Alcohol abuse has a potential association with unfavourable clinical course and brain atrophy in patients with status epilepticus.

AIM: To evaluate chronological changes on serial magnetic resonance imaging (MRI) examinations and clinical prognosis in patients with status epilepticus (SE), as well as the effect of alcohol abuse and heavy alcohol use on clinicoradiological findings. MATERIALS AND METHODS: This retrospective, single-centre study was approved by the institutional review board. Among 345 patients with seizures between January 2010 and October 2021, 27 patients with SE who had undergone both initial MRI (within a week after onset) and follow-up MRI (within 1 month after the initial MRI) were included. Five and three patients with concurrent or previous alcohol abuse and heavy alcohol-use history were included, respectively, and they were classified into the AL (Alcohol use) group. The remaining 19 patients were classified into the non-AL group. Two neuroradiologists independently evaluated both initial and follow-up MRI examinations of each patient; MRI findings were compared between the AL and non-AL groups using Fisher's exact test. In 15 patients, including four patients from the AL group, clinical information 6 months after the onset of SE was available; this information was compared between the two groups. RESULTS: Brain atrophy (5/8 versus 2/19, p=0.011; odds ratio, 12.29 [95% confidence interval, 1.32-189.2]) and unfavourable clinical course with uncontrollable seizures (3/4 versus 1/11, p=0.033; odds ratio, 30[1.43-638.19]) were significantly more frequent in the AL group than in the non-AL group. CONCLUSION: Among patients with SE, alcohol abuse and heavy alcohol-use history were associated with unfavourable seizure control and brain atrophy.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study.

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients.

Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies ( p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

A comparison of gastric emptying of soluble solid meals and clear fluids matched for volume and energy content: a pilot crossover study.

We previously demonstrated that the gastric emptying time of different liquids with the same volume mainly depended on their energy content, regardless of differences in composition. In this crossover study, we investigated whether the same applies when soluble solid foods are ingested with water. Ten healthy volunteers ingested one of five test diets consisting of two test meals (Calorie Mate® 100 and 200 kcal) and three test solutions (water and glucose solutions of 100 and 200 kcal), each given in a volume of 400 ml, and then underwent ultrasonography to measure the gastric antral cross-sectional area every 10 min for 120 min. The gastric emptying time was defined as the time for the antral cross-sectional area to revert to its initial value. When test diets with the same energy content were ingested, the gastric emptying curves were nearly identical, regardless of whether the original form was solid or liquid. The median (IQR[range]) gastric emptying times of Calorie Mate® of 100 kcal with water vs. isocaloric glucose solution were 65 (60-78 [50-80]) vs. 65 (60-70 [50-80]) min (p = 0.58), and for Calorie Mate® of 200 kcal with water vs. isocaloric glucose solution they were 100 (93-108 [90-120]) vs. 105 (90-110 [90-120]) min (p = 0.54). The median (IQR [range]) for water was 40 (30-40 [30-50]) min. Energy content may be a critical determinant of the gastric emptying time when ingesting soluble solid diets with water.

Determinants of liquid gastric emptying: comparisons between milk and isocalorically adjusted clear fluids.

BACKGROUND: Although current preoperative fasting guidelines apply restrictions to drinks containing milk because of delayed gastric emptying, the safe volume of milk that can be consumed up to 2 h before surgery on a theoretical basis has not yet been defined. We aimed to determine whether delayed gastric emptying depended mainly on the total amount of calories irrespective of compositional differences between milk and clear fluids. METHODS: We prepared five beverages with a uniform volume (500 ml) and step-wise increments in calories (0, 220, and 330 kcal), comprised mainly of non-human milk, pulpless orange juice, water, and gum syrup. The gastric emptying rate of each beverage was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by eight healthy fasting volunteers. RESULTS: The emptying rates of 500 ml of orange juice and 330 ml of non-human milk with 170 ml of water (both were 220 kcal) from the stomach were similar. Furthermore, 450 ml of orange juice with 50 ml of gum syrup and 500 ml of non-human milk (both were 330 kcal) left the stomach at similar rates. The 220 kcal beverages emptied faster than the 330 kcal beverages. CONCLUSIONS: There were no significant differences in liquid gastric emptying after drinking equal volumes of either orange juice or milk as long as both had the same amount of calories. Liquid gastric emptying depends chiefly on the total caloric content. CLINICAL TRIAL REGISTRATION: UMIN000012537.

Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells.

BACKGROUND: Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels and clinical severity of atopic patients. However, the precise mechanism has not been fully elucidated. We investigated the role of Phf11 in class switch recombination (CSR) to IgE by activated B cells. METHODS: We generated Phf11 transgenic (Lckd-Phf11-Tg) mice that express the exogenous murine Phf11 in lymphocytes under the control of distal Lck promoter. We examined IL-4-induced CSR to IgE in activated Lckd-Phf11-Tg B cells in vitro. We analyzed production of ovalbumin (OVA)-specific IgE and nose-scratching symptoms in Lckd-Phf11-Tg mice using an OVA-induced allergic rhinitis model. RESULTS: The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (GLT) γ1 and GLT ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT γ1 and GLT ε promoters through permissive histone modifications and binding of NF-κB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT ε promoter with increased binding of NF-κB. Silencing of the endogenous Phf11 reduced the frequency of CSR to IgE and GLT ε expression, but not to IgG1 or GLT γ1 expression, in activated B cells. In an allergic rhinitis model, Lckd-Phf11-Tg mice showed a significant increase in the production of OVA-specific IgE and the frequency of nose scratching. CONCLUSION: Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of GLT ε promoter and contributes to the exacerbation of allergic responses. These findings provide a novel therapeutic target for allergic diseases.

MicroRNAs miR-629-3p, miR-1202 and miR-1225-5p as potential diagnostic and surgery outcome biomarkers for mesial temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is a symptomatic epilepsy syndrome clinically characterized by high prevalence, pharmacoresistance, good surgical prognosis and hippocampal sclerosis (HS); however, no singular criteria can be considered sufficient for the MTLE-HS diagnosis. MicroRNAs (miRNAs) are small non-coding molecules that act as important gene-expression regulators at post-transcriptional level. Evidences on the involvement of miRNAs in epilepsy pathogenesis as well as their potential to be employed as biomarkers claim for investigations on miRNAs' applicability as epilepsy diagnosis and prognosis biomarkers. Consequently, the present study aimed to evaluate the applicability of three specific miRNAs as biomarkers of diagnosis and surgical outcomes in adult patients with MTLE-HS. METHOD: Hippocampus, amygdala and blood samples from 20 patients with MTLE-HS were analyzed, 10 with favorable surgical prognosis (Engel I) and 10 with unfavorable surgical prognosis (Engel III-IV). For the control groups, hippocampus and amygdala from necropsy and blood samples from healthy individuals were adopted. The miRNAs expression analysis was performed using Real-Time Quantitative Polymerase Chain Reaction for miRNAs highlighted from microarray as being involved in GABAergic neurotransmission. RESULTS: The miRNAs miR-629-3p, miR-1202 and miR-1225-5p were found to be hyper-expressed in MTLE-HS patients' blood. CONCLUSIONS: Our data suggest the existence of three circulating miRNAs (miR-629-3p, miR-1202 and miR-1225-5p) that could possibly act as additional tools in the set of factors that contribute to MTLE-HS diagnose.

Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation.

BACKGROUND: There is synteny in the CC-type chemokine gene clusters between humans (CCL2/MCP-1, CCL7MCP-3, CCL11/eotaxin, CCL8/MCP-2, CCL13/MCP-4, and CCL1/I-309) and mice (CCL2, CCL7, CCL11, CCL12/MCP-5, CCL8, and CCL1). OBJECTIVE: As many putative Bcl6/STAT-binding sequences are observed in the clusters, we examined the roles of a transcriptional repressor Bcl6 and the regional histone modification in the expression of these chemokine genes in pulmonary epithelium. METHODS: We generated transgenic (Tg) mice carrying the Bcl6 or the dominant-negative (DN)-Bcl6 gene under the control of the surfactant protein C (SPC) promoter that induces the exogenous gene expression in the distal lung epithelium. For in vitro studies, A549, alveolar type II-like epithelial cell line transfected with the SPC-DN-Bcl6 gene were stimulated with IL-4+TNF-α, and Bcl6 or STAT6 binding to and histone modification of the cluster in the transfectants were analysed by chromatin immunoprecipitation assays. Tg mice sensitized with ovalbumin (OVA) were challenged with OVA inhalation. The amounts of mRNAs in each sample were analysed by quantitative RT-PCR. RESULTS: The amount of Bcl6 bound to the cluster decreased in A549 cells stimulated with IL-4 and TNF-α, whereas STAT6 binding increased in association with regional histone H3-K9/14 acetylation and H3-K4 methylation. The expression of all chemokine genes in the gene cluster was augmented in activated A549 cells transfected with the DN-Bcl6 gene. We also induced allergic airway inflammation in Tg mice. Expression of the chemokine genes and infiltrated cell numbers in the lungs of these Tg mice with allergic airway inflammation were inversely correlated with the amount of Bcl6 in the lungs. CONCLUSION AND CLINICAL RELEVANCE: Expression of the pulmonary epithelium-derived CC-type chemokine genes in the cluster is orchestrated by the conserved machinery related to Bcl6. Thus, Bcl6 in pulmonary epithelium may be a critical regulator for pathogenesis of various pulmonary inflammatory diseases.

