Pain freedom after 2 hours should be the primary outcome in controlled trials treating migraine attacks

Background Pain freedom after 2 hours is the recommended primary endpoint by the International Headache Society in randomized trials investigating drug treatment of acute migraine attacks. In order to demonstrate an early effect of a drug, some drug companies, however, have promoted headache relief (improvement from severe or moderate pain to mild or no pain) at earlier time points than 2 hours as outcome parameter. Methods and results We analyzed the relationship between pain freedom and headache relief in acute migraine trials and observed that persistent mild headache constituted 90% of headache relief after 0.5 hour and 40% of headache relief after 2 hours. Conclusion Headache relief at 2 hours should in our view only be used as an outcome measure for comparison with historic data. Prior to 2 hours, headache relief varies with time from intake and the therapeutic gain is very small. Therefore, pain freedom should be used at these early time points.

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Early Physical Activity Adoption Predicts Longer-Term Physical Activity Among Individuals Inactive at Baseline

Journal of Physical Activity and Health ◽

10.1123/jpah.2020-0114 ◽

2020 ◽

Vol 17 (12) ◽

pp. 1205-1212

Author(s):

Jessica L. Unick ◽

Michael P. Walkup ◽

Michael E. Miller ◽

John W. Apolzan ◽

Peter H. Brubaker ◽

...

Keyword(s):

Physical Activity ◽

At Risk ◽

Weight Loss ◽

Confidence Interval ◽

Lifestyle Intervention ◽

Early Time ◽

Intervention Strategies ◽

Behavioral Weight Loss ◽

Time Points ◽

The Relationship

Background: To examine the relationship between early physical activity (PA) adoption (2, 3, and 4 mo) and longer-term PA adherence (1 y) among individuals who were inactive at baseline and received a lifestyle intervention. Methods: Participants (n = 637) received weekly behavioral weight loss sessions, calorie reduction, and PA goals (50–175 min/wk progression). PA was assessed via self-reported measures at baseline, months 2 to 4, and 1 year. Results: PA at months 2 to 4 was significantly correlated with PA at 1 year (rs = .29–.35, P < .01). At all early time points, those failing to meet the prescribed PA goal (early nonadopters) engaged in significantly less PA at 1 year than those meeting the early PA goal (initial adopters). For example, using 2-month criteria, initial adopters engaged in 108.3 minutes per week more at 1 year compared with early nonadopters (P < .01) and had 2.8 times the odds (95% confidence interval, 1.9–4.2) of meeting the 1-year PA goal (≥175 min/wk, P < .01). Conclusions: Failure to achieve PA goals at 2, 3, or 4 months results in less overall PA at 1 year. Thus, PA observed as early as month 2 may be a useful indicator for identifying at-risk individuals who may benefit from more intensive PA intervention strategies.

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Correlation between L-Lactate Concentrations in Beef Cattle, Obtained Using a Hand-Held Lactate Analyzer and a Lactate Assay Colorimetric Kit

Animals ◽

10.3390/ani11040926 ◽

2021 ◽

Vol 11 (4) ◽

pp. 926

Author(s):

Daniela M. Meléndez ◽

Sonia Marti ◽

Luigi Faucitano ◽

Derek B. Haley ◽

Timothy D. Schwinghamer ◽

...

Keyword(s):

Statistical Significance ◽

Road Transportation ◽

Long Distance ◽

Suitable Alternative ◽

Blood Samples ◽

Time Points ◽

Pooled Data ◽

Red Angus ◽

Relationship Of ◽

The Relationship

Lactate is a product of anaerobic glycolysis, used in animal research as an indicator of muscle fatigue. Therefore, it has been used as an indicator of cattle response to long distance transportation. The aim of this study was to assess the relationship of L-lactate concentrations measured using a Lactate Scout+ analyzer and a traditional lactate assay colorimetric kit. Blood samples were collected by venipuncture from 96 steers (Black or Red Angus × Hereford/Simmental and Black or Red Angus × Charolais; 247 ± 38.2 kg BW) prior to loading (LO1) and after 36 h of transport, and prior to reloading and after an additional 4 h of road transportation, and on d 1, 2, 3, 5, 14, and 28 after transport. The Lactate Scout+ analyzer strip was dipped in blood at the time of sampling, while blood samples were collected into sodium fluoride tubes for use in the colorimetric analysis. Pearson correlations were calculated to assess the strength of the relationship between the experimental methods for the quantification of L-lactate concentrations. The magnitude and direction of the correlation, and the level of statistical significance varied over the observed time points, ranging from r = −0.03 (p = 0.75; LO1) to r = 0.75 (p < 0.0001; d 3). The correlation for the pooled data was weak but statistically significant (r = 0.33, p < 0.0001). Based on the low magnitude of the correlation due to variability across sampling time points in this study, the Lactate Scout+ analyzer is not a suitable alternative to a lab-based assay (considered the gold standard) for measuring L-lactate in transported cattle.

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PSVII-3 Correlations between L-lactate concentrations obtained using a handheld lactate analyser and a lactate assay colorimetric kit in beef cattle transported by road

Journal of Animal Science ◽

10.1093/jas/skaa278.535 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 296-297

Author(s):

Daniela M Meléndez ◽

Sonia Marti ◽

Luigi Faucitano ◽

Derek B Haley ◽

Timothy D Schwinghamer ◽

...

Keyword(s):

Statistical Significance ◽

Cost Effective ◽

Road Transportation ◽

Long Distance ◽

Suitable Alternative ◽

Blood Samples ◽

Handheld Device ◽

Time Points ◽

Relationship Of ◽

The Relationship

Abstract Blood metabolites are used to assess a variety of animal conditions for veterinary diagnosis and research. Concentration of metabolites in blood can be measured using a commercially-available lab-based assay or in real-time using a handheld device developed to be more time- and cost-effective than the lab-based method. Lactate is a product of anaerobic glycolysis, used in animal research as an indicator of muscle fatigue. Therefore, it has been used as an indicator of cattle response to long distance transportation. The aim of this study was to assess the relationship of L-lactate concentrations measured using a Lactate Scout+ analyzer (Lactate Scout, EFK Diagnostics, Barleben, Germany) and a lactate assay colorimetric kit (Lactate Assay Kit, Cell Biolabs Inc., San Diego, CA). Blood samples were collected by venipuncture from 96 steers (245 ± 35.7 kg BW) prior to (L1) and after 36 h, and prior to and after an additional 4 h of road transportation, and on d 1, 2, 3, 5, 14, and 28 after transport. The Lactate Scout+ analyzer strip was dipped in blood at the time of sampling, while blood samples were collected into sodium fluoride tubes for use in colorimetric analysis. Pearson correlations were calculated to determine the relationship between the experimental methods for the quantification of L-lactate concentrations. The strengths and levels of statistical significance of the correlation varied over the observed time points, r = -0.03, P = 0.75 (L1) to r = 0.75, P = < 0.0001 (d 3). The correlation for the pooled data was weak but statistically significant (r = 0.33, P < 0.001). Based on the experimental results, the Lactate Scout+ analyzer is not