Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Grewia Gum as a Suspending Agent on Ibuprofen Pediatric Formulation

The purpose of this work was to evaluate the potential of grewia gum (GG) as a suspending agent in pharmaceutical oral formulation using ibuprofen as model drug. Ibuprofen pediatric suspension (25 mg/5 mL) was formulated with grewia gum (0.5% w/v) as the suspending agent. Similar suspensions of Ibuprofen containing either sodium carboxymethylcellulose (Na-CMC) or hydroxymethylpropylcellulose (HPMC) were also produced. The suspensions were evaluated for ease of redispersion, sedimentation, rheological properties, and the effect of aging on the rheological properties at 25°C. The particle size and particle size distributions of the dispersed solute were determined. The redispersion time was 19, 11, and 0.5 min, respectively, for formulation containing Na-CMC, HPMC, and GG . The sedimentation volumes were 0.05, 0.05, and 0.125 mL, respectively, for Na-CMC, HPMC, and GG . Viscosities of suspensions at spindle speed of 25 rpm were of the order: GG > HPMC > Na-CMC when freshly prepared and of the order: HPMC > GG > Na-CMC within 6 months of storage. The particles size was 72.72, 73.82, 81.93, and 83.41 μm, respectively, for suspensions containing Na-CMC, ibuprofen alone, HPMC, and GG. Greatest hysteresis was observed in formulation containing HPMC. All the formulations were stable. It was our conclusion that the difference in the physicochemical properties of ibuprofen pediatric formulations was influenced more by the suspending agent used in the formulations than the drug. GG combined better redispersion with minimal changes in viscosity on storage compared to Na-CMC and HPMC as suspending agent. Thus GG may serve as a good suspending agent requiring no further aid in suspension redispersibility.
Antibody responses to Ascaris‐derived proteins and glycolipids: the role of phosphorylcholine

In addition to proteins, glycolipids can be targets of antibody responses and contribute to host–pathogen interaction. Following the structural analysis of Ascaris lumbricoides‐derived glycolipids, the antibody responses of a group of children with no, light and heavy infections were analysed. The role of the phosphorylcholine moiety, present on Ascaris glycoproteins and glycolipids, in antibody reactivity of these infected individuals was determined.
The efficacy of switching from etanercept to infliximab in patients with rheumatoid arthritis.

OBJECTIVE To describe the degree of clinical benefit in patients with rheumatoid arthritis (RA) who receive infliximab therapy after lack of efficacy with etanercept. METHODS In a retrospective study among 6 centers primarily designed to assess the safety of infliximab in combination with leflunomide, a standardized chart review form was used to collect data on 93 patients with RA. During that study, it was noted that some of these patients had switched from etanercept to infliximab. In this study, we compared the response of subjects switching from etanercept to infliximab (n = 20) to that of subjects receiving infliximab with no prior tumor necrosis factor (TNF) therapy (n = 73). RESULTS The swollen and tender joint count, patient and physician global assessments, morning stiffness, and C-reactive protein all improved substantially in both groups, with no statistical difference in the degree of benefit between the groups. At the time of chart review, switchers had received a statistically higher dose of infliximab than controls (4.4 vs 3.19 mg/kg; p = 0.006) with a total of 5.7 and 5 infusions, respectively. CONCLUSION In this retrospective study, previous lack of efficacy with etanercept did not predict lack of efficacy with infliximab. Indeed, the degree of clinical improvement was similar in both groups, although switchers were receiving a higher dose of infliximab at the time of chart review. Our findings suggest that clinical response may differ between anti-TNF agents, and lack of response to one agent may not predict a lack of response to another.
Perioperative Granulocyte Colony-Stimulating Factor Does Not Prevent Severe Infections in Patients Undergoing Esophagectomy for Esophageal Cancer: A Randomized Placebo-Controlled Clinical Trial

