐1 is member of the DnaJ/heat shock protein (Hsp) 40 chaperone protein family. It is present in mouse testis and spinal cord. In particular, MSJ‐1 is localized in post‐meiotic cells and in motoneurones of the ventral horns. To assess whether the role of this protein is evolutionarily conserved, we have investigated if msj‐1 gene is expressed in the frog, Rana esculenta. Using reverse transcription‐polymerase chain reaction (RT‐PCR), a msj‐1‐like transcript was detected in testis, brain, and spinal cord. Homology ranging from 42.3 to 46.0% was found as compared with the mammalian counterparts. Muscle did not show any signal. By Western blot analysis, a signal of the predicted size of 30 kDa was evidenced in testis, brain, and spinal cord but not in ovary, heart, liver, kidney, and muscle. MSJ‐1 fluctuations in the testis reveal that it appeared in concomitance with post‐meiotic events during the annual sexual cycle, as shown in a previous study. The protein is localized in spermatids and is still retained in mature spermatozoa, where it has perinuclear and centriolar localization. MSJ‐1 levels did not change in brain and spinal cord. Furthermore, in the brain MSJ‐1 was mainly present in diencephalon and mesencephalon, while in spinal cord MSJ‐1 was localized into several motoneurones of the cervical and thoracic tract. A putative role in vesicle trafficking is briefly discussed. Mol. Reprod. Dev. 68: 149–158, 2004. © 2004 Wiley‐Liss, Inc.
Poorer is riskier.

To examine the relationship between economic well being and health status, two economic concepts were explored: the permanent-income hypothesis and the transitory-income hypothesis. A regression analysis of time-series mortality data for the period of 1950-1988 was conducted. The regression results indicated that the total mortality rate is negatively associated with permanent income and positively associated with the transitory income. Results are also reported for the 8 major causes of death in the United States. The implications for risk analysis are discussed.
Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage.

The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.
The effects of gender and migrant status on physical and psychological well-being

Adolescents (n = 962; 55% migrant and 45% native) between the age of 11 and 19 were administered the Kovac's Children Depression Inventory (CDI), Children Trait Anxiety Inventory (CTAI), Offer's Self-Image Questionnaire (OSIQ), and Brähler's Checklist of Symptom Complaints (GBB). Foreign-born and German-born samples were matched for age, gender, and educational status. Females were more anxious and complained more about physical ailments, particularly tiredness, stomach disorders, colds, and circulatory ailments than males, but not for depression. Adolescent migrants did not display any significant differences in terms of physical health, but they did report more depression and anxiety measures. The association between anxiety, depression, and physical ill-health was significant for both males and females, but tended to be more pronounced for females. There was scarce evidence of gender making an impact on the migration-health linkage. The implications of the results are discussed within the framework of migration and health policies for second generation children and their families.
Recovery of performance during sleep following sleep deprivation.

Very few studies have systematically examined recovery of performance after sleep deprivation. In the present study, 12 young adult males were sleep deprived for periods of 40 and 64 hrs. Each period was preceded by baseline nights of sleep and followed by two recovery nights of sleep. Immediate recall and reaction time were tested at 2300, 0145, 0400, 0615, and 0830 during baseline, deprivation, and recovery nights. Performance efficiency showed a progressive decline after 2 hrs of recovery sleep following both periods of deprivation. Return to baseline was apparent after 4 hrs of steep following 40 hrs awake and after 8 hrs of sleep following 64 hrs awake. These results suggested that, in terms of behavioral efficiency, an equal amount of sleep is not required to compensate for sleep lost.
Morphologic and confocal investigation on Salzmann nodular degeneration of the cornea.

