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Policy Points Strategically purchasing health care has been and continues to be a popular policy idea around the world. Key asymmetries in information, market power, political power, and financial power hinder the effective implementation of strategic purchasing. Strategic purchasing has consistently failed to live up to its promises for these reasons. Future strategies based on strategic purchasing should tailor their expectations to its real effectiveness.
Strategic purchasing of health care has been a popular policy idea around the world for decades, with advocates claiming that it can lead to improved quality, patient satisfaction, efficiency, accountability, and even population health. In this article, we report the results of an inquiry into the implementation and effects of strategic purchasing.
We conducted three in-depth case studies of England, the Netherlands, and the United States. We reviewed definitions of purchasing, including its slow acquisition of adjectives such as strategic, and settledbe worthwhile. Instead, policymakers may need to focus on the real sources of power in a health care system. Policy for systems with existing purchasing relationships should take into account the asymmetries, ways to work with them, and the constraints that they create.This study compared the differences in neural and muscular mechanisms related to explosive torque in chronically strength-trained young and older men (>5 years). Fifty-four participants were allocated into four groups according to age and strength training level older untrained (n = 14; 65.6 ± 2.9 years), older trained (n = 12; 63.6 ± 3.8 years), young untrained (n = 14; 26.2 ± 3.7 years), and young trained (n = 14; 26.7 ± 3.4 years). Knee extension isometric voluntary explosive torque (absolute and normalized as a percentage of maximal voluntary torque) was assessed at the beginning of the contraction (ie, 50, 100, and 150 ms-T50, T100, and T150, respectively), and surface electromyogram (sEMG) amplitude (normalized as a percentage of sEMG recorded during maximal voluntary isometric contraction) at 0-50, 50-100, and 100-150 time windows. Supramaximal electrically evoked T50 was assessed with octet trains delivered to the femoral nerve (8 pulses at 300 Hz). Voluntary T50, T100, and T150 were higher for trained than untrained in absolute (P 0.417). Chronically strength-trained young and older men presented a greater explosive torque than their untrained pairs. In young trained, the greater explosive performance was attributed to enhanced muscular and neural mechanisms, while in older trained to neural mechanisms only.Malaria is a worldwide serious-threatening infectious disease caused by Plasmodium and the parasite resistance to antimalarial drugs has confirmed a significant obstacle to novel therapeutic antimalarial drugs. In this article, we assessed the antioxidant and anti-inflammatory activity of nanoparticles prepared from Indigofera oblongifolia extract (AgNPs) against the infection with Plasmodium chabaudi caused in mice spleen. AgNPs could significantly suppress the parasitaemia caused by the parasite to approximately 98% on day 7 postinfection with P. chabaudi and could improve the histopathological induced spleen damage. Also, AgNPs were able to increase the capsule thickness of the infected mice spleen. In addition, the AgNPs functioned as an antioxidant agent that affects the change in glutathione, nitric oxide and catalase levels in the spleen. Moreover spleen IL1β, IL-6 and TNF-α-mRNA expression was regulated by AgNPs administration to the infected mice. These results indicated the anti-oxidant and the anti-inflammatory protective role of AgNPs against P. chabaudi-induced spleen injury.The influence of the language context on language control has been widely discussed in the bilingualism literature, and there is an increase in studies examining the effect of language context on domain-general executive control. However, it remains unclear how language contexts affect executive control performance. In the present study, we created single- and mixed-language comprehension contexts. Unbalanced Chinese-English bilinguals completed a modified flanker task that was interleaved with a single-language or mixed-language picture-word matching task. The effects of language comprehension context on language control were reflected by the N2 and LPC effects. Executive control processes also differed depending on the language comprehension context, with faster behavioral responses and larger N2 but smaller P3 electrophysiological components in the mixed-language context. Moreover, the LPC amplitude in the mixed-language context predicted the behavioral performance in the executive control task. These findings suggested that flexible language control during language comprehension altered executive control processes in unbalanced bilinguals.Cystine/glutamic acid reverse transporter (System Xc- ), a member of the amino acid transporter family, consists of two subunits, light chain xCT and heavy chain 4F2hc. xCT is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11), which promotes cystine uptake and glutathione biosynthetic, thus protecting against oxidative stress and ferroptosis. Studies have confirmed that xCT is highly expressed in a variety of tumour and is associated with tumour proliferation, invasion, metastasis, drug resistance and ferroptosis, and can be used as a potential target for tumour treatment. This review provides insights into the biological effects of xCT and contribute to the development of new xCT-based strategies.The current knowledge of the long-term consequences of social exclusion mostly relies on theoretical assumptions. (Williams, 2009, Adv. Exp. Soc. Psychol., 41, 275) hypothesized that chronic ostracism drives individuals into a stage of resignation (depression, alienation, unworthiness, helplessness). We focused on asylum seekers (N = 112) as a social group at risk of experiencing prolonged instances of exclusion. Applying a three-wave longitudinal design with a three-month interval between each wave, we sought to advance the knowledge of the temporal development of chronic social exclusion. Cross-lagged panel analyses showed that social exclusion influenced the development of feelings of resignation in the long term, from baseline to six months and between three and six months. In the same time frame, the perception of social exclusion became stable and chronic. These findings provide empirical evidence that chronic exclusion predicts resignation and shed light on the temporal development of the detrimental impact that pervasive exclusion can have on people belonging to marginalized social groups.
