Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ‐56914845 (GSK2336805) in subjects with hepatic impairment

JNJ‐56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open‐label, parallel‐group, 2‐part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ‐56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort). Severity of hepatic impairment was categorized using Child‐Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort. JNJ‐56914845 plasma AUC0–∞ was 26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic impairment, respectively, relative to healthy subjects with no difference in half‐life among the groups. The apparent oral clearance and volume of distribution were higher in subjects with hepatic impairment. The lower plasma concentrations were largely explained by decreased plasma protein binding in hepatically impaired subjects. One subject with severe hepatic impairment had 2 non‐drug‐related serious adverse events: an esophageal bleed requiring hospitalization, encephalopathy. Although hepatically impaired subjects have lower exposures than healthy matched controls, they had similar or slightly higher exposures than those observed in past studies of noncirrhotic, CHC patients, suggesting that no dose adjustments for hepatic impairment will be needed.
Proteína C reativa como indicador de inflamação de baixa intensidade em crianças e adolescentes com e sem obesidade

OBJECTIVES: To determine the levels of high sensitivity C-reactive protein (hsCRP) in children/adolescents with and without obesity and their correlation with body mass index (BMI) and clinical and laboratory variables. METHODS: A cross-sectional study comparing two parallel groups, one a group of overweight or obese children/adolescents (obesity group, n = 131) and the other a control group of children/adolescents without obesity (control group, n = 114). High sensitivity nephelometry was used to determine hsCRP concentrations. RESULTS: The obesity group exhibited greater hsCRP concentrations than the control group (p < 0.0005). There were relationships between hsCRP and BMI (p < 0.0001) and hsCRP and triglycerides (p = 0.05). The relationship between hsCRP and triglycerides was attenuated by adjustment for BMI, losing its statistical significance (p = 0.10). CONCLUSIONS: The hsCRP concentrations increased as BMI increased. The majority of individuals who were not overweight exhibited hsCRP concentrations of less than 2 mg/L.
Stress response of Salmo salar (Linnaeus 1758) facing low abundance infestation of Caligus rogercresseyi (Boxshall & Bravo 2000), an object in the tank, and handling.

This study looks at how low infestation loads of adult Caligus rogercresseyi and other stressors affect the physiology of Salmo salar. Experimental fish groups were with (infested) or without (control) exposure to the parasite. The parasite cohort was followed for 78 days post-infestation (dpi), and only adult lice were observed. Additional stressors were applied at 60 and 75 dpi. The analysis included measurements of fish physiology and weight. Low-level infestations by adult C. rogercresseyi for more than 50 dpi induced moderate stress in S. salar as well as a high energy demand and increased small skin mucous cells. Threshold lice loads were identified, and above those loads, a high stress response was observed. Additional stressors altered fish physiology, inducing downregulation of the cortisol response after the first stressor and upregulation after the second stressor, but infested fish responded more strongly. Parasitism by C. rogercresseyi is energetically demanding, affecting the primary and secondary responses (e.g. cortisol and glucose levels), as well as the tertiary response (fish weight).
Local resistance switching at grain and grain boundary surfaces of polycrystalline tungsten oxide films

Resistance switching behavior has been investigated in as-prepared and oxygen-annealed polycrystalline tungsten oxide films using conductive atomic force microscopy. The oxygen-annealed film appeared more insulative than the as-prepared films. The local current distributions demonstrated the lower conductivity at the grain boundaries than at the grains in the oxygen-annealed films. Reversible resistance switching behavior only occurred at the grain surface region of the oxygen-annealed films and the resistance switching process was described by the local valence change of tungsten ions induced by electrochemical migration of protons or oxygen vacancies. This different resistance switching behavior between the grain and grain boundary surface was attributed to the different oxygen vacancy density caused by the post-annealing process. The present results would be especially meaningful for the fabrication of nanoscale resistive nonvolatile memory devices.
A detailed understanding of the electronic bipolar resistance switching behavior in Pt/TiO2/Pt structure

