Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneous Functional Effects of Concomitant B Cell Receptor and TLR Stimulation in Chronic Lymphocytic Leukemia with Mutated versus Unmutated Ig Genes

We recently reported that chronic lymphocytic leukemia (CLL) subgroups with distinct clonotypic BCRs present discrete patterns of TLR expression, function, and/or tolerance. In this study, to explore whether specific types of BCR/TLR collaboration exist in CLL, we studied the effect of single versus concomitant BCR and/or TLR stimulation on CLL cells from mutated (M-CLL) and unmutated CLL (U-CLL) cases. We stimulated negatively isolated CLL cells by using anti-IgM, imiquimod, and CpG oligodeoxynucleotide for BCR, TLR7, and TLR9, respectively, alone or in combination for different time points. After in vitro culture in the absence of stimulation, differences in p-ERK were identified at any time point, with higher p-ERK levels in U-CLL versus M-CLL. Pronounced p-ERK induction was seen by single stimulation in U-CLL, whereas BCR/TLR synergism was required in M-CLL, in which the effect was overall limited in scale. An opposite pattern was observed regarding induction of apoptosis, as studied by Western blotting for the cleaved fragment of poly(ADP-ribose) polymerase, and the active isoform of caspase-8, with M-CLL responding even to single stimulation, contrasting with U-CLL that showed minimal response. Our findings suggest that concomitant engagement of BCR and TLR leads to differential responses in CLL depending on the mutational status of the BCR. Differential intensity and duration of responses in M-CLL versus U-CLL indicates that the differences in signal transduction between the two subgroups may be primarily quantitative rather than qualitative.
Identiﬁcation and Characterization of an Autolysin-Encoding Gene of Streptococcus mutans

We identiﬁed a gene ( atlA ) encoding autolytic activity from Streptococcus mutans Xc. The AtlA protein predicted to be encoded by atlA is composed of 979 amino acids with a molecular weight of 107,279 and has a conserved (cid:1) -1,4- N -acetylmuramidase (lysozyme) domain in the C-terminal portion. Sodium dodecyl sulfate extracts of strain Xc showed two major bacteriolytic bands with molecular masses of 107 and 79 kDa, both of which were absent from a mutant with inactivated atlA . Western blot analysis revealed that the 79-kDa band was derived from the 107-kDa peptide by cleavage of its N-terminal portion. The inactivation of atlA resulted in a marked decrease in autolysis and the formation of very long chains of cells compared to the case for the parent strain. Although both the parent and mutant strains formed bioﬁlms in the presence of sucrose, the bioﬁlms formed by the mutant had a sponge-like architecture with large gaps and contained 30% less biomass than those formed by the parent strain. Furthermore, strain Xc formed glucose-dependent, loose bioﬁlms in the absence of sucrose, but the mutant lost this ability. These results suggest that AtlA may play an important role in bioﬁlm formation by S. mutans . The antibody produced against the C-terminal peptide containing the (cid:1) -1,4- N -acetylmuramidase domain drastically inhibited the autolytic activity of strain Xc. This inhibition was speciﬁc among the oral streptococci to S. mutans . These results indicate that the catalytic domain of AtlA is located at the C terminus, suggesting that further characterization of this domain may provide a means to control cariogenic dental plaque formation.
Perceptions of the Religion-Health Connection Among African American Church Members

In this qualitative study, the authors examine perceptions of the religiosity-health connection among African American church members. They conducted 33 interviews with members of predominately African American churches. The clergy and members from each congregation completed semistructured interviews. Participants described the religiosity-health connection in their own words and talked about whether and how their religious beliefs and practices affect their health. The authors derived an open coding scheme from the data using an inductive process. Themes that emerged spontaneously and consistently included but were not limited to spiritual health, mental health’s effects on physical health, importance of the church family, giving problems up to God, and the body as a temple of God. These religion-health themes might hold promise for integration into church-based health promotion interventions for this population.
Childhood nutrition and poverty

