Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Assessment of Potential Long-Term On-Target Side Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitors

Background: Although short-term trials have suggested that PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are safe and reduce risk of cardiovascular diseases, their long-term safety is unclear. Genetic variants associated with lower activity of a gene can act as proxies to identify potential long-term side effects of drugs as recently exemplified by association of LDL (low-density lipoprotein)-lowering variants in the HMGCR (target for statins) and PCSK9 genes with increased risk of type 2 diabetes mellitus (T2DM). However, analyses of the full spectrum of potential side effects of PCSK9 inhibition using a genetic approach have not been undertaken. Methods: We examined the association of an LDL-lowering variant in the PCSK9 gene (T allele of rs1159147), as well as 2 LDL-lowering HGCMR variants (G allele of rs17238484 and T allele of rs12916) with 80 diseases and traits in up to 479 522 individuals in UK Biobank. Results: The PCSK9 T allele was significantly (Bonferroni P<6.25×10−4) associated with risk of T2DM, increased body mass index, waist circumference, waist-hip ratio, diastolic blood pressure, type 1 diabetes mellitus, and insulin use. The HMGCR variants were also associated with risk of T2DM, although their previously reported associations with anthropometric traits were found to be confounded. Mediation analysis suggested that the association of the PCSK9 T allele with risk of T2DM but not diastolic blood pressure was largely independent of its association with body mass index and central obesity. Nominally significant associations of the PCSK9 T allele were also seen with peptic ulcer disease, depression, asthma, chronic kidney disease, and venous thromboembolism. Conclusions: Our findings support previous genetic analyses suggesting that long-term use of PCSK9 inhibitors, like statins, may be associated with increased risk of T2DM. Some other potential side effects need to be looked for in future studies of PCSK9 inhibitors, although we did not find signals that raise substantial concerns about their long-term safety.
Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

RATIONALE & OBJECTIVE Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes. STUDY DESIGN Post hoc analysis of a randomized controlled trial. SETTING & PARTICIPANTS Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n=590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). EXPOSURE Randomized treatment assignment (darbepoetin vs placebo). OUTCOMES All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. ANALYTICAL APPROACH Proportional hazards regression. RESULTS Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n=298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3±1.6 and 9.5±1.5g/dL (P<0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7). LIMITATIONS Post hoc analyses of a subgroup of study participants. CONCLUSIONS Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.
Age-Associated Distribution of Antimicrobial-Resistant Salmonella enterica and Escherichia coli Isolated from Dairy Herds in Pennsylvania, 2013-2015.

Antimicrobial resistance has become a major global public health concern, and agricultural operations are often implicated as a source of resistant bacteria. This study characterized the prevalence of antimicrobial-resistant Salmonella enterica and Escherichia coli from a total of 443 manure composite samples from preweaned calves, postweaned calves, dry cows, and lactating cows from 80 dairy operations in Pennsylvania. A total of 1095 S. enterica and 2370 E. coli isolates were screened and tested for resistance to 14 antimicrobials on the National Antimicrobial Resistance Monitoring System Gram-negative (NARMS GN) panel. Salmonellae were isolated from 67% of dairy operations, and 99% of the isolates were pan-susceptible. Salmonella were isolated more frequently from lactating and dry cow samples than from pre- and postweaned calf samples. Overall, the most prevalent serotypes were Cerro, Montevideo, Kentucky, and Newport. E. coli were isolated from all the manure composite samples, and isolates were commonly resistant to tetracyclines, sulfonamides, and aminoglycosides. Resistance was detected more frequently in the E. coli isolates from pre- and postweaned calf samples than in isolates from dry and lactating cow samples (p < 0.05). Multidrug-resistant E. coli (i.e., resistant to >3 antimicrobial classes) were isolated from 66 farms (83%) with significantly greater prevalence in preweaned calves (p < 0.05) than in the older age groups. The blaCTX-M and blaCMY genes were detected in the cephalosporin-resistant E. coli from 4% and 35% of the farms, respectively. These findings indicate that dairy animals, especially the calf population, serve as significant reservoirs for antimicrobial-resistant bacteria. Additional research on the colonization and persistence of resistant E. coli in calves is warranted to identify potential avenues for mitigation.
Gels in the Conservation of Art

Gels in the Conservation of Art Lora Angelova, Bronwyn Ormsby, Joyce H. Townsend, Richard Wolbers (eds) London: Archetype Publications Ltd, 2017 ISBN: 9781909492509 Dimensiones:297 x 210. Páginas: 406 Ilustraciones en color
Increased Nociceptive Responses in Streptozotocin-Induced Diabetic Rats and the Related Expression of Spinal NR2B Subunit of N-Methyl-D-Aspartate Receptors

Background This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli. Methods Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed. Results DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B. Conclusion We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.
The Year in Cardiology 2018: imaging.

