Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of the HIV Protease Inhibitor Ritonavir on GLUT4 Knock-out Mice*

HIV protease inhibitors acutely block glucose transporters (GLUTs) in vitro, and this may contribute to altered glucose homeostasis in vivo. However, several GLUT-independent mechanisms have been postulated. To determine the contribution of GLUT blockade to protease inhibitor-mediated glucose dysregulation, the effects of ritonavir were investigated in mice lacking the insulin-sensitive glucose transporter GLUT4 (G4KO). G4KO and control C57BL/6J mice were administered ritonavir or vehicle at the start of an intraperitoneal glucose tolerance test and during hyperinsulinemic-euglycemic clamps. G4KO mice exhibited elevated fasting blood glucose compared with C57BL/6J mice. Ritonavir impaired glucose tolerance in control mice but did not exacerbate glucose intolerance in G4KO mice. Similarly, ritonavir reduced peripheral insulin sensitivity in control mice but not in G4KO mice. Serum insulin levels were reduced in vivo in ritonavir-treated mice. Ritonavir reduced serum leptin levels in C57BL/6J mice but had no effect on serum adiponectin. No change in these adipokines was observed following ritonavir treatment of G4KO mice. These data confirm that a primary effect of ritonavir on peripheral glucose disposal is mediated through direct inhibition of GLUT4 activity in vivo. The ability of GLUT4 blockade to contribute to derangements in the other molecular pathways that influence insulin sensitivity remains to be determined.
Developmental expression of α4 protein phosphatase regulatory subunit in tissues affected by Opitz syndrome

Mutations in the Mid1 gene are responsible for X‐linked Opitz syndrome, characterized by midline defects of the brain, face, heart, and trachea. The regulatory subunit α4 binds protein phosphatase 2A to Mid1 and promotes Mid1 dephosphorylation, in opposition to MAP kinase. To examine the relationship between α4 expression and human defects in Opitz syndrome, developmental expression of α4 in embryonic day (E) 8–E16 mouse embryos was mapped by immunohistochemistry. At E10, α4 was first detected only in the heart. At E11, α4 was expressed in epithelium of the mandibular and maxillary arches and in specific subsets of mesenchymal cells within the arches. The fetal heart and brain also highly expressed α4. At E16, α4 expression broadened to include the heart, brain, skeletal muscle, and tracheal and esophageal epithelium but not smooth muscle. Consistent with immunolocalization in embryos, Western immunoblotting of adult rabbit tissues demonstrated high levels of α4 expression in brain, heart, lung, liver, and skeletal muscle with low expression in kidney, uterus, and intestine. Expression in slow type I skeletal muscle was much higher than in fast type II muscle. By using double immunohistochemical staining, α4 was coexpressed in mouse skeletal muscle cells containing slow type myosin. Expression of α4 overlaps with the tissue defects in Opitz syndrome. The α4 gene lies in the linkage interval for FG syndrome, characterized by skeletal muscle and brain defects that coincide closely to the expression pattern of α4. © 2002 Wiley‐Liss, Inc.
In Vitro Comparison of the Effect of Different Slice Thicknesses on the Accuracy of Linear Measurements on Cone Beam Computed Tomography Images in Implant Sites

