Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of efavirenz, nevirapine, etravirine, and raltegravir administration on the pharmacokinetics of ritonavir-boosted darunavir in a population of HIV-infected patients.

Abstract The influence of efavirenz, etravirine, raltegravir, and nevirapine administration on the pharmacokinetics of ritonavir-boosted darunavir was investigated using population pharmacokinetics analysis. The population was composed of 142 patients infected with HIV: darunavir plus nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), 54 patients (group A); darunavir plus efavirenz±NRTI, 4 patients (group B); darunavir plus etravirine±NRTI, 5 patients (group C); darunavir plus nevirapine±NRTI, 21 patients (group D); darunavir plus raltegravir±NRTI, 38 patients (group E); and darunavir plus raltegravir and etravirine±NRTI, 20 patients (group F). A significant increase in darunavir clearance in combination with nevirapine (+66%) and efavirenz (+235%) was observed. A significant decrease (p<0.05) in trough plasma concentration was observed in groups B and D compared with the other groups. Our study indicates that the combination of ritonavir-boosted darunavir and etravirine or raltegravir has no significant influence on the pharmacokinetics of darunavir in contrast to the combination of ritonavir-boosted darunavir and nevirapine or efavirenz, which involves an increase in darunavir clearance and a decrease in the plasma concentration of darunavir.
Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and Intestinal Permeability Are MyD88-Dependent: Role of the Innate Immune Response in Celiac Disease1

Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD.
A review of steroids from Sarcophyton species

Abstract This review reports the structural diversity of steroids from Sarcophyton species based on literature from the beginning of marine steroid research until now. There are 65 compounds studied from eight species. Most of them are polyhydroxy-type steroids of C-27–C-31 carbon skeleton. Their biological activities are highly diverse ranging from cytotoxic, antibacterial, antifungal, antiviral, anti-inflammatory, antidiabetic to antiosteoporosis properties.
Difference in weight loss based on ethnicity, age and comorbidity status in a publicly funded adult weight management centre: 1‐year results

Limited evidence is available on the effectiveness of publicly funded weight loss (WL) clinics. We examined the 1‐year WL outcomes and investigated predictors of WL and discontinuation of 1566 overweight and obese adults, who attended the Wharton Medical Clinic (WMC) weight management centre for at least 6 months. Overall, 42.7% (n = 669) of the entire sample achieved a ≥5%WL over the entire follow‐up period from July 2008 to February 2012. On average, patients lost 5.6 ± 7.2 kg (5.0 ± 6.3%) of initial body weight (BW), while a subsample of patients attending the clinic for at least 1 year had a mean weight reduction of 6.6 ± 7.9 kg (5.9 ± 7.2%) of BW. Older patients were more likely to achieve a greater WL in comparison with young patients while White patients and those without type 2 diabetes (T2D) lost almost twice as much weight and %BW in comparison with Asian patients and patients with T2D, respectively (P < 0.05). Discontinuing patients did not differ in terms of sex, body mass index, education and smoking status from those who continued treatment (P > 0.05). Results of this study demonstrate that the WMC provides a practical model for clinically effective lifestyle‐based treatment, accessible to a wide range of demographically diverse adults.
Association between adiponectin concentrations and diabetic retinopathy in patients with type 2 diabetes: a meta analysis

Background Numerous studies have investigated the association between adiponectin concentrations and diabetic retinopathy (DR) caused by type 2 diabetic mellitus. However, the results remain conflicting. We performed a metaanalysis to explore the relationship between adiponectin concentrations and risk of DR caused by type 2 diabetic mellitus from published articles. Methods A published literature search was performed through the PubMed, Cochrane Library, EMBASE, Science Citation Index Expanded database, Chinese CNKI, and Chinese Wan Fang databases for articles published in English and Chinese. Pooled standardized mean differences (SMDs) and 95% confidence intervals (95% CIs) were calculated using random or fixed effects model. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Results Nineteen studies with a total of 1 545 cases and 1 502 controls were retrieved. The original meta‐analysis found a significant difference in the adiponectin concentrations between the DR and non‐DR (NDR) groups. After excluding the high heterogeneity studies, the second meta‐analysis also demonstrated the significant association (SMD (95% CI) =‐0.62 (‐0.80 to ‐0.44), P=0.0001). According to the available data, there was statistical significance in the adiponectin concentrations considering non‐proliferative DR (NPDR) versus NDR, PDR versus NPDR in Chinese populations with high heterogeneity. Conclusion Adiponectin concentrations are correlated with DR; however, the relationship between adiponectin concentrations and DR needs more in‐depth investigations with larger sample sizes.
MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model.

