Miracle-dz/UniFAR-FTUs huggingface dataset:
Sigma-2 receptor ligand anchored telmisartan loaded nanostructured lipid particles augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in prostate cancer cells

Abstract Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in this investigation, sigma-2 receptor ligand, 3-(4-cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells. The mean particle size of TEL-NLPs was measured to be 25.4 ± 3.2 nm, significantly (p < 0.05) lower than 32.6 ± 5.3 nm of CPPA-TEL-NLPs. Correspondingly, the zeta-potential of TEL-NLPs was measured to be −15.4 ± 2.3 mV significantly (p < 0.05) higher than −9.6 ± 2.7 mV of CPPA-TEL-NLPs. The encapsulation efficiency of CPPA-TEL-NLPs was estimated to be 72.7 ± 4.3%, significantly (p < 0.05) lower than 77.5 ± 5.4%, displayed by TEL-NLPs. In addition, FT-IR and PXRD confirmed the molecular encapsulation of the drug in amorphous state. In vitro drug release study was conducted to determine the drug delivery potential of tailored nanoparticles. TEL-NLPs released 93.36% of drug significantly (p < 0.05) higher than 85.81%, released by CPPA-TEL-NLPs in 24 h. The IC50 of CPPA-TEL-NLPs was measured to be 20.3 µM significantly (p < 0.05) lower than 36.3 µM presented by TEL-NLPs in PC-3 cells. In contrast, CPPA-TEL-NLPs displayed the IC50 of 41.3 µM, significantly (p > 0.05) not different from 43.4 µM, exhibited by TEL-NLPs in PNT-2 cells. We elucidated that CPPA-TEL-NLPs entered the PC-3 cells via receptor mediated endocytosis pathway and thus exhibited superior cytotoxicity, apoptosis and greater extent of cellular uptake in PC-3 cells. In conclusion, CPPA-TEL-NLPs may be a promising nanomedicine and warrant further in vivo investigations for gaining clinical success.
Application of Peracetic Acid and Quarternary Ammonium Disinfectants as a Part of Sanitary Treatment in a Poultry House and Poultry Processing Plant

Hygiene and sanitation play a major role in any effective disease control programme for poultry production and processing premises. Various deficiencies in disinfection may induce that chains of infections are not broken from one stock to another. The present study investigated the efficacy of disinfection on a broiler farm and in a plant processing poultry from the investigated farm. Besides inspection of disinfection, the influence of contamination on broiler carcasses and consequences of this contamination on sanitation of the processing lines were studied. Swabs from surfaces coming into contact with the handled raw material were taken and evaluated. The results obtained by a standard microbiological swab method were evaluated and compared with an ATP‐bioluminescence method. The investigations included determination of total counts of microorganisms, coliform bacteria and moulds. When employing the standard plate‐count method, the total counts of microorganisms (TCM) reached <1, 1–100 and >100 CFU in 0, 12 and 88% swabs on poultry farm and in 22%, 36% and 42% swabs in the processing plant, respectively. The bioluminescence method was used only in the processing plant and contamination corresponding to <100, 100–300 and >300 relative light units (RLU) was detected in 80%, 10% and 10% swabs respectively.
Tumor Necrosis Factor Alpha- and Inducible Nitric Oxide Synthase-Producing Dendritic Cells Are Rapidly Recruited to the Bladder in Urinary Tract Infection but Are Dispensable for Bacterial Clearance

ABSTRACT The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b+ F4/80+ CD8− Gr-1− myeloid subtype. Also, tumor necrosis factor alpha (TNF-α)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2−/− mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-α-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.
Comparison of Audiological Results Between a Transcutaneous and a Percutaneous Bone Conduction Instrument in Conductive Hearing Loss