The detailed mechanism of electronic bipolar resistance switching (BRS) in the Pt/TiO2/Pt structure was examined. The conduction mechanism analysis showed that the trap-free and trap-mediated space-charge-limited conduction (SCLC) governs the low and high resistance state of BRS, respectively. The SCLC was confirmed by fitting the current–voltage characteristics of low and high resistance states at various temperatures. The BRS behavior originated from the asymmetric potential barrier for electrons escaping from, and trapping into, the trap sites with respect to the bias polarity. This asymmetric potential barrier was formed at the interface between the trap layer and trap-free layer. The detailed parameters such as trap density, and trap layer and trap-free layer thicknesses in the electronic BRS were evaluated. This showed that the degradation in the switching performance could be understood from the decrease and modified distribution of the trap densities in the trap layer.
Dense hydroxyapatite inserted into postextraction sockets: a histologic and histomorphometric 20-year case report.

BACKGROUND The biologic behavior, i.e., the degradation of hydroxyapatite (HA) in the human body, is of relevance for clinicians. The present investigation is a long-term (20-year) histologic and histomorphometric evaluation of dense HA used in postextraction sockets. METHODS Dense HA particles were used in a patient in postextraction alveolar sockets to maintain the alveolar ridge height. The patient returned after 20 years for implant treatment. A ridge remodeling was necessary during implant insertion surgery, and the HA/bone tissue was harvested with bone-cutting forceps from the canine and premolar area. The specimen was processed for histology and histomorphometry at the Implant Retrieval Centre, Dental School, University of Chieti-Pescara. RESULTS Most of the particles (56%) were surrounded partially by bone, whereas some particles (39%) were surrounded completely. At higher magnification, bone was in close contact with the particles, and neither gaps nor fibrous tissues were present at the bone-biomaterial interface. Microscopically, the particles had a dense appearance. In only a few fields, it was possible to observe that the outer part of some particles had detached from the original particles' surface. Histomorphometry showed that bone represented 25.4% +/- 3.2%, marrow spaces represented 41.3% +/- 5.2%, and residual HA particles represented 38.1% +/- 4.1%. CONCLUSIONS Intimate binding between bone and HA particles was present after a long-term implantation period (20 years). The fact that HA particles were surrounded closely by bone is very promising for the long-term stability of the augmentation.
HEALTH INSURANCE IN ITS RELATION TO PUBLIC HEALTH

It is not an easy matter to condense within a fifteen minute paper the entire comprehensive subject of compulsory health insurance, but perhaps such an effort is at present unnecessary. So much has been said and written on the subject within the last few months that some familiarity with the subject may be expected from members of the medical profession. The valuable work done within the last year or two by the Public Health Service and the splendid reports of your Judicial Council, of which the first was presented about a year ago and the second one is to be made available to the medical profession in the very near future, have paved the way at least for a general understanding of the problem by American physicians. It seems sufficient, therefore, to present the entire subject at this time in a concise and somewhat schematic manner, bringing forth for special
Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib Treatment Using a Population Pharmacokinetic‐Pharmacodynamic Modeling and Simulation Approach

Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin‐dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic‐pharmacodynamic model was developed to describe the time course of absolute neutrophil count (ANC) and quantify the exposure‐response relationship for neutropenia. These analyses help in understanding neutropenia associated with palbociclib and its comparison with chemotherapy‐induced neutropenia. In the model, palbociclib plasma concentration was related to its antiproliferative effect on precursor cells through drug‐related parameters (ie, maximum estimated drug effect and concentration corresponding to 50% of the maximum effect), and neutrophil physiology was mimicked through system‐related parameters (ie, mean transit time, baseline ANC, and feedback parameter). Sex and baseline albumin level were significant covariates for baseline ANC. It was demonstrated by different model evaluation approaches (eg, prediction‐corrected visual predictive check and standardized visual predictive check) that the final model adequately described longitudinal ANC with good predictive capability. The established model suggested that higher palbociclib exposure was associated with lower longitudinal neutrophil counts. The ANC nadir was reached approximately 21 days after palbociclib treatment initiation. Consistent with their mechanisms of action, neutropenia associated with palbociclib (cytostatic) was rapidly reversible and noncumulative, with a notably weaker antiproliferative effect on precursor cells relative to chemotherapies (cytotoxic). This pharmacokinetic‐pharmacodynamic model aids in predicting neutropenia and optimizing dosing for future palbociclib trials with different dosing regimen combinations.
Lung Function: Assessment and Application in Medicine

