Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of medetomidine, L-methadone, and their combination on arterial blood gases in dogs.

OBJECTIVE To investigate the influence of L-methadone on medetomidine-induced changes in arterial blood gases and clinical sedation in dogs. STUDY DESIGN Prospective experimental cross-over study (Latin square design). ANIMALS Five 1-year-old purpose bred laboratory beagle dogs of both sexes. METHODS Each dog was treated three times: medetomidine (20 microg kg(-1) IV), L-methadone (0.1 mg kg(-1) IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter. RESULTS Arterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/L-methadone administration (range 55.2-86.7 mmHg, 7.4-11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l-methadone and medetomidine/L-methadone (42.6 +/- 2.9 and 44.7 +/- 2.4 mmHg, 5.7 +/- 0.4 and 6.0 +/- 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of L-methadone and medetomidine/L-methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/L-methadone, and no differences were detected between the two treatments. Most dogs panted after administration of L-methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/L-methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/L-methadone. CONCLUSIONS AND CLINICAL RELEVANCE At the doses used in this study, L-methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.
Structural rearrangement of the intracellular domains during AMPA receptor activation

Significance α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the main excitatory receptors in the brain. Although neurotransmitter binding to AMPARs is well understood, knowledge regarding their activation mechanisms remains incomplete. We exploited genetic insertion of fluorescent proteins to create AMPARs displaying fluorescence resonance energy transfer and allow optical monitoring of conformational changes in the receptor. Ligand-driven conformational changes are observed to occur in two intracellular domains of the receptor that are distant from the extracellular site where glutamate binds. The C terminus extends laterally from the receptor and remains relatively close to the plasma membrane. By measuring the activation of receptors electrically and optically at the same time, this study reveals AMPAR conformational changes occurring during receptor state transitions for a region not resolved in structural studies. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are ligand-gated ion channels that mediate the majority of fast excitatory neurotransmission in the central nervous system. Despite recent advances in structural studies of AMPARs, information about the specific conformational changes that underlie receptor function is lacking. Here, we used single and dual insertion of GFP variants at various positions in AMPAR subunits to enable measurements of conformational changes using fluorescence resonance energy transfer (FRET) in live cells. We produced dual CFP/YFP-tagged GluA2 subunit constructs that had normal activity and displayed intrareceptor FRET. We used fluorescence lifetime imaging microscopy (FLIM) in live HEK293 cells to determine distinct steady-state FRET efficiencies in the presence of different ligands, suggesting a dynamic picture of the resting state. Patch-clamp fluorometry of the double- and single-insert constructs showed that both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane. Our time-resolved measurements revealed unexpectedly complex fluorescence changes within these intracellular domains, providing clues as to how posttranslational modifications and receptor function interact.
Patient-controlled room air insufflation versus automated carbon dioxide delivery for CT colonography.

OBJECTIVE Our objective was to prospectively compare colonic distention and patient comfort at screening CT colonography (CTC) with patient-controlled room air (RA) insufflation versus automated carbon dioxide (CO2) delivery. SUBJECTS AND METHODS Two hundred eight adults undergoing CTC were randomized to RA or CO2 (104 per method). Colonic distention was prospectively assessed by segment using a 4-point scale (1 = optimal, 2 = adequate, 3 = inadequate, 4 = collapsed). Adequacy of combined supine/prone segmental evaluation was also recorded. Patients provided discomfort ratings on a 0-10 scale (0-1 = none/insignificant, 2-3 = minimal, 4-6 = intermediate, 7-10 = significant) before, during, and after the procedure. RESULTS No significant differences in segmental distention were observed in the prone position between techniques. In the supine position, CO2 resulted in significantly greater distention in the sigmoid, descending, and transverse segments (p < 0.01). After combined supine/prone assessment, two/104 (1.9%) and three/104 (2.9%) patients were judged to have an inadequately evaluated segment on RA and CO2, respectively (four sigmoid, one transverse). Mean discomfort scores for RA and CO2 were 3.97 and 5.08 during the examination (p < 0.01); 0.91 and 0.42 immediately after (p < 0.01); 0.51 and 0.25 15 min later (p < 0.05); and 0.15 and 0.04 2 hours later (p < 0.01), respectively. During active distention, 19 (18.3%) and 33 (31.7%) patients reported significant transient discomfort with RA and CO2, respectively (p < 0.05). Beyond 15 min, only two (1.9%) patients with RA and no patients with CO2 had a discomfort level higher than 3. CONCLUSION Although patient-controlled RA insufflation and automated CO2 delivery each resulted in negligible postprocedure discomfort and reliable colonic distention, CO2 was better for both categories.
Efficacy of Occupational Therapy Task-oriented Approach in Upper Extremity Post-stroke Rehabilitation.

