Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Simian Immunodeficiency Virus SIVSM/Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

ABSTRACT Human immunodeficiency virus type 2 (HIV-2)/simian immunodeficiency virus SIVSM Vpx is incorporated into virion particles and is thus present during the early steps of infection, when it has been reported to influence the nuclear import of viral DNA. We recently reported that Vpx promoted the accumulation of full-length viral DNA following the infection of human monocyte-derived dendritic cells (DCs). This positive effect was exerted following the infection of DCs with cognate viruses and with retroviruses as divergent as HIV-1, feline immunodeficiency virus, and even murine leukemia virus, leading us to suggest that Vpx counteracted an antiviral restriction present in DCs. Here, we show that Vpx is required, albeit to a different extent, for the infection of all myeloid but not of lymphoid cells, including monocytes, macrophages, and monocytoid THP-1 cells that had been induced to differentiate with phorbol esters. The intracellular localization of Vpx was highly heterogeneous and cell type dependent, since Vpx localized differently in HeLa cells and DCs. Despite these differences, no clear correlation between the functionality of Vpx and its intracellular localization could be drawn. As a first insight into its function, we determined that SIVSM/HIV-2 and SIVRCM Vpx proteins interact with the DCAF1 adaptor of the Cul4-based E3 ubiquitin ligase complex recently described to associate with HIV-1 Vpr and HIV-2 Vpx. However, the functionality of Vpx proteins in the infection of DCs did not strictly correlate with DCAF1 binding, and knockdown experiments failed to reveal a functional role for this association in differentiated THP-1 cells. Lastly, when transferred in the context of a replication-competent viral clone, Vpx was required for replication in DCs.
Overexpression of p53 as a Possible Prognostic Factor in Human Thyroid Carcinoma

A total of 110 cases of thyroid carcinomas were examined immunohistochemically to evaluate the overexpression of mutant forms of p53 protein in the light of their relationship with their histological subtypes. A polyclonal antibody, CM-1, was applied to the routine formalin-fixed, paraffin-embedded tissues for this survey. Overall, immunohistochemically detected p53 expression confined to the nucleus was identified in 22.7% of the thyroid carcinomas. A significant difference in the positivity of p53 among histological subtypes was noted; the positivity was 11.1% of the cases in well-differentiated papillary carcinoma, 14.3% in well-differentiated follicular carcinoma, 40.9% in poorly differentiated carcinoma, and 63.6% in undifferentiated carcinoma. No immunohistochemical positivity was found in adjacent non-neoplastic tissues or in benign lesions, including follicular adenoma, adenomatous goiter, and chronic thyroiditis. These results suggest that overexpression of p53 is not a responsible factor for the oncogenesis itself, but rather that it plays a crucial role in aggressive subtypes of thyroid carcinomas. Additionally, the distinct entity of poorly differentiated carcinoma, previously categorized in the well-differentiated carcinoma under the name of papillary or follicular carcinoma, was statistically confirmed.
Watching stem cells in the skin of living mice noninvasively

We demonstrate noninvasive, high-resolution multiphoton tomography of nestin-expressing stem cells of hair follicles in living transgenic nude mice. An imaging system comprised of a compact femtosecond laser, 3D scan head mounted on a flexible mechano-optical articulated arm for simultaneous intra-tissue fluorescence and second harmonic detection (SHG) detection was used. This noninvasive method enables long-term in vivo tracking of intra-tissue stem cells in living animals. Multiphoton animal sectioning with subcellular resolution can visualize the real-time behavior of single stem cells in their native tissue microenvironment.
Oxidative stress in Egyptian hemodialysis children.

INTRODUCTION Nitric oxide (NO) is one of the endothelium-dependent relaxing factors released by the vascular endothelium. It is decreased in chronic kidney disease. It was found that higher levels of circulating proinflammatory cytokines such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-13 are associated with mortality. The aim of our study was to evaluate the disturbance in NO in chronic kideny failure and its relationship with hypertension and inflammatory and nutritional parameters, as indirect indexes of uremic oxidative stress. MATERIALS AND METHODS This study included 31 children consisting of 23 children, aged from 4 to 18 years old, with ESRD, on regular hemodialysis, and 8 children admitted to hospital for other diseases (control group). Predialysis blood samples were tested for IL-1beta, TNF-alpha, and NO, and were compared with the control group. RESULTS Serum levels of TNF-alpha and IL-1beta were significantly higher in children on hemodialysis as compared to the control group (TNF-alpha, 104.54 +/- 17.31 pg/mL versus 48.19 +/- 6.28 pg/mL, P = .005; IL-1beta, 5.35 +/- 0.75 pg/mL versus 2.13 +/- 0.61 pg/mL, P = .02; respectively). However, the levels of NO, albeit higher in this group had no significant difference with the controls. CONCLUSIONS The levels of cytokines are high in pediatric patients on hemodialysis, which reflects a state of oxidative stress.
The Optimization of Short-Term Hepatocyte Preservation Before Transplantation

