Miracle-dz/UniFAR-FTUs huggingface dataset:
Streptozotocin-Induced Diabetes Mellitus Causes Changes in Primary Sensory Neuronal Cytoskeletal mRNA Levels That Mimic Those Caused by Axotomy

Dorsal root ganglion (DRG) sensory neurons are particularly vulnerable to diabetes mellitus. There is evidence that the disease decreases both circulating and retrogradely transported neurotrophic factors that are essential to the normal maintenance and function of these cells. A substantive loss of trophic support should cause DRG neurons to respond as though they were axotomized and, like an axotomy, cause significant changes in cytoskeletal gene expression within these cells. Such changes might contribute to the deficits in sensory neuronal function that characterize diabetic neuropathy. The current study used quantitative in situ hybridization to test the hypothesis that streptozotocin-induced diabetes, like an axotomy, increases class III beta-tubulin gene expression and decreases neurofilament 68-kDa gene expression in lumbar DRG neurons. In animals that had been diabetic for 8 weeks with mean blood glucose levels of 340 mg/dl, lumbar DRG class III beta-tubulin mRNA mean steady-state levels were twofold higher than those in age-matched nondiabetic controls. Moreover, in the same animals, diabetes decreased lumbar DRG 68-kDa neurofilament mRNA mean steady-state levels by more than half. These data show that diabetes causes changes in primary sensory neuronal cytoskeletal gene expression that mimic those caused by axotomy. Moreover, they support the idea that a loss of neurotrophic support contributes to the pathogenesis of diabetic neuropathy.
Novel Role of Resveratrol: Suppression of High-Mobility Group Protein Box 1 Nucleocytoplasmic Translocation by the Upregulation of Sirtuin 1 in Sepsis-Induced Liver Injury

ABSTRACT Background: High-mobility group protein box 1 (HMGB1) is essential in the response to injury during sepsis. We hypothesized that resveratrol (RESV) administration would inhibit nuclear-cytoplasmic HMGB1 translocation in hepatocytes, which is associated with sirtuin 1 (SIRT1) upregulation. We investigated the regulatory role of SIRT1 in HMGB1 nucleocytoplasmic translocation and its effect on sepsis-induced liver injury. Methods: Rats were randomly assigned to pretreatment with RESV (60 mg/kg per day), nicotinamide (60 mg/kg per day), or vehicle (olive oil), which was administered by gavage for 3 days directly before cecal ligation and puncture was performed to induce sepsis. Parallel control groups were established. Rats were killed 24 h after surgery, and cytokine production, histology, apoptosis, SIRT1, serum HMGB1, nuclear and cytoplasmic HMGB1/ac-HMGB1, and the interaction between SIRT1 and HMGB1 were evaluated. In vitro evaluations were performed in human liver L02 cells subjected to lipopolysaccharide-induced injury, and siRNA-mediated SIRT1 knockdown experiments were performed. Results: Sepsis-induced serum aminotransferase activities and proinflammatory chemokine levels were reduced by RESV pretreatment, which also improved liver histological parameters in association with SIRT1 upregulation. Resveratrol inhibited HMGB1 cytoplasmic translocation. Nicotinamide, an SIRT1 inhibitor, reduced the SIRT1-mediated suppression of HMGB1 translocation and aggravated cecal ligation and puncture–induced liver damage. Sirtuin 1 knockdown in vitro confirmed that RESV increased the SIRT1-mediated repression of HMGB1 translocation. In vivo, SIRT1 and HMGB1 physically interacted in the nucleus, and SIRT1 regulated HMGB1 acetylation in response to septic liver injury. Conclusions: Resveratrol protects against sepsis-induced liver injury through the SIRT1-mediated HMGB1 nucleocytoplasmic translocation pathway, a new potential therapeutic target in sepsis-induced liver injury.
Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury

Enterohemorrhagic Escherichia coli produce ribotoxic Shiga toxins (Stx), which are responsible for kidney injury and development of hemolytic uremic syndrome. The endoplasmic reticulum (ER) stress response is hypothesized to induce apoptosis contributing to organ injury; however, this process has been described only in vitro. ER stress marker transcripts of spliced XBP1 (1.78-fold), HSP40 (4.45-fold) and CHOP (7.69-fold) were up-regulated early in kidneys of Stx2 challenged mice compared to saline controls. Anti-apoptotic Bcl2 decreased (-2.41-fold vs. saline) and pro-apoptotic DR5 increased (6.38-fold vs. saline) at later time points. Cytoprotective activated protein C (APC) reduced early CHOP expression (-3.3-fold vs. untreated), increased later Bcl2 expression (5.8-fold vs. untreated), and had early effects on survival but did not alter DR5 expression. Changes in kidney ER stress and apoptotic marker transcripts were observed in Stx2-producing C. rodentium challenged mice compared to mice infected with a non-toxigenic control strain. CHOP (4.14-fold) and DR5 (2.81-fold) were increased and Bcl2 (-1.65-fold) was decreased. APC reduced CHOP expression and increased Bcl2 expression, but did not alter mortality. These data indicate that Stx2 induces renal ER stress and apoptosis in murine models of Stx2-induced kidney injury, but decreasing these processes alone was not sufficient to alter survival outcome.
Round robin investigation of methods for the recovery of poliovirus from drinking water

Six laboratories actively involved in water virology research participated in a methods evaluation study, conducted under the auspices of the American Society for Testing and Materials Committee on Viruses in the Aquatic Environment, Task Force on Drinking Water. Each participant was asked to examine the Viradel (virus adsorption-elution) method with cartridge-type Filterite filters for virus adsorption and organic flocculation and aluminum hydroxide-hydroextraction for reconcentration. Virus was adsorbed to filter media at pH 3.5 and eluted with either glycine buffer (pH 10.5) or beef extract-glycine (pHG 9.0). Considerable variation was noted in the quantity of virus recovered from four 100-liter samples of dechlorinated tapwater seeded with low (350 to 860 PFU) and high (1,837 to 4,689 PFU) doses of poliovirus type 1. To have a more uniform standard of comparison, all the test samples were reassayed in one laboratory, where titers were also determined for the virus seed. Test results of the Viradel-organic flocculation method indicated that the average percentage of virus recovery for low-input experiments was 66%, with a range of 8 to 20% in two laboratories, 49 to 63% in three laboratories, and 198% in one laboratory. For the high-input experiments, two laboratories reported recoveries of 6 to 12%, and four laboratories reported recoveries of 26 to 46%. For the Viradel aluminum hydroxide-hydroextraction procedure, two laboratories recovered 9 to 11%, whereas four obtained 17 to 34% for low-input experiments. For the high-input tests, two laboratories reported a recovery of 3 to 5%, and four recovered 11 to 18% of the seeded virus. (ABSTRACT TRUNCATED AT 250 WORDS)
[Erysipelas in the young population of a military hospital].

INTRODUCTION Erysipelas usually affects either elderly patients or patients with predisposing factors. We studied erysipelas in a young healthy military population. SUBJECTS AND METHODS A retrospective study of patients, less than 30 years old, admitted to the Hôpital d'Instruction des Armées Robert Picqué between 1991 and 1997 was performed. RESULTS Eighty-one patients were studied, 80 were men, mean age was 21.4 years. Localization of erysipelas was: face: 2; leg: 74. Facilitating factors were: portal of entry in 100 p. 100; venous insufficiency in 1 case; alcohol abuse in 1 case. Anti-inflammatory agents had been given at the beginning of treatment in 32.1 p. 100 cases. 7.1 p. 100 patients had a recurrence. Complications were: abscess in 8 cases and bursitis in 1 case. No facilitating factor was detected. The course was not related with bacterial findings. No thrombo-embolic complication was observed. DISCUSSION In a young healthy population, erysipelas is not a rare infection. Face is an exceptional localization of erysipelas in relation to older population. The main risk factor for developing this infection is local factor found in 100 p. 100 cases but general factors as repeated hikes, care access, long standing could also be incriminated. Use of anti-inflammatory agents is frequent but role of anti-inflammatory agents in developing complications is not clear. Complications are rare and benign except for frequence of recurrences while the good health.
Serum Brain-Derived Neurotrophic Factor Mediates the Relationship between Abdominal Adiposity and Executive Function in Middle Age