Objective:Esophagectomy for esophageal cancer is associated with substantial postoperative morbidity as a result of infectious complications. In a prior phase II study, granulocyte colony-stimulating factor (G-CSF) was shown to improve leukocyte function and to reduce infection rates after esophagectomy. The aim of the current randomized, placebo-controlled, multicenter phase III trial was to investigate the clinical efficacy of perioperative G-CSF administration in reducing infection and mortality after esophagectomy for esophageal cancer. Patients and Methods:One hundred fifty five patients with resectable esophageal cancer were randomly assigned to perioperative G-CSF at standard doses (77 patients) or placebo (76 patients), administered from 2 days before until day 7 after esophagectomy. The G-CSF and placebo groups were comparable as regards age, gender, risk, cancer stage, frequency of neoadjuvant radiochemotherapy, and type of esophagectomy (transthoracic or transhiatal esophageal resection). Results:Of 155 randomized patients, 153 were eligible for the intention-to-treat analysis. The rate of infection occurring within the first 10 days after esophagectomy was 43.4% (confidence interval 32.8–55.9%) in the placebo and 44.2% (confidence interval 32.1–55.3%) in the G-CSF group (P = 0.927). 30-day mortality amounted to 5.2% in the G-CSF group versus 5.3% in the placebo group (P = 0.985). Similar results were found in the per-protocol analysis. Conclusion:Perioperative administration of G-CSF failed to reduce postoperative morbidity, infection rate, or mortality in patients with esophageal cancer who underwent esophagectomy.
The efficacy of short-term interferon-beta therapy for type C cirrhotic patients with genotype 2a and low virus load.

OBJECTIVE The aim of this study was to elucidate the efficacy of short-term interferon (IFN) therapy for type C cirrhotic patients with genotype 2a and low virus load. METHODS The present study was retrospective cohort study. Inclusion criteria were liver cirrhosis, hepatitis C virus (HCV) genotype 2a, the serum HCV RNA level of less than 100 KIU/mL, and IFN period of 6 or 8 weeks. Twenty-five consecutive patients who satisfied the above criteria were treated with IFN-beta daily at the dosage of 6 MU for 6 or 8 weeks. Independent factors that might have influenced sustained virologic response (SVR) were studied using multiple logistic regression analysis. RESULTS Background of clinical profiles were as follows: median (range) age=64 (53-76) years, male/female=13/12, and median (range) HCV-RNA=31 (8-90) KIU/mL. Out of 25, 14 patients (56.0%) had SVR by the intention-to-treat analysis. The SVR was significantly associated with serum HCV RNA level. Logistic analysis showed that SVR occurred when HCV RNA level was <50 KIU/mL (p=0.047). Based on the difference of the serum HCV RNA level, the SVR rate was 68.4% (13/19) in patients with a serum HCV RNA level of <50 KIU/mL and 16.7% (1/6) in patients with a serum HCV RNA level of > or =50 KIU/mL. CONCLUSIONS The 6 or 8-week IFN-beta therapy is a possible selection of therapy for cirrhotic patients with HCV genotype 2a and a serum HCV RNA level of <50 KIU/mL.
Ubiquitin Sorts Proteins into the Intralumenal Degradative Compartment of the Late‐Endosome/Vacuole

Many studies have demonstrated a role for ubiquitin (Ub) in the down‐regulation of cell surface proteins. In yeast, down‐regulation is marked by the internalization of proteins, followed by their delivery to the lumen of the vacuole where both the cytosolic and lumenal domains are degraded. It is generally believed that the regulatory step of this process is internalization from the plasma membrane and that protein delivery to the lysosome or vacuole is by default. By separating the process of internalization from degradation, we demonstrate that incorporation of proteins into intralumenal vesicles represents a distinct sorting step along the endocytic pathway that is controlled by recognition of ubiquitin. We show that attachment of a single ubiquitin can serve as a specific sorting signal for the degradative pathway by redirecting recycling Golgi proteins and resident vacuolar proteins into intralumenal vesicles of the yeast vacuole. This pathway is independent of PtdIns(3,5) P2 and does not rely on the specific composition of transmembrane domain segments. These data provide a physiological basis for how ubiquitination of cell surface proteins guides their degradation and removal from the recycling pathway.
Semantic, phonological, and mediated priming in reading and lexical decisions.

