Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of Human Dickkopf-1, an Antagonist of wingless/WNT Signaling, in Human Hepatoblastomas and Wilms’ Tumors

Hepatoblastomas (HBs) represent the most frequent malignant liver tumors of childhood; yet little is known about the molecular pathogenesis and the alterations in expression patterns of these tumors. We used a suppression subtractive hybridization approach to identify new candidate genes that may play a role in HB tumorigenesis. cDNA species derived from corresponding liver and fetal liver were subtracted from HB cDNAs, and a series of interesting candidates were isolated that were differentially expressed. One of the transcripts overexpressed in HB was derived from the human Dickkopf-1 (hDkk-1) gene, which encodes a secreted protein acting as a potent inhibitor of the wingless/WNT signaling pathway. We examined the hDkk-1 expression levels in 32 HB biopsy specimens and in the corresponding liver samples, in 4 HB cell lines, and in a panel of other tumors and normal tissues using a differential PCR approach and Northern blotting. Eighty-one percent of the HBs but none of the normal pediatric or fetal liver tissues showed hDkk-1 expression. hDkk-1 transcripts were also present in 5 of 6 Wilms’ tumors but only weakly detectable in 2 of 20 hepatocellular carcinoma samples and in 1 of 5 medulloblastoma cell lines; transcripts were absent in malignant gliomas and breast cancer. The central effector molecule in the WNT developmental control pathway is the β-catenin protein. Interestingly, activating mutations of the β-catenin gene have previously been identified in 48% of HBs, and more than 85% of HBs show accumulation of β-catenin protein as the indicator for an activated pathway. The overexpression of the inhibitor Dkk-1 may therefore be related to uncontrolled wingless/WNT signaling and may represent a negative feedback mechanism. hDkk-1 expression represents a novel marker for HBs and Wilms’ tumors.
Astroglial c-Myc Overexpression Predisposes Mice to Primary Malignant Gliomas*

Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2–3 weeks of age. The genetically engineered murine (GEM) gliomas harbor a molecular signature resembling that of human primary glioblastoma multiforme, including up-regulation of epidermal growth factor receptor and Mdm2. The GEM gliomas seem to originate in an abnormal population of glial fibrillary acidic protein-expressing cells in the ventricular zone and, analogous to human glioblastomas, exhibit molecular and morphological heterogeneity. Levels of connexin 43 in the majority of the tumors are unaltered from normal tissue, indicating that GEM tumors have retained the capacity to establish syncytial networks. In line with this, individual glioma foci are composed of a mixture of actively proliferating cells expressing c-Myc and proliferating cell nuclear antigen and less dividing bystander cells that express glial fibrillary acidic protein and the broad complex tramtrack bric-a-brac/poxvirus and zinc finger domain protein HOF. A subset of the transgenic mice harbored, in addition to brain tumors, vestigial cerebellums in which granule cell migration and radial Bergman glial cell differentiation were disturbed. These observations argue for a window of vulnerability during astrocyte development where c-Myc overexpression is sufficient to trigger the neoplastic process, presumably by inducing the sustained growth of early astroglial cells. This is in contrast to most other transgenic studies in which c-Myc overexpression requires co-operating transgenes for rapid tumor induction.
Efficacy of enteric-coated protease in preventing attachment of enterotoxigenic Escherichia coli and diarrheal disease in the RITARD model

In this study, we report on a novel approach based on modification of the intestinal surface to prevent diarrhea caused by enterotoxigenic Escherichia coli (ETEC). The removable intestinal tie adult rabbit diarrhea (RITARD) model was used to test the efficacy of an enteric-coated protease preparation (Detach; Enzacor Technology Pty. Ltd.) in the prevention of bacterial attachment and diarrheal disease caused by colonization factor antigen I-positive (CFA/I+) E. coli H10407. Protease was administered orally to rabbits 18 h prior to challenge with 10(11) bacteria. Four groups of rabbits were inoculated with different ETEC strains which produced different combinations of adhesin and enterotoxin or with sterile phosphate-buffered saline. Occurrence of diarrhea during the subsequent 24-h incubation period was recorded. Oral administration of protease was successful in reducing diarrhea and diarrhea-induced death in six of seven (86%) rabbits infected with CFA/I+, heat-stable and heat-labile toxin-positive E. coli (H10407). Seven of eight (87%) rabbits not protected by protease treatment died or developed severe diarrhea. Quantitative analysis of bacterial cultures obtained from the small intestine of rabbits showed a significant (P less than 0.001) 2,000-fold reduction in CFU per centimeter of intestine following treatment with protease. The efficacy of protease treatment was 99.5%, with very wide confidence limits (greater than 0 to 99.9%). The data indicate that the use of protease to prevent ETEC diarrheal disease has considerable potential.
Renal Denervation for Resistant Hypertension Fails to Improve Insulin Resistance as Assessed by Hyperinsulinemic-Euglycemic Step Clamp