1Heart Lung Centrum, Leiden University Medical Center, The Netherlands; 2University of Medicine and Pharmacy "Carol Davila" Euroecolab, Institute of Cardiovascular Diseases „Prof. Dr. C. C. Iliescu”, Bucharest, Romania; 3Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, United Kingdom; 4Department of Cardiology, Friedrich-Alexander-Universität, Erlangen, Germany; 5Turku PET Centre, University of Turku and Turku University Hospital
Linking the behavioral assessment screening tool to the international classification of functioning, disability, and health as a novel indicator of content validity

Abstract Purpose: To use the International Classification of Functioning, Disability, and Health (ICF) to classify and describe the concepts of the Behavioral Assessment Screening Tool (BAST), a measure of behavioral disruptions after traumatic brain injury (TBI). Methods: Meaningful concepts in the BAST were linked to the International Classification of Functioning to (1) further explore the validity of the conceptual model of behavior; (2) demonstrate ICF linking as a novel indicator of the content validity; (3) identify International Classification of Functioning concepts that characterize behavior; (4) determine the comprehensiveness of the BAST. Results: The body functions component and the activities and participation component were most frequently addressed in the BAST. The majority of the TBI Core Set categories were included in the BAST and the manifest and latent coders agreed 85% of the time. Conclusions: Linking BAST concepts to the International Classification of Functioning demonstrated the BAST’s content validity and comprehensiveness. This approach provides a model for how ICF coding could be used to assess content validity. Implications for Rehabilitation ICF coding can be used to assess content validity and refine rehabilitation measures. The Behavioral Assessment Screening Tool can be used for clinical and research purposes to assess behavior as it relates to a wide range of ICF TBI Core Set categories.
The association of adelmidrol with sodium hyaluronate displays beneficial properties against bladder changes following spinal cord injury in mice

The disruption of coordinated control between the brain, spinal cord and peripheral nervous system caused by spinal cord injury (SCI) leads to several secondary pathological conditions, including lower urinary tract dysfunction. In fact, urinary tract dysfunction associated with SCI is urinary dysfunction could be a consequence of a lack of neuroregeneration of supraspinal pathways that control bladder function. The object of the current research was to explore the effects of adelmidrol + sodium hyaluronate, on bladder damage generated after SCI in mice. Spinal cord was exposed via laminectomy, and SCI was induced by extradural compression at T6 to T7 level, by an aneurysm clip with a closing force of 24 g. Mice were treated intravesically with adelmidrol + sodium hyaluronate daily for 48 h and 7 days after SCI. Adelmidrol + sodium hyaluronate reduced significantly mast cell degranulation and down-regulated the nuclear factor-κB pathway in the bladder after SCI both at 48 h and 7days. Moreover, adelmidrol + sodium hyaluronate reduced nerve growth factor expression, suggesting an association between neurotrophins and bladder pressure. At 7 days after SCI, the bladder was characterized by a marked bacterial infection and proteinuria; surprisingly, adelmidrol + sodium hyaluronate reduced significantly both parameters. These data show the protective roles of adelmidrol + sodium hyaluronate on bladder following SCI, highlighting a potential therapeutic target for the reduction of bladder changes.
Religious Head Covering, Being Perceived as Foreigners, Victimization, and Adjustment Among Sikh American Adolescents