Background and AimsUse of dental implants in edentulous patients has become a common treatment modality. Treatment of such implants requires radiographic evaluation, and in most cases, several different imaging techniques are necessary to evaluate the height, width, and structure of the bone at the implant site. In the current study, an attempt was made to evaluate the accuracy of measurements on cone beam computed tomography (CBCT) images with different slice thicknesses so that accurate data can be collected for proper clinical applications. Materials and MethodsIn the present in vitro study, 11 human dry mandibles were used. The width and height of bone at the central, canine, and molar teeth areas were measured on the left and right sides by using digital calipers (as gold standard) and on CBCT images with 0.5-, 1-, 2-, 3-, 5-, and 10-mm slice thicknesses. Data were analyzed with SPSS 16, using paired t-test, Tukey test, and inter class correlation. ResultsData were collected by evaluation of 11 skulls and 63 samples on the whole. There were no significant differences in bone width in any area (P > 0.05). There were significant differences in bone height in the central and molar teeth areas (P = 0.02). The measurements were not significant only at 4-mm slice thickness option and 5-mm slice thickness option for height compared with the gold standard (P = 0.513 and 0.173, respectively). The results did not show any significant differences between the observers (P = 0.329). ConclusionThe highest measurement accuracy of CBCT software program was observed at 4-mm slices for bone width and 5-mm slice thickness for bone height.
The Impact of Socioeconomic, Organizational and Individual Factors on Government Organizational Performance: Evidence from China

The purpose of this study is to examine several key elements of organizational performance in the public sector empirically. By exploring the effects of socioeconomic, organizational as well as individual factors based on responses from a primary survey, the authors find that those governmental organizations with more public orientation, more employee orientation, clearer goals, less procedure constraints are more effective than their counterparts. Governmental organizations located in the area of higher new economic index usually have higher levels of performance than those lower. Those employees with higher levels of public service motivation tend to report higher organizational performance perception than those less. The study suggests that strengthening the culture of public interest, improving organizational management, and enhancing employees' public service motivation may be the efficient ways to improve the performance.
Local and systemic oxidative stress status in chronic obstructive pulmonary disease patients.

BACKGROUND Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVES To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. METHODS Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). RESULTS MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). CONCLUSIONS Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients.
Representative case series from public hospital admissions 1998 II: surgical adverse events.

AIMS To examine a representative case series of surgical adverse events in New Zealand public hospitals with a view to assessing their occurrence, causation, patient impact and preventability. METHODS An analysis was carried out on 326 surgical adverse events classified by reviewing physicians. These were identified from among 850 adverse events determined by two-stage retrospective review of a representative sample of 6579 medical records drawn from 13 public hospitals in 1998. RESULTS From the four surgical categories--operative, fracture management, therapeutic, and system--there were 326 surgical adverse events, 38.4% of all adverse events identified. Surgical events had the same profile as adverse events overall. Four-fifths of surgical events were directly related to a surgical operation; these affected older patients and were less preventable than adverse events overall. A third of operative events were attributable to technical problems, another third to infections, with the remainder divided between haemorrhagic and cardiovascular complications. Therapeutic and system events had high preventability, and a significant proportion was related to delay in treatment. Half of events in fracture management were infection-related, patients were younger and, system events apart, had fewer extra bed days than other surgical events or events overall. The major causes of preventable events were avoidable delay in treatment (19.9%) and inadequate monitoring and supervision (13.6%), followed by personnel practising outside their expertise (8.0%) and inappropriate treatment (7.4%). CONCLUSIONS On average, surgical events are associated with an extra 9.9 days in hospital, but they have a lower level of preventability than adverse events overall. Problems of infection, delay, and other aspects of the quality of care are identified for further consideration.
Investigation of myringosclerosis development in different grafting materials after myringo-/tympanoplasty.

OBJECTIVES This study aims to investigate the prevalence of myringosclerosis in tragal perichondrium (TP) and temporalis fascia (TF) grafts after myringo-/tympanoplasty. PATIENTS AND METHODS Thirty patients, who were diagnosed with non-suppurative chronic otitis media and administered myringo-/tympanoplasty under general anesthesia using TP or TF as grafting material in our clinic between January 2012 and May 2013, were recruited in this retrospective case-control study. Patients were divided into two groups according to used graft material as group 1 (TP) (9 males, 6 females; median age 35.4 years; range 20 to 62 years) and group 2 (TF) (7 males, 8 females; median age 39.8 years; range 19 to 63 years). Occurrence of myringosclerosis on the intact tympanic membrane grafts was evaluated postoperatively by the same surgeon under surgical microscope. RESULTS Postoperative myringosclerosis was detected in six patients (40%) in TP group and 13 patients (86.7%) in TF group. CONCLUSION Prevalence of myringosclerosis on graft materials used in myringo-/tympanoplasty was lower in TP group compared to TF group. We believe that this may be due to different vascular structures of different graft tissues and that the low predisposition of perichondrium towards development of myringosclerosis can be considered as an advantage for this graft. We hope that this study adds a new dimension to etiopathogenesis of myringosclerosis and assists otologists in the prevention and treatment of this lesion.
Biochemical Changes in Micro-Fungi Fermented Cassava Flour Produced from Low- and Medium-Cyanide Variety of Cassava Tubers