Four experiments were conducted to investigate whether semantic activation of a concept spreads to phonologically and graphemically related concepts. In lexical decision or self-paced reading tasks, subjects responded to pairs of words that were semantically related (e.g., light-lamp), that rhymed (e.g., lamp-damp), or that combined both of these relations through a mediating word (e.g., light-damp). In one version of each task, test lists contained word-word pairs (e.g., light-lamp) as well as nonword-word (e.g., pown-table) and word-nonword pairs (e.g., month-poad); in another version, test lists contained only word-word pairs. The lexical decision and self-paced reading tasks were facilitated by semantic and rhyming relations regardless of the presence or absence of nonwords on the test lists. The effect of the mediated relation, however, depended on the presence of nonwords among the stimuli. When only words were included, there was no effect of the mediated relation, but when nonwords were included, lexical decision and self-paced reading responses were inhibited by the mediated relation. These inhibitory effects are attributed to processes occurring after lexical access, and the relative advantages of the self-paced reading task are discussed.
Heterogeneity in the immune response to serotype b LPS of Actinobacillus actinomycetemcomitans in inbred strains of mice.

We investigated the heterogeneity of the humoral immune responses to whole cells and lipopolysaccharide (LPS) of Actinobacillus actinomycetemcomitans serotype b and production of cytokines in inbred strains of mice. Nine such strains were tested: A/J (H-2(a)), C57BL/6 (H-2(b)), BALB/c (H-2(d)), DBA/2 (H-2(d)), B10.BR (H-2(k)), C3H/He (H-2(k)), C3H/HeJ (H-2(k)), DBA/1 (H-2(q)) and B10.S (H-2(s)). Mice were immunized intraperitoneally with whole cells of A. actinomycetemcomitans ATCC 43718 (serotype b) in phosphate buffered saline (PBS; pH 7.2) emulsified with an equal volume of Freund's incomplete adjuvant. Serum immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) levels against A. actinomycetemcomitans were measured by an ELISA system. ELISA analysis, using LPS fractions from serotype a, b or c strains of A. actinomycetemcomitans as the coating antigens, revealed that mice strains C3H/He, C3H/HeJ, B10.BR and B10.S had an extremely high-IgM response against serotype b LPS. High-IgM titer sera contain also elevated levels of IgA antibodies to the antigen. To compare the cytokine production among inbred mice, the amounts of interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-6 (IL-6) released from mouse splenocytes were measured using ELISA systems specific for these cytokines. A. actinomycetemcomitans serotype b LPS stimulation induced IL-6 release from murine splenocytes of all tested strains. However, IL-4 and IL-5 were detected only in high-IgM/IgA responders to A. actinomycetemcomitans serotype b LPS, not in low-IgM/IgA responders. Thus, we found a relationship between the humoral immune response to LPS of A. actinomycetemcomitans serotype b and production of type 2 cytokines by splenocytes.
The Effects of Remifentanil and Esmolol on Increase in Intraocular Pressure Due to Laryngoscopy and Tracheal Intubation: A Double-Blind, Randomized Clinical Trial

Purpose:This study aimed to compare the effects of remifentanil and esmolol on the elevation of intraocular pressure (IOP) and hemodynamic response. Methods:After approval of the institutional Ethics Committee and obtaining informed consent, 60 adult patients with American Society of Anesthesiologists I-II status undergoing elective, nonophthalmic surgery were included in the study. Exclusion criteria were preexisting eye disease, neuromuscular disease, esophageal reflux, hiatus hernia, allergy to any of the study drugs, and the use of &bgr;-blockers, diuretics, or other antihypertensive agents. The patients were randomized into 2 groups by using the sealed-envelope method, as follows: group E (esmolol) and group R (remifentanil). A single intravenous dose of esmolol (0.5 mg/kg) or remifentanil (1 &mgr;g/kg) just before induction agents were given to patients in groups E and R, respectively. IOP, heart rate (HR), and mean arterial pressure (MAP) values were recorded before intubation and at 1, 3, 5, and 10 minutes after intubation. Results:The IOP decrease in group R was statistically significant compared with group E (P<0.01). HR values at 10 minutes after intubation were significantly decreased in group E compared with group R (P<0.05). There was no significant difference in MAP values between the groups. Conclusions:It was concluded that remifentanil is more effective than esmolol in preventing IOP elevation related to laryngoscopy and tracheal intubation, while there is no significant difference between the 2 agents in terms of HR and MAP.
Central neurocytoma: long-term outcomes of multimodal treatments and management strategies based on 30 years' experience in a single institute.