One in three children in Britain lives in poverty (households whose income was less than 50 % average earnings). Low income is associated with poor nutrition at all stages of life, from lower rates of breast-feeding to higher intakes of saturated fatty acids and lower intakes of antioxidant nutrients. Moreover, there is increasing evidence that poor nutrition in childhood is associated with both short-term and long-term adverse consequences such as poorer immune status, higher caries rates and poorer cognitive function and learning ability. These problems arise primarily because parents do not have enough money to spend on food, not because money is being spent unwisely. Policy options to improve the dietary health of poor children include: giving more money to the parents by increasing Income Support (social security) payments, providing food stamps or vouchers, and using food budget standards to inform the levels of income needed to purchase an adequate diet; feeding children directly at school (not only at lunchtime but also at breakfast or homework clubs), by providing free fruit at school, and by increasing entitlement to free food amongst children living in households with low incomes; improving access to a healthy and affordable diet by first identifying ‘food deserts’ and then considering with retailers and local planners how best to provide food in an economical and sustainable way. The value of using food budget standards is illustrated with data relating expenditure on food to growth in children from ‘at-risk’ families (on low income, overcrowded, headed by a lone parent or with four or more children under 16 years of age) living in a poor area in London. Lower levels of expenditure are strongly associated with poorer growth and health, independent of factors such as birth weight, mother’s height, or risk score. The present paper provides evidence that supports the need to review Government legislation in light of nutrition-related inequalities in the health of children.
Bedwetting, behaviour and self-esteem: a review of the literature.

AIM The aim of this review was to examine the empirical evidence on the impact of bedwetting and its treatment on a child's self-esteem and behaviour. INCLUSION CRITERIA The inclusion criteria for this review were empirical studies conducted on children, aged 5-16 years old, with primary nocturnal enuresis using measures of self-esteem or behaviour. Studies utilizing psychological measurement scales completed by children were the main focus although those that used scales completed by parents were also included. SEARCH STRATEGIES The electronic databases from 1981 to 1999 were searched, and hand searching of the literature dating back to 1973 was conducted using the reference lists of key papers. RESEARCH FINDINGS Fifteen empirical studies matched the inclusion criteria. There was only one randomised-controlled trial and the rest of the studies were cohort, case-control or cross-sectional design. Evidence of sample bias predominantly due to the use hospital-based and/or 'volunteer' subjects was found in five studies. A further five studies used birth cohort data, which excludes important variables such as the impact of treatment. Four studies used single parent-reported measures, which may under or over-estimate the problem. No large cohort studies were available which compare the self-esteem of bedwetting children with matched controls. The most interesting line of enquiry is pursued by studies looking at whether self-esteem improves with successful treatment. However, the use of self-selected subject groups does not make the current evidence convincing and more work is required to determine outcomes for all children. There is empirical evidence for increased behavioural problems in bedwetting children. Studies conducted on younger children report less behavioural problems with more reported in studies conducted on older children with complex wetting disorders. This may point towards wetting being the primary problem, but more work is needed, as causation in any direction is difficult to ascertain from the literature.
A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023.