We assessed whether insulin sensitivity improved after renal denervation (RDN) for resistant hypertension. Twenty-three patients underwent a two-step hyperinsulinemic-euglycemic clamp (HEC) with glucose tracer and labeled glucose infusion and oral glucose tolerance test (OGTT) before and 6 months after RDN. Eighteen patients had metabolic syndrome at baseline. Blood pressure declined significantly after RDN, whereas mean (SD) fasting plasma glucose concentration (5.9 ± 0.7 mmol/L), median (minimum–maximum) insulin concentration (254 pmol/L [88–797 pmol/L]), and median C-peptide concentration (2.4 nmol/L [0.9–5.7 nmol/L]) remained unchanged. Endogenous glucose release during HEC was less suppressed after RDN, suggesting a slight decrease in hepatic insulin sensitivity. During high-dose insulin infusion, whole-body glucose disposal was low and remained unchanged after RDN, indicating persistent peripheral insulin resistance (IR). Area under the curve for 0–120 min for glucose and insulin during OGTT, Quantitative Insulin Sensitivity Check Index, Simple Index Assessing Insulin Sensitivity Oral Glucose Tolerance, and HOMA-IR were high, and did not improve after RDN. Despite a significant decrease in blood pressure, neither peripheral nor hepatic insulin sensitivity improved 6 months after RDN treatment in this group of insulin-resistant patients without diabetes and with resistant hypertension, as measured with gold standard methods.
Employment equity in the South African retail sector: Legal versus competence and business imperatives

In 2013/14 a study entitled â€œInterventions to achieve employment equity objectives in the wholesale and retail sectorâ€ was conducted by the Wholesale and Retail Leadership Chair (WRLC) at the Cape Peninsula University of Technology on behalf of the W&RSETA (Sector Education and Training Authority). Objectives included assessing the impact of implementation of the Employment Equity Act (EEA) on retail organisations, and determining what supportive action regulatory authorities (the Department of Labour and the W&RSETA) and businesses could take to achieve employment equity (EE) goals. The study is therefore useful across the spectrum of the W&R industry, especially for employment relations practitioners and those tasked with EE implementation. The study followed a mixed-methods approach, using questionnaire surveys, in-depth interviews, case studies, focus groups and secondary data. Results indicated that EE tends to be numbers-driven at the expense of competence and talent management. Most respondentsâ€™ perceptions of EE implementation were negative, with the implication that a different approach is needed because the pace of change and transformation in the South African workplace is too slow. Although the small sample size limits generalisation of the findings, the study provides insight and direction for further research. This paper acknowledges that because EE is currently driven largely by meeting mandated targets for demographic change, the development of talent â€“ in essence, competence â€“ is lacking or inadequate. Thus, the recommendations propose a competency model linked to a performance management system, which could lead to an efficient EE talent management process. This process will enable organisations to develop, within the shortest possible period, competent individuals able to perform adequately in their positions, thereby maintaining or improving productivity; it also addresses effective succession planning.
The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis‐like phenotype and early onset cancer

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis‐like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12–14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis‐like group, two subjects had already developed high‐grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory.
Recovery of Rotators Strength after Latarjet Surgery

Abstract The purposes of this study were to prospectively determine changes in rotator cuff strength before and after surgical shoulder stabilization by Bristow-Latarjet procedure and to better estimate time needed for rotator cuff strength recovery. 20 patients with recurrent anterior posttraumatic shoulder dislocation underwent internal (IR) and external (ER) rotator isokinetic evaluation before and 3, 6 and 21 months after Bristow-Latarjet surgery. In a seated position with 45° of shoulder abduction in the scapular plane, both shoulders were evaluated concentrically with a Con-Trex® isokinetic dynamometer at 180°∙s − 1, 120°∙s − 1 and 60°∙s − 1. 3 months post-surgery, IR and ER strength of the operated shoulder were significantly lower than before surgery ( − 28±20% for IR, − 17±17% for ER) (P<0.05). At 6 and 21 months post-surgery, IR and ER strength were comparable to strength before surgery; strength recovery is seen at 6 months post-surgery with long-term maintenance at 21 months. Given the weakness 3 months post-surgery, return to sports (including overhead and contact sports) should be discussed, and 6 months post-surgery may be a better point for an athlete to resume practicing sports. Isokinetic rotator cuff strength evaluation appears to be relevant in helping to determine the need of continuing strength rehabilitation. Pre-surgical evaluation contributes to the relevance of later comparisons.
Suppression of T and B cell responses by Pterodon pubescens seeds ethanolic extract.