The third edition of Cotes' well-known text continues in the same format as previous editions. The first 14 chapters are valuable overviews of the different facets of pulmonary physiology and pathophysiology, as well as brief descriptions of the testing methods used to demonstrate functional abnormalities. There is, as well, a small section on selected basic laboratory equipment, as previously. On the dust cover the publisher states that this book has been extensively revised. However, the total number of pages is essentially as in the second edition, and as one reads through the book, most pages read almost as in the previous edition. However, some portions have been rewritten and more current data entered. The 15th and 16th chapters relate to lung function in disease. Of necessity, only brief detail could be presented; and since other current texts have detailed evaluations of physiologic abnormality in these situations, I believe the author
Influence of Cu nanoparticle size on the photo-electrochemical response from Cu–multiwall carbon nanotube composites

We show that Cu metal nanoparticle–multiwall carbon nanotube (MWCNT) assemblies can act as a new hybrid photoactive layer in photo-electrochemical devices. The carbon nanotube (CNT) composites were formed by a controlled thermal deposition of copper which produced crystalline metal nanoparticles localized on the carbon tube outer walls. The photoresponse evaluated in terms of IPCE (incident photon-to-charge carrier generation efficiency) varied for different sized-Cu–MWCNT samples across all the visible and near ultraviolet photon energy range with respect to the response of bare MWCNTs. In the case of 0.2 nm Cu nominal thickness, the IPCE increased, reaching 15%, a value 2.5 times higher than that measured for bare MWCNTs. As the Cu nominal coverage thickened, the IPCE started to decrease and become totally ineffective after 1 nm deposited Cu. The IPCE increase found was interpreted as being the result of a remarkable charge transfer between the Cu metal nanoparticles and the CNTs due to the formation of a strong ionic bond at their interface. The results obtained prove that the metal nanoparticle–CNT composites have optical, electrical and structural properties that can be applied in a variety of nanoscale architectures for novel photo-electrochemical devices.
Piscine orthoreovirus‐3 is prevalent in wild seatrout (Salmo trutta L.) in Norway

Abstract In 2017, a PCR‐based survey for Piscine orthoreovirus‐3 (PRV‐3) was conducted in wild anadromous and non‐anadromous salmonids in Norway. In seatrout (anadromous Salmo trutta L.), the virus was present in 16.6% of the fish and in 15 of 21 investigated rivers. Four of 221 (1.8%) Atlantic salmon (Salmo salar L.) from three of 15 rivers were also PCR‐positive, with Ct‐values indicating low amounts of viral RNA. All anadromous Arctic char (Salvelinus alpinus L.) were PCR‐negative. Neither non‐anadromous trout (brown trout) nor landlocked salmon were PRV‐3 positive. Altogether, these findings suggest that in Norway PRV‐3 is more prevalent in the marine environment. In contrast, PRV‐3 is present in areas with intensive inland farming in continental Europe. PRV‐3 genome sequences from Norwegian seatrout grouped together with sequences from rainbow trout (Oncorhynchus mykiss Walbaum) in Norway and Coho salmon (Oncorhynchus kisutch Walbaum) in Chile. At present, the origin of the virus remains unknown. Nevertheless, the study highlights the value of safeguarding native fish by upholding natural and artificial barriers that hinder introduction and spread, on a local or national scale, of alien fish species and their pathogens. Accordingly, further investigations of freshwater reservoirs and interactions with farmed salmonids are warranted.
Alcohol Intoxication Reduces Systemic Interleukin-6 Levels and Leukocyte Counts After Severe TBI Compared With Not Intoxicated TBI Patients