PURPOSE This phase II trial was performed to assess the feasibility, toxicity, and efficacy of dose-intense accelerated radiation therapy using weekly fractionated stereotactic radiotherapy (FSRT) boost for patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS Patients with histologically confirmed GBM with postoperative enhancing tumor plus tumor cavity diameter <60 mm were enrolled. A 50-Gy dose of standard radiation therapy (RT) was given in daily 2-Gy fractions. In addition, patients received four FSRT treatments, once weekly, during Weeks 3 to 6. FSRT dosing of either 5 Gy or 7 Gy per fraction was given for a cumulative dose of 70 or 78 Gy in 29 (25 standard RT + 4 FSRT) treatments over 6 weeks. After the RT course, carmustine (BCNU) at 80 mg/m(2) was given for 3 days, every 8 weeks, for 6 cycles. RESULTS A total of 76 patients were analyzed. Toxicity included: 3 Grade 4 chemotherapy, 3 acute Grade 4 radiotherapy, and 1 Grade 3 late. The median survival time was 12.5 months. No survival difference is seen when compared with the RTOG historical database. Patients with gross total resection (41%) had a median survival time of 16.6 months vs. 12.0 months for historic controls with gross total resection (p = 0.14). CONCLUSION This first, multi-institutional FSRT boost trial for GBM was feasible and well tolerated. There is no significant survival benefit using this dose-intense RT regimen. Subset analysis revealed a trend toward improved outcome for GTR patients suggesting that patients with minimal disease burden may benefit from this form of accelerated RT.
Inhibited Insulin Signaling in Mouse Hepatocytes Is Associated with Increased Phosphatidic Acid but Not Diacylglycerol*

Background: The mechanism underlying the association of triacylglycerol storage and insulin resistance is unclear. Results: Increasing phosphatidic acid (PA) in primary hepatocytes via de novo synthesis or action of phospholipase D or diacylglycerol kinase-θ disrupts insulin signaling. Conclusion: PA derived from different sources inhibits insulin signaling. Significance: Increases in hepatocyte PA may mechanistically link lipid storage and insulin action. Although an elevated triacylglycerol content in non-adipose tissues is often associated with insulin resistance, the mechanistic relationship remains unclear. The data support roles for intermediates in the glycerol-3-phosphate pathway of triacylglycerol synthesis: diacylglycerol (DAG), which may cause insulin resistance in liver by activating PKCϵ, and phosphatidic acid (PA), which inhibits insulin action in hepatocytes by disrupting the assembly of mTOR and rictor. To determine whether increases in DAG and PA impair insulin signaling when produced by pathways other than that of de novo synthesis, we examined primary mouse hepatocytes after enzymatically manipulating the cellular content of DAG or PA. Overexpressing phospholipase D1 or phospholipase D2 inhibited insulin signaling and was accompanied by an elevated cellular content of total PA, without a change in total DAG. Overexpression of diacylglycerol kinase-θ inhibited insulin signaling and was accompanied by an elevated cellular content of total PA and a decreased cellular content of total DAG. Overexpressing glycerol-3-phosphate acyltransferase-1 or -4 inhibited insulin signaling and increased the cellular content of both PA and DAG. Insulin signaling impairment caused by overexpression of phospholipase D1/D2 or diacylglycerol kinase-θ was always accompanied by disassociation of mTOR/rictor and reduction of mTORC2 kinase activity. However, although the protein ratio of membrane to cytosolic PKCϵ increased, PKC activity itself was unaltered. These data suggest that PA, but not DAG, is associated with impaired insulin action in mouse hepatocytes.
Peritoneal Fibrosis Intervention

Peritoneal fibrosis (PF) is invariably observed in patients undergoing long-term peritoneal dialysis (PD). The condition is thought to occur in response to a variety of insults, including bioincompatible dialysates (acidic solution, high glucose, glucose degradation products, or a combination), peritonitis, uremia, and chronic inflammation. Recently, the pathophysiologic mechanisms that contribute to the fibrosing process have been intensively studied. Transforming growth factor-β has been shown to be a key mediator of PF. Loss of the mesothelial cell layer has been identified in several studies and shown to correlate with submesothelial thickening and vasculopathy. An association has also been identified between increased submesothelial thickness in the peritoneal membrane and increased solute transport, suggesting a relationship between PF and loss of ultrafiltration capacity. Thus, to maintain long-term PD and improve quality of life for patients, it is important to develop interventions for prevention and treatment of PF. Several strategies for peritoneal fibrosis intervention have been reported, including developing biocompatible dialysate, targeting mediators responsible for inflammation and fibrosis, and reconstituting the peritoneum using mesothelial or bone marrow–derived cells. Recent experimental trials in animal models and clinical studies are presented in this review.
[Diastolic dysfunction types in the prediction of viable myocardium functional recovery].

