Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential Mechanisms by Which Certain Foods Promote or Inhibit the Development of Spontaneous Diabetes in BB Rats: Dose, Timing, Early Effect on Islet Area, and Switch in Infiltrate From Th1 to Th2 Cells

Certain diets can have major effects on the development of IDDM in DP-BB rats, but data are scant on the timing, dose, and mechanisms involved. We therefore determined the dose response, timing, and duration of exposure required to induce diabetes, and characterized the effects of nutritionally adequate diets with widely different diabetogenicity on the pancreatic islet area and cytokines. DP-BB rats were fed a diabetogenic, cerealbased, NIH-07 (NIH) diet or a protective, casein or hydrolyzed casein (HC)-based, semipurified diet. Rats were fed from weaning to 50 or 100 days with the HC diet and then switched to the NIH diet, or fed the NIH diet from weaning to 50 days and switched to the HC diet. Pancreas histology and diabetes outcome were determined. Semiquantitative morphometric analyses of hematoxylin and eosin–stained sections of pancreas from 41-day-old rats were also carried out. Diet-induced effects on pancreatic cytokine levels were measured at 70 days using reverse transcriptase–polymerase chain reaction analysis of γ-interferon (IFN-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β). Long-term daily exposure, particularly around the beginning of puberty to late adolescence (50–100 days), was important for development of diabetes. DP-BB rats could be rescued from diabetes development by feeding them a low-diabetogen HC diet as late as 50 days. Diabetes frequency was highest in rats fed 70% and 100% NIH diets. By age 41 days, before classic insulitis, the islet area in HC-fed DP-BB rats was 65% greater than in NIH-fed rats. By 70 days, when mononuclear cells were visible in the islets of most NIH-fed, but not HC-fed rats, the more pronounced inflammatory process in NIH-fed rats was associated with a Thl cytokine pattern (high IFN-γ and low IL-10 and TGF-β), whereas the pancreases of HC-fed rats showed fewer infiltrating cells, low levels of IFN-7, and high levels of TGF-p, typical of a Th2 cytokine pattern. Thus dietary modification can occur as late as puberty. Further, long-term exposure to sufficient amounts of food diabetogens between 50 and 100 days was required for maximum diabetes induction. The islet area was modified by diet before signs of classic insulitis. Pancreatic inflammation in NIH-fed animals is a Thl-dependent phenomenon. The HC diet inhibited insulitis and was associated with a Th2 cytokine pattern in the pancreas, protecting diabetes-prone rats from developing diabetes.
Activation of Akt through gp130 Receptor Signaling Is Required for Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphatic Reprogramming of Endothelial Cells

ABSTRACT Kaposi's sarcoma (KS) is the most common tumor of AIDS patients worldwide. KS-associated herpesvirus (KSHV) is the infectious cause of this highly vascularized skin tumor. The main cell type found within a KS lesion, the spindle cell, is latently infected with KSHV and has markers of both blood and lymphatic endothelial cells. During development, lymphatic endothelial cells differentiate from preexisting blood endothelial cells. Interestingly, KSHV infection of blood endothelial cells induces lymphatic endothelial cell differentiation. Here, we show that KSHV gene expression is necessary to maintain the expression of the lymphatic markers vascular endothelial growth factor receptor 3 (VEGFR-3) and podoplanin. KSHV infection activates many cell signaling pathways in endothelial cells and persistently activates STAT3 through the gp130 receptor, the common receptor of the interleukin 6 family of cytokines. We find that KSHV infection also activates the phosphatidylinositol 3-OH-kinase (PI3K)/Akt cell signaling pathway in latently infected endothelial cells and that gp130 receptor signaling is necessary for Akt activation. Using both pharmacological inhibitors and small interfering RNA knockdown, we show that the gp130 receptor-mediated activation of both the JAK2/STAT3 and PI3K/Akt cell signaling pathways is necessary for KSHV-induced lymphatic reprogramming of endothelial cells. The induction of the lymphatic endothelial cell-specific transcription factor Prox1 is also involved in KSHV-induced lymphatic reprogramming. The activation of gp130 receptor signaling is a novel mechanism for the differentiation of blood endothelial cells into lymphatic endothelial cells and may be relevant to the developmental or pathological differentiation of lymphatic endothelial cells as well as to KSHV pathogenesis.
Optical Measure of Enamel Health: Ability to Triage High Risk Children in Communities without Dental Practitioners