There is a need for more effective rehabilitation methods for individuals post-stroke. Occupational Therapy Task-Oriented (TO) approach has not been evaluated in a randomized clinical trial. The purpose of this study was to evaluate functional and impairment efficacies of TO approach on the more-affected Upper Extremity (UE) of persons post-stroke. A randomized single-blinded cross-over trial recruited 20 participants post-stroke (mean chronicity = 62 months) who demonstrated at least 10° active more-affected shoulder flexion and abduction and elbow flexion-extension. Participants were randomized into immediate (n = 10) and delayed intervention (n = 10) groups. Immediate group had 6 weeks of 3 hr/week TO intervention followed by 6 weeks of no-intervention control. Delayed intervention group underwent the reversed order. Functional measures included Canadian Occupational Performance Measure (COPM), Motor Activity Log (MAL), and Wolf Motor Function Test (WMFT). Impairment measures included UE Active Range of Motion (AROM) and handheld dynamometry strength. Measurements were obtained at baseline, cross over, and end of the study. TO intervention showed statistically higher functional change scores. COPM performance and satisfaction scores were 2.83 and 3.46 units greater respectively (p < .001), MAL amount of use and quality of use scores were 1.1 and 0.87 units greater, respectively (p < .001), WMFT time was 8.35 seconds faster (p = .009). TO impairment outcomes were not significantly larger than control ones. TO approach appears to be an effective UE post-stroke rehabilitation approach inducing clinically meaningful functional improvements. More studies are needed with larger samples and specific stroke chronicity and severity. Copyright © 2016 John Wiley & Sons, Ltd.
Distinct Pathological Features of the Gallyas‐ and Tau‐positive Glia in the Parkinsonism‐Dementia Complex and Amyotrophic Lateral Sclerosis of Guam

We examined 50 patients with parkinsonism-dementia complex of Guam (Guam PDC). 10 Guamanian patients with amyotrophic lateral sclerosis (ALS), 5 patients with combined PDC and ALS (PDC-ALS), and 20 non-PDC non-ALS Guamanians, who had been autopsied between 1979 and 1982, paying special attention to glial inclusions. Gallyas-positive and tau-immunopositive intracytoplasmic inclusions were observed in many of the glial cells, in addition to extensive neurofibrillary tangles (NFTs) in the brains of Guam PDC and PDC-ALS patients. Granular hazy inclusions were seen in the astrocytes, and some crescent/coiled inclusions were observed in the oligodendroglia. Many granular hazy inclusions were observed in the amygdaloid nucleus, inferior olivary nucleus, and lateral funiculus of the spinal cord. The crescent/coiled inclusions were observed predominantly in the anterior nucleus of the thalamus, motor cortex, midbrain tegmentum, pyramids of the medulla oblongata, and lateral funiculus of the spinal cord. The granular hazy inclusions have never been reported previously, and the topographic distribution of the crescent/coiled inclusions in Guam PDC and PDC-ALS differs from those reported previously in other NFT-forming diseases. These findings indicate that Guam PDC and PDC-ALS involve not only neurons but also glia, and that their morphological and topographic differences from other NFT-forming diseases may provide further insights into their distinct etiopathogenesis, and thus prove useful for diagnosis.
The human orthologue of CdGAP is a phosphoprotein and a GTPase‐activating protein for Cdc42 and Rac1 but not RhoA