Background No optimal methods for short-term hepatocyte preservation have been established. We have recently developed a prominent oxygen-permeable bag (Tohoku Device [TD]) for pancreatic islet culture and transplantation. In this study, we investigated whether TD is also effective for hepatocyte preservation and tried to optimize other conditions. Methods Hepatocytes were preserved in the following conditions, and their outcomes were observed. First, the effectiveness of TD was investigated. Second, hepatocyte medium (HM) and organ preservation solutions with or without fetal bovine serum (FBS) were compared. Third, as supplementations, FBS and human serum albumin (HSA) were compared. Fourth, low, room and high temperature were compared. And finally, hepatocytes preserved in various conditions were transplanted into the subrenal capsule space of nonalbumin rats and engrafted areas were assessed. Results The survival rate of hepatocytes preserved in TD tended to be higher and their viability and function were maintained significantly greater than those of non-TD group. Irrespective of FBS supplementation, the survival rate of HM group was significantly higher than those of organ preservation solution group while viabilities and plating efficiency were similar among them. Although survival rates of groups without FBS were extremely low, results of HSA supplemented group were not inferior to FBS supplemented group. Hepatocytes preserved at high temperature had the worst results. The engrafted area of TD group tended to be higher than those of other groups. Conclusions TD is effective for short-term hepatocyte preservation. HSA is a useful substitute for FBS, and preserving in HM at low temperature is recommended.
The contribution of prone sleeping position to the racial disparity in sudden infant death syndrome: the Chicago Infant Mortality Study.

BACKGROUND Rates of sudden infant death syndrome (SIDS) are over twice as high among African Americans compared with Caucasians. Little is known, however, about the relationship between prone sleeping, other sleep environment factors, and the risk of SIDS in the United States and how differences in risk factors may account for disparities in mortality. OBJECTIVE To assess the contribution of prone sleeping position and other potential risk factors to SIDS risk in a primarily high-risk, urban African American population. DESIGN, SETTING, AND POPULATION Case-control study consisting of 260 infants ages birth to 1 year who died of SIDS between November 1993 and April 1996. The control group consists of an equal number of infants matched on race, age, and birth weight. Prospectively collected data from the death scene investigation and a follow-up home interview for case infants were compared with equivalent questions for living control participants to identify risk factors for SIDS. MAIN OUTCOME MEASURES Risk of SIDS related to prone sleeping position adjusting for potential confounding variables and other risk factors for SIDS, and comparisons by race-ethnicity. RESULTS Three quarters of the SIDS infants were African American. There was more than a twofold increased risk of SIDS associated with being placed prone for last sleep compared with the nonprone positions (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.6-3.7). This OR increased after adjusting for potential confounding variables and other sleep environment factors (OR: 4.0; 95% CI: 1.8-8.8). Differences were found for African Americans compared with others (OR: 1.8; 95% CI: 1.2-2.6 and OR: 10.3, 95% CI: 10.3 [3.2-33.8, respectively]). The population attributable risk was 31%. Fewer case mothers (46%) than control mothers (64%) reported being advised about sleep position in the hospital after delivery. Of those advised, a similar proportion of case mothers as control mothers were incorrectly told or recalled being told to use the prone position, but prone was recommended in a higher proportion of black mothers (cases and controls combined) compared with nonblack mothers. CONCLUSIONS Prone sleeping was found to be a significant risk factor for SIDS in this primarily African American urban sample, and approximately one third of the SIDS deaths could be attributed to this factor. Greater and more effective educational outreach must be extended to African American families and the health personnel serving them to reduce prone prevalence during sleep, which appears, in part, to contribute to the higher rates of SIDS among African American infants.
The Effects of Pulmonary Vasodilating Agents on Right Ventricular Parameters in Severe Group 3 Pulmonary Hypertension: A Pilot Study