To develop and test the psychometric properties of occupational low back pain prevention behaviours questionnaire in nursing personnel.
A qualitative and quantitative research design to develop and validate an instrument.
A qualitative study was conducted from May - October 2017 with 20 participants to generate an item pool. Then, content and face validity was carried out. Next, the questionnaire was distributed among a sample of nurses. In all, 150 nurses participated (mean age 34.1; SD 7.66years) in the study. Exploratory factor analysis used to determine the factor structure of the questionnaire. Item-scale correlation matrix was provided to examine the construct validity. Internal consistency (Cronbach's alpha) was estimated to assess reliability and intraclass correlation coefficient was calculated to examine stability.
Six factors with 30 items emerged from the exploratory factor analysis that jointly accounted for 67.9% of the variance observed. Item-scale correlation matrix showed satisfactory results lending support to construct validity of the questionnaire. The Cronbach's alpha coefficient for the whole scale showed excellent internal consistency (0.92), although this was not true for the knowledge subscale. The intraclass correlation coefficient with a 2-week interval also indicated that the questionnaire had satisfactory stability (0.97).
This study provides initial support for reliability and validity of the Occupational Low Back Pain Prevention Behaviour Questionnaire.
This study offers an instrument to assess low back pain preventive behaviours among nurses. The instrument is useful for nursing personnel and could be used in hospitals and healthcare settings to implement appropriate interventions.
This study offers an instrument to assess low back pain preventive behaviours among nurses. The instrument is useful for nursing personnel and could be used in hospitals and healthcare settings to implement appropriate interventions.Policy Points Changes in US state policies since the 1970s, particularly after 2010, have played an important role in the stagnation and recent decline in US life expectancy. Some US state policies appear to be key levers for improving life expectancy, such as policies on tobacco, labor, immigration, civil rights, and the environment. US life expectancy is estimated to be 2.8 years longer among women and 2.1 years longer among men if all US states enjoyed the health advantages of states with more liberal policies, which would put US life expectancy on par with other high-income countries.
Life expectancy in the United States has increased little in previous decades, declined in recent years, and become more unequal across US states. Those trends were accompanied by substantial changes in the US policy environment, particularly at the state level. State policies affect nearly every aspect of people's lives, including economic well-being, social relationships, education, housing, lifestyles, and access to medilongevity.Resilience is a protective health variable that contributes to successful adaptation to stressful experiences. However, in spite of its relevance, few studies have examined the psychophysiological and neuropsychological mechanisms involved in resilience. The present study analyzes, in a sample of 54 young women, the relationships between high- and low-resilience, measured with the Spanish versions of Connor-Davidson Resilience Scale questionnaire and the Resilience Scale, and two indices of psychophysiological and neuropsychological adaptability, the cardiac defense response (CDR) and cognitive flexibility. The CDR is a specific reaction to an unexpected intense noise characterized by two acceleration-deceleration heart rate components. Cognitive flexibility, defined as the ability to adapt our behavior to changing environmental demands, is measured in this study with the CAMBIOS neuropsychological test. The results showed that the more resilient people, in addition to having better scores on mental health questionnaires, had a larger initial acceleration-deceleration of the CDR-indicative of greater vagal control, obtained better scores in cognitive flexibility, and evaluated the intense noise as less unpleasant than the less resilient people. No group differences were found in the second acceleration-deceleration of the CDR-indicative of sympathetic cardiac control, in the skin conductance response, or in subjective intensity of the noise. The present findings broaden the understanding of how resilient people change their adaptable responses to address environmental demands.The value of dermoscopy in the detection of skin cancer is well established. Less is published on the utility of dermoscopy in the evaluation of pediatric skin disease. Our review (in two parts) aims to serve as an update on pediatric dermoscopy and to provide readers with a practical application for the use of dermoscopy in pediatric dermatology clinics. In part I, we propose a dermoscopy algorithm for pediatric skin disease and melanocytic growths, and in part II, we address vascular growths, common skin infections, and inflammatory conditions for which dermoscopy is valuable.The 'one-way' expert model of science communication is out of date. The new dialogue model requires from scientists more than just providing expert knowledge to the publics.
The best disposition of chest pain patients who rule out for myocardial infarction (MI) but have non-low clinical risk scores in the high-sensitivity troponin era is not well studied.
In carefully selected patients who rule out for MI, and have a high-sensitivity troponin T ≤ 50 ng/L with an absolute increase less than 5 ng/L on repeat measurements, early emergency room (ER) discharge might be equivalent to inpatient evaluation in regards to 30-day incidence of adverse cardiac events (ACEs) regardless of the clinical risk score.