BACKGROUND Neuropathic pain is a common side-effect of chemotherapy. Although precise mechanisms are unclear, oxidative stress and mitochondrial damage are involved. We investigated whether the mitochondria targeted antioxidant, MitoVitE, provided better protection against paclitaxel-induced mitochondrial damage in rat dorsal root ganglion (DRG) cells, than a non-targeted form of vitamin E, Trolox. We also determined whether MitoVitE, compared with duloxetine, could limit paclitaxel-induced mechanical hypersensitivity in rats. METHODS Mitochondrial function was measured in DRG cells exposed to paclitaxel with and without MitoVitE or Trolox. The effect of MitoVitE or Trolox on paclitaxel-induced cell killing in cancer cell lines was also determined. Rats received a cumulative dose of 8 mg kg-1 paclitaxel plus either MitoVitE (2 mg-1 kg day-1), duloxetine (10 mg kg-1 day-1) or vehicle control daily. Mechanical hind paw withdrawal thresholds were measured every two days. RESULTS Paclitaxel caused loss of membrane potential in DRG cells. At 100 µM paclitaxel median [range] change was 61[44-78]%, P < 0.0001, which was ameliorated by MitoVitE (86[62-104]%) but not Trolox (46[46-57]%). Similarly, loss of metabolic activity and glutathione induced by paclitaxel (both P < 0.0001) were reduced by MitoVitE but not Trolox. Cytotoxicity of paclitaxel was not affected by co-exposure of ovarian cancer cells to either MitoVitE or Trolox, but was slightly reduced against breast cancer cells, in the presence of Trolox. Mean (SD) areas under the curve of withdrawal thresholds at 6 h after injection in rats given paclitaxel + control, or + MitoVitE (P < 0.0001) or + duloxetine (P < 0.0001) were 110 (5), 145 (10) and 156 (13) respectively. CONCLUSIONS Paclitaxel affected mitochondrial function and glutathione in DRG cells, which was abrogated by MitoVitE but not Trolox, without decreasing cancer cell cytotoxicity. In rats, paclitaxel-induced mechanical hypersensitivity was ameliorated by MitoVitE treatment to an extent similar to duloxetine. These data confirm mitochondria as a mechanistic target for paclitaxel-induced damage and suggest mitochondria targeted antioxidants as future therapeutic strategies.
How Personal Values Influence Romanian CSR Managers` Involvment in CSR Campaigns

This study focuses on identifying the ratio between the individual and organization authority of CSR managers concerning decision making within the campaigns they coordinate. The sample includes the top 100 Romanian companies selected by turnover. The way in which the managers' values interact with the organization authority is a subject treated poorly in both international and Romanian literature. This study, which has an exploratory character, investigates how personal values lead Romanian CSR managers to develop and coordonate CSR campaigns and to what extent these values are part of the campaign messages compared to the values of the company for which they are made. The main results of this scientific paper refers to the correlation between the CSR managers' values and the campaigns that they coordinate.
Modeling dichromatic and trichromatic sensitivity to the color properties of fruits eaten by squirrel monkeys (Saimiri sciureus)

Most platyrrhines have a visual polymorphism that is characterized by the presence of multiple alleles of the M/LWS gene on the X chromosome. This polymorphism is probably maintained by selection. There are two possible mechanisms by which this can be explained: First, heterozygous females may have perceptual advantages over dichromats, such that trichromacy would be favored via the existence of different visual pigments. This is known as selection by heterosis. Second, dichromacy may be advantageous in some situations, with polymorphism being maintained by frequency‐dependent selection. In this study the reflectance spectra of fruits and flowers eaten by a troop of squirrel monkeys (Saimiri sciureus) in Eastern Amazon were measured using a spectrophotometer. S. sciureus have an SWS cone with a spectral tuning of approximately 430 nm, and three M/LWS alleles with spectral tunings of 535 nm, 550 nm, and 562 nm. Based on the spectral tunings of the different phenotypes and the spectral data obtained from the food items, the responses of the different visual systems to the measured objects were modeled and then compared. The model predicted that trichromatic phenotypes would have an advantage over dichromats in detecting fruits and flowers from background foliage, which suggests that heterosis is the mechanism for maintaining polymorphism in S. sciureus. On the other hand, a large proportion of fruits could not be detected by any of the phenotypes. Additional studies are necessary to determine whether other important aspects of the primates' visual world, such as prey, predator, and conspecific detection, favor tri‐ or dichromacy. Am. J. Primatol. 68:1129–1137, 2006. © 2006 Wiley‐Liss, Inc.
Ambulatory Discharge After Long-Acting Peripheral Nerve Blockade: 2382 Blocks with Ropivacaine