BACKGROUND/AIM It is well known that patients with coronary artery disease and viable tissue as a guarantee of contractile recovery (CR), despite of decreasing ejection fraction (EF) and systolic dysfunction, could have benefit from surgical revascularization. Therefore, relationship between diastolic filling type and early postoperative recovery and complications need to be established. The aim of this study was to investigate the relation between different left ventricular (LV) diastolic filling types and CR in patients after surgical revascularization with differently preserved systolic function. METHODS We investigated 60 patients. All of them had CR estimated by stress echocardiography regardless the extent of recovery of the heart systolic function. Echocardiographic evidence of diastolic dysfunction was estimated by Doppler examination of transmitral diastolic flow. According to the derived different diastolic filling types the patients were divided into three groups: I--patients with disorder of LV relaxation, II--with pseudovascularisation, and III--with restrictive filling type, and according to the value of systolic function into two subgroups: (1) relatively recovered systolic function--EF > 40% and (2) pronounced LV dysfunction--EF < 40%. Echocardiographic evaluation was performed before and two week after surgical revascularization. In the preoperative period the medication therapy was optimized. We estimated CR by echocardiografic pare meters but also by detection of cardiovascular events. RESULTS After CABG the mean value of WMISI LV tended to decrease in any groups: in the group I (n = 12) from 1.64 +/- 0.22 to 1.34 +/- 0.22; in the group II (n = 22) from 1.85 +/- 0.16 to 1.53 +/- 0.42, and in the group III (n=26) from 1.92 +/- 0.29 to 1.81 +/- 0.52. The lowest improvement of systolic function according to EF value expressed by the number of patients was found in the group of patients with restrictive LV filling type (12; 53.8%) as contrasting to the group with pseudonormalisation (15; 78.9%). In the group of patients with restrictive diastolic filling type also was recorded the highest number of lethal outcomes (6; 23.1%), as well as cardiovascular complications (10; 38.5%). CONCLUSIONS Restrictive LV diastolic filling type was the marker of poor prognosis in the patients with clinical heart failure undergoing surgical revascularization. The patients with heart failure and preserved systolic function were associated with similar prognosis.
Reduction of pain at venous cannulation in children with a eu tec tic mixture of lidocaine and prilocaine (EMLA® cream): comparison with placebo cream and no local premedication

The local analgesic efficacy of a cream formulation of lidocaine and prilocaine (EMLA®) in reducing pain at venous cannulation was investigated in children scheduled for elective surgery. Forty children participated in a double‐blind, randomized comparison between EMLA and inactive placebo cream. Another group of 18 children without any local treatment was studied as an additional control material. Subjective pain scores, expressed with a visual analogue scale, were significantly lower in the EMLA group compared with both the group treated with placebo cream (P<0.001) and the open control group (no cream; P<0.01). Local pallor and slight oedema were the only side‐effects, registered in both cream‐treated groups. A preliminary study was also carried out with 10 children (five with EMLA and five without) in order to determine whether catecholamine and vasopressin levels in venous blood are affected by the stress and anxiety associated with venepuncture in children premedicated with oral flunitrazepam. No significant hormone responses were, however, detected. The lidocaine concentrations measured in venous blood taken from the application site of EMLA cream were low, and there were no measurable levels of lidocaine in simultaneous blood samples from the opposite extremity. In our opinion EMLA cream is safe and alleviates effectively the pain associated with venepuncture, and thus deserves a place in the routine premedication of children.
Phonological awareness and print knowledge of preschool children with cochlear implants.