A total of 12 847 chest pain patients presenting to our health system ERs from January 2017 to September 2019 were retrospectively investigated. A propensity score matching algorithm was used to account for baseline differences between admitted and discharged cohorts. We then estimated and compared the incidence of 30-day and 1-year composite ACEs (MI, urgent revascularization, or cardiovascular death) between both groups. A multivariate Cox regression model was used to evaluate the effect of admission on outcomes.
A total of 2060 patients were matched in 11 fashion. The primary endpoint of 30-day composite ACEs occurred in 0.6% and 0.4% of the admission and the discharged cohorts, respectively (P = .76). One-year composite ACEs was also similar between both groups (4% vs 3.7%, P = .75). In a multivariate Cox regression model, the effect of inpatient evaluation was neutral (hazard ratio 1.1, confidence interval 0.62-1.9, P = .75).
Inpatient evaluation was not associated with better outcomes in our selected group of patients. Larger-scale randomized trials are needed to confirm our findings.
Inpatient evaluation was not associated with better outcomes in our selected group of patients. Larger-scale randomized trials are needed to confirm our findings.
To examine the predictive validity of the FRAIL scale for mortality, and diagnostic test accuracy (DTA) against the frailty phenotype (FP).
Frailty was measured in 846 community-dwelling adults (mean age 74.3 [SD 6.3] years, 54.8% female) using a modified FRAIL scale and modified FP. Mortality was matched to death records.
The FRAIL scale demonstrated significant predictive validity for mortality up to 10years (Frail adjHR 2.60, P<.001). DTA findings were acceptable for specificity (86.8%) and Youden index (0.50), but not sensitivity (63.6%), or area under the receiver operator curve (auROC) (0.75). DTA estimates were more acceptable when a cut-point of ≥2 characteristics was used rather than ≥3 in the primary DTA analysis.
The FRAIL scale is a valid predictor of mortality. DTA estimates depend on FRAIL scale cut-point used. This instrument is a potentially useful frailty screening tool.
The FRAIL scale is a valid predictor of mortality. DTA estimates depend on FRAIL scale cut-point used. This instrument is a potentially useful frailty screening tool.The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than the PK data analysis itself.
The recent proliferation of methods of 3D model generation has enabled the development of new approaches to the analysis of dental form, function and wear. This article assesses whether Structure-from-motion (SfM) photogrammetry is capable of producing virtual 3D models of teeth of adequate quality for assessing fine scale surface details, such as dental macrowear patterns. Reference models were generated using a high resolution structured light scanner to assess the accuracy of the photogrammetric models generated.
Dental gypsum models of the molar teeth of human individuals from St. Michael's Litten, Chichester, Post-medieval assemblage (n = 17) were used for 3D model generation. Photogrammetry was performed using Agisoft Metashape and reference 3D models were generated using a GOM ATOS 80 scanner. Focus stacking was explored as a method of enhancing 3D model detail. Differences between the photogrammetric and reference models were assessed using CloudCompare and the quality of the surface detail was examined quantitatively using Occlusal Fingerprint Analysis.
Photogrammetric model generation was highly replicable and the tooth models produced closely approximated the overall geometry of those derived from the structured light scanner. Dental wear facet area measurements on the photogrammetric models differed significantly, however, from those derived from the structured light scanning reference models.
Photogrammetry can create virtual dental models from which crude quantitative size and shape data can be obtained. Finer scale surface details are not accurately reproduced on SfM models using the methods outlined in the current article due to high levels of surface noise.
Photogrammetry can create virtual dental models from which crude quantitative size and shape data can be obtained. Finer scale surface details are not accurately reproduced on SfM models using the methods outlined in the current article due to high levels of surface noise.Only about 0.3% of the entries in UniProt database have manually curated annotation. Annotation at the molecular level often relies on low-throughput one-protein-at-a-time approach. Computational methods bridge this gap by assigning function based on sequence and/or fold similarity. Left-handed beta helix (LbH) consists of three repeating six-stranded beta-strands forming an 18-mer turn of the helix. Analysis of LbH-domains showed that variations are found in the number of residues in a beta-strand (5-7, 6 being the most common), number of turns (4-10) of the helix, insertions of one or more loops of variable length (0-36 residues), and the location of loop insertion. An 18-mer HMM profile was created which identifies LbH-domain containing proteins using sequence as the only input; the number of false positives is zero when proteins tested were those with known 3D structures. 136 474 entries of TrEMBL database were found to contain LbH-domain. Rules developed by analyzing LbH-domain containing acyltransferases, gamma-class carbonic anhydrases, and nucleotidyltransferases have led to the annotation of 17 389 TrEMBL entries which currently have no functional tag.
This paper explores how changes in demography, service use and the aged care system have implications for the appropriateness of the denominator in the aged care provision ratio.
Official statistics were analysed to create five alternative scenarios for residential care planning in a 2000-2027 time series.