Bullying victimization related to race or religion is a problem that permeates schools in the United States for minority students. One group of students that are at higher risk for victimization is Sikh American adolescents, which may result from them being stereotyped as foreigners. We used path analysis to examine the relationships among self-reports of (a) wearing religious head coverings, (b) being perceived as a foreigner, (c) victimization (i.e., physical, verbal, and relational), and (d) adjustment outcomes (i.e., self-esteem, depressive symptoms, and anxiety related to perceptions of school safety) by Sikh American adolescents. Survey data were collected from 199 Sikh American adolescents from 120 schools in 61 cities in California (54% male, mean age = 14.19 years, SD = 1.86). Results indicated that a large percentage (76.4%) of Sikh American adolescents reported at least one type of victimization during the school year, and victimization appeared to relate to race and religion for many students. Wearing a religious head covering related to Sikh American adolescents’ perceptions that they were stereotyped as foreigners, which, in turn, related to verbal and relational victimization (indirect effect = 0.05 and 0.06) but not physical victimization. Being a male predicted more verbal victimization (&bgr; = 0.38). In addition, being perceived as a foreigner was related to higher victimization, which was also related to lower self-esteem and higher depressive and anxious symptoms (indirect effect = −0.05, 0.08, and 0.06, respectively). Implications for school psychologists to reduce victimization and improve school climate for Sikh American students are discussed.
Single wall and multiwall carbon nanotubes induce different toxicological responses in rat alveolar macrophages

Human exposure to airborne carbon nanotubes (CNT) is increasing because of their applications in different sectors; therefore, they constitute a biological hazard. Consequently, developing studies on CNT toxicity become a necessity. CNTs can have different properties in term of length, size and charge. Here, we compared the cellular effect of multiwall (MWCNTs) and single wall CNTs (SWCNTs). MWCNTs consist of multiple layers of graphene, while SWCNTs are monolayers. The effects of MWCNTs and SWCNTs were evaluated by the water‐soluble tetrazolium salt cell proliferation assay on NR8383 cells, rat alveolar macrophage cell line (NR8383). After 24 hours of exposure, MWCNTs showed higher toxicity (50% inhibitory concentration [IC50] = 3.2 cm2/cm2) than SWCNTs (IC50 = 44 cm2/cm2). Only SWCNTs have induced NR8383 cells apoptosis as assayed by flow cytometry using the annexin V/IP staining test. The expression of genes involved in oxidative burst (Ncf1), inflammation (Nfκb, Tnf‐α, Il‐6 and Il‐1β), mitochondrial damage (Opa) and apoptotic balance (Pdcd4, Bcl‐2 and Casp‐8) was determined. We found that MWCNT exposure predominantly induce inflammation, while SWCNTs induce apoptosis and impaired mitochondrial function. Our results clearly suggest that MWCNTs are ideal candidates for acute inflammation induction. In vivo studies are required to confirm this hypothesis. However, we conclude that toxicity of CNTs is dependent on their physical and chemical characteristics.
Colorectal cancer screening in Middle Eastern countries: Current status and future strategies to enhance screening

Colorectal cancer (CRC) screening has been proven effective to reduce mortality[1] and has been proposed by international guidelines and the Asia Pacific Consensus Statements[2,3] as important preventive strategies in individuals aged 50–75 years. In the past decade, many studies have examined the knowledge, attitude, screening uptake, and colonoscopy yield in numerous nations,[4,5] yet few have been conducted in Saudi Arabia. In the Saudi guidelines, average‐risk individuals are recommended to start CRC screening at 45 years and colonoscopy was the first‐line screening modality. [6]
The Relationship Between Obsessive Belief Level and Cognitive Flexibility in Patients with Obsessive Compulsive Disorder.

Introduction It is known that dysfunctional beliefs are important in the onset and maintenance of symptoms of Obsessive Compulsive Disorder (OCD) according to the cognitive model of OCD. OCD patients with higher obsessive beliefs would be expected to have greater deficits in cognitive flexibility. In this study, we aimed to examine the relationship between obsessive belief levels and cognitive flexibility in OCD patients. Methods Patients with OCD (50) and Panic Disorder (30) as a control group were evaluated and diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders. A socio-demographic data form, Beck Depression Inventory, Beck Anxiety Inventory and Wisconsin Card Sorting Test (WCST) were administered to all the patients. The Yale-Brown Obsessive Compulsive Scale and Obsessive Beliefs Questionnaire-44 (OBQ-44) were administered to the OCD group. The OCD group was divided into two subgroups as higher obsessive beliefs (OCD-H) (n=29) and lower obsessive beliefs (OCD-L) (n=21) according to a cluster analytic approach. Results When the subgroups were compared according to WCST; the number of completed categories was statistically significantly lower, and the numbers of total errors, perseverative errors and non-perseverative errors were significantly higher in the OCD-H group. Conclusion The results of our study show that cognitive flexibility is impaired in OCD patients with higher obsessive beliefs.
Frequency and outcomes of maternal thyroid function abnormalities in early pregnancy