Background: The effect of alcohol consumption on inflammatory state and outcome in brain-injured patients remains controversial. We analyzed the influence of positive blood alcohol concentration (BAC) on inflammatory changes, inhospital complications, and mortality in traumatic brain injury (TBI) patients. Patients and Methods: Patients with an Injury Severity Score (ISS) at least 16 and Abbreviated Injury Scale of head (AIS-head) at least 3 were included upon arrival in the emergency room and grouped according to positive BAC (>0.5‰, BAC) vs. less than 0.5‰ alcohol (no BAC). Injury severity, vital signs, complications, mortality, and systemic interleukin (IL)-6 levels were prospectively determined, and BAC was quantified. According to ISS, AIS-head, age, and sex, we performed matched-pair analysis. Results: A total of 101 TBI patients were included. Of them 74 patients were dedicated to no BAC group and 27 to BAC group. ISS was significantly higher in the no BAC group. Positive BAC group required significantly less packed red blood cells and fresh frozen plasma (P < 0.05). Shorter ICU stays were found in BAC-positive patients. Inhospital complications, including single/multiple organ failure, systemic inflammatory response syndrome, sepsis, pneumonia, and acute respiratory distress syndrome, showed no significant differences. Systemic IL-6 levels and leukocyte counts (IL-6: 65.0 ± 8.0 vs. 151.8 ± 22.3; leukocytes: 10.2 ± 0.9 vs. 13.2 ± 0.8, both P < 0.05) were significantly lower in BAC-positive patients. Matched-pair analysis was performed with 27 pairs. No significant differences in transfusions were monitored after matching. However, lowered systemic IL-6 levels and leukocyte counts in the BAC group were also detected after matching, indicating that this effect is ISS-independent. Conclusions: This study shows that positive BAC in TBI patients is associated with lower systemic IL-6 levels and leukocyte numbers, indicating that positive BAC may have immunosuppressive effects in this cohort of patients compared with TBI patients who were not alcohol intoxicated.
Trauma-Related Acute Lung Injury Develops Rapidly Irrespective of Resuscitation Strategy in the Rat

Background: Acute lung injury (ALI) has been observed clinically after severe trauma. We have recently developed a rat model of polytrauma that shows evidence of multi-organ failure and coagulopathy. In this study, we investigate whether ALI occurs after severe trauma and resuscitation, and the cellular mechanisms involved. Methods: Polytrauma and hemorrhage was induced in anesthetized Sprague-Dawley rats. Five groups were prepared: control, no resuscitation, and resuscitation with Lactated Ringer (LR), fresh whole blood or whole blood stored 7days at 4°C. Resuscitation was begun 1 hr after trauma. Lung injury was determined by lung wet/dry weight ratios. Results: Polytrauma and hemorrhage (no resuscitation) led to a significant increase in the number of neutrophils, monocytes, macrophages, platelets, and the levels of myeloperoxidase, pro-inflammatory cytokines (IL-6, IL-1&agr;, IL-1&bgr;), anti-inflammatory Th2 cytokines (IL-4, IL-10, IL-13), and chemokines (MIP-1&agr;, GRO KC) in the lung tissue. Resuscitation with LR, fresh whole blood or stored blood led to a significant change in the lung wet/dry ratio signifying fluid movement into the lungs. However, fluid did not move into the lungs in non-resuscitated controls. Conclusion: This study shows that trauma related acute lung injury occurs early after polytrauma and hemorrhage in rat. This ALI is secondary to the trauma, and likely due to an elevation in leukocytes, platelets, inflammatory cytokines and myeloperoxidase in the lung tissue prior to any resuscitation. Resuscitation with either LR or whole blood demonstrated similar lung edema. Blood was neither more protective nor more damaging than LR during early resuscitation.
Patient Violence in Community Mental Health: A Review of the Literature