The 3MTM CavilonTM barrier prevents erasure of surgical skin markings with removal of povidone iodine adhesive draping.

The 3M Cavilon barrier is a no-sting film which acts as a physical barrier to protect the skin from friction and contamination.The 3M Cavilon barrier prevents erasure of surgical skin markings with removal of povidone iodine adhesive draping.

Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis.

A novel subset of T cells characterized by the expression of an invariant T cell antigen receptor (TCR) encoded by V alpha 24J alpha Q gene segments was investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction analysis demonstrated that the V alpha 24 TCR repertoire was selectively used in CD4-CD8- double-negative T cells both in patients and in healthy individuals, while almost all families of TCR V alpha were expressed in single-positive T cell fractions. The V alpha 24+ double-negative T cells were increased by approximately fivefold in patients. However, sequence analysis clearly showed significant differences in the V alpha 24 TCR repertoire dominating in patients and healthy donors. In healthy individuals, the invariant V alpha 24J alpha Q was expanded and comprised 20-50% of the total TCR-alpha, while their selective reduction was observed in SSc patients who also showed expansion of invariant V alpha 24 TCR other than V alpha 24J alpha Q. Analogous to murine invariant V alpha 14J alpha 281 TCR, these results suggest that T cells with invariant V alpha 24J alpha Q TCR would function as regulatory T cells, whereas T cells bearing other invariant V alpha 24 TCR in SSc patients could be autoaggressive T cells in nature.

Prolonged carbon dioxide insufflation under general anesthesia for endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Carbon dioxide (CO (2)) insufflation for endoscopy has been reported to provide superior recovery and is expected to reduce the risk of serious complications, including air embolism and tension pneumothorax, whereas general anesthesia offers some advantages not found under intravenous sedation. Little is known about the effect of prolonged CO (2) insufflation into gastrointestinal tracts on arterial CO (2) tension (PaCO (2)). Here we introduce the use of general anesthesia with CO (2) insufflation for esophagogastroduodenal endoscopic submucosal dissection (ESD). PATIENTS AND METHODS: A prospective observational study was conducted in a university-affiliated hospital. A total of 100 patients were scheduled for esophagogastroduodenal ESD under general anesthesia with CO (2) insufflation, using standardized anesthesia techniques and unchanged ventilatory settings. Arterial blood gas analyses were repeated at predetermined time intervals. RESULTS: Of the initial 100 participants, 94 patients undergoing ESD and four patients undergoing endoscopic mucosal resection completed the study. The median procedure time was 122 minutes (range 29 - 309 minutes). The median baseline PaCO (2) of 28 mmHg increased to a median peak PaCO (2) of 39 mmHg ( P < 0.001), with marked inter-individual variability in the time courses of changes in PaCO (2). The correlation coefficient of PaCO (2) with the procedure time was low (r = 0.194; n = 577, P < 0.0001). FEV (1.0) % (forced expiratory volume in 1 second/forced vital capacity) of < 70 % and esophagoscopy vs. gastroduodenoscopy were relative enhancement factors of PaCO (2). CONCLUSION: Increases of PaCO (2) during esophagogastroduodenal ESD under general anesthesia with CO (2) insufflation remained within acceptable or readily controllable ranges, and are little enhanced by prolongation of the procedure. Esophagogastroduodenal ESD can be performed safely and feasibly with this procedure.

[Spontaneous rupture of the thoracic aorta diagnosed rupture of the acute stanford type B aortic dissection at preoperation; report of a case].