Abstract Objectives: Excessive adipose tissue, especially in the abdominal area, is associated with increased risk of dementia in older adults. However, the mechanisms underlying this relationship are poorly understood. As increased adiposity is also associated with lower circulating levels of brain-derived neurotrophic factor (BDNF), a key molecule modulating brain plasticity and neuronal regeneration, we hypothesized that the changes in cognition that occur as a result of excessive abdominal adiposity would be driven by lower levels of circulating BDNF. Methods: Fasting blood samples were obtained from 60 participants aged 40–60 years (mean±SD=52.3±5.6) and BDNF levels were assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was measured using a ratio of waist circumference to hip circumference (WHR). Participants also completed a neuropsychological assessment battery to assess executive function. Statistical mediation was assessed using traditional causal steps and nonparametric bootstrapping. Results: Higher WHR was significantly associated with poorer performance on the Controlled Oral Word Association (COWA) letter fluency test (β=−0.489; p=.003) and lower levels of circulating BDNF (β=−0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (β=0.60; 95% confidence interval [−3.79, −0.26]). Conclusions: The relationship between higher WHR and verbal fluency was fully statistically mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable mechanism through which executive function decline occurs in individuals with high abdominal adiposity. BDNF enhancing interventions (physical exercise and dietary restriction) could thus be used to improve executive function in these individuals. (JINS, 2016, 22, 1–8)
Complications encountered during lengthening over an intramedullary nail.

BACKGROUND In limb-lengthening, the quest for increased patient comfort and a reduced period of external fixation has led to techniques such as lengthening over an intramedullary nail. The goals of this study were to investigate the rate and types of complications encountered during lengthening over an intramedullary nail and to identify solutions to these complications. METHODS Forty-two segments (thirty-five femora and seven tibiae) in thirty-five patients were lengthened. The mean age of the patients was 26.6 years, the mean amount lengthened was 6.3 cm (range, 2.5 to 11.5 cm), the mean external fixation index was 18.7 days/cm, and the mean lengthening index was 31.2 days/cm. The patients were followed for a mean period of forty-four months postoperatively. RESULTS Eighteen complications occurred in sixteen (38%) of the forty-two segments for a rate of 0.43 complication per segment. Complications were classified, according to the system of Paley et al., as two problems, thirteen obstacles, and three sequelae. Sixteen of them required additional surgical interventions. A preoperative score of >6.5 on the system of Paley et al., a lengthening of >6 cm, and a lengthening percentage of >21.5% of the original bone length were indicators of a higher probability of the occurrence of complications. CONCLUSIONS Lengthening over an intramedullary nail provides increased patient comfort and reduces the external fixation period. If the problems encountered are treated aggressively, the result of the treatment can be quite satisfactory.
The Candida albicans Lanosterol 14-α-Demethylase (ERG11) Gene Promoter Is Maximally Induced after Prolonged Growth with Antifungal Drugs

ABSTRACT The azole antifungal drugs that target lanosterol 14-α-demethylase, encoded by the ERG11 gene, are used to treat a variety of infections caused by Candida albicans. Azoles are known to induce expression of ERG11 mRNA. The ERG11 promoter was cloned 5′ of the luciferase-coding region, and the induction of ERG11 expression by azoles was monitored by luciferase assays. Maximal induction of the ERG11 promoter by azoles occurs not during logarithmic growth but after the diauxic shift and requires azoles to be present throughout logarithmic growth. The effects of pH, carbon source, and aerobic or anaerobic growth on induction of the ERG11 promoter by azoles were analyzed. Treatment with terbinafine and fenpropimorph, which target other enzymes in the ergosterol biosynthetic pathway, also resulted in a delayed induction of ERG11 promoter activity. Nascent sterol synthesis was shown to parallel ERG11 promoter activity, and total sterols were reduced coincident with the timing of ERG11 promoter activation. These results as a whole suggest that expression of the ERG11 promoter is regulated in response to sterol depletion.
The Accuracy-Enhancing Effect of Biasing Cues