Objectives: In conductive, mixed hearing losses and single-sided-deafness bone-anchored hearing aids are a well-established treatment. The transcutaneous transmission across the intact skin avoids the percutaneous abutment of a bone-anchored device with the usual risk of infections and requires less care. In this study, the audiological results of the Bonebridge transcutaneous bone conduction implant (MED-EL) are compared to the generally used percutaneous device BP100 (Cochlear Ltd., Sydney, Australia). Methods: Ten patients implanted with the transcutaneous hearing implant were compared to 10 matched patients implanted with a percutaneous device. Tests included pure-tone AC and BC thresholds and unaided and aided sound field thresholds. Speech intelligibility was determined in quiet using the Freiburg monosyllable test and in noise with the Oldenburg sentence test (OLSA) in sound field with speech from the front (S0). The subjective benefit was assessed with the Abbreviated Profile of Hearing Aid Benefit. Results: In comparison with the unaided condition there was a significant improvement in aided thresholds, word recognition scores (WRS), and speech reception thresholds (SRT) in noise, measured in sound field, for both devices. The comparison of the two devices revealed a minor but not significant difference in functional gain (Bonebridge: PTA = 27.5 dB [mean]; BAHA: PTA = 26.3 dB [mean]). No significant difference between the two devices was found when comparing the improvement in WRSs and SRTs (Bonebridge: improvement WRS = 80% [median], improvement SRT = 6.5 dB SNR [median]; BAHA: improvement WRS = 77.5% [median], BAHA: improvement SRT = 6.9 dB SNR [median]). Conclusion: Our data show that the transcutaneous bone conduction hearing implant is an audiologically equivalent alternative to percutaneous bone-anchored devices in conductive hearing loss with a minor sensorineural hearing loss component.
Effects of self-generated versus experimenter-provided cues on the representation of future events

Most experimental studies of prospection focused on episodic forms of future events prompted by means of verbal cues. However, there is evidence suggesting that future events differ considerably according to whether they are produced in response to external, experimenter-provided verbal cues or they are self-generated. In the present study, we compared the quality, the phenomenal characteristics, the temporal distribution, and the content of imagined events prompted by experimenter-provided cues (i.e., cue-words and short verbal sentences) or elicited by means of verbal cues that were self-generated in an autobiographical fluency task. The results showed that future events prompted by means of self-generated cues contained fewer event-specific details than future events prompted by experimenter-provided cues. However, future events elicited by means of self-generated and by experimenter-provided cues did not differ with respect to their phenomenal characteristics. The temporal distribution and the thematic content of future representations were also affected by the type of cue used to elicit prospection. These results offer a holistic view of the properties of future thinking and suggest that the content and the characteristics of envisioned future events may be affected by the method used to elicit prospection.
Modeling and forecasting electricity prices with input/output hidden Markov models

In competitive electricity markets, in addition to the uncertainty of exogenous variables such as energy demand, water inflows, and availability of generation units and fuel costs, participants are faced with the uncertainty of their competitors' behavior. The analysis of electricity price time series reflects a switching nature, related to discrete changes in competitors' strategies, which can be represented by a set of dynamic models sequenced together by a Markov chain. An input-output hidden Markov model (IOHMM) is proposed for analyzing and forecasting electricity spot prices. The model provides both good predictions in terms of accuracy as well as dynamic information about the market. In this way, different market states are identified and characterized by their more relevant explanatory variables. Moreover, a conditional probability transition matrix governs the probabilities of remaining in the same state, or changing to another, whenever a new market session is opened. The model has been successfully applied to real clearing prices in the Spanish electricity market.
Eye movements are coordinated with pectoral fin beats during locomotion in a marine teleost fish

ABSTRACT Animals must simultaneously engage multiple functional systems in order to navigate, feed and survive in complex environments. Nearly all vertebrates perform rapid gaze-shifting eye movements called saccades, but we know little about the behaviour of saccades during rhythmic locomotion. This study examined how saccades are coordinated with locomotor movements in a pectoral-fin-propelled teleost fish, Cymatogaster aggregata, the shiner surfperch. Individual fish were filmed swimming in a flow tank at 10 cm s−1, and timing data were analysed using circular statistics. The results reveal that C. aggregata generates saccades non-uniformly throughout the pectoral fin cycle. Saccades primarily occur during fin abduction, when a large amount of thrust is produced, and rarely occur during the thrust-free refractory phase. Because vision is known to be impaired during saccades, we hypothesize that C. aggregata synchronizes saccades with periods of high acceleration in order to stabilize retinal images during low-acceleration phases, which are nearly saccade-free. Summary: Rapid gaze-shifting eye movements called saccades occur primarily during abduction of the pectoral fins, when a large amount of thrust is produced, possibly to stabilize retinal images during thrust-free phases.
Novel PEX1 mutations and genotype–phenotype correlations in Australasian peroxisome biogenesis disorder patients