The anti-arthritic property of hydro alcoholic extract of Pterodon pubescens seeds was previously demonstrated using the Collagen Induced Arthritis (CIA) in mice, the most similar arthritis experimental model to human rheumatoid arthritis. This disease is characterized by chronic inflamed joints resulting from exacerbated functions of macrophages and T and B lymphocytes. Anti-inflammatory and antinociceptive activities by ethanolic extract of Pterodon pubescens seeds (EEPp) have been also reported. This study describes the effects of EEPp on T and B lymphocytes functions from healthy mice. Delayed Type Hypersensitivity (DTH), in vivo antibody production, T and B lymphocyte proliferation and NO production were determined. Mice treated orally for 7 days with EEPp had inhibited 58% of B cell antibody production (10(-3) mg kg(-1) b.wt. ) and 33% of the DTH response (10(-4) mg kg(-1) b.wt. ), also reducing tissue leukocyte infiltration. EEPp (10(-2) mg mL(-1)) also inhibited in vitro T (89%) and B (68%) lymphocytes proliferation and NO production (53%) by macrophage cell line J774. The immunosuppression here described for EEPp supports its potential therapeutic use to control exacerbated humoral and/or cellular immune response as in autoimmune and chronic inflammatory diseases.
Influence of community satisfaction with individual happiness: comparative study in semi-urban and rural areas of Tikapur, Nepal

Happiness is a subjective indicator of overall living conditions and quality of life. Recently, community- and national-level investigations connecting happiness and community satisfaction were conducted. This study investigated the effects of community satisfaction on happiness in Nepal. A factor analysis was employed to examine 24 items that are used to measure community satisfaction, and a multiple regression analysis was conducted to investigate the effects of these factors on happiness. In semi-urban areas, sanitation showed a positive relationship with happiness. In rural areas, edu-medical services were negatively related to happiness, while agriculture was positively related. Gender and perceived health were closely associated with happiness in rural areas. Both happiness and satisfaction are subjective concepts, and are perceived differently depending on the socio-physical environment and personal needs. Sanitation, agriculture (food) and edu-medical services were critical factors that affected happiness; however, the results of this study cannot be generalized to high-income countries.
A General Theoretical Integrative Model of Individual Differences in Interests, Abilities, Personality Traits, and Academic and Occupational Achievement: A Commentary on Four Recent Articles

This commentary integrates the contents of four recent articles on individual differences (Nye, Su, Rounds, & Drasgow, 2012; Schmidt, 2011; Valla & Ceci, 2011; von Stumm, Hell, & Chamorro-Premuzic, 2011) in a causal theoretical model. In this model, introversion and fluid intelligence cause interest in general learning (intellectual curiosity), which in turn is a major cause of crystallized intelligence. Certain specific interests and fluid intelligence also contribute to crystallized intelligence. Prenatal testosterone hormone conditioning is postulated to cause sex differences in certain specific interests but not in others. Crystallized intelligence, specific interests, and the personality trait of conscientiousness cause adult academic and occupational performance, whereas crystallized intelligence is the main cause of good mental functioning at older ages. Research is presented supporting each link in the model.
Common local founder effects for Wilson's disease and hereditary hemochromatosis; mutation studies of a large family

Abstract Wilson's disease (WND) and hereditary hemochromatosis (HH) are two metal loading diseases of copper and iron, respectively, and are both recessively inherited. In central Sweden, where HH is common, 9 Wilson kindred (14 members) were identified. Aims of the study were to test whether nine WND families shared a common origin, a common mutation and if carrying HFE mutations affected their phenotype Results. The nine families were traced through 13 generations to a common founder origin in the mid-seventeenth century. Despite identity of descent, four different ATP7B mutations appeared with homozygosity in four, with two different mutations, W779X and T977M. There were three compound heterozygotes, W779X/T977M, R1319X/H1069Q and one T977M combined with a new, previously not described mutation, probably of Finnish origin. The founder family also included 26 descendant kindred (55 members) with HH as shown by HFE mutations. This admixture coincided with a migration out of the original parish into hemochromatosis-rich localities. One WND patient had iron overload (serum ferritin 672 µg/l and raised liver enzymes), but lacked HFE mutations. In another family with serious hemochromatosis (two sons dying from bronze diabetes), the coinheritance of congenital spherocytosis was probably the cause rather than an additional effect of WND. Conclusions. WND though a rare disease may become aggregated like HH in certain areas due to local founder effects. Despite extensive pedigree studies leading back to the local founder family, the authors were unable to find a single defining mutation of the ATP7B gene.
To share or not to share? The contribution of self-disclosure to stress-related growth among suicide survivors

