Miracle-dz/UniFAR-FTUs huggingface dataset:
Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading

The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real‐time reverse transcription‐quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase‐2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon.
Bacteremia, Acute Physiology and Chronic Health Evaluation II and Modified End Stage Liver Disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure

Objectives:To determine what physiological and biochemical factors predict development of bacteremia in nontransplanted patients with acute on chronic liver failure and, on diagnosis of bacteremia, what is the natural history of bacteremic patients versus control subjects (acute on chronic liver failure). Interventions:None. Design:Retrospective analysis of data collected prospectively and entered into a dedicated physiology database. Setting:Specialist liver intensive therapy unit. Patients:Critically ill non-transplanted patients with acute on chronic liver failure admitted between January 2003 and July 2005. Measurements and Main Results:One hundred eighty-four patients were defined with acute on chronic liver failure; 67 (36%) had bacteremia. One hundred seventeen (64%) patients did not (acute on chronic liver failure). Fifty-eight percent of isolates were Gram-negative organisms, 36% were Gram-positives, and 6% fungemia. Median time to first bacteremia was 8 days (range, 3–12 days). On admission (univariate), bacteremic patients had significantly higher Modified End Stage Liver Disease scores (27 vs. 24, p = .037), Acute Physiology and Chronic Health Evaluation II scores (23 vs. 21, p = .049), and greater degrees of encephalopathy (Glasgow Coma Scale score 10 vs. 12, p = .001). During their liver intensive therapy unit course, bacteremic patients had significantly greater requirements for renal replacement therapy (64% vs. 49%, p = .043), mechanical ventilation (88% vs. 68%, p = .002), and a longer median liver intensive therapy unit stay (16 vs. 5 days, p < .001). Survival to hospital discharge was worse in the bacteremic group (25% vs. 56%, p < .001). Multivariate analysis (logistic regression) was performed separately modeling with Acute Physiology and Chronic Health Evaluation II and Modified End Stage Liver Disease. In the first model, Acute Physiology and Chronic Health Evaluation II (odds ratio 1.24) and bacteremia (2.24) were independent predictors of mortality. In the later model, Modified End Stage Liver Disease (odds ratio, 1.06), requirement for renal replacement therapy (3.08), Glasgow Coma Scale (0.72), and bacteremia (2.30) were significant. Both models performed similarly (Modified End Stage Liver Disease area under the receiver operating characteristic curve, 0.864; Acute Physiology and Chronic Health Evaluation II, 0.862). Conclusions:In nontransplanted patients with acute on chronic liver failure, bacteremia was associated with increased severity of illness on admission, greater requirements for organ support, and independently adversely impacted on survival. Higher Acute Physiology and Chronic Health Evaluation II and Modified End Stage Liver Disease scores were also independently predictive of mortality.
Chemoattractant‐induced activation of vaculoar H+ pumps and of an H+‐selective conductance in neutrophils

Upon binding to their receptors on the surface of neutrophils, chemotactic peptides elicit a burst of metabolic activity. The excess acid generated by this burst must be rapidly extruded in order to maintain intracellular pH and preserve normal microbicidal responses. Recently, H+‐pumping vacuolar‐type ATPases (V‐pumps) and a H+‐selective conductance were described in the membrane of neutrophils. However, these systems are virtually quiescent in resting cells. In this report, we analyzed whether the V‐pumps and the conductance become active and contribute to pH regulation following cell activation by chemoattractants. Formyl‐Met‐Leu‐Phe (fMLP) was found to stimulate V‐pumps, as assessed by the appearance of bafilomycin‐sensitive H+ extrusion. Concomitantly, the chemoattractant also activated the H+ conductance, detected as a voltage‐dependent and Zn2+‐sensitive net H+ efflux. In both cases, activation was prevented by treatment with competing antagonistic peptides or with pertussis toxin, implying mediation by a receptor copuled to a heterotrimeric G protein. The signalling pathways downstream of the G proteins were also investigated. Stimulation of neither th V‐pump nor the conductace required activation of protein kinase C. An elevation of cytosolic calcium ([Ca2+]i) comparable to that induced by fMLP did not suffice to trigger either transporter. Moreover activation of the conductance remained unaffected when the chemoattractant‐induced increase in [Ca2+]i was precluded. In contrast, stimulation of the V‐pump was substantially (∞50%) depressed when [Ca2+]i was prevented from rising. Tyrosine phosphorylation of several polypeptides accompanies stimulation by fMLP. Prevention of phosphotyrosine accumulation resulted in a pronounced inhibition of H+‐pumping and of the H+ conductance. Together, these data indicate that engagement of surface receptors by chemotactic peptides can lead to stimulation of two voltage‐sensitive pH regulatory pathways, a pump and a conductance, by a pathway that requires tyrosine phosphorylation. Both pathways are capable of sizable H+ extrusion, thereby contributing to pH regulation during the metabolic burst. © 1995 Wiley‐Liss Inc.
Detection and Characterization of Diarrheagenic Escherichia coli from Young Children in Hanoi, Vietnam