The peroxisome biogenesis disorders (PBDs) are a group of neuronal migration/neurodegenerative disorders that arise from defects in PEX genes. A major subgroup of the PBDs includes Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). These three disorders represent a clinical continuum with Zellweger syndrome the most severe. Mutations in the PEX1 gene, which encodes a protein of the AAA ATPase family involved in peroxisome matrix protein import, account for the genetic defect in more than half of the patients in this PBD subgroup. We report here on the results of PEX1 mutation detection in an Australasian cohort of PEX1‐deficient PBD patients. This screen has identified five novel mutations, including nonsense mutations in exons 14 and 19 and single nucleotide deletions in exons 5 and 18. Significantly, the allele carrying the exon 18 frameshift mutation is present at moderately high frequency (approx. 10%) in this patient cohort. The fifth mutation is a missense mutation (R798G) that attenuates, but does not abolish PEX1 function. We have evaluated the cellular impact of these novel mutations, along with that of the two most common PEX1 mutations (c.2097‐2098insT and G843D), in PBD patients by determining the levels of PEX1 mRNA, PEX1 protein, and peroxisome protein import. The findings are consistent with a close correlation between cellular phenotype, disease severity, and PEX1 genotype. Hum Mutat 20:342–351, 2002. © 2002 Wiley‐Liss, Inc.
Structural Basis for Conformational Dynamics of GTP-bound Ras Protein*

Ras family small GTPases assume two interconverting conformations, “inactive” state 1 and “active” state 2, in their GTP-bound forms. Here, to clarify the mechanism of state transition, we have carried out x-ray crystal structure analyses of a series of mutant H-Ras and M-Ras in complex with guanosine 5′-(β,γ-imido)triphosphate (GppNHp), representing various intermediate states of the transition. Crystallization of H-RasT35S-GppNHp enables us to solve the first complete tertiary structure of H-Ras state 1 possessing two surface pockets unseen in the state 2 or H-Ras-GDP structure. Moreover, determination of the two distinct crystal structures of H-RasT35S-GppNHp, showing prominent polysterism in the switch I and switch II regions, reveals a pivotal role of the guanine nucleotide-mediated interaction between the two switch regions and its rearrangement by a nucleotide positional change in the state 2 to state 1 transition. Furthermore, the 31P NMR spectra and crystal structures of the GppNHp-bound forms of M-Ras mutants, carrying various H-Ras-type amino acid substitutions, also reveal the existence of a surface pocket in state 1 and support a similar mechanism based on the nucleotide-mediated interaction and its rearrangement in the state 1 to state 2 transition. Intriguingly, the conformational changes accompanying the state transition mimic those that occurred upon GDP/GTP exchange, indicating a common mechanistic basis inherent in the high flexibility of the switch regions. Collectively, these results clarify the structural features distinguishing the two states and provide new insights into the molecular basis for the state transition of Ras protein.
Kinetics of Marek's disease virus (MDV) infection in broiler chickens 1: effect of varying vaccination to challenge interval on vaccinal protection and load of MDV and herpesvirus of turkey in the spleen and feather dander over time

Two experiments in commercial broiler chickens vaccinated with herpesvirus of turkeys (HVT) and challenged with Marek's disease virus (MDV) investigated the effects of the vaccination-to-challenge interval (VCI) on vaccinal protection against Marek's disease, and the kinetics of MDV and HVT load in the spleen and feather dander determined using real-time quantitative polymerase chain reaction. Experiment 1 in isolators tested VCI of 2, 4 and 7 days, while Experiment 2 in floor pens tested VCI of 0, 2, 4, 7 and 10 days. MDV challenge induced gross Marek's disease lesions in 14% to 74% of chickens by 56 days post-challenge. Vaccinal protection increased from ∼40% to ∼80% with increasing VCI between days 2 and 7 in both experiments, but not thereafter. MDV was detected in both the spleen and dander at 7 days post-challenge and increased rapidly to approximately 21 days post-challenge, after which levels plateaued, rose or fell gradually depending on treatment. HVT was also shed in significant amounts, 1 to 2 logs lower than for MDV, with a clear peak around 14 to 21 days post-vaccination. Vaccination significantly reduced the log10MDV load in the spleen (vaccinated, 2.99±0.20/106 spleen cells; unvaccinated, 4.60±0.23/106 spleen cells) and dander (vaccinated, 5.28±0.13/mg; unvaccinated, 6.00±0.18/mg) from infected chickens. The MDV load had a significant negative association with the VCI and the level of vaccinal protection. Measurement of dander production in Experiment 1 and the dust content of air in Experiment 2, combined with determination of the MDV load in these, enabled estimation of total daily shedding rates of MDV per chicken and of the MDV load in air for the first time.
Additive endocrine therapy for advanced breast cancer – back to the future