Background information. Rho GTPases regulate a wide range of cellular functions affecting both cell proliferation and cytoskeletal dynamics. They cycle between inactive GDP‐ and active GTP‐bound states. This cycle is tightly regulated by GEFs (guanine nucleotide‐exchange factors) and GAPs (GTPase‐activating proteins). Mouse CdGAP (mCdc42 GTPase‐activating protein) has been previously identified and characterized as a specific GAP for Rac1 and Cdc42, but not for RhoA. It consists of an N‐terminal RhoGAP domain and a C‐terminal proline‐rich region. In addition, CdGAP‐related genes are present in both vertebrates and invertebrates. We have recently reported that two predominant isoforms of CdGAP (250 and 90 kDa) exist in specific mouse tissues.
Circulating CUDR, LSINCT‐5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls

The examination of circulating nucleic acids (CNAs) is an emerging noninvasive diagnostic technique. However, it is unclear if serum long noncoding RNAs (lncRNAs) represent a novel marker to detect gastric cancer (GC). In this study, we measured 39 candidate cancer‐associated lncRNAs by reverse transcription and quantitative polymerase chain reaction (RT‐qPCR) in sera from 110 patients with GC, 106 age‐ and sex‐matched healthy subjects and 15 patients with gastric peptic ulcer, markers were validated and assessed by RT‐qPCR. The correlation of the expression levels of the candidate serum lncRNAs with clinical parameters of GC patients was performed. A three‐lncRNA signature, including CUDR, LSINCT‐5 and PTENP1, was identified that may be potential diagnostic marker for GC. The areas under the receiver operating characteristic (ROC) curve for this serum three‐lncRNA signature were 0.920 and 0.829 for the two sets of serum samples. Moreover, a risk model for the serum three‐lncRNA signature demonstrated that healthy samples can be distinguished from early GC samples. Three‐lncRNA signature in serum was identified as diagnostic marker for GC. This work may facilitate the detection of GC and serve as the basis for further studies of the clinical value of serum lncRNAs in maintaining surveillance and forecasting prognosis.
Molecular Characterization of Antigen‐Induced Lung Inflammation in a Murine Model of Asthma

Abstract: Asthma is one of the foremost contributors to morbidity and mortality in industrialized countries. Our objective was to characterize the acute response to allergen and to identify potentially novel molecular targets for pharmacological intervention in asthma. We therefore designed a study to identify genes whose regulation was altered following ovalbumin (OVA) challenge in the presence and absence of treatment with glucocorticoids in BALB/c mice. RNA was isolated from lungs for gene profiling from 8‐week‐old sensitized mice, 3 and 18 hours post OVA challenge on days 1, 4, and 7 of aerosol challenge. Taqman (real time RT‐PCR) analysis of marker genes indicative of Th2 (IL‐4, IL‐13), eosinophil (RANTES, eotaxin), Th1/macrophage (IFNγ) and epithelial cell (MUC5AC) phenotypes were used to characterize responses to allergen challenge. Histological evaluation of lungs from additional challenged animals revealed inflammatory infiltrates on days 4 and 7, but not on day 1 post challenge. We postulate that expression of IL‐4, IL‐13 and other genes by OVA at day 1 probably reflects activation of resident cells, whereas the fivefold increase in the number of regulated genes at day 7 reflects the contribution of recruited cells. Of the regulated genes, only a subset was counter‐regulated by dexamethasone treatment. Although regulated genes included genes in many protein families, herein we report regulation of two proteases whose role in response to OVA challenge has not been characterized. This model will be used to generate disease hypotheses for which may play an important role in initiating disease pathology in this model.
Development and Validation of a Photonumeric Scale for Evaluation of Static Horizontal Forehead Lines