ABSTRACT Diarrhea continues to be one of the most common causes of morbidity and mortality among infants and children in developing countries. Escherichia coli is an emerging agent among pathogens that cause diarrhea. The development of a highly applicable technique for the detection of different categories of diarrheagenic E. coli is important. We have used multiplex PCR by combining eight primer pairs specific for enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), enterohemorrhagic E. coli, enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). This facilitates the identification of five different categories of diarrheagenic E. coli from stool samples in a single reaction simultaneously. The prevalences of diarrheagenic E. coli were 22.5 and 12% in the diarrhea group and the control group, respectively. Among 587 fecal samples from Vietnamese children under 5 years of age with diarrhea, this technique identified 132 diarrheagenic E. coli strains. This included 68 samples (11.6%) with EAEC, 12 samples (2.0%) with EIEC, 39 samples (6.6%) with EPEC, and 13 samples (2.2%) with ETEC. Among the 249 age-matched controls, 30 samples were positive for diarrheagenic E. coli. The distribution was 18 samples (7.2%) with EAEC, 11 samples (4.4%) with EPEC, and 1 sample (0.4%) with ETEC.
Evaluation of the X-linked high-grade myopia locus (MYP1) with cone dysfunction and color vision deficiencies.

PURPOSE X-linked high myopia with mild cone dysfunction and color vision defects has been mapped to chromosome Xq28 (MYP1 locus). CXorf2/TEX28 is a nested, intercalated gene within the red-green opsin cone pigment gene tandem array on Xq28. The authors investigated whether TEX28 gene alterations were associated with the Xq28-linked myopia phenotype. Genomic DNA from five pedigrees (with high myopia and either protanopia or deuteranopia) that mapped to Xq28 were screened for TEX28 copy number variations (CNVs) and sequence variants. METHODS To examine for CNVs, ultra-high resolution array-comparative genomic hybridization (array-CGH) assays were performed comparing the subject genomic DNA with control samples (two pairs from two pedigrees). Opsin or TEX28 gene-targeted quantitative real-time gene expression assays (comparative CT method) were performed to validate the array-CGH findings. All exons of TEX28, including intron/exon boundaries, were amplified and sequenced using standard techniques. RESULTS Array-CGH findings revealed predicted duplications in affected patient samples. Although only three copies of TEX28 were previously reported within the opsin array, quantitative real-time analysis of the TEX28 targeted assay of affected male or carrier female individuals in these pedigrees revealed either fewer (one) or more (four or five) copies than did related and control unaffected individuals. Sequence analysis of TEX28 did not reveal any variants associated with the disease status. CONCLUSIONS CNVs have been proposed to play a role in disease inheritance and susceptibility as they affect gene dosage. TEX28 gene CNVs appear to be associated with the MYP1 X-linked myopia phenotypes.
Perceptions of Teachers’ Communicative Style and Students’ Intrinsic and Extrinsic Motivation

This study considers how students’ perceptions of their teachers’ communicative style, particularly the extent to which teachers are perceived to support students’ autonomy and to provide useful feedback about students’ learning progress, are related to students’ extrinsic and intrinsic motivational orientations. It also examines the link between these variables and various language learning outcomes, including effort, anxiety, and language competence. Students registered in a summer French immersion course (N = 78) completed a questionnaire that was used to assess the constructs described above. Correlational analyses determined that stronger feelings of intrinsic motivation were related to positive language learning outcomes, including greater motivational intensity, greater self-evaluations of competence, and a reduction in anxiety. Moreover, perceptions of the teacher’s communicative style were related to intrinsic motivation, such that the more controlling and the less informative students perceived the teacher to be, the lower students’ intrinsic motivation was. The implications of perceptions of teacher communicative style for motivation and language learning outcomes are discussed.
A 60-Hz sinusoidal magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species