The four age-based denominators and a revised denominator incorporating age- and sex-specific disability rates generated diverse levels of absolute supply. The 75+ denominator produced 1400 fewer beds than the 70+ denominator by 2018, but over 14000 additional beds by 2027.
The 70+ based ratio developed almost forty years ago has served its purpose reasonably well. However, changes in the nature of the aged care system, different patterns of use by age and sex, and demographic changes suggest that long-term aged care planning requires careful review in choosing a more robust version of the provision ratio for the future.
The 70+ based ratio developed almost forty years ago has served its purpose reasonably well. However, changes in the nature of the aged care system, different patterns of use by age and sex, and demographic changes suggest that long-term aged care planning requires careful review in choosing a more robust version of the provision ratio for the future.Wood is a prototypical biological material, which adapts to mechanical requirements. The microarchitecture of cellulose fibrils determines the mechanical properties of woody materials, as well as their actuation properties, based on absorption and desorption of water. Herein it is argued that cellulose fiber orientation corresponds to an analog code that determines the response of wood to humidity as an active material. Examples for the harvesting of wood activity, as well as bioinspiration, are given.Introduction of anti-tachycardia pacing (ATP) therapy and longer detection intervals delivery have allowed to safely reduce unnecessary shocks, improving survival and quality of life in implantable cardioverter defibrillator (ICD) patients. However, there are still outstanding issues, especially regarding the mode of arrhythmias termination after ATP or shock delivery. Regardless of ICD therapy efficacy, the arrhythmia interruption does not always occur abruptly, indeed both nonsustained tachy- or bradyarrhythmias have been described after ICD therapy delivery, being the former classified as type 2 interruption. Several physiopathological mechanisms have been suggested to be responsible for this phenomenon. Our aim is to review current data on postshock and post-ATP arrhythmias and to give insights on their possible mechanisms.
To evaluate the clinical, aesthetic and radiographical outcome of single immediate implant placement (IIP) after 10years (a) and to identify putative risk factors for advanced mid-facial recession (b).
Periodontally healthy patients with a thick gingival biotype and intact buccal bone wall were consecutively treated with a single immediate implant and crown in the aesthetic zone (15-25). Flapless surgery and socket grafting with deproteinized bovine bone mineral were performed. Seven patients received a connective tissue graft (CTG) at 3months due to obvious alveolar process deficiency (n=5) or advanced mid-facial recession (n=2). Clinical, aesthetic and radiographical outcomes at 10years were compared to those at 5years and CBCTs were taken at 10years.
Twenty-two patients (10 women; mean age 50) were consecutively treated and 18 could be re-examined. Two implants failed and two patients died. None of the parameters differed between the 5- and 10-year re-assessment (marginal bone loss 0.31mm; plaque score 15%; probing depth 3.4mm; bleeding on probing 32%; pink aesthetic score 10.61; mesial papillary recession -0.03mm; distal papillary recession 0.22mm; mid-facial recession 0.58mm). Six implants (33%) demonstrated ≥1mm mid-facial recession. Putative risk factors were merely based on descriptive statistics and included buccal shoulder position, no CTG, convex emergence profile and central incisor position. Three implants (17%) had no visible buccal bone on CBCT. One of these was too buccally positioned, another yielded peri-implant mucositis and another demonstrated peri-implantitis.
Advanced mid-facial recession is common in the long term following IIP. Therefore, caution is required for IIP in the aesthetic zone.
Advanced mid-facial recession is common in the long term following IIP. Therefore, caution is required for IIP in the aesthetic zone.
Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates' resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10).
Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t test or chi-square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood.
Participation was 55.3% (N=199). Baseline RISC-10 averaged 32.0±5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores<26.3 (representing>1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23-5.77; P=.01).
One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.
One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.Recently, Li-ion batteries (LIBs) have attracted extensive attention owing to their wide applications in portable and flexible electronic devices. Such a huge market for LIBs has caused an ever-increasing demand for excellent mechanical flexibility, outstanding cycling life, and electrodes with superior rate capability. Herein, an anode of self-supported Fe3 O4 @C nanotubes grown on carbon fabric cloth (CFC) is designed rationally and fabricated through an in situ etching and deposition route combined with an annealing process. These carbon-coated nanotube structured Fe3 O4 arrays with large surface area and enough void space can not only moderate the volume variation during repeated Li+ insertion/extraction, but also facilitate Li+ /electrons transportation and electrolyte penetration. This novel structure endows the Fe3 O4 @C nanotube arrays stable cycle performance (a large reversible capacity of 900 mA h g-1 up to 100 cycles at 0.5 A g-1 ) and outstanding rate capability (reversible capacities of 1030, 985, 908, and 755 mA h g-1 at 0.15, 0.3, 0.75, and 1.5 A g-1 , respectively). Fe3 O4 @C nanotube arrays still achieve a capacity of 665 mA h g-1 after 50 cycles at 0.1 A g-1 in Fe3 O4 @C//LiCoO2 full cells.
To evaluate outcomes associated with pharmacist-led medication reviews in residential aged care facility (RACF) residents with dementia.