The past decade has seen an increasing focus on care in the community. During this period, the media has given a high profile to a number of incidents where members of the public and health service staff have been assaulted by patients of mental health services. Many occupational therapists work in community mental health teams and there is a nationally acknowledged need for risk assessment and management. Despite this, an electronic search of five major databases and eight occupational therapy journals revealed no literature within the occupational therapy profession examining risk assessment and management. The existing literature is from the nursing and medical professions. A systematic review of 10 studies, two conducted in the United Kingdom and eight in the United States of America, is presented. It is suggested that the occupational therapy profession urgently needs to address this gap in its literature and consider what can be learned from other professions.
Optimizing Within Session Training Emphasis

CURRENT MONITORING PRACTICES TYPICALLY PROVIDE RETROSPECTIVE QUANTIFICATION OF A RESISTANCE TRAINING SESSION. THAT IS, THE INFORMATION COLLECTED SUMMARIZES A COMPLETED SESSION AND IS THEREFORE USED TO MODIFY A SUBSEQUENT SESSION. WHEN THE FOCUS OF A CONDITIONING PROGRAM PROGRESSES TO THE DEVELOPMENT OF POWER, HAVING DYNAMOMETRY THAT ALLOWS ATHLETES TO GAIN INSTANTANEOUS FEEDBACK AS TO POWER OUTPUT OR VELOCITY OF MOTION MAY RESULT IN MORE GOAL-ORIENTED MOVEMENT THAT INCREASES THE LIKELIHOOD OF TRANSFERENCE TO ON-FIELD PERFORMANCE OR AT THE VERY LEAST IMPROVES THE MECHANICAL VARIABLE OF INTEREST.
Cognitive‐behaviour therapy for the management of sickle cell disease pain: An evaluation of a community‐based intervention

Objectives. To evaluate the immediate effectiveness of a cognitive-behavioural group therapy intervention for the management of sickle cell disease SCD pain. Design. This study is taken from an ongoing longitudinal, multi-centred, randomized controlled trial. Method. Ninety-seven patients with SCD recruited from seven London hospitals were randomly allocated to one of three treatment conditions after giving written consent: a CBT pain management group, an attention placebo group and a nointervention control. All participants completed a number of measures at baseline and post-intervention to assess psychological well-being, pain and coping. Results. Results are presented for the 59 participants who met the study entrance criteria, attended treatment group sessions above the cut-off point selected for treatment completion, and completed sessions both baseline and post-intervention assessments. Significant post-intervention treatment group differences in favour of the CBT intervention were identified for nearly all of the psychological measures using the Kruskal-Wallis test. Within-group significant differences over time were also found for the CBT condition for the majority of the measures. Following the identification of centre differences in baseline measures, two-way ANCOVAs were conducted with centre and condition for the ranked data of each psychological measure using ranked baseline scores as covariates. Observation of the adjusted means indicated that most of the post-intervention effect was accounted for by centres 1 and 2, with centre 4 having a minimal effect and, for centre 3, some of the measures showing a reverse effect to that predicted. Conclusions. Overall, the cognitive-behavioural approach employed appears to be immediately effective for the management of SCD pain in terms of reducing psychological distress and pain, and improving coping. Further analysis of longitudinal and cost-effectiveness data currently being collated will indicate whether long-term and financial benefits are to be gained.
Rapid on‐site evaluation by endosonographer during endoscopic ultrasound‐guided fine needle aspiration for pancreatic solid masses

Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is an established diagnostic method for patients with suspected pancreatic ductal carcinoma. Rapid on‐site evaluation (ROSE) has been reported to improve the accuracy. However, an on‐site cytopathologist is not routinely available in many institutions. One of the solutions may be ROSE by endosonographer. The aim was to examine whether diagnostic accuracy increases through ROSE by endosonographer using our cytological criteria.