BACKGROUND: Spontaneous rupture of the thoracic aorta is extremely rare. It is very difficult to diagnose it preoperatively. CASE: A 71-year-old woman suffered the sudden onset of severe chest and back pain and was admitted to our hospital. Enhanced computed tomography (CT) showed mediastinal hematoma and apparent aortic dissection in the aortic arch and descending aorta. We diagnosed the rupture of Stanford type B dissection and performed an emergency operation. 20 mm tear was found in the intima of lesser curvature of aortic arch and 5 mm perforation was found in the adventitia of this part. There was no flap or false lumen suggestive of a dissection nor was there aortic aneurysm. Total aortic arch replacement was performed. RESULT: The surgery was followed by an uneventful postoperative course. CONCLUSION: A case of spontaneous rupture of the thoracic aorta which was diagnosed the rupture of Stanford type B dissection preoperatively was successfully treated.

Control of homeostasis of CD8+ memory T cells by opposing cytokines.

Memory T cells maintain their numbers for long periods after antigen exposure. Here we show that CD8+ T cells of memory phenotype divide slowly in animals. This division requires interleukin-15 and is markedly increased by inhibition of interleukin-2 (IL-2). Therefore, the numbers of CD8+ memory T cells in animals are controlled by a balance between IL-15 and IL-2.

[Thoracic aortic dissection complicating autosomal dominant polycystic kidney disease; report of a case].

A 55-year-old man underwent aortic valve replacement for aortic valve insufficiency 12 years ago. At that time, autosomal dominant polycystic kidney disease was diagnosed. Subsequently, renal failure developed gradually. In August 2007, the patient was admitted to the hospital because of dull back pain. Computed tomography (CT) revealed aortic dissection extending from the ascending aorta to the bifurcation of the iliac artery (Stanford type A). However, the patient had no severe symptoms associated with aortic dissection On the basis of the results of CT and blood testing, chronic aortic dissection was diagnosed. Because the patient also had chronic renal failure we decided to perform elective surgery. In January 2008, ascending aortic and aortic arch replacement with a distal elephant trunk was performed. After surgery, we were concerned about the risk of renal failure. However, the patient recovered uneventfully, without requiring dialysis. Aortic dissection can occur as a complication in patients with autosomal dominant polycystic kidney. Strict control of blood pressure is therefore essential in such patients.

Expression of pulmonary vasoactive factors after sevoflurane anaesthesia in rats: a quantitative real-time polymerase chain reaction study.

BACKGROUND: Sevoflurane is a fluorinated volatile anaesthetic agent that lowers arterial pressure, in part by vasodilation. We previously showed, in rat lungs, that sevoflurane affected the expression of endothelin-1 (ET-1), a potent vasoconstrictor peptide. Therefore, we hypothesized that the vasodilation induced by sevoflurane involved vasodilatory and vasoconstrictor components. METHODS: Rats were anaesthetized with sevoflurane 4% for 0, 2, and 6 h (n=9 each group) before death. In addition, a further group (n=9) were anaesthetized for 6 h then awoken for 2 h before death (n=9). We measured expression of mRNA encoding ET-1, nitric oxide synthase-1, 2, 3 (NOS1, 2, 3), haeme oxygenase-1, 2 (HO-1, 2), adrenomedullin (ADM), calcitonin gene-related peptide, vasoactive intestinal peptide, and prostacyclin synthase in whole lung using real-time reverse transcriptase-polymerase chain reaction. RESULTS: Expressions of ET-1 and ADM were significantly increased by inhalation of sevoflurane for 2 and 6 h (P<0.05). Expression of NOS3 was significantly increased at 6 h (P<0.05). After awaking from anaesthesia, the expressions of NOS3, ET-1, and ADM returned to baseline levels. CONCLUSIONS: Sevoflurane increased the expressions of ET-1, NOS3, and ADM. Our results suggest that the increased expressions of NOS3 and ADM may counteract that of ET-1 and so regulate pulmonary circulation under sevoflurane anaesthesia.

Deletion of TLS polymerases promotes homologous recombination in Arabidopsis.