Comparative studies were carried out on the ability of pure strain of Rhizopus oryzae and Saccharomyces cerevisae to alter the nutritional quality of cassava flour produced from low-and medium-cyanide variety of cassava tuber. Low- and medium-cyanide variety of cassava tubers were collected from International Institute of Tropical Agriculture (IITA), Ibadan, Nigeria. These tubers were washed, peeled, grated and aseptically inoculated with pure strains of Rhizopus oryzae and Saccharomyce cerevisae in nutrient solution respectively, before allowing them to ferment aerobically for 3 days. The fermented mash was subsequently dried and milled into cassava flour. Subsequently, the proximate, mineral and the antinutrinet composition of the cassava flour were determined. The results of the study revealed that the unfermented flour from low-cyanide cassava variety had higher protein, fibre, ash, fat, Ca, Na and K; while those produced from medium-cyanide variety, had higher antinutrinet (tannin, cyanide & phytate), Zn, Mg and Fe content. However, solid substrate fermentation of the cassava mash using Rhizopus oryzae and Saccharomyces cerevisae respectively caused a significant (P<0.05) increase in the protein and fat content. The nutrient enrichment was significantly higher (P<0.05) in flour produced from low-cyanide cassava variety. In addition, Saccharomyces cerevisae fermentation brought about a higher increase in the nutrient content than Rhizopus oryzae fermentation. Conversely, fermentation of the cassava caused a significant decrease (P<0.05) in the antinutrient content of the flour; although, the level of decrease was more in the flour produced from low-cyanide variety than medium-cyanide variety. Nevertheless, there was no significant difference (P>0.05) in the ability of the fungi to decrease the antinutrient (except phytate) of the cassava flour. Furthermore, micro-fungi fermentation did not cause a significant change (P<0.05) in mineral content (except Mg and K) of the fermented cassava flour. In conclusion, unfermented cassava flour produced from low-cyanide cassava tubers had high nutrient composition and low antinutrient content and more susceptible to micro-fungi nutrient enrichment and detoxification than medium-cyanide variety. Furthermore, Saccharomyces cerevisae was more efficient in the nutrient enrichment of the cassava flour than Rhizopus oryzae.
Social Network and Coronary Artery Calcification in Asymptomatic Individuals

Background: Psychosocial factors are associated with the development of coronary artery disease. However, studies examining psychosocial factors as risk indicators for coronary artery calcification (CAC) have been inconclusive. Methods: Seven hundred eighty-three participants (mean age 57.4 ± 9.3 years, 47% female) underwent CAC imaging using electron beam tomography. Psychosocial measures included social network (number of people in the household, marital status), socioeconomic status (education, income, and work status), history of depression, and current depressive symptoms as assessed with the Center for Epidemiologic Studies Depression (CES-D) scale. Assessments were also made for lipid profile, blood glucose, blood pressure, and health behaviors (smoking status, exercise, and diet). Results: Calcification was present in 351 (44.8%) participants (CAC score range 0–3022; mean 111.5 ± 307.2). Indicators of social isolation (being single or widowed) were independently associated with elevated risk for the presence of CAC, even after adjustment for age, sex, systolic blood pressure, blood glucose, and low-density lipoprotein (adjusted odds ratios 1.80, 95% confidence interval [CI] = 1.05–3.10, and 2.48, 95% CI = 1.02–6.03, respectively). By contrast, health behaviors, socioeconomic status, and depressive symptoms were not related to CAC. Conclusions: Social network indices such as being single or widowed are associated with CAC, independent of age and coronary risk factors. Because coronary calcification has been identified as a potential marker of early atherosclerosis, these findings may partially explain the predictive value of limited social networks for future adverse cardiovascular health outcomes. BMI = body mass index; CAC = coronary artery calcification; CAD = coronary artery disease; CES-D = Center for Epidemiologic Studies Depression; CI = confidence interval; DBP = diastolic blood pressure; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio; SBP = systolic blood pressure.
Enhanced metastases of a mouse carcinoma after in vitro treatment with murine interferon gamma