BACKGROUND A validated scale is needed for objective and reproducible comparisons of static forehead lines before and after treatment in practice and clinical studies. OBJECTIVE To describe the development and validation of the 5-point photonumeric Allergan Forehead Lines Scale. METHODS The Allergan Forehead Lines Scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each scale grade. The clinical significance of a 1-point score difference was evaluated in a review of multiple image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 295) completed during 2 sessions occurring 3 weeks apart. RESULTS A difference of ≥1 point on the scale was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 1.06 [0.91–1.21] for clinically different image pairs and 0.38 [0.26–0.51] for not clinically different pairs). Intrarater agreement between the 2 live-subject validation sessions was almost perfect (mean weighted kappa = 0.87). Interrater agreement was almost perfect during the second rating session (0.86, primary end point). CONCLUSION The Allergan Forehead Lines Scale is a validated and reliable scale for physician rating of static horizontal forehead lines.
Localization of the cellular expression of inhibin in trophoblastic tissue

Inhibin is a peptide hormone which is normally produced by ovarian granulosa cells and which inhibits the release of follicle stimulating hormone from the pituitary gland, thus acting as a modulator of folliculogenesis. Serum inhibin levels are higher during pregnancy than during the normal menstrual cycle and the placenta is thought to be a source of circulating inhibin. Previous studies have yielded conflicting results as to the cellular localization of inhibin in the placenta and the aim of the present study was to investigate the immunohistochemical localization of the hormone in placental tissue. We also wished to investigate whether inhibin could be demonstrated in choriocarcinoma and in non‐gestational trophoblastic tissue.
Up‐regulation of L‐type high voltage‐gated calcium channel subunits by sustained exposure to 1,4‐ and 1,5‐benzodiazepines in cerebrocortical neurons

The aim of this study is to examine how sustained exposure to two 1,4‐benzodiazepines (BZDs) with different action period, diazepam and brotizolam, and a 1,5‐BZD, clobazam, affects L‐type high voltage‐gated calcium channel (HVCC) functions and its mechanisms using primary cultures of mouse cerebral cortical neurons. The sustained exposure to these three BZDs increased [45Ca2+] influx, which was due to the enhanced [45Ca2+] entry through L‐type HVCCs but not through of Cav2.1 and Cav2.2. Increase in [3H]diltiazem binding after the exposure to these three BZDs was due to the increase in the binding sites of [3H]diltiazem. Western blot analysis showed increase of Cav1.2 and Cav1.3 in association with the increased expression of α2/δ1 subunit. Similar changes in [3H]diltiazem binding and L‐type HVCC subunit expression were found in the cerebral cortex from mouse with BZD physical dependence. These results indicate that BZDs examined here have the potential to increase L‐type HVCC functions mediated via the enhanced expression of not only Cav1.2 and Cav1.3 but also α2/δ1 subunit after their sustained exposure, which may participate in the development of physical dependence by these BZDs.
Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM1 and CMTM3 as priority targets

The novel CKLF‐like Marvel Transmembrane Domain‐containing gene family (CMTM) consists of 8 members (CMTM1–8). As little is known about the oncogenic impact of these genes, we aimed to systematically investigate the relevance of CMTMs to glioblastoma pathogenesis. We performed mRNA expression analyses and survival correlations in glioblastoma patients. Moreover, we analyzed the impact of RNAi‐based silencing and overexpression of CMTM family genes on tumor cell proliferation and invasion in vitro. CMTMs appeared to be widely regulated in the group of glioblastomas relative to non‐neoplastic brain (NB) tissue (significant upregulation for CMTM2, 3, and 6 and significant downregulation for CMTM 4 and 8). For CMTM1, 5 and 7, we found aberrant expression levels in individual tumors. Functionally, CMTM1, 3, and 7 promoted tumor cell invasion, while CMTM1 additionally enhanced cell proliferation. In a large clinically annotated dataset, higher CMTM1 and 3 expression was significantly correlated with shorter overall survival. Our data thus suggest CMTM1 and 3 as priority targets in glioblastomas. Using a human phosphokinase protein expression profiling assay, we can provide first insights into signalling of these two genes that might be conveyed by growth factor receptor, Src family kinase and WNT activation. © 2015 Wiley Periodicals, Inc.
Turkish women's knowledge of osteoporosis.