Abstract Thyroid function in pregnant women is of clinical importance considering the crucial role of thyroid hormones during fetal brain development, but the current level of evidence is insufficient to recommend for or against the routine testing of thyroid function in pregnant women. As part of this debate, it is important to evaluate the frequency of undiagnosed and untreated thyroid function abnormalities in pregnant women and to address challenges related to the biochemical assessment of maternal thyroid function in early pregnancy. A hypothesis of fetal programming by maternal thyroid disease has been proposed, but more evidence in humans is needed to extend the hypothesis and to evaluate child neurodevelopmental outcomes after in utero exposure to different abnormalities in maternal thyroid function. The nationwide registers in the Nordic countries provide unique opportunities within reproductive epidemiology to study the impact of various in utero exposures, and stored blood samples from pregnant women in nationwide birth cohorts provide a valuable source for the establishment of pregnancy specific reference ranges. This review addresses the frequency and outcomes of thyroid function abnormalities in pregnant women mainly focusing on observational studies that combine data from the Danish nationwide registers and biological specimens from the Danish National Birth Cohort. Dynamic changes in the reference range of maternal TSH and free T4 during the first trimester of pregnancy are described and discussed. A high frequency of unidentified maternal thyroid function abnormalities is illustrated, and outcomes of child neurodevelopment are evaluated according to subtypes and severity of maternal thyroid dysfunction.
Prognostic significance of PCT and CRP evaluation for adult ICU patients with sepsis and septic shock: retrospective analysis of 59 cases

Objective To investigate the prognostic significance of serum procalcitonin (PCT) and C-reactive protein (CRP) in patients with sepsis and those with septic shock. Methods Fifty-nine patients were divided into sepsis and septic shock groups, as well as survivor and non-survivor groups, according to the severity of the disease and patient survival. Serum PCT and CRP measurements at the time of hospitalization in the intensive care unit were examined. Results On the 2nd, 3rd, and 5th days, the CRP level was higher in the non-survivor group than in the survivor group, and the serum CRP level was higher in patients in the septic shock group than in patients in the sepsis group. Regarding changes in serum PCT level in each group, the levels of PCT were significantly different between non-survivor and survivor groups, whereas they did not differ between patients in the sepsis and septic shock groups. Serum PCT kinetics (ΔPCT) were similar between groups. Conclusions Serum PCT and CRP have good clinical diagnostic and prognostic value for patients with sepsis and septic shock. Kinetic studies of PCT and CRP can improve sensitivity and accuracy when evaluating the prognosis of patients with sepsis and those with septic shock.
Anti-Depressive Effectiveness of Baicalin In Vitro and In Vivo

Baicalin (BA), a major polyphenol compound isolated from the extracts of Scutellaria radix, has been previously reported to ameliorate depressive-like behaviors in mice with chronic unpredictable mild stress (CUMS). However, its underlying antidepressant mechanisms remain unclear. This study was designed to confirm the antidepressant-like effects of BA on CUMS induced behavioral abnormalities in mice, and sought to explore the pharmacological mechanisms in vivo and in vitro. The CUMS procedure was carried out to induce depression in mice. Afterwards, the tail suspension test (TST), forced swim test (FST), and open field test (OFT) were performed within 24 h, then sucrose preference test (SPT) was conducted. Additionally, PC12 cells were pretreated with BA for 2 h, then further stimulated with corticosterone for 24 h. The levels of Interleukin-1β (IL-1β), IL-6 and Tumor Necrosis Factor-α (TNF-α) in serum, hippocampus homogenate and cell culture medium were determined using the enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of inhibition of high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathways in hippocampus and PC12 cells were detected. Our results showed that CUMS-treated mice presented notable depressive-like symptoms, such as decreased sucrose consumption, increased FST and TST immobility time. While BA (25, 50 mg/kg) significantly attenuated these changes. Besides, BA treatment considerably inhibited inflammatory cytokinesl (IL-1β, IL-6, TNF-α) levels in serum, hippocampus homogenate and cell culture medium. Western blot analysis indicated that BA inhibited the expressions of HMGB1, TLR4, and p-NF-κBp65 both in vivo and in vitro. In conclusion, the present study confirmed that BA possessed efficient antidepressant effects on depression, which was possibly related to the inhibition of HMGB1/TLR4/NF-κB pathways.