PURPOSE To determine whether preschool-age children with cochlear implants have age-appropriate phonological awareness and print knowledge and to examine the relationships of these skills with related speech and language abilities. METHOD The sample comprised 24 children with cochlear implants (CIs) and 23 peers with normal hearing (NH), ages 36 to 60 months. Children's print knowledge, phonological awareness, language, speech production, and speech perception abilities were assessed. RESULTS For phonological awareness, the CI group's mean score fell within one standard deviation of the Test of Preschool Early Literacy's (Lonigan, Wagner, Torgesen, & Rashotte, 2007) normative sample mean but was more than one standard deviation below the NH group mean. The CI group's performance did not differ significantly from that of the NH group for print knowledge. For the CI group, phonological awareness and print knowledge were significantly correlated with language, speech production, and speech perception. Together these predictor variables accounted for 34% of variance in the CI group's phonological awareness but no significant variance in their print knowledge. CONCLUSIONS Children with CIs have the potential to develop age-appropriate early literacy skills by preschool age but are likely to lag behind their NH peers in phonological awareness. Intervention programs serving these children should target these skills with instruction and by facilitating speech and language development.
Idiopathic Chronic Pancreatitis With Periductal Lymphoplasmacytic Infiltration: Clinicopathologic Features of 35 Cases

To clarify clinicopathologic features of idiopathic chronic pancreatitis with lymphoplasmacytic infiltration, we carried out a study of 35 cases. There were two histologic groups, which we have designated lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric chronic pancreatitis. Lymphoplasmacytic sclerosing pancreatitis (22 cases) was a fibrosing process with diffuse lymphoplasmacytic infiltrates involving pancreatic lobules and ducts, adipose tissue, blood vessels, and common bile duct. Obliterative phlebitis was found in every case except for one. The histologic features were similar to other idiopathic fibrosclerosing disorders, and one patient also had retroperitoneal fibrosis. Affected patients tended to be elderly men. Idiopathic duct-centric chronic pancreatitis (13 cases) was characterized by inflammatory infiltrates (including neutrophils) that were denser in the lobules than in interlobular fibrotic areas. Neutrophils were also prominent in the ducts, and destruction of the duct epithelium was commonly seen. Patient ages were more broadly distributed than in lymphoplasmacytic sclerosing pancreatitis. Two patients had inflammatory bowel disease. We conclude that idiopathic chronic pancreatitis with lymphoplasmacytic infiltration, sometimes called autoimmune pancreatitis, consists of at least two different processes. One of these, lymphoplasmacytic sclerosing pancreatitis, is a histologically unique lesion and could be a pancreatic manifestation of idiopathic fibrosclerosing disorders.
Vitamin D target proteins: Function and regulation

Recent findings have indicated that calbindin‐D28k, the first known target of vitamin D action, is present in osteoblasts and protects against TNF and glucocorticoid induced apoptosis of osteoblastic cells. Cytokine mediated destruction of pancreatic β cells, a cause of insulin dependent diabetes, is also inhibited by calbindin‐D28k. In calbindin‐D28k transfected pancreatic β cells free radical formation by cytokines is inhibited by calbindin. Thus, besides its role as a facilitator of calcium diffusion, calbindin has a major role in protecting against cellular degeneration in different cell types. Besides calbindin, the other known pronounced effect of 1,25(OH)2D3 in intestine and kidney is increased synthesis of 25(OH)D3 24‐hydroxylase (24(OH)ase) which is involved in the catabolism of 1,25(OH)2D3. We have noted that CCAAT enhancer binding protein β (C/EBPβ) is induced by 1,25(OH)2D3 in kidney and osteoblastic cells and can enhance the transcriptional response of 24(OH)ase to 1,25(OH)2D3. These studies establish C/EBPβ as a novel 1,25(OH)2D3 target gene and indicate a role for C/EBPβ in 24(OH)ase transcription. These studies extend our previous studies related to factors that affect vitamin D receptor (VDR) mediated 24(OH)ase transcription (YY1, TFIIB, CBP) and the effect of signaling pathways on 24(OH)ase transcription and cofactor recruitment. J. Cell. Biochem. 88: 238–244, 2003. © 2002 Wiley‐Liss, Inc.