Discharging patients with a long-acting peripheral nerve block remains controversial. Concerns about accidental injury of the limb or surgical site because of an insensate extremity are common despite a lack of data on the subject. We report a study examining the efficacy and complications of discharge after long-acting block. This prospective study included 1791 patients receiving an upper or lower extremity nerve block with 0.5% ropivacaine and discharged the day of surgery. Efficacy (conversion to general anesthesia and opioid use), persistent motor or sensory weakness, complications, satisfaction, and unscheduled health care visits were assessed in the postanesthesia care unit (PACU) and at 24 h and 7 days postoperatively using a detailed questionnaire. There were 2382 blocks placed: 1119 upper extremity blocks and 1263 lower extremity blocks. Efficacy was demonstrated by a small conversion to general anesthesia (1%–6%) and a lack of patients requiring opioids in the PACU (89%–92%). A large percentage of patients continued to use opioids at 7 days (17%-22%). Despite the requirement for opioids, satisfaction with the anesthesia experience was high at 24 h and 7 days (Liekert scale [1–5] mean at 24 h, 4.88 ± 0.44; mean at 7 days, 4.77 ± 0.69) and most (98%) would choose the same anesthetic again. Thirty-seven patients (1.6%) were identified with symptoms or complaints at 7 days. After review, 6 of them (0.25%) had a persistent paresthesia that may have been related to the block or discharge. We conclude that long-acting peripheral nerve blockade may be safely used in the ambulatory setting with a high degree of efficacy, safety, and satisfaction. This technique is associated with an infrequent incidence of neurologic complications and injuries. Given the frequent incidence of persistent pain at 7 days, prolongation of the analgesia would be beneficial.
Lower red blood cell counts in middle‐aged subjects with shorter peripheral blood leukocyte telomere length

Although telomere biology was revealed to play an important role in several hematopoietic disorders, its impact on the age‐dependent dynamics of regular hematopoiesis is poorly understood. In vitro results suggest that particularly the erythropoietic capacity might be limited by critically short telomere length (TL). However, it remains unclear whether TL also affects erythropoiesis in healthy individuals in vivo. Therefore, we analyzed the associations between relevant hematopoietic parameters and peripheral blood leukocyte TL in the apparently healthy Asklepios study population, aged approximately 35–55 years (N > 2500). Our data indicate a clear positive, age and paternal age at birth adjusted, correlation between TL and red blood cell count, both in men (p < 0.001) and women (p = 0.011). This association was particularly significant in the older segment of the population (> 45 years old, both sexes: p = 0.003) and in younger men (p = 0.013), but not in younger women (p = 0.521). Further adjustment for known determinants in a general linear model revealed that peripheral blood leukocyte TL is most probably an independent predictor of red blood cell count (p < 0.001), suggesting that critical telomere shortening might also limit erythropoiesis in vivo. While negligible in a middle‐aged population, the clinical consequences might be important in the elderly (e.g. in anemia of chronic disease). Further studies are required to confirm the impact of our results.
Molecular characterization of FRAXB and comparative common fragile site instability in cancer cells

The common fragile site, FRA3B, has been shown to be a site of frequent homozygous deletions in some cancers, resulting in loss of expression of the associated FHIT gene. It has been proposed that FHIT is a tumor suppressor gene that is inactivated as a result of the instability of FRA3B in tumorigenesis. More recently, deletions at other common fragile sites, FRA7G and FRA16D, have been identified in a small number of cancer cell lines. Here, we have mapped and molecularly characterized the frequently observed common fragile site FRAXB, located at Xp22.3. Like other common fragile sites, it spans a large genomic region of approximately 500 kb. Three known genes, including the microsomal steroid sulfatase locus (STS), map within the fragile site region. We examined FRAXB and four other fragile sites (FRA3B, FRA7G, FRA7H, FRA16D), and several associated genes, for deletions and aberrant transcripts in a panel of cancer cell lines and primary tumors. Deletions within FRAXB were seen in 4/27 (14.8%) of the primary tumors and cell lines examined. Three of the 21 (14.3%) cell lines examined were characterized by loss of expression of one or more FRAXB‐associated genes. Moreover, all of the fragile sites examined were characterized by genomic deletions within the fragile site regions in one or more tumors or cell lines, including FRAXB, which is not associated with any known tumor suppressor genes or activity. Our results further support the hypothesis that common fragile sites and their associated genes are, in general, unstable in some cancer cells.
Human papilloma virus detection in neoplastic and non-neoplastic nasopharyngeal tissues in Taiwan