Extrinsic cues such as price and irrelevant attributes have been shown to bias consumers' product judgments. Results in this article replicate those findings in pretrial judgments but show that such biasing cues can improve quality judgments at a later point in time. Initially biasing cues can even yield more accurate judgments than cues that do not bias pretrial judgments and can help consumers after a delay (e.g., at the time of repeat purchase) to determine how much they had liked a product when they tried it before. These results suggest that trying to deceive consumers with the use of biasing cues may induce trial in the short term but may come back to haunt the deceiver at the time of repeat purchase.
Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis.

BACKGROUND Multiple sclerosis is an inflammatory disease of the central nervous system that destroys myelin, oligodendrocytes, and axons. Since most of the lesions of multiple sclerosis are not remyelinated, enhancement of remyelination is a possible therapeutic strategy that could perhaps be achieved with the transplantation of oligodendrocyte-producing cells into the lesions. We investigated the frequency distribution and configuration of oligodendrocytes in chronic lesions of multiple sclerosis to determine whether these factors limit remyelination. METHODS Forty-eight chronic lesions obtained at autopsy from 10 patients with multiple sclerosis were examined immunocytochemically for oligodendrocytes and oligodendrocyte progenitor cells. Using confocal microscopy, we examined the three-dimensional relations between axons and the processes of premyelinating oligodendrocytes. RESULTS Thirty-four of the 48 chronic lesions of multiple sclerosis contained oligodendrocytes with multiple extended processes that associated with demyelinated axons but failed to myelinate them. These axons were dystrophic and contained multiple swellings. In some regions, the densities of premyelinating oligodendrocytes (25 per square millimeter of tissue) were similar to those in the developing rodent brain (23 per square millimeter). In the patients with disease of long duration (more than 20 years), there were fewer lesions with premyelinating oligodendrocytes (P<0.001). CONCLUSIONS Premyelinating oligodendrocytes are present in chronic lesions of multiple sclerosis, so remyelination is not limited by an absence of oligodendrocyte progenitors or their failure to generate oligodendrocytes. Our findings suggest that in the chronic lesions of multiple sclerosis, the axons are not receptive for remyelination. Understanding the cellular interactions between premyelinating oligodendrocytes, axons, and the microenvironment of lesions of multiple sclerosis may lead to effective strategies for enhancing remyelination.
2014-5 Student Loans and Repayment: Theory, Evidence and Policy

Rising costs of and returns to college have led to sizeable increases in the demand for student loans in many countries. In the U.S., student loan default rates have also risen for recent cohorts as labor market uncertainty and debt levels have increased. We discuss these trends as well as recent evidence on the extent to which students are able to obtain enough credit for college and the extent to which they are able to repay their student debts after. We then discuss optimal student credit arrangements that balance three important objectives: (i) providing credit for students to access college and finance consumption while in school, (ii) providing insurance against uncertain adverse schooling or post-school labor market outcomes in the form of income-contingent repayments, and (iii) providing incentives for student borrowers to honor their loan obligations (in expectation) when information and commitment frictions are present. Specifically, we develop a two-period educational investment model with uncertainty and show how student loan contracts can be designed to optimally address incentive problems related to moral hazard, costly income verification, and limited commitment by the borrower. We also survey other research related to the optimal design of student loan contracts in imperfect markets. Finally, we provide practical policy guidance for re-designing student loan programs to more efficiently provide insurance while addressing information and commitment frictions in the market.
Utility of HbA1c in the Detection of Subclinical Post Renal Transplant Diabetes

Background. We hypothesized that the use of HbA1c testing would help identify postrenal transplant diabetes (PTDM). Methods. In all, 199 adult kidney transplant recipients at least 3 months posttransplant without previous history of diabetes or elevated fasting blood sugar were studied. Medical history, a fasting blood glucose, calcineurin inhibitor blood level, and HbA1c were obtained. Primary outcome was the incidence of subjects with HbA1c ≥6.1%. The covariates were use of cyclosporine or tacrolimus, time posttransplant, body mass index (BMI) at transplant and change since transplant, current steroid dose, history of graft rejection, current fasting glucose, age, and race. Proportions were compared between HbA1c <6 and ≥6.1% using Fisher's exact test. Means were compared using Student's t test. Logistic regression was used to identify risk factors associated with elevated HbA1c. Results. Twenty subjects (10.1%) had an elevated HbA1c. High normal fasting glucose (P=0.003) and African American race (P=0.08, marginally significant) were found to be associated with an elevated HbA1c. Subjects with normal and abnormal HbA1c levels were otherwise similar. There was no difference in HbA1c in tacrolimus versus cyclosporine treated subjects or in the percent of subjects with elevated HbA1c between these groups. Conclusions. HbA1c levels were found to be more a more sensitive test than fasting blood glucose levels in PTDM, with 10.1% of all patients and 19.4% of blacks found to have an elevated HbA1c. HbA1c testing should be considered as a screening test for PTDM, especially in African Americans.
Myofibroblasts in the healing lapine medial collateral ligament: Possible mechanisms of contraction

The specific objective of this study was to determine the chronology of the appearance of the myofibroblast in the healing ligament. The overall goal of our work is to elucidate the cellular mechanism of contraction in this tissue. The myofibroblast has been found to be responsible for wound contraction in many tissues and to be the cause of the contracture in several pathological conditions. This cell type contains the actin isoform previously thought to be unique to smooth muscle cells and displays certain characteristic features at the ultrastructural level. In 26 New Zealand White male rabbits, the right medial collateral ligament was transected, whereas the left medial collateral ligament received a sham operation. The central third of the ligament (ligament scar tissue) was evaluated at 2, 3, 6, 8, 10, and 12 weeks postoperatively by immunohistochemical techniques, transmission electron microscopy, and Western blot analyses. Three other rabbits served as anatomic controls. During the early reparative phase (2 and 3 weeks after transection), there was an increase in the number of cells containing α‐smooth muscle actin as well as augmentation of the α‐smooth muscle actin content within each cell—a finding attributed to smooth muscle cells and pericytes associated with neovascularity. No myofibroblasts were detected at this stage, immediately postoperatively, or in the sham‐operation controls. Ligaments in the remodeling phase of healing (6, 8, 10, and 12 weeks) exhibited α‐smooth muscle actin in fibroblasts (myofibroblasts) as well as in vascular pericytes and smooth muscle cells. During this stage of healing, transmission electron microscopy demonstrated an increase in the number of cells displaying myofibroblastic features. It was estimated that at 12 weeks of healing 10% of the cells at the site of injury were myofibroblasts. This is the first definitive finding of myofibroblasts in the injury site of the healing ligament, to our knowledge. The appearance of myofibroblasts in the 6–12 week healing period, the interval during which the ligament has been shown to contract in studies by other investigators, is a rationale for a hypothesis that a cellular contractile apparatus comprising α‐smooth muscle actin (i.e., the myofibroblast) may contribute to the recovery of original ligament length (and normal in situ strain).
Transcription factor binding study by capillary zone electrophoretic mobility shift assay

Regulation of gene expression through interaction of proteins with specific DNA sequences is a central issue in functional genomics. Capillary electrophoretic mobility shift assay is an efficient novel method for the investigation of sequence specific protein‐DNA interactions, allowing rapid and sensitive quantification of the complex formation. In this paper, we present a pilot study on capillary zone electrophoretic mobility shift assay (CZEMSA) to investigate the interaction between the transcription factors of HeLa nuclear extract and Sp1‐specific fluorescein‐labeled oligonucleotide, using the unlabeled probe as competitor. The mobility shift assay was accomplished by CZE in coated capillaries without polymeric buffer additives. Specificity of the DNA protein complex formation was verified by competition experiments, as well as by supershift assay with an anti‐Sp1 antibody. The applied electric field strength did not affect the stability of DNA‐protein complex during the electrophoretic analysis, allowing rapid identification and quantification of the protein DNA interaction. A practical application to study the interaction between Oryza sativa MADS‐box transcription factor 4 (OsMADS4) and its consensus sequence is also reported.