We have studied the influence of inter ferons (IFNs) on the metastatic potential of mouse colon adenocarcinoma, COLON 26, cells. Pre‐treatment of the cells in vitro for 24 hr with recombinant murine IFN‐γ (rMuIFN‐γ) significantly in‐creased the number of lung tumour nodules when cells were injected i.v. into immunocompetent BALB/c mice and BALB/ c nude mice. However when MulFN‐γ‐pre‐treated cells were injected into beige (NK‐deficient) nude mice or anti‐asialoGM I (as GMI)‐serum‐treated BALB/c mice (NK‐depleted) no enhancement of metastatic potential was seen. Pre‐treatment of COLON 26 cells with recombinant human IFN‐α A/D (Bgl I), an IFN with equal activity on human and mouse cells, did net significantly enhance their subsequent metastases in immunocompetent or immunodeficient mice. In fact, there was a small but significant decrease in the number of tumour nodules in the lungs of beige nude and asGM I ‐treated mice. The e effects of rMuIFN‐γ on COLON 26 cells did not appear to be related to an alteration in MHC expression. COLON 26 eel Is constitutively express H‐2D and H‐2K antigens and both IFNs had equal enhancing (approx. 2‐fold) activity on the expression of these antigens at the doses used in this experiment (103 U/ml). We conclude that pre‐treatment with rMuIFN‐γ renders COLON 26 cells resistant to in vivo NK‐cell lysis via a mechanism that does not involve changes in MHC expression.
How deep should you squat to maximise a holistic training response? Electromyographic, energetic, cardiovascular, hypertrophic and mechanical evidence.

Skeletal muscle possesses the ability to change its structural and mechanical characteristics in response to its external environment (i.e. it is adaptable). The exact nature of such adaptations is manipulated by, amongst other things, the mechanical stimulus provided to the said muscle. Resistance exercise is an example of one such stimulus, and is used in a variety of settings, such as athletic performance, general health and fitness, injury prevention and rehabilitation. It is also now commonplace for resistance exercise to be used to offset the debilitating effects of illness, disease and sarcopenia (the latter being a term used to describe the age-related loss in muscle mass, which is also accompanied by increased fatty tissue infiltration and the ensuing decrement in muscle ‘quality’). The objectives of the resistance exercise protocol therefore, will vary due to the unique nature of each setting, and therefore should be optimised in order to bring about a specific and desirable set of adaptations. Frequent adaptations that are sought from resistance exercise regimes include an increase in muscle cross-sectional area (CSA) and strength [1], alterations to muscle architecture (spatial arrangement of muscle fibres within a muscle [2]), and greater maximal activation of the musculature [3].
Liver-to-Plasma Vaniprevir (MK-7009) Concentration Ratios in HCV-Infected Patients