Pulmonary arterial hypertension (PAH)–approved vasodilators improve right ventricular (RV) function in patients with PAH. However, whether PAH-approved drugs ameliorate RV morphology and function in lung disease–associated pulmonary hypertension (lung-PH) remains unclear. We aimed to prospectively evaluate the changes in RV volume and ejection fraction (RVEF) in 14 consecutive severe lung-PH patients treated with PAH-approved vasodilators. Severe lung-PH was defined as a mean pulmonary arterial pressure (MPAP) of ≥35 mmHg or an MPAP of ≥25 mmHg with a cardiac index (L/min/m2) of <2. Right heart catheterization and cardiac magnetic resonance (CMR) imaging were performed at baseline and at 3 months after starting sildenafil with or without other PAH-approved drugs. Follow-up was conducted at 3 months in 11 participants; compared with baseline values, MPAP and pulmonary vascular resistance (PVR) decreased by 18% and 37%, respectively. Baseline CMR imaging revealed an elevated RV end-diastolic volume index (RVEDVI; mL/m2) of 117.5 ± 35.9 and a below-average RVEF of 25.2% ± 7.2%; after 3 months, RVEDVI decreased by 23.7% (P = 0.0061) and RVEF increased by 32.9% (P = 0.0165). Among the 11 patients, 3 were thought to be a stable and homogenous subset in terms of background lung disease and medical management administered. These 3 patients exhibited similar ameliorations in PVR and RVEF, compared with the other 8 patients. PAH-approved drug treatment may improve RV dilatation and systolic function among patients with severe lung-PH. This study was approved by University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) on September 1, 2013 (UMIN000011541).
Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemotherapy.

BACKGROUND In patients with breast cancer (BC) undergoing systemic chemotherapy, cancer-related fatigue (CRF) is a common problem that can negatively impact quality of life. Guarana (Paullinia cupana) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times. OBJECTIVE The purpose of this study was to evaluate the effectiveness of guarana extract on fatigue, sleep quality, anxiety, depression symptoms, and menopause in a group of BC chemotherapy patients. PATIENTS AND METHODS Patients with progressive fatigue after their first cycle of chemotherapy were randomized to receive either guarana 50 mg by mouth twice daily (32 patients) or placebo (43 patients) for 21 days. After a 7-day washout period, patients were crossed over to the opposite experimental arm. All patients were evaluated on days 1, 21, and 49. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire score, and secondary endpoints were the results of the Functional Assessment of Chronic Illness Therapy-Endocrine Symptoms (FACT-ES), Brief Fatigue Inventory (BFI), Pittsburg Sleep Quality Index, Chalder Fatigue Scale, and Hospital Anxiety and Depression Scale. RESULTS Guarana significantly improved the FACIT-F, FACT-ES, and BFI global scores compared to placebo on days 21 and 49 (p < 0.01). The Chalder Scale improved significantly on day 21 (p < 0.01) but not on day 49 (p = 0.27). Guarana did not produce any Common Terminology Criteria for Adverse Events grades 2, 3, or 4 toxicities and did not worsen sleep quality or cause anxiety or depression. CONCLUSIONS Guarana is an effective, inexpensive, and nontoxic alternative for the short-term treatment of fatigue in BC patients receiving systemic chemotherapy. Further studies are needed to confirm these results and to evaluate their generalizability to chronic CRF and to other types of cancer.
Efficacy of parenteral administration of three antimicrobial agents in treatment of clinical mastitis in lactating cows: 487 cases (1989-1995).

OBJECTIVE To evaluate the efficacy of parenteral administration of procaine penicillin G, spiramycin, or enrofloxacin in the treatment of clinical mastitis in lactating cows. DESIGN Noncontrolled, clinical retrospective study. ANIMALS 487 cows with mastitis involving 543 quarters. PROCEDURE Clinical signs, histories, and results of bacteriologic examination, somatic cell count, and N-acetyl-beta-D-glucosaminidase activity of milk samples taken before and 3 to 4 weeks after treatment were retrieved from hospital records. Cows treated parenterally with procaine penicillin G, spiramycin, or enrofloxacin for 3 to 5 days were included. Supportive treatment alone was given to 35 cows infected with Escherichia coli. Factors possibly affecting outcome were analyzed, using ANOVA, correlation analyses, and the Mann-Whitney test. chi 2 Test was used to compare bacteriologic cure rates. RESULTS Bacteriologic cure rates for mastitis caused by Staphylococcus aureus, coagulase-negative staphylococci, and streptococci were 34, 76, and 65%, respectively. Cure rates in cows in their first lactation and infected with S aureus and coagulase-negative staphylococci were significantly higher than those for older cows. In cows with mastitis caused by E coli, the cure rate was 74% for those treated with penicillin G and 71% for those not treated with antimicrobials. High N-acetyl-beta-D-glucosaminidase activity in milk samples obtained at initial examination indicated a poor outcome in S aureus and streptococcal mastitis. Cows infected in the early lactation period had more severe inflammatory responses and clinical signs if infected with coagulase-negative staphylococci and coliforms. CLINICAL IMPLICATIONS 3 to 5 days of treatment with parenterally administered penicillin G for clinical mastitis caused by penicillin-susceptible S aureus strains is efficacious in young cows. Parenteral administration of spiramycin or enrofloxacin does not give satisfactory results in mastitis caused by penicillin-resistant S aureus. Use of antimicrobials in the treatment of mastitis caused by coliform bacteria is questionable.
Counting the Costs: Case Management Implications of Spinal Cord Stimulation Treatment for Failed Back Surgery Syndrome