Six scientific databases were searched. All study designs investigating pharmacist-led medication reviews in RACF residents with dementia were considered. The protocol was registered with PROSPERO (CRD42019121681).
One randomised controlled trial (RCT) and five observational studies were identified. Two studies reported reductions in medication usage per resident, and one study reported improved appropriateness of psychotropic use following reviews as part of multi-faceted, collaborative interventions. In three studies, reviews undertaken as an isolated intervention or by a visiting pharmacist with minimal collaboration with physicians were associated with low implementation rates of recommendations to alter therapy.
Pharmacist-led medication reviews, when conducted collaboratively, may improve the use of medicines in RACF residents with dementia. However, robust conclusions cannot be drawn, largely due to the low quality of evidence available, including only one RCT.
Pharmacist-led medication reviews, when conducted collaboratively, may improve the use of medicines in RACF residents with dementia. However, robust conclusions cannot be drawn, largely due to the low quality of evidence available, including only one RCT.
To describe the nature of readmission to acute care and identify patient characteristics associated with avoidable readmission to acute care from inpatient brain injury rehabilitation.
A retrospective cohort design.
Data prospectively documented between 1 January 2012 -31 December 2018 in local clinical and administrative database were used. Patient medical records were accessed when missing data were identified. Descriptive statistics were used to describe the nature of readmission episodes and univariate and multivariable logistic regression were used to identify patient characteristics associated with readmission to acute care.
Of the 383 patients admitted for rehabilitation, 83 (22%) experienced readmission to acute care for a total of 171 episodes. Thirty-seven percent of readmission episodes were due to hospital acquired complications and therefore potentially avoidable. Infection accounted for 63% of hospital acquired complications. Patients with an avoidable readmission episode (N=38) were morive prevention, early recognition of complications and discrete escalation care pathways.
Research into readmission to acute care in the mixed brain injury inpatient rehabilitation population is limited. In this patient population, readmission to acute care is a contemporary issue that can occur at any time during a patient's rehabilitation admission. This study provides valuable information informing practice change for preventing avoidable readmission episodes. Locally developed policy aimed at preventing readmission episodes should include proactive prevention, early recognition of complications and discrete escalation care pathways.
To investigate the meaning of spirituality and spiritual care among people from Chinese backgrounds living in England.
Strauss and Corbin's grounded theory design was used.
Twenty-five participants were recruited from Chinese community centres after which data saturation was reached in September 2016. In-depth interviews in Chinese were carried out. Transcribed digital recordings were translated into English. Data analysis followed the techniques of open coding, axial coding, and selective coding, using NVivo11. Data collection and analysis were conducted simultaneously.
Three themes emerged from the data which provide an understanding of spirituality and spiritual care in the study context 'essence and nature of life', 'driving forces', 'self-support'.
This study provides an understanding of spirituality and spiritual care from a Chinese cultural perspective. From a Daoist tradition, spirituality is seen as essence and driving force in the human body. From a Confucian viewpoint, it appears that patwhat constitutes spiritual care. Further research is recommended among the wider community of health and social care workers to explore spirituality and spiritual care among people from Chinese backgrounds living in England.Robustness of fear conditioning and extinction paradigms has become increasingly important for many researchers interested in improving the study of anxiety and trauma disorders. We recently illustrated the wide variability in data analysis techniques in this paradigm, which we argued may result in a lack of robustness. In the current study, we resampled data from six of our own fear acquisition and extinction data sets, with skin conductance as the outcome. In the resampled and original data sets, we found that effect sizes that were calculated using discrepant statistical strategies, sourced from a non-exhaustive search of high-impact articles, were often poorly correlated. The main contributors to poor correlations were the selection of trials from different stages of each experimental phase and the use of average compared to trial-by-trial analysis. These findings reinforce the importance of focusing on robustness in the psychophysiological measurement of fear acquisition and extinction in the laboratory and may guide prospective researchers in which decisions may most impact the robustness of their results.Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset of patients with chronic cough are troubled with a cough that persists despite optimal treatment of presumed associated common and uncommon conditions (refractory chronic cough; RCC) or in which no diagnosable cause for cough can be identified despite extensive assessment (unexplained chronic cough; UCC). Many of these patients exhibit clinical features of cough hypersensitivity, including laryngeal paresthesia, hypertussia, and allotussia. Over-the-counter cough remedies are ineffective and can lead to intolerable side effects when used for RCC/UCC, and the lack of approved treatments indicated for these conditions reflects a major unmet need. An increased understanding of the anatomy and neurophysiology of protective and pathologic cough has fostered a robust clinical development pipeline of several targeted therapies for RCC/UCC. This manuscript reviews the mechanisms presumed to underly RCC/UCC together with the rationale and clinical evidence for several targeted therapies currently under clinical investigation, including transient receptor potential channel antagonists, P2X3-receptor antagonists, voltage-gated sodium channel blockers, neuromodulators, and neurokinin-1-receptor antagonists. Finally, we provide an overview of targets that have been investigated in preclinical models of cough and other airway diseases that may hold future promise for clinical studies in RCC/UCC. Development of targeted therapies with different sites of action may foster a precision medicine approach to treat this heterogeneous, underserved patient population.