BACKGROUND Preventive measures including patient education can reduce hip fractures related to osteoporosis. Sometimes osteoporosis can be diagnosed with fractures or with a serious health problem, and most women are probably unaware of the risk factors which can be changed by prevention. The first step in preventing osteoporosis in women should be to make them aware of the risk factors. OBJECTIVES Our aim was to determine Turkish women's knowledge about and attitudes to osteoporosis and its prevention. METHODS A total of 311 women who applied to the Family Medicine department of the Middle East Technical University Medical Center were asked to fill in a questionnaire about osteoporosis. Only 270 of the 311 women who completed the entire questionnaire were included in the study. RESULTS Nearly 90% of the women surveyed thought they were somewhat familiar with osteoporosis. However, >65% were unaware that the disease is directly responsible for disabling hip fractures, and >40% were unable to identify significant risk factors. Only 36% of the respondents could correctly identify the calcium-rich foods among the choices. CONCLUSION According to our survey, a considerable number of the Turkish women in our settlement are unaware of the risk factors and the consequences of osteoporosis. Therefore, the women have inadequate knowledge of osteoporosis. There should be information resources easily accessible for the patients. The most important organizational incentives for providing patient information are further health promotion by the health authorities and the support of family physicians and the primary health care team.
Hepatitis C virus infection and risk of Parkinson’s disease: a systematic review and meta-analysis

Background/objective Hepatitis C virus (HCV) infection is one of the most common infections worldwide. Recent epidemiologic studies have suggested that patients with HCV infection might be at an increased risk of Parkinson’s disease. However, the data on this relationship remain inconclusive. This meta-analysis was conducted with the aim to summarize all available evidence. Patients and methods A literature search was performed using MEDLINE and EMBASE database from inception to May 2017. Studies that reported relative risks, odd ratios (ORs), or hazard ratios comparing the risk of Parkinson’s disease among HCV-infected patients versus participants without HCV infection were included. Pooled OR and 95% confidence interval were calculated using a random-effect, generic inverse variance method. Results Of 468 studies, five studies with 323 974 participants met our eligibility criteria and were included in the analysis. We found a higher risk of Parkinson’s disease among patients with chronic HCV infection compared with participants without HCV infection with the pooled OR of 1.35 (95% confidence interval: 1.19–1.52). The statistical heterogeneity of this study was insignificant (I2=3%). The main limitation of this meta-analysis was the limited accuracy of diagnosis in the primary studies as they were coding-based studies. Conclusion This study demonstrated a higher risk of Parkinson’s disease among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in the clinical picture.
Fuzzy Knuth Moris pratt algorithm for knowledge management system model on knowledge heavy metal content in oil plants

Knowledge Management system is a system that can provide accommodation and storage of knowledge. Storage of useful knowledge for the business processes necessary to sustain existing knowledge. Knowledge management system can accommodate knowledges, so that if needed at any time can be reused. Storage of knowledge in this system, to get it back to do a search string to facilitate the search for knowledge needed. String search method in this study with Fuzzy Algorithm Knuth Morris pratt. In this study, Fuzzy Knuth Morris Pratt algorithm used for modeling knowledge management system in the heavy metal content of oil crops. Application of fuzzy search string vague where the string matched only have similar characters determined by the method Knuth Morriss Pratt. The analysis of the heavy metal content can be performed to determine the content of heavy metal in the oil palm. By knowing the content of heavy metals in soil, plants and oil palm fresh fruit bunches then mitigation solutions can be determined accurately. The results of this research is the search string matching method with Fuzzy Algorithm Knuth Morriss Pratt on the model of Knowledge Management System that stores a variety of knowledge and experience about the metal content and solutions to overcome them. Novelty in this research is the application of Knuth Morris pratt algorithm combined with fuzzy knowledge on modeling heavy metal content in the palm. So the search for the Knowledge Management System can be done more quickly and accurately.