Purpose: To explore the effects of power frequency magnetic fields (MF) on cell growth in prostate cancer, DU145, PC3, and LNCaP cells were examined in vitro. Materials and methods: The cells were exposed to various intensities and durations of 60-Hz sinusoidal MF in combination with various serum concentrations in the media. To analyze MF effects on cell growth, cell counting, trypan blue exclusion assay, Western blot analysis, flow cytometry, enzyme-linked immunosorbent assay (ELISA), semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence microscopy, and spectrofluorometry were used. Results: MF exposure induced significant cell growth inhibition and apoptosis in an intensity- and time-dependent manner, in which cell cycle arrest, cleaved Caspase-3, and reactive oxygen species (ROS) increased. Pretreatment with a Caspase-3 inhibitor or antioxidant, N-acetyl-L-cysteine (NAC), significantly attenuated MF-induced cell growth inhibition and cell death. Media replacement experiments failed to show any notable change in the MF effects. Conclusions: These results demonstrate 60-Hz sinusoidal MF-activated cell growth inhibition of prostate cancer in vitro. Apoptosis together with cell cycle arrest were the dominant causes of the MF-elicited cell growth inhibition, mediated by MF-induced ROS. These results suggest that a possibility of using 60-Hz MF in radiation therapy of prostate cancer could usefully be investigated.
Low-Dose Sertraline Improves Receptive Language in Children with Fragile X Syndrome When Eye Tracking Methodology is Used to Measure Treatment Outcome

Submit Manuscript | http://medcraveonline.com Abbreviations: FXS: Fragile X syndrome; PVET: Passive-Viewing Eye Tracking Task; MSEL: Mullen Scales of Early Learning; PLS: Preschool Language Scale; FMR1: Fragile X Mental Retardation 1; FMRP: FMR1 Protein; SSRI: Selective Serotonin Reuptake Inhibitor; ASD: Autism Spectrum Disorder; CA: Chronological Age; MA: Mental Age; CDI: MacArthur-Bates Communicative Development Inventory Background
They can because they think they can

Based on interviews with practising speech and language therapists, Hersh (2010) identifies three key areas that constitute challenging aspects of ending therapy, fundamentally to do with client and clinician expectations of what therapy has to offer, managing therapy relationships that need to be robust yet temporary, and balancing client empowerment with the need to achieve fair distribution of resources. In this commentary I take a closer look at the first two of these aspects by dissecting an incident from my own therapy experience. I highlight particularly the importance of the way therapy is set up to the way in which it ends. Given the increasing importance attributed to client involvement in decisions regarding therapy, I also reflect briefly on the centrality of established evaluation measures to the potential for achieving informed consent and informed participation.
Chromosomal abnormalities among children born with conotruncal cardiac defects.

BACKGROUND Conotruncal heart defects compose 25% to 30% of nonsyndromic congenital heart defects. This study describes the frequency of chromosome abnormalities and microdeletion of 22q11 associated among infants and fetuses delivered with conotruncal heart malformations. METHODS From a population base of 974,579 infants/fetuses delivered, 622 California infants/fetuses were ascertained with a defect of aortopulmonary septation. Infants whose primary cardiac defect was tetralogy of Fallot (n = 296) or d-transposition of the great arteries (n = 189) were screened for microdeletion of 22q11. RESULTS Of the infants who had routine karyotypes, 5% had chromosomal abnormalities, including four with extra sex chromosomes. Thirty infants had chromosome 22q11 microdeletions, providing a cause for 10% of infants whose primary defect was tetralogy of Fallot. Right aortic arch, abnormal branching patterns of the major arteries arising from the thoracic aorta, and pulmonary artery abnormalities were observed more frequently among infants with tetralogy of Fallot caused by 22q11 microdeletion. CONCLUSIONS We found an unusual number of infants with an extra sex chromosome and a conotruncal defect. Infants with tetralogy of Fallot owing to 22q11 microdeletion showed more associated vascular anomalies than infants with tetralogy without a 22q11 microdeletion. Although these associated vascular anomalies provide clues as to which infants with tetralogy of Fallot are more likely to carry the microdeletion, the overall risk of 10% among infants with tetralogy of Fallot warrants chromosome analysis and fluorescent in situ hybridization (FISH) testing routinely, which may be supplanted by genome-wide copy number testing as it becomes more widely utilized.
Expression of MAGE and GAGE genes in medulloblastoma and modulation of resistance to chemotherapy. Laboratory investigation.