ABSTRACT This study examined to what extent suicide survivors can experience growth in the aftermath of suicide loss, as well as the role of self-disclosure and coping strategies in stress-related growth (SRG) among suicide survivors, compared to bereavement following sudden and expected death types. One hundred forty-five bereaved individuals (aged 18–73) completed questionnaires measuring SRG, self-disclosure, and coping strategies. Significant interaction between self-disclosure and types of death was found, in which suicide survivors with low levels of self-disclosure manifested the lowest level of SRG compared to other subgroups. This finding suggests that sharing intimate information can be beneficial in struggling with a situation of suicide in the family.
Feeling Vigorous and the Risks of All-Cause Mortality, Ischemic Heart Disease, and Diabetes: A 20-Year Follow-up of Healthy Employees

Objective: To investigate prospectively the effects of vigor at work on the end points of mortality and the prevalence of ischemic heart disease (IHD) and diabetes. Methods: We tested the hypothesized beneficial effects of feeling vigorous at work at baseline on the risks of all-cause mortality, IHD, and diabetes during a 20-year follow-up. Participants were healthy employees (n = 968) who underwent a routine health check at baseline. We calculated the risk of all-cause mortality, IHD, and diabetes, with days as the time scale, using the Cox proportional hazard model. In our analyses, we predicted the above end points by baseline vigor, age, gender, and educational level, adjusting for the physiological risk factors of total cholesterol, glucose, and body mass index, the behavioral risk factors of smoking, alcohol intake, and physical activity, and the psychological risk factors of depressive and anxiety symptoms. Results: As hypothesized, we found that, after the above adjustments, baseline vigor decreased the risk of follow-up mortality by 26% (hazard ratio, 0.74; 95% confidence interval, 0.58–0.95) and the risk of diabetes by 17% (hazard ratio, 0.83; 95% confidence interval, 0.68–0.98). However, vigor did not have a significant effect on the risk of IHD. Conclusions: Independently of physiological, behavioral, and psychological risk factors, feeling vigorous at work protected the participants from diabetes and reduced their risk of mortality. IHD = ischemic heart disease; CHS = Clalit Health Services; BMI = body mass index; SES = socioeconomic status.
The Role of Complement, C5a and Its Receptors in Sepsis and Multiorgan Dysfunction Syndrome

Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS.
Voice restoration after laryngectomy: Experience with the Blom–Singer extended‐wear indwelling tracheoesophageal voice prosthesis

The Blom‐Singer tracheoesophageal voice prosthesis has undergone continuous design modifications during the last 18 years to make it more effective, anatomically compatible, and easier to use. This evolution continues with the recent introduction of an indwelling‐style voice prosthesis intended for use by individuals who are unable or disinclined to use a self‐removable‐style voice prosthesis. The a priori set‐lifespan goal of the indwelling prosthesis was 180 days.
Occult Cardiotoxicity—Toxic Effects on Cardiac Ischemic Tolerance

The outcome of cardiac ischemic events depends not only on the extent and duration of the ischemic stimulus but also on the myocardial intrinsic tolerance to ischemic injury. Cardiac ischemic tolerance reflects myocardial functional reserves that are not always used when the tissue is appropriately oxygenated. Ischemic tolerance is modulated by ubiquitous signal transduction pathways, transcription factors and cellular enzymes, converging on the mitochondria as the main end effector. Therefore, drugs and toxins affecting these pathways may impair cardiac ischemic tolerance without affecting myocardial integrity or function in oxygenated conditions. Such effect would not be detected by current toxicological studies but would considerably influence the outcome of ischemic events. The authors refer to such effect as “occult cardiotoxicity. ” In this review, the authors summarize current knowledge about main mechanisms that determine cardiac ischemic tolerance, methods to assess it, and the effects of drugs and toxins on it. The authors offer a view that low cardiac ischemic tolerance is a premorbid status and, therefore, that occult cardiotoxicity is a significant potential source of cardiac morbidity. The authors propose that toxicologic assessment of compounds would include the assessment of their effect on cardiac ischemic tolerance.