Printed educational materials are widely used dissemination strategies to improve the quality of healthcare professionals' practice and patient health outcomes. Traditionally they are presented in paper formats such as monographs, publication in peer-reviewed journals and clinical guidelines. This is the fourth update of the review.
To assess the effect of printed educational materials (PEMs) on the practice of healthcare professionals and patient health outcomes. To explore the influence of some of the characteristics of the printed educational materials (e.g. source, content, format) on their effect on healthcare professionals' practice and patient health outcomes.
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), HealthStar, CINAHL, ERIC, CAB Abstracts, Global Health, and EPOC Register from their inception to 6 February 2019. We checked the reference lists of all included studies and relevant systematic reviews.
We included randomised trials (RTs), controlleing the expected effect of the intervention, or acknowledging the presence of a secular trend.
The results of this review suggest that, when used alone and compared to no intervention, PEMs may slightly improve healthcare professionals' practice outcomes and patient health outcomes. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.
The results of this review suggest that, when used alone and compared to no intervention, PEMs may slightly improve healthcare professionals' practice outcomes and patient health outcomes. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.The pathogenesis of chronic spontaneous urticaria (CSU), also called chronic idiopathic urticaria, has been considered to be associated with the activation of the extrinsic blood coagulation cascade. However, the trigger for the extrinsic coagulation cascade in patients with CSU remains unclear. We previously reported that histamine and lipopolysaccharide (LPS) synergistically induced the expression of tissue factor (TF), a trigger for the extrinsic coagulation cascade, in human umbilical vein endothelial cells (HUVEC). Because the elevation of tumor necrosis factor (TNF)-α, interleukin (IL)-33, IL-1β and vascular endothelial growth factor (VEGF) in serum has also been observed in patients with CSU, we examined the effects of LPS, TNF-α, IL-33, IL-1β, VEGF and histamine on TF expression in HUVEC by reverse transcription polymerase chain reaction and flow cytometry, as well as examining the activity that triggers the extrinsic coagulation cascade and induces intercellular gap formation of HUVEC in the presence of plasma by Actochrome® TF activity assay and impedance sensor, respectively. The expression of TF mRNA and surface protein of TF on HUVEC in response to histamine or VEGF were synergistically enhanced by the treatment with LPS, TNF-α, IL-33 or IL-1β. Moreover, the activation of the extrinsic coagulation pathway and intercellular gap formation of HUVEC in response to histamine or VEGF were also synergistically increased in the presence of TNF-α and LPS. Thus, TF expression on vascular endothelial cells was strongly enhanced by co-stimulation with CSU-related molecules in blood. Blocking a common pathway of LPS, TNF-α, IL-33 and IL-1β, and/or that of VEGF and histamine may be an effective therapeutic measure for patients with severe and refractory CSU.Hemalin, initially described in Haemaphysalis longicornis, is a protein with anticoagulant activity. We retrieved a gene fragment functionally annotated as hemalin from H. flava salivary gland transcriptomic library, but its full-length complementary DNA (cDNA) and antithrombogenicity have not been investigated in the species. Here we cloned the full length of hemalin (Hf-hemalin) by 3'-end rapid-amplification of cDNA ends, and the open reading frame (ORF) of Hf-hemalin was expressed in Escherichia coli. The recombinant protein (rHf-Hemalin) was tested for antithrombogenicity. The full-length of Hf-hemalin was 607 bp with an ORF of423 bp. Protein encoded by Hf-hemalin was predicted to contain 2 Kunitz domains and a signal peptide. The expression of Hf-hemalin in salivary glands, midguts and ovaries was higher in the semi-engorged than the fully engorged. Prokaryotic expression yielded a product of 40 kDa containing a glutathione S-transferase (GST) tag. Incubation of rHf-Hemalin with rat plasma significantly extended prothrombin time and activated partial thromboplastin time compared with normal saline and GST controls. Our data demonstrated that Hemalin from H. flava shared a similar primary structure with that from H. longicornis, and was also anticoagulant. Further investigations are needed to test its feasibility to be an antigen candidate for the development of vaccines against ticks.Conversation-based training programmes are known to be effective in enhancing theory of mind (ToM). The possible consequences of such training programmes on the understanding of other constructs have rarely been investigated. The present research aimed to evaluate the effects of two different types of conversation-based training on ToM and loneliness. Two hundred and ten fourth and fifth graders (52% boys; Mage = 9.66 years, SD = 0.85), randomly divided into two groups (ToM and no-ToM training condition), were administered at a 5-week intervention. ToM and loneliness were measured before and twice after the intervention (1 week and 2 months later). Linear mixed-effects models showed that, soon after the intervention, children in the ToM training condition obtained significantly higher ToM scores and significantly lower loneliness scores compared to children in the no-ToM training condition. Nonetheless, at the follow-up, ToM and loneliness scores were not significantly different for the two training conditions. These findings suggest that a relatively short intervention based on group discussion of mental states is sufficient to improve mentalizing abilities and to tackle feelings of loneliness among fourth and fifth graders in the short but not in the long term.