As prevalence of dental caries in children rises worldwide, there is an increasing need for a safe, easy to use and cost-effective technique to detect and identify childhood caries at an early stage where remineralization of the tooth is possible and damage may be reversed. We have developed a simple and robust autofluorescence (AF) laboratory device that uses the dental AF spectra from 405 nm and 532 nm laser excitation and computes a ratio of the integrated areas of the spectra. Ten human extracted teeth with early stage natural caries lesions and an additional 8 human extracted teeth with artificially created erosion lesions were used for the study. The 405/532 nm AF ratio was obtained from healthy as well as unhealthy enamel regions for all teeth. A clear distinction between the ratios for healthy enamel and unhealthy enamel was seen. A percent change in 405/532 nm AF ratio of 62% was seen between natural white spot lesions and healthy enamel, with progressively more severe lesions leading to greater percent changes in AF ratios. The 405/532 nm AF ratio is a promising technique that may be used to detect the presence of early stage dental caries and triage high risk children. A cost effective clinical device can be developed which utilizes the proposed technique to screen children in underserved communities.
Minimum Local Analgesic Dose: Effect of Different Volumes of Intrathecal Levobupivacaine in Early Labor

Background:This double-blind, randomized study was aimed at detecting the effect of three different volumes of intrathecal levobupivacaine on the minimum local analgesic dose in early labor. Methods:Ninety-three nulliparous women requesting combined spinal–epidural analgesia, at more than 37 weeks gestation, with spontaneous onset of labor, cervical dilatation from 2 to 5 cm, were enrolled. Parturients received 10 ml (group 10), 5 ml (group 5), or 2.5 ml (group 2.5) of the spinal solution containing plain levobupivacaine diluted with 0.9% wt/vol saline to achieve the desired dose and volume at room temperature. A lumbar epidural catheter was then placed. The initial dose for each group was 2.0 mg, and the following doses were determined by the response of the previous patient using up–down sequential allocation. The authors required the test solution to achieve a visual analog pain score of 10 mm or less to be considered effective. The up–down sequences were analyzed using the Dixon and Massey formula and regression logistic model. Results:The minimum local analgesic dose of spinal levobupivacaine in spontaneously laboring women was 1.35 mg (95% confidence interval, 1.25–1.45 mg) in group 10, 1.63 mg (95% confidence interval, 1.51–1.76 mg) in group 5, and 1.97 mg (95% confidence interval, 1.89–2.05 mg) in group 2.5. A unit change in volume increased the odds of an effective response multiplicatively by a factor of 1.8. Conclusions:Analgesia can be achieved using lower doses and higher volumes even in subarachnoid space. The important role of the volume should be considered not only in epidural but also in spinal analgesia.
Identification of both Myt‐1 and Wee‐1 as necessary mediators of the p21‐independent inactivation of the cdc‐2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein

The G2/M cell‐cycle arrest is one mechanism by which genistein exerts its anti‐proliferative effects, and the proposed underlying causes encompass the transcriptional repression of cyclin B1 and the activation of p21. However, the involvement of upstream kinases Myt‐1 and Wee‐1 in this arrest remains to be elucidated.
Concurrent and predictive validity of drug use and psychiatric diagnosis among first-time DWI offenders.

BACKGROUND Previous studies have found that driving while intoxicated (DWI) offenders report high rates of substance dependence and other psychiatric disorders. METHOD The current study evaluated the prevalence, clinical correlates at program admission, and prognostic significance over a 1-year follow-up of 2 diagnostic subgroup variables (drug abuse or dependence; mood or anxiety disorder) among 290 first-time DWI offenders receiving group counseling interventions. RESULTS A lifetime diagnosis of drug abuse or dependence (42% of sample) was associated with higher levels of alcohol consumption, lower coping confidence, greater readiness to change, increased alcohol, drug, and legal problems, and more alcohol-related negative consequences at the initiation of DWI intervention. Significant decreases in drinking were noted at intervention termination for the drug diagnoses subgroup, but were not sustained at 1-year follow-up. The presence of a lifetime diagnosis of anxiety or mood disorder (30% of sample) was associated with lower coping confidence, greater readiness to change, and with greater and more enduring negative consequences of drinking during the DWI intervention and 1-year follow-up period. CONCLUSIONS Results suggest that a psychiatric diagnosis might guide the intervention and aftercare planning for DWI offenders to reduce recidivism and drinking.
Arthroplasty Rates Are Increased Among US Patients with Systemic Lupus Erythematosus: 1991–2005