Background Human papilloma virus (HPV) has been implicated in the carcinogenesis and prognosis of certain head and neck cancers. Whether it also has a role in the pathogenesis of nasopharyngeal carcinoma (NPC) in Taiwan is unclear. Methods Detection and genotyping of HPVs were performed in 43 primary NPCs (one WHO-I and 42 WHO-II/III) and 40 nasopharyngeal controls using PCR-based HPV genotyping arrays. Localisation of high-risk HPV and Epstein–Barr virus genomes was performed in another 46 primary NPCs (five WHO-I and 41 WHO-II/III) and seven paired metastatic WHO-II/III NPCs using in situ hybridisation. Results In the HPV genotyping cohort, oncogenic HPVs were detected equally in WHO-II/III NPCs (31%, 13/42) and nasopharyngeal controls (35%, 14/40). Tumour high-risk HPV status did not correlate with the prognosis of patients with NPC. In the high-risk HPV in situ hybridisation cohort, 14 (88%) of the 16 oncogenic HPV-positive WHO-II/III NPCs showed a unique cytoplasmic/perinuclear staining pattern, which is distinct from the typical dot/punctate nuclear staining pattern indicating HPV genome integration. In addition, oncogenic HPVs were not always retained in NPC cells during the process of metastasis. Conclusions This study does not support an association between oncogenic HPV and the carcinogenesis or prognosis of WHO-II/III NPCs in Taiwan.
Dietary Intakes of Retinol, Carotenes, Vitamin C, and Vitamin E and Colorectal Cancer Risk: The Fukuoka Colorectal Cancer Study

It has long been a matter of interest whether antioxidant vitamins are protective against colorectal cancer as well as human cancers in general, but epidemiological evidence is inconclusive. We investigated associations of dietary intakes of retinol and antioxidant vitamins with colorectal cancer risk in 816 incident cases of histologically confirmed colorectal cancer and 815 controls randomly selected for the Fukuoka colorectal cancer study in Japan. Dietary intakes were assessed by a PC-assisted interview regarding 148 food items. Statistical adjustment was made for body mass index, physical activity, calcium, and n-3 fatty acid intake and other factors. Retinol intake was significantly, inversely associated with colorectal cancer risk; the odds ratio for the highest vs. lowest was 0.55 (95% CI: 0.35, 0.88; P trend = 0.01) in women, but a modest increase in the risk was observed among men with the highest intake of retinol. Liver was the major source of retinol intake and showed similar associations with colorectal cancer risk in men and women. Intake of carotenes, vitamin C, and vitamin E were not related to colorectal cancer risk in either men or women. The study did not support a hypothesis that dietary intake of antioxidant vitamins is protective in the development of colorectal cancer.
Effect of surgical lung volume reduction on breathing patterns in severe pulmonary emphysema.

Surgical lung volume reduction may improve pulmonary function and dyspnea in advanced pulmonary emphysema. To investigate mechanisms of these beneficial effects we studied breathing patterns before and after surgery. Nineteen patients with diffuse pulmonary emphysema (FEV1 < 35% of predicted, total lung capacity > 130% predicted) were studied within 1 mo before, and 1.5 to 7 mo after thoracoscopic volume reduction. Changes of rib cage and abdominal volumes were monitored with calibrated respiratory inductive plethysmography for 20 to 60 min during natural breathing at rest. Pulmonary function and dyspnea were also assessed. Postoperative tidal volumes, respiratory cycle times, and minute ventilation were not significantly different from preoperative values. The contribution of abdominal volume changes to tidal volumes increased from a mean +/- SD of 43 +/- 17% preoperatively to 58 +/- 14% postoperatively (p = 0.03). The fraction of inspiratory time with abdominal paradoxical motion decreased from 12.3 +/- 8.3% preoperatively to 5.1 +/- 5.1% postoperatively (p = 0.02). The phase shift between rib cage and abdominal motion was reduced postoperatively. Hyperinflation, airway obstruction, and subjective ratings of dyspnea were significantly improved. The better synchronization of rib cage-abdominal motion and the greater contribution of abdominal volume changes to tidal volumes are consistent with a reduction of inspiratory loading and a greater force-generating capacity of the diaphragm after surgery.
Scaling Movement Amplitude: Adaptation of Timing and Amplitude Control in a Bimanual Task

ABSTRACT Participants traced two circles simultaneously and the diameter of one circle was scaled as the diameter of the other circle remained constant. When the scaled circle was larger, amplitude error shifted from overshooting to undershooting, while shifting from undershooting to overshooting when this circle was smaller. Asymmetric coordination was unstable when the left arm traced a circle larger than the right arm, yet stable when the left arm traced a smaller circle. When producing symmetric coordination and the left arm traced the larger circle, relative phase shifted by 30°, but a right arm lead predominated. When the left arm traced the smaller circle and symmetric coordination was required, a 30° shift in relative phase occurred, but hand lead changed from left to right. The modulation of movement amplitude and relative phase emerged simultaneously as a result of neural crosstalk effects linked to initial amplitude conditions and possibly visual feedback of the hands’ motion.