OBJECT Cancer testis antigens (CTAs) were initially identified by their ability to elicit autologous T-cell-mediated immune responses in patients with melanoma. The CTA genes are widely expressed in a variety of human cancers, such as melanoma, breast cancer, lung cancer, esophageal cancer, and hepatocellular carcinoma; however, their expression in pediatric brain tumors, such as medulloblastoma (MB), has not been the subject of in-depth analysis. The MAGE proteins are members of the CTA family and have been shown to correlate with tumor development, aggressive clinical course, or resistance to chemotherapeutic agents. The authors undertook this study to examine the expression and role of MAGE proteins in human MB cell lines and specimens. METHODS From a transcriptional profiling study in which 47,000 genes in MB cell lines were examined, the authors identified members of the MAGE and GAGE families as being highly expressed. A series of MB tumors was examined using both immunohistochemistry and Western blot analysis with antibodies to the MAGE-A family, MAGE-A1, and GAGE proteins. RESULTS Western blot analysis showed expression of these 3 proteins (MAGE-A family, MAGE-A1, and GAGE) in 62, 46, and 84%, respectively, of MB specimens examined. In addition, a correlation was observed between the expression of MAGE and GAGE genes and resistance of MB cells to chemotherapeutic agents. The functional significance of this correlation was examined in MAGE knockdown studies, and increased drug-induced cytotoxicity was observed in UW426 MB cells following treatment with chemotherapeutic drugs. Cleaved caspase-3 was found in UW426/MAGE small interfering (si)RNA-inhibited cells treated with cisplatin, but not in UW426 cells treated with cisplatin alone at the same concentration. CONCLUSIONS These data show that MAGE and GAGE family members are expressed in MB cell lines and specimens, and that inhibition of MAGE and GAGE genes by siRNA increases apoptosis of MB cells and sensitizes them to certain chemotherapeutic agents such as cisplatin and etoposide.
Management of atlantoaxial metastases with posterior occipitocervical stabilization.

OBJECT The treatment of atlantoaxial spinal metastases is complicated by the region's unique biomechanical and anatomical characteristics. Patients most frequently present with pain secondary to instability; neurological deficits are rare. Recently, some authors have performed anterior approaches (transoral or extraoral) for resection of upper cervical metastases. The authors review their experience with a surgical strategy that emphasizes posterior stabilization of the spine and avoidance of poorly tolerated external orthoses such as the rigid cervical collar or halo vest. METHODS The authors performed a retrospective review of 19 consecutively treated patients with C-1 or C-2 metastases who underwent surgery at The University of Texas M. D. Anderson Cancer Center between 1994 and 2001. Visual analog pain scores were reduced at 1 and 3 months (p < 0.005, Wilcoxon signed-rank test); however, evaluation of pain at 6 months and 1 year was limited by the remaining number of surviving patients. Analgesic medication consumption was unchanged. There were no cases of neurological decline or sudden death secondary to residual or recurrent atlantoaxial disease during the follow-up period. One patient underwent revision of hardware at 11 months. The mean follow-up period was 8 months (range 1-32 months). Median survival determined by Kaplan-Meier analysis was 6.1 months (95% confidence interval 2.99-9.21). CONCLUSIONS Occipitocervical stabilization provided durable pain relief and preservation of ambulatory status over the remaining life span of patients. Because of the palliative goals of surgery, the authors have not found an indication for anterior-approach tumor resection in these patients. Successful stabilization obviates the need for an external orthosis.
Assessment of menstrual blood loss using a pictorial chart

Summary. Objective menstrual blood loss measurements (in ml) were compared with the score obtained from a pictorial blood loss assessment chart (PBAC) which took into account the degree to which each item of sanitary protection was soiled with blood as well as the total number of pads or tampons used. Twenty eight women used the chart during 55 menstrual cycles and a single observer assessed 122 cycle collections in a similar manner. A pictorial chart score of 100 or more, when used as a diagnostic test for menorrhagia, was found to have a specificity and sensitivity of >80%. Demonstration of the relation between self assessed pictorial chart scores and the objective measurement of blood loss enables us to provide a simple, cheap and reasonably accurate method of assessing blood loss before embarking upon treatment.
MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2

The p53R2 protein, a newly identified member of the ribonucleotide reductase family that provides nucleotides for DNA damage repair, is directly regulated by p53. We show that p53R2 is also regulated by a MEK2 (ERK kinase 2/MAP kinase kinase 2)-dependent pathway. Increased MEK1/2 phosphorylation by serum stimulation coincided with an increase in the RNR activity in U2OS and H1299 cells. The inhibition of MEK2 activity, either by treatment with a MEK inhibitor or by transfection with MEK2 siRNA, dramatically decreased the serum-stimulated RNR activity. Moreover, p53R2 siRNA, but not R2 siRNA, significantly inhibits serum-stimulated RNR activity, indicating that p53R2 is specifically regulated by a MEK2-dependent pathway. Co-immunoprecipitation analyses revealed that the MEK2 segment comprising amino acids 65–171 is critical for p53R2–MEK2 interaction, and the binding domain of MEK2 is required for MEK2-mediated increased RNR activity. Phosphorylation of MEK1/2 was greatly augmented by ionizing radiation, and RNR activity was concurrently increased. Ionizing radiation-induced RNR activity was markedly attenuated by transfection of MEK2 or p53R2 siRNA, but not R2 siRNA. These data show that MEK2 is an endogenous regulator of p53R2 and suggest that MEK2 may associate with p53R2 and upregulate its activity.