Unrepaired DNA damage hinders the maintenance of genome integrity because it blocks the catalytic activity of replicase. The stalled replication fork can be processed through either translesion synthesis (TLS) with specific polymerases, or replication using the undamaged template. To investigate how TLS activities are regulated and how the stalled replication fork is processed in plants, reversion frequencies and homologous recombination (HR) frequencies were analyzed using GUS-based substrates. The HR frequencies in plants deficient in DNA polymerase ζ (Pol ζ) or Rev1 were higher than that in wildtype plants under normal conditions, and were significantly increased by ultraviolet light irradiation. Heat shock protein (HSP) 90 is known to be involved in various stress responses. To examine the role of HSP90 in the regulation of damage tolerance, we analyzed reversion frequencies and HR frequencies in plants grown in the presence of a HSP inhibitor, geldanamycin (GDA). Reversion frequency was lower in GDA-treated plants than in mock-treated plants. Though the HR frequency was higher in GDA-treated wildtype plants than in mock-treated plants, no significant difference was detected in Rev1-deficient plants. In yeast, TLS polymerases interacted with each other or with a replication clump component, proliferating cell nuclear antigen (PCNA). HSP90 interacted with REV1 or REV7 in Nicotiana benthamiana cells. These results suggest that HSP90 interacts with TLS polymerase(s), which promotes error-prone TLS in plants.

Di-(2-ethylhexyl) phthalate suppresses IL-12p40 production by GM-CSF-dependent macrophages via the PPARα/TNFAIP3/TRAF6 axis after lipopolysaccharide stimulation.

Activation of peroxisome proliferator-activated receptor α (PPARα) by di-(2-ethylhexyl) phthalate (DEHP) has an anti-inflammatory effect. This study investigated the potential combined influence of PPARα, tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), and tumor necrosis factor receptor-associated factor 6 (TRAF6) on interleukin (IL)-12p40 production by macrophages exposed to DEHP and stimulated with lipopolysaccharide (LPS). LPS upregulated IL-12p40 expression by granulocyte-macrophage colony-stimulating factor-dependent macrophages (on day 9 of culture), whereas adding DEHP to cultures significantly attenuated the response of IL-12p40 to LPS stimulation. PPARα protein was also reduced by DEHP. Interestingly, transfection of macrophages with small interfering RNA (siRNA) duplexes for PPARα, TNFAIP3/A20, or dual oxidase 2 restored the response of IL-12p40 protein to LPS stimulation in the presence of DEHP. siRNAs for various protein kinase Cs (PKCs) (α, ß, γ, or δ) also restored IL-12p40 production by macrophages exposed to LPS and DEHP. While LPS upregulated both IL-12p40 and TNFAIP3/A20 production, adding DEHP to cultures dramatically reduced IL-12p40 and TNFAIP3/A20 levels. Silencing of PKCα reduced TNFAIP3/A20 production, whereas PKCγ siRNA (but not PKCß or δ siRNA) significantly increased TNFAIP3/A20. TRAF6 was also attenuated by macrophages with DEHP. The PPARα/TNFAIP3/TRAF6 axis may have an important role in the mechanism through which DEHP reduces IL-12p40 production by LPS-stimulated macrophages.

Influence of Adhesive Type and Placement Technique on Postoperative Sensitivity in Posterior Composite Restorations.

PURPOSE: This double blind, randomized clinical trial compared the postoperative sensitivity of the placement technique (incremental and bulk fill) in posterior composite resin restorations bonded with two different adhesive strategies (self-etch and etch-and-rinse). METHODS: Posterior dental cavities of 72 participants (n=236), with a cavity depth of at least 3 mm, were randomly divided into four groups. The restorations were bonded using either the etch-and-rinse Tetric N-Bond (Ivoclar Vivadent) or the self-etch Tetric N-Bond SE (Ivoclar Vivadent). The composite resin Tetric N-Ceram Bulk Fill (Ivoclar Vivadent) was placed either incrementally or using the bulk-fill technique. Two experienced and calibrated examiners evaluated the restorations using World Dental Federation criteria after one week of clinical service. Spontaneous postoperative sensitivity was assessed using a 0-4 numerical rating scale and a 0-10 and 0-100 visual analog scale up to 48 h after the restorative procedure and after one week. RESULTS: The risk (p>0.49) and intensity of spontaneous postoperative sensitivity (p>0.38) was not affected by the adhesive strategy or the filling technique. The overall risk of postoperative sensitivity was 20.3% (95% confidence interval 15.7-25.9) and typically occurred within 48 hours after the restorative procedure. CONCLUSIONS: The overall risk of immediate postoperative sensitivity was 20.3% and was not affected by either the adhesive strategy (etch-and-rinse/self-etch) or the filling technique (incremental/ bulk).