Objective. To evaluate population-based systemic lupus erythematosus (SLE) arthroplasty rates and compare them with rates in patients with no inflammatory or autoimmune conditions. Methods. Administrative hospital discharge databases from 10 American states were used to compare knee, hip, and shoulder arthroplasty rates from 1991 to 2005 in patients with SLE and in patients with no inflammatory or autoimmune conditions. Results. Arthroplasties were performed on patients with SLE (n = 4253) and patients with noninflammatory conditions (n = 2,762,660). Arthroplasty rates for patients with noninflammatory conditions almost doubled from 1991 to 2005 (124.5 cases/100,000 persons vs 247.5/100,000; p < 0.001). A similar trend was observed for SLE (0.17/100,000 vs 0.38/100,000; p < 0.001). The mean age at arthroplasty in patients with noninflammatory conditions decreased (71.5 ± 11.8 vs 69.0 ± 12.0; p < 0.001), whereas the mean age in patients with SLE increased (47.3 ± 17.0 vs 56.8 ± 16.0; p < 0.001). When stratified by age and sex, arthroplasty in cases of SLE increased in all groups except for women < 44 years old. In 1991, osteonecrosis accounted for 53% and osteoarthritis (OA) 23% of cases of SLE; by 2005 this relationship had reversed, with osteonecrosis accounting for 24% and OA 61% of cases of SLE. Conclusion. From 1991 to 2005, arthroplasty rates increased in patients with SLE in similar proportions to overall joint replacement rates. The age of patients with SLE arthroplasty increased and fewer cases were due to osteonecrosis. These data suggest significant changes are occurring — patients with SLE are now living long enough to develop OA and are healthy enough to undergo elective surgery.
The Clinical Impact of Ventilator-Associated Events: A Prospective Multi-Center Surveillance Study

OBJECTIVE The Centers for Disease Control and Prevention (CDC) has developed an approach to ventilator-associated events (VAE) surveillance. Using these methods, this study was performed to investigate VAE incidences and to test whether VAEs are associated with poorer outcomes in China. DESIGN A 4-month, prospective multicenter surveillance study between April and July 2013. SETTING Our study included 15 adult intensive care units (ICUs) of 15 hospitals in China. PATIENTS Patients admitted to ICUs during the study period METHODS Patients on mechanical ventilation (MV) were monitored for VAEs: ventilator-associated conditions (VACs), infection-related ventilator-associated complications (IVACs), and possible or probable ventilator-associated pneumonia (VAP). Patients with and without VACs were compared with regard to duration of MV, ICU length of stay (LOS), overall hospital LOS, and mortality rate. RESULTS During the study period, 2,356 of the 5,256 patients admitted to ICUs received MV for 8,438 ventilator days. Of these patients, 636 were on MV >2 days. VACs were identified in 94 cases (4.0%; 11.1 cases per 1,000 ventilator days), including 31 patients with IVACs and 16 with possible VAP but none with probable VAP. Compared with patients without VACs, patients with VACs had longer ICU LOS (by 6.2 days), longer duration on MV (by 7.7 days), and higher hospital mortality rate (50.0% vs 27.3%). The mortality rate attributable to VACs was 11.7%. Compared with those with VACs alone, patients with IVACs had longer duration on MV and increased ICU LOS but no higher mortality rates. CONCLUSIONS In China, surveillance of VACs and IVACs is able to identify MV patients with poorer outcomes. However, surveillance of possible and probable VAP can be problematic. Infect. Control Hosp. Epidemiol. 2015;36(12):1388–1395
Reliable polarization control of VCSELs through monolithically integrated surface gratings: a comparative theoretical and experimental study

Vertical cavity surface-emitting lasers (VCSELs) with a well-defined and predictable polarization of the emitted light are sought for a number of applications. In this paper, we show that one can define and stabilize the polarization of single- and multimode oxide-confined VCSELs with a monolithically integrated dielectric surface grating. In recent years, we have developed a three-dimensional, fully vectorial model for VCSELs, which proved to nicely reproduce the experimental results of quite complex structures, such as noncircular devices and phase-coupled VCSEL arrays. This software allows for the first time to analyze the effects of a dielectric grating in the output facet cap layer and its capability to fix the polarization of the emitted light. It is here employed as a design tool, yielding excellent agreement with the experimental data. Since the simulations predict the polarization behavior to be sensitively dependent on the grating parameters, hundreds of VCSELs with 99 different parameter sets, two grating orientations and active diameters of 4 and 7 /spl mu/m have been analyzed. Even VCSELs with eight or more coexisting modes turned out to be linearly polarized with an orthogonal polarization suppression ratio in excess of 15 dB. Theoretical and experimental emission far-fields are compared, and it is shown that diffraction side lobes can be prevented with properly chosen grating parameters which simultaneously ensure full polarization stability.
The Onchocerciasis Control Programme in West Africa (OCP)