Cholestatic liver injury leads to cell death and subsequent inflammation and fibrosis. As shown for primary biliary cholangitis (PBC) the mechanisms and circuits between different cell death pathways leading to disease progression are incompletely defined. Ligation of the common bile duct (BDL) is a well-established murine model to mimic cholestatic liver injury. Here, we hypothesised that pyroptotic cell death by the Nlrp3 inflammasome plays an essential role during human and murine cholestasis.
NLRP3 activation was analysed in humans with cholestatic liver injury. WT and Nlrp3
mice were subjected to BDL for 2 or 28 days.
Chronic cholestasis in humans and mice is associated with NLRP3 activation and correlates with disease activity. Acute BDL in Nlrp3-deficient mice triggered increased inflammation as well as liver injury, associated with stronger apoptotic and necroptotic cell death. In contrast, NLRP3 deletion led to decreased liver injury and inflammation in chronic cholestasis. Moreover, bridging fibrosis was observed in WT, but not in NLRP3 knockout mice 28 days after BDL In contrast, lack of NLRP3 expression attenuated kidney injury and fibrosis after acute and chronic BDL. Importantly, MCC950 administration - a NLRP3 small molecule inhibitor - reduced BDL-induced disease progression in WT mice.
NLRP3 activation correlates with disease activity in PBC patients. NLRP3 has a differential role during acute and chronic cholestatic liver injury in contrast to kidney injury. Disease progression during chronic cholestasis can be targeted via small molecules and thus suggests a potential clinical benefit for humans, attenuating liver and kidney injury.
NLRP3 activation correlates with disease activity in PBC patients. NLRP3 has a differential role during acute and chronic cholestatic liver injury in contrast to kidney injury. Disease progression during chronic cholestasis can be targeted via small molecules and thus suggests a potential clinical benefit for humans, attenuating liver and kidney injury.
Hypothermic storage transforms red blood cells (RBC) from smooth biconcave discocytes into increasingly spherical spiculated echinocytes and, ultimately, fragile spherocytes (S). Individual cells undergo this transformation at different rates, producing a heterogeneous mixture of RBCs at all stages of echinocytosis in each unit of stored blood. Here we investigated how washing (known to positively affect RBC properties) changes morphology of individual RBCs at the single-cell level.
We tracked the change in shape of individual RBCs (n = 2870; drawn from six 4- to 6-week-old RBC units) that were confined in an array of microfluidic wells during washing in saline (n = 1095), 1% human serum albumin (1% HSA) solution (n = 999), and the autologous storage supernatant (control, n = 776).
Shape recovery proceeded through the disappearance of spicules followed by the progressive smoothening of the RBC contour, with the majority of changes occurring within the initial 10 minutes of being exposed to the washing solution. Approximately 57% of all echinocytes recovered by at least one morphologic class when washed in 1% HSA (36% for normal saline), with 3% of cells in late-stage echinocytosis restoring their discoid shape completely. Approximately one-third of all spherocytic cells were lysed in either washing solution. Cells washed in their autologous storage supernatant continued to deteriorate during washing.
Our findings suggest that the replacement of storage supernatant with a washing solution during washing induces actual shape recovery for RBCs in all stages of echinocytosis, except for S that undergo lysis instead.
Our findings suggest that the replacement of storage supernatant with a washing solution during washing induces actual shape recovery for RBCs in all stages of echinocytosis, except for S that undergo lysis instead.The COVID-19 disease caused by the SARS-CoV-2 has emerged as a worldwide pandemic and caused huge damage to the lives and economy of more than hundred countries. As on May 10, 2020, more than 4,153,300 people stand infected from the virus due to an unprecedented rate of transmission and 282,700 have lost their lives because of the disease. In this context, medicinal plants may provide a way to treat the disease by targeting specific essential proteins of the virus. We screened about 51 medicinal plants and found that Tea (Camellia sinensis) and Haritaki (Terminalia chebula) has potential against SARS-COV-2 3CLpro , with an IC50 for Green Tea as 8.9 ± 0.5 μg/ml and Haritaki 8.8 ± 0.5 μg/ml. The in-silico studies suggested that Tea component Thearubigins binds to the cysteine 145 of protease active site and could be a pharmacoactive molecule. We predict that the inhibition in protease activity may be able to halt the SARS-CoV-2 replication cycle and therefore, we propose Green Tea, Black Tea, and Haritaki plant extracts as potential therapeutic candidates for SARS-CoV-2 infection. Further investigation on role of bioactive constituents of extracts is needed to establish the molecular basis of inhibition and towards expedited drug discovery.The present study aims at identifying reliable markers of neural preparatory processes during hypnosis. To this goal, we recorded the electroencephalographic activity of 23 volunteers regardless of their hypnotizability score. Somatosensory evoked potentials (SEPs) were elicited while participants received non-painful electrical stimuli on the left median nerve in the conditions of relaxation and hypnosis with suggestions of reduced sensation. SEPs analysis was focused on the pre-stimulus activity and revealed two main components the prefrontal negativity (pN) and the somatosensory negativity (sN) over the frontal and parietal areas of the scalp, respectively. Results showed reduced