BACKGROUND A thorough investigation of the long-term outcomes of central neurocytoma (CN) after different treatments is required to establish optimal management strategies. OBJECTIVE We retrospectively reviewed the long-term clinical outcomes of patients with CN according to various treatments and suggest treatment strategies based on 30 years of experience in a single institution. METHODS Fifty-eight consecutive patients with CN were treated at our institution between 1982 and 2008. Patient demographics, overall survival, local control rates according to multimodal treatments, and functional outcomes were evaluated. The mean clinical and radiological follow-up periods were 119 months (range, 18-304 months) and 98 months (range, 13-245 months), respectively. RESULTS The initial treatment modality was classified into 4 subgroups: operation only (34 patients), operation followed by radiation therapy (7 patients) or radiosurgery (7 patients), and radiosurgery alone (10 patients). The actuarial overall survival was 91% at 5 years and 88% at 10 years. The actuarial overall survival and local tumor control rate did not differ significantly according to the various treatments and the initial extent of the surgical resection. However, functional outcomes, such as the postoperative seizure outcome at the last follow-up, differed according to the surgical approach. CONCLUSION The long-term clinical outcomes of CN after multimodal treatment seem to be excellent. Our study suggests that treatment strategies for CN should focus on the patient's quality of life, as well as on tumor control, because of the benign nature of CN.
Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes

The astrocytic aquaporin-4 (AQP4) water channel is the target of pathogenic antibodies in a spectrum of relapsing autoimmune inflammatory central nervous system disorders of varying severity that is unified by detection of the serum biomarker neuromyelitis optica (NMO)-IgG. Neuromyelitis optica is the most severe of these disorders. The two major AQP4 isoforms, M1 and M23, have identical extracellular residues. This report identifies two novel properties of NMO-IgG as determinants of pathogenicity. First, the binding of NMO-IgG to the ectodomain of astrocytic AQP4 has isoform-specific outcomes. M1 is completely internalized, but M23 resists internalization and is aggregated into larger-order orthogonal arrays of particles that activate complement more effectively than M1 when bound by NMO-IgG. Second, NMO-IgG binding to either isoform impairs water flux directly, independently of antigen down-regulation. We identified, in nondestructive central nervous system lesions of two NMO patients, two previously unappreciated histopathological correlates supporting the clinical relevance of our in vitro findings: (i) reactive astrocytes with persistent foci of surface AQP4 and (ii) vacuolation in adjacent myelin consistent with edema. The multiple molecular outcomes identified as a consequence of NMO-IgG interaction with AQP4 plausibly account for the diverse pathological features of NMO: edema, inflammation, demyelination, and necrosis. Differences in the nature and anatomical distribution of NMO lesions, and in the clinical and imaging manifestations of disease documented in pediatric and adult patients, may be influenced by regional and maturational differences in the ratio of M1 to M23 proteins in astrocytic membranes.
Using Incentives to Reduce Bycatch and Discarding: Results Under the West Coast Catch Share Program

Abstract Catch share management was implemented in the bottom trawl sector of the West Coast Groundfish fishery in 2011 to address a range of issues including high bycatch and discard rates. The catch share program was designed to remove the incentives to discard through full catch accounting, tradeable quotas, increased flexibility in fishing, and penalties for catch overages. We assess the effectiveness of the program in meeting its environmental objectives by comparing discard weights, proportions, and variability from 2004–2010 with 2011–2016. We analyzed these metrics for species managed using quota, including historically overfished stocks, as well as for non-quota species caught in the fishery. Discard amounts decreased over time for all species and declined to historic lows after the implementation of the program, remaining low through 2016 with much less inter-annual variability. Mean annual discards of two highly-targeted quota species, sablefish and Dover sole, showed the greatest decreases, falling by 97 and 86%, respectively. The discard proportion of overfished quota species fell by 50% on average. The unanticipated decline in discards of non-quota species as well as the decreased variability in discard amounts for all species indicate that the incentives produced by catch share management provided additional ecosystem benefits.
Noninvasive measurement of cerebral metabolic rate of glucose using standardized input function.