Abstract The Onchocerciasis Control Programme in West Africa (OCP) started operations in 1975. Its main objectives were to eliminate human onchocerciasis, as a disease of public-health importance and an obstacle to socio–economic development, from the Programme area. By the end of 2002, the OCP covered 11 West African countries, and had introduced large-scale Mectizan (ivermectin) distribution to about 10 million people, through the communitydirected treatment approach, with treatment coverages ranging from 51%–81%. Research on large-scale Mectizan use illustrated the importance of evidence-based results, the power of multicountry studies, the need for social science in community-driven endeavours and operations research, and the value of empowering communities as allies in disease control. The generous donation of Mectizan by Merck & Co., Inc., has increased general interest in health-related public–private partnerships and generated the momentum for other donations to tackle other diseases. The vector control on which the OCP was initially based successfully interrupted the transmission of the parasite causing human onchocerciasis, Onchocerca volvulus, in many areas. The introduction of Mectizan led to the decline in anterior-segment lesions in the eye and the arrest of posterior-segment lesions. The drug continues to be highly effective in morbidity control, although recently there have been reports of sub-optimal responses in some adult O. volvulus, albeit in a few, very small and isolated foci.
Acute coronary syndromes in smokers: clinical and angiographic characteristics.

UNLABELLED Smoking is a major and reversible risk factor for coronary artery disease. The present work aims to define the risk factors, angiographic and clinical characteristics and evolution of acute coronary syndromes in smokers. METHODS We studied 521 consecutive patients with acute coronary syndrome admitted to the intensive care unit who underwent catheterization. We assessed the population in terms of risk factors, pathology (unstable angina or acute myocardial infarction), coronary morphology, left ventricular function, the need for intervention, evolution and complications over a one-year period. The characteristics of smokers were then compared with those of non-smokers. RESULTS Of the 521 patients with acute coronary syndrome (391 men), 182 (35 %) were smokers. The smokers were younger than the non-smokers (56.3+/-9.5 versus 66.4 +/- 7.8; p < 0.001), were more frequently male (91 versus 66%; p < 0.001), and presented more risk factors (43% with 3 or more risk factors versus 17% in non-smokers; p < 0.001), more obesity (11 versus 5%; p < 0.01), and less diabetes (19 versus 37%; p < 0.001). Smokers presented greater prevalence of acute myocardial infarction (57 versus 40%; p < 0.001) and less unstable angina. Coronary morphology was not significantly different in smokers compared to non- smokers and left ventricular function after the aculte coronary syndrome was similar in both groups. Smokers less frequently underwent surgery during hospitalization (22% versus 35%; p < 0.01) but needed angioplasty as often as non-smokers (48% versus 16%; NS). Smokers presented more frequent complications (angina, heart failure, re-infarction or CABG) than non-smokers (26% versus 17%; p < 0.01), during the first year of follow-up. One-year mortality was similar in both groups. The results were not significantly different when adjusted for gender. CONCLUSIONS On average, acute coronary syndrome occurred 10 years earlier in smokers than in non-smokers. The former generally presented more risk factors, lower prevalence of diabetes and higher of obesity, more myocardial infarctions and less unstable angina. After the acute coronary syndrome, at one year, smokers presented more complications than non-smokers but had similar mortality.
Direct-acting antiviral-based triple therapy on alpha-fetoprotein level in chronic hepatitis C patients.