PURPOSE To investigate the ultrastructure of advanced Salzmann nodular degeneration (SND) and to correlate it to confocal in vivo findings. METHODS The corneal degenerative nodules from four patients with SND were examined with confocal microscopy and then removed and processed for light microscopy (LM) and transmission electron microscopy (TEM). RESULTS The confocal examination revealed elongated basal epithelial cells and activated keratocytes in the anterior stroma near the nodules. Occasional subbasal nerves and tortuous stromal nerve bundles were observed. With LM and TEM, five zones were described: one internodular and four pertaining the nodule, each characterized by peculiar aspects of the epithelium and stroma. As also confirmed by the morphometry, in the zones corresponding to the nodules, the epithelium was lower and with fewer cell layers than the peripheral zones. Over the nodules, the basement membrane was discontinuous or absent and the Bowman's layer, when present, had a granular-filamentous appearance. The nodular stroma was formed by many activated keratocytes and irregular lamellae. Subbasal nerves were always isolated and had degenerative changes in the center of the nodule. CONCLUSIONS This work illustrates the confocal microscopic findings associated with LM and TEM observations in patients with advanced SND. Our data revealed milder changes of the epithelium together with more pronounced changes of the basement membrane and Bowman's layer, which are aspects of increased keratocyte activity and an altered nerve pattern. All of these structures seem to contribute to the characteristic corneal disorganization of SND.
Approaches for the direct estimation of u , and demographic contributions to u , using capture-recapture data

We first consider the estimation of the finite rate of population increase or population growth rate, u i , using capture-recapture data from open populations. We review estimation and modelling of u i under three main approaches to modelling openpopulation data: the classic approach of Jolly (1965) and Seber (1965), the superpopulation approach of Crosbie & Manly (1985) and Schwarz & Arnason (1996), and the temporal symmetry approach of Pradel (1996). Next, we consider the contributions of different demographic components to u i using a probabilistic approach based on the composition of the population at time i + 1 (Nichols et al., 2000b). The parameters of interest are identical to the seniority parameters, n i , of Pradel (1996). We review estimation of n i under the classic, superpopulation, and temporal symmetry approaches. We then compare these direct estimation approaches for u i and n i with analogues computed using projection matrix asymptotics. We also discuss various extensions of the estimation approaches to multistate applications and to joint likelihoods involving multiple data types.
Microbiology of otitis media in the Paris, France, area from 1987 to 1997.

PURPOSE OF THE STUDY To investigate epidemiologic trends in the bacteriology of acute otitis media, data were recorded during a 10-year period by the same group of investigators during clinical studies in pediatric outpatients. METHODS Bacterial samples were obtained before antibiotic treatment from 2149 children (age 3 to 36 months) with acute otitis media. All samples were transported, handled and cultured in the same way throughout the 10-year period. RESULTS From the study patients 1862 samples of middle ear secretion were collected by tympanocentesis and 287 samples were collected from spontaneous otorrhea occurring within 24 h. Pathogens were isolated from 70% of patients. Pathogens included Haemophilus influenzae (40%), Streptococcus pneumoniae (31%) and Moraxella catarrhalis (8%). The incidence of beta-lactamase-producing H. influenzae was approximately 20% from 1987 to 1989, was approximately 35% from 1990 to 1995 and increased to 60 and 70% during the last 2 years. The rate of S. pneumoniae with decreased susceptibility to penicillin gradually increased from 7% in 1987 to 70% in 1996 and 1997. CONCLUSION The very high incidence of antimicrobial resistant strains reached during a short period in pediatric acute otitis media in our area, emphasizes the need for frequent epidemiologic studies.
Analysis of mRNA decay and rRNA processing in Escherichia coli multiple mutants carrying a deletion in RNase III

RNase III is an endonuclease involved in processing both rRNA and certain mRNAs. To help determine whether RNase III (rnc) is required for general mRNA turnover in Escherichia coli, we have created a deletion-insertion mutation (delta rnc-38) in the structural gene. In addition, a series of multiple mutant strains containing deficiencies in RNase II (rnb-500), polynucleotide phosphorylase (pnp-7 or pnp-200), RNase E (rne-1 or rne-3071), and RNase III (delta rnc-38) were constructed. The delta rnc-38 single mutant was viable and led to the accumulation of 30S rRNA precursors, as has been previously observed with the rnc-105 allele (P. Gegenheimer, N. Watson, and D. Apirion, J. Biol. Chem. 252:3064-3073, 1977). In the multiple mutant strains, the presence of the delta rnc-38 allele resulted in the more rapid decay of pulse-labeled RNA but did not suppress conditional lethality, suggesting that the lethality associated with altered mRNA turnover may be due to the stabilization of specific mRNAs. In addition, these results indicate that RNase III is probably not required for general mRNA decay. Of particular interest was the observation that the delta rnc-38 rne-1 double mutant did not accumulate 30S rRNA precursors at 30 degrees C, while the delta rnc-38 rne-3071 double mutant did. Possible explanations of these results are discussed.