Background Some drugs that are actively taken up into the liver exhibit greater than dose proportional increases in plasma exposure, although human liver-to-plasma concentration ratios have rarely been evaluated. Understanding these relationships has implications for drug concentrations at the target site for certain classes of compounds, such as direct-acting antivirals, targeted towards HCV. Methods Treatment-experienced, chronic HCV non-cirrhotic patients (n=3) received vaniprevir (600 mg or 300 mg twice daily) on days 1–3 and (600 mg or 300 mg single dose) on day 4. Core needle biopsy was performed at 6 or 12 h post-dose on day 4. Blood samples were collected pre-dose on days 1 and 4, and for 24 h post-dose on day 4. The primary study objective was the hepatic concentration of vaniprevir at 6 and 12 h post-dose. Results Vaniprevir plasma pharmacokinetic parameters increased in a greater than dose-proportional manner between the 300 mg and 600 mg doses, with approximately fivefold increases in AUC0–12 and Cmax associated with a twofold increase in dose (AUC0–12, 10.6 μM/h to 59.5 μM/h; Cmax, 2.60 μM to 13.5 μM). In the 300 mg and 600 mg dose groups, mean liver concentrations of vaniprevir were 84.6 μM and 169 μM at 6 h post-dose, and 29.4 μM and 53.7 μM at 12 h post-dose. Liver concentrations were higher than plasma with liver-to-plasma concentration ratios of approximately 20–280. Conclusions These data confirm higher vaniprevir concentrations in human liver compared with plasma and demonstrate that measurement of human liver drug concentration using needle biopsy is feasible.
Role of ATM in the Formation of the Replication Compartment during Lytic Replication of Epstein-Barr Virus in Nasopharyngeal Epithelial Cells

ABSTRACT Epstein-Barr virus (EBV), a type of oncogenic herpesvirus, is associated with human malignancies. Previous studies have shown that lytic reactivation of EBV in latently infected cells induces an ATM-dependent DNA damage response (DDR). The involvement of ATM activation has been implicated in inducing viral lytic gene transcription to promote lytic reactivation. Its contribution to the formation of a replication compartment during lytic reactivation of EBV remains poorly defined. In this study, the role of ATM in viral DNA replication was investigated in EBV-infected nasopharyngeal epithelial cells. We observed that induction of lytic infection of EBV triggers ATM activation and localization of DDR proteins at the viral replication compartments. Suppression of ATM activity using a small interfering RNA (siRNA) approach or a specific chemical inhibitor profoundly suppressed replication of EBV DNA and production of infectious virions in EBV-infected cells induced to undergo lytic reactivation. We further showed that phosphorylation of Sp1 at the serine-101 residue is essential in promoting the accretion of EBV replication proteins at the replication compartment, which is crucial for replication of viral DNA. Knockdown of Sp1 expression by siRNA effectively suppressed the replication of viral DNA and localization of EBV replication proteins to the replication compartments. Our study supports an important role of ATM activation in lytic reactivation of EBV in epithelial cells, and phosphorylation of Sp1 is an essential process downstream of ATM activation involved in the formation of viral replication compartments. Our study revealed an essential role of the ATM-dependent DDR pathway in lytic reactivation of EBV, suggesting a potential antiviral replication strategy using specific DDR inhibitors. IMPORTANCE Epstein-Barr virus (EBV) is closely associated with human malignancies, including undifferentiated nasopharyngeal carcinoma (NPC), which has a high prevalence in southern China. EBV can establish either latent or lytic infection depending on the cellular context of infected host cells. Recent studies have highlighted the importance of the DNA damage response (DDR), a surveillance mechanism that evolves to maintain genome integrity, in regulating lytic EBV replication. However, the underlying molecular events are largely undefined. ATM is consistently activated in EBV-infected epithelial cells when they are induced to undergo lytic reactivation. Suppression of ATM inhibits replication of viral DNA. Furthermore, we observed that phosphorylation of Sp1 at the serine-101 residue, a downstream event of ATM activation, plays an essential role in the formation of viral replication compartments for replication of virus DNA. Our study provides new insights into the mechanism through which EBV utilizes the host cell machinery to promote replication of viral DNA upon lytic reactivation.