AIM To investigate the impact of telaprevir-based triple therapy on the serum alpha-fetoprotein (AFP) level of chronic hepatitis C patients. METHODS A total of 210 patients with chronic hepatitis C genotype 1 of high viral load (baseline serum hepatitis C virus RNA > 5.0 log10 IU/mL) were divided into two groups by type of treatment: triple therapy with telaprevir, pegylated-interferon-α (PEG-IFNα), and ribavirin (RBV) for 24 wk (n = 88), or dual therapy with PEG-IFNα and RBV for 48 wk (n = 122). The relationship between virological response and the change in the serum AFP level from baseline to 24 wk after the end of treatment was examined. RESULTS No significant difference in mean baseline AFP level was found between the triple and dual therapy groups (8.8 ng/mL vs 7.8 ng/mL). Triple therapy produced significant declines in the AFP level in sustained virological response (SVR) and non-SVR patients (7.8 ng/mL at baseline to 3.5 ng/mL at 24 wk after the end of treatment, P < 0.001 and 14.3 ng/mL to 9.5 ng/mL, P = 0.004, respectively). In contrast, dual therapy resulted in a significant decline in AFP level only in SVR patients (4.7 ng/mL to 2.8 ng/mL, P < 0.001), but not in non-SVR patients (10.2 ng/mL to 10.1 ng/mL). Among patients with a high-baseline AFP level (≥ 10 ng/mL), the decline in the AFP level was significantly higher in the triple therapy than in the dual therapy group (15.9 ng/mL vs 1.6 ng/mL, P = 0.037). CONCLUSION Regardless of virological response, telaprevir-based triple therapy reduced the serum AFP level.
Dimerization of CXCR4 in living malignant cells: control of cell migration by a synthetic peptide that reduces homologous CXCR4 interactions

Chemokine receptor CXCR4 (CD184) may play a role in cancer metastasis and is known to form homodimers. However, it is not clear how transmembrane regions (TM) of CXCR4 and receptor homotypic interactions affect the function of CXCR4 in living cells. Using confocal microscopy and flow cytometric analysis, we showed that high levels of CXCR4 are present in the cytoplasm, accompanied by lower expression on the cell surface in CXCR4 transfectants, tumor cells, and normal peripheral blood lymphocytes. CXCR4 homodimers were detected in tumor cells, both on the cell surface membrane and in the cytoplasm using fluorescence resonance energy transfer and photobleaching fluorescence resonance energy transfer to measure energy transfer between CXCR4-CFP and CXCR4-YFP constructs. Disruption of lipid rafts by depletion of cholesterol with methyl-β-cyclodextrin reduced the interaction between CXCR4 molecules and inhibited malignant cell migration to CXCL12/SDF-1α. A synthetic peptide of TM4 of CXCR4 reduced energy transfer between molecules of CXCR4, inhibited CXCL12-induced actin polymerization, and blocked chemotaxis of malignant cells. TM4 also inhibited migration of normal monocytes toward CXCL12. Reduction of CXCR4 energy transfer by the TM4 peptide and methyl-β-cyclodextrin indicates that interactions between CXCR4s may play important roles in cell migration and suggests that cell surface and intracellular receptor dimers are appropriate targets for control of tumor cell spread. Targeting chemokine receptor oligomerization and signal transduction for the treatment of cancer, HIV-1 infections, and other CXCR4 mediated inflammatory conditions warrants further investigation. [Mol Cancer Ther 2006;5(10):2474–83]
Effect of lengthening rate on angiogenesis during distraction osteogenesis

This study investigated the angiogenic response to four varying rates (0.3, 0.7, 1.3, and 2.7 mm/day) of distraction in a rabbit model of leg‐lengthening. Immunostaining was performed with use of specific antibodies to type‐IV collagen and endothelial cell antigen to examine semiquantitatively the presence of blood vessels in the developing tissues. With use of the Chalkley counting method, the greatest number of positive staining blood vessel cells was found in the central fibrous zone of the groups that underwent lengthening at 0.7 and 1.3 mm/day compared with any other zone in any group (p < 0.05, t test). There were no statistical differences in the positive labeling indices in the mineralization front and the new bone zone adjacent to the mineralization front in any of the groups. However, the decrease in the number of positive‐staining blood vessel cells in the new bone zone distant to the mineralization front compared with any other zone in any group was statistically significant. The results suggest that during distraction osteogenesis, the precursor cells of new capillaries were present in abundance within the fibrous interzone. These cells connected into the capillary network at the junction of the mineralization front and the fibrous zone. The angiogenic response was weaker in the more mature regions within the new bone zones. A slow rate of distraction (0.3 mm/day) did not maximally stimulate angiogenesis in the central fibrous zone, whereas high rates (2.7 mm/day) appeared to impair this response. In this model of distraction osteogenesis, the vascularization process in the central fibrous zone was maximally stimulated at distraction rates of 0.7 and 1.3 mm/day.