UNLABELLED The purpose of this study was to propose and validate a method for the noninvasive measurement of cerebral metabolic rate of glucose (CMRGlc) by fluorodeoxyglucose (FDG) PET with a standardized input function (SIF) and an autoradiographic method. METHODS Plasma input functions, measured by intermittent arterial blood samplings after the intravenous injection of FDG, in 44 patients who had fasted for at least 6 h, were used to generate the SIF. The input function of each patient was normalized with the net injected dose (nID) of FDG and body mass as indicated by body surface area (BSA) or body weight (BW). The SIF was generated as an average of 44 normalized input functions. The estimation of the input function and CMRGlc with SIF was validated in 10 additional patients, who underwent FDG PET after fasting for at least 6 h. CMRGlc was estimated with a simulated input function (IFsim) generated with the following equation: IFsim = SIF x (nID/body mass). The estimated CMRGlc was compared with the measured CMRGlc. RESULTS Based on BSA, the percentage error of the area under the curve of IFsim was 3.5%+/-2.2%. The percentage error of CMRGlc was 2.9%+/-1.9% in gray matter and 3.4%+/-2.2% in white matter. A similar percentage error was obtained based on BW. CONCLUSION The proposed method is noninvasive and accurate, and therefore is clinically acceptable for measuring CMRGlc in patients in fasting states.
Poorer ART Outcomes with Increasing Age at a Large Public Sector HIV Clinic in Johannesburg, South Africa

Background: As the current HIV-positive population ages, the absolute number of patients >50 years on treatment is increasing. Methods: We analyze the differences in treatment outcomes by age category (18-29, 30-39, 40-49, 50-59, and ≥60) among 9139 HIV-positive adults initiating ART in South Africa. Results: The adjusted hazard ratios (HRs) for all-cause mortality increased with increasing age, with the strongest association in the first 12 months of follow-up among patients 50 to 59 years (HR 1.67; 95% confidence interval [CI]: 1.24-2.23) versus those <30 years. However, patients 50 to 59 years were less likely to be lost during 24 months on antiretroviral therapy ([ART] HR 0.75; 95% CI: 0.59-0.94) versus patients <30 years. By 6 and 12 months on treatment, older patients were less likely to increase their CD4 count by ≥50 cells/mm3. Conclusion: Although older patients are at higher risk of mortality and have poorer immunological responses than their younger counterparts, they are more likely to adhere to care and treatment in the first 24 months on ART.
Postexercise Myogenic Gene Expression: Are Human Findings Lost During Translation?

Muscle progenitor cell (MPC) activity is exercise responsive. Post resistance-exercise alterations in myogenic messenger RNAs (mRNAs) found by us and others may initiate these events. However, these mRNA data in the absence of microscopic MPC activity data have limited this interpretation. Alternatively, with our acute exercise data as our basis, we propose that these genes may control other hypertrophic processes in postmitotic fibers.
Progesterone receptor downregulates breast cancer resistance protein expression via binding to the progesterone response element in breast cancer

Breast cancer resistance protein (BCRP) plays a major role in multidrug resistance (MDR). Sequence analysis reveals there is a novel progesterone response element (PRE) in the BCRP promoter, suggesting progesterone receptor (PR) may have a function in the regulation of BCRP expression. We examined the expressions of BCRP, PR, estrogen receptor α (ERα), androgen receptor (AR) and Her‐2 in 95 breast cancer samples by immunohistochemistry. Then, to identify the role of PR in the regulation of BCRP expression, two constructs encoding full length BCRP cDNA driven by putative PRE promoter or constitutive CMV promoter were transfected into MCF‐7 and MDA‐MB‐231, respectively. Reverse transcription‐polymerase chain reaction (RT‐PCR) and western blotting were used to detect the expression of BCRP. Further electrophoretic mobility shift assay (EMSA) was used to verify the nuclear protein‐DNA specific binding. We innovatively found that the expression of BCRP negatively related with that of PR and ERα in breast cancer by immunohistochemistry. While at a cellular level, after being treated by progesterone and 17β‐estradiol, BCRP mRNA and protein levels were significantly reduced in a concentration‐dependent manner in MCF‐7/P‐BCRP cells with PR bound to the identified PRE in BCRP promoter. Our results demonstrated that active PR inactived BCRP expression via progesterone‐PR complexes binding to PRE in BCRP promoter in breast cancer cells. (Cancer Sci 2012; 103: 959–967)