amplitudes for both components under hypnosis, mostly for the pN, suggesting a change of top-down control of parietal and prefrontal areas. Furthermore, the sLORETA source imaging showed a deactivation of the lateral and anterior portions of the prefrontal cortex (PFC) during the hypnotic state. The present study highlights the downregulation of the PFC as a core aspect of the adopted hypnotic task and confirms the ability of hypnosis to modulate the activity of frontal executive functions. Further, since the majority of participants fell into the medium range of hypnotizability, the present findings could reflect the hypnosis effects in most of the population.Rhizomelic chondrodysplasia punctata is a rare, often fatal disease that shares many clinical dysmorphologic features with the rare often non-lethal chondrodysplasia punctata due to maternal autoimmune disease. Characteristic findings of both conditions include mid-face hypoplasia, stippled epiphyses of the vertebrae and long bones, and growth failure. A growing association with anti-ribonucleoprotein antibodies is emerging amongst patients with chondrodysplasia punctata due to maternal autoimmune disease and also neonatal lupus that have potential important screening implications. We present a unique case of chondrodysplasia punctata with neonatal lupus in the setting of positive anti-RNP antibodies and negative anti-Ro/SSA and -La/SSB antibodies born to a mother with mixed connective tissue disease and Raynaud's syndrome.Borreliosis (Lyme disease) is a spirochetal disease caused by the species complex of Borrelia burgdorferi transmitted by Ixodes spp. ticks. Recorded to be the most common tick-borne disease in the world, the last two decades have seen an increase in disease incidence and distribution, exceeding 360 000 cases in Europe alone. If untreated, infection may cause skin symptoms, arthritis, and neurological or cardiac complications. Borrelia spirochetes have developed strategies to evade the mammalian host immune system. These include the complement system, which is an important first-line defense mechanism against invading microbes. To evade the complement, spirochetes bind soluble complement regulators factor H (FH), factor H-like protein, and C4bp to their outer surfaces. B. burgdorferi spirochetes can inhibit the classical pathway of complement by the outer surface protein (Osp) BBK32, which blocks the activation of the C1 complex, composed of C1q, C1r, and C1s. The FH-binding proteins of borreliae include Osps OspE, CspA, and CspZ. Following repeated infections, antibodies against these proteins develop and may provide functional immunity against borreliosis. This review discusses critical immune evasion strategies, focusing on complement evasion by borreliae.
COVID-19 convalescent plasma (CCP) represents an appealing approach to the treatment of patients with infections due to SARS-CoV-2. We endeavored to quickly establish a sustainable CCP transfusion program for a regional network of health care facilities.
A regional collaborative group was activated to address the issues necessary to implementing a CCP transfusion program and making the program sustainable. A wide range of health care providers including physicians (critical care, infectious disease, transfusion medicine), nurses, pharmacists, laboratorians, and information technology (IT) specialists were required to make the program a success.
The CCP implementation team initially consisted of four members but quickly grew to a group of nearly 20 participants based on different issues related to program implementation. Overall, six major implementation "themes" were addressed (a) registration of individual hospitals and principal investigators with a national investigational new drug research protocol;tation.
A large number of digestates have not been fully utilized due to a lack of scientific, reasonable guidance, as well as imperfect technology. Hybrid giant Napier has great potential for use as a type of energy plant. As such, this study investigated the effects of digestate on the growth of a candidate energy crop and examined whether digestate was an ecologically viable means for soil restoration.
The results showed that the total yields of all treatment groups receiving irrigation of digestate were higher (5.19-26.00%) than those of the control. The total phosphorus, total potassium, available nitrogen, available phosphorus, and available potassium content of the soil had also increased after digestate application, compared with the control. Urease activities for all treatments increased 15.28 to 69.44% more than that of the corresponding control. Soil dissolved organic matter (DOM) mainly contained humic-like and fulvic-like components through the application of digestate. More fluorescent components were also identified by two-dimensional correlation spectroscopy (2D-COS). These fluorescent components can improve the aromaticity and molecular weight of soil DOM so as to improve soil quality.
Digestate improved not only the aboveground biomass accumulation, but also the chemical properties of the soil, which was an appropriate strategy for restoring soil quality and contributing to the sustainable development of marginal. The long-term impact of digestate application on soil quality will require additional long-term experiments. © 2020 Society of Chemical Industry.
Digestate improved not only the aboveground biomass accumulation, but also the chemical properties of the soil, which was an appropriate strategy for restoring soil quality and contributing to the sustainable development of marginal. The long-term impact of digestate application on soil quality will require additional long-term experiments. © 2020 Society of Chemical Industry.
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