While novel endocrine treatment options have been implemented in the advanced – as well as adjuvant setting, recent results suggest a place for “old-fashioned” additive treatment with estrogens in advanced breast cancer. This paper reviews the biological rationale for endocrine therapy in general and additive treatment with estrogens in particular. The finding that patients becoming resistant to treatment with aromatase inhibitors may subsequently respond to estrogen therapy adds important information to our understanding of therapy resistance in general. Moreover, the return of a therapeutic option abandoned more than 20 years ago, now to be used in a different sequential setting, suggests a critical examination whether there may be other conventional treatment options still earning a place as treatment in advanced disease as well. While ablative therapies including surgical oophorectomy, hypophysectomy and adrenalectomy are not candidate treatment options due to morbidity, there are additive treatment options apart from estrogen therapy that may be considered. Androgens administered at therapeutic doses are not feasible for toxicity reasons; yet, the potential of adding androgens in small doses as adjuvant to aromatase inhibitors should be further explored. Whether patients become resistant to other treatment options may still benefit from megestrol acetate, remains to be explored.
Cloning of rat grp75, an hsp70‐family member, and its expression in normal and ischemic brain

Following metabolic stress a variety of gene products are induced in cells in the brain, some of which may protect the tissue from subsequent stresses. The heat shock proteins (hsps), in particular hsp70, have been widely studied in this context, but evidence for the involvement of known hsps in protection of the CNS is inconclusive. We have therefore undertaken the search for other stress‐induced proteins which may mitigate ischemic injury. Beginning with degenerate RT‐PCR, we have isolated a rat‐brain cDNA encoding a protein highly similar to human grp75, a mitochondrial member of the hsp 70‐family of stress proteins. It is also highly similar to two non‐mitochondrial proteins; mortalin, a senescence‐related gene product, and pbp74, a protein implicated in B‐cell peptide processing. Sequence structure and phylogenetic analyses predict mitochondrial localization and induction by a calcium ionophore and glucose deprivation in PC12 cells support its identification as rat grp75. In situ analysis of normal brain reveals an unusual distribution, with very high expression in neurons of the basal forebrain, reticular and subthalamic nuclei, globus pallidus, amygdala and elsewhere. grp75‐mRNA is upregulated following focal brain ischemia in a distinctive fashion. When the degree of injury is small, induction occurs in the area of injury, similar to the pattern observed for hsp70. However, when the injury is extensive, hsr is upregulated in neurons outside the ischemic area. The induction of grp75 may represent a sensitive marker of metabolically compromised tissue. © 1995 Wiley‐Liss, Inc.
Pharmacy residents and students as an adjunct to current smoking cessation education

Objective The purpose of this study was to evaluate the impact of individualized tobacco cessation counseling provided by pharmacy residents and students to patients in the inpatient setting at an academic medical center. Methods Documented tobacco users were evaluated for study inclusion. The intervention group received counseling specific to their readiness to quit. After discharge, patients in the intervention group received weekly phone calls for additional counseling and data collection. One month after discharge, the standard therapy group received one phone call for data collection. Results No significant differences were found between groups for demographic variables or number of years smoking. At baseline, the intervention group reported significantly fewer quit attempts and more packs per day than the control group. The odds ratio (OR) for the primary outcome, abstinence, was 1.68 [95%CI=0.29:9.748] favoring the intervention group. The OR for patients using outpatient pharmacotherapy was 3.20 [95%CI=0.484:21.167] for the intervention group compared to the control group. The percentage of patients using outpatient treatment programs was 5.26% in the control group vs. 0% in the intervention group. Conclusions Results showed a trend toward significance for abstinence and increased use of outpatient pharmacotherapy; however, our sample size and study period limit conclusions that may be drawn. Further study is warranted for definitive results.
Positive versus negative priming of older adults’ generative value: do negative messages impair memory?

ABSTRACT Objectives: A considerable volume of experimental evidence demonstrates that exposure to aging stereotypes can strongly influence cognitive performance among older individuals. However, whether such effects extend to stereotypes regarding older adults’ generative (i.e. contributory) worth is not yet known. The present investigation sought to evaluate the effect of exposure to positive versus negative generative value primes on an important aspect of later life functioning, memory. Method: Participants of age 55 and older (n = 51) were randomly assigned to read a mock news article portraying older individuals as either an asset (positive prime) or a burden (negative prime) to society. Upon reading their assigned article, participants completed a post-priming memory assessment in which they were asked to recall a list of 30 words. Results: Those exposed to the negative prime showed significantly poorer memory performance relative to those exposed to the positive prime (d = 0.75), even when controlling for baseline memory performance and sociodemographic covariates. Conclusion: These findings suggest that negative messages regarding older adults’ generative social value impair memory relative to positive ones. Though demonstrated in the short term, these results also point to the potential consequences of long-term exposure to such negative ideologies and may indicate a need to promote more positive societal conceptualizations of older adults’ generative worth.