Purpose/objectives: The purpose of this article is to review clinical and health economic evidence supporting the use of spinal cord stimulation (SCS) for failed back surgery syndrome (FBSS) and to discuss implications for case managers' decision making. Primary practice settings: Primary settings include hospital and home environments. Findings/conclusions: Patients with FBSS experience persistent or recurring pain in the lower back, legs, or both after one or more spinal surgeries. Surgical revision and nonsurgical FBSS therapies often result in minimal or no clinical improvement, and reoperations often result in more pain. The efficacy and safety of SCS have improved as a result of earlier intervention, technological advances, and increased awareness of SCS proper patient selection. A recent randomized controlled trial (RCT) demonstrated that at mean 3-year follow-up, SCS achieves significantly more pain relief and treatment satisfaction and lower opiate analgesic use than reoperation in patients with FBSS. Another RCT demonstrated that at 6-month follow-up, more patients with FBSS achieve pain relief, enhanced quality of life, improved functioning, and higher treatment satisfaction levels with SCS than with conventional medical management (CMM). Health-economic FBSS studies show that SCS is more cost-effective than CMM or reoperation. SCS is a well-established FBSS treatment option with demonstrated efficacy and cost-effectiveness in selected patients. Implications for CM practice: Case Managers should consider recommending SCS as one modality prior to reoperation in patients with FBSS who meet the clinical criteria for its appropriate use.
Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol

The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.
Deficiency in DNA mismatch repair increases the rate of telomere shortening in normal human cells

DNA mismatch repair (MMR) is essential for genome stability and inheritance of a mutated MMR gene, most frequently MSH2 or MLH1, results in cancer predisposition known as Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC). Tumors that arise through MMR deficiency show instability at simple tandem repeat loci (STRs) throughout the genome, known as microsatellite instability (MSI). The STR instability is dominated by errors that accumulate during replication in the absence of effective MMR. In this study we show that there is a high level of instability within telomeric DNA with a tendency toward deletions in tumor‐derived MMR defective cell lines. We downregulated MSH2 expression in a normal fibroblast cell line and isolated four clones, with differing levels of MSH2 depletion. The telomere‐shortening rate was measured at the Xp/Yp, 12q, and 17p telomeres in the MSH2 depleted and three control clones. Interestingly the mean telomere‐shortening rate in the clones with MSH2 depletion was significantly greater than in the control clones. This is the first demonstration that MSH2 deficiency alone can lead to accelerated telomere shortening in normal human cells. Hum Mutat 32:939–946, 2011. © 2011 Wiley‐Liss, Inc.
Are Social Judgements Made by Children in Relation to Orthodontic Appliances?

Objective There is evidence to suggest that social judgements are made on the basis of dental appearance. This study sought to determine how children view other children with fixed orthodontic appliances. Design Cross‐sectional, self‐completion questionnaire. Subjects and methods Year 7 (aged 11–12 years) and year 10 (aged 14–15 years) school children (the participants) were invited to look at colour photographs of one girl and one boy (the subjects) and to make a social judgement about these children. Participants were randomly allocated either pictures of the two children without fixed orthodontic appliances or pictures of the same children with fixed orthodontic appliances. Using a previously validated child‐centred questionnaire, participants rated subjects using a four‐point Likert scale for three negative and six positive attributes. Multivariate analysis of variance was used to determine whether participant year group or gender and the presence of the orthodontic appliance had a significant effect on total attribute score. Results Three hundred and twenty‐two children completed the questionnaires, giving a response rate of 69%. There was a significant effect of year group (P = 0·003) and gender of the participant (P = 0·031) on the attribute score. There was no effect according to the presence or absence of an orthodontic appliance (P = 0·791). Female participants gave more positive ratings than their male peers. Conclusion This study has found that children do not make social judgements about other children purely on the basis of wearing a fixed orthodontic appliance, suggesting that they are viewed as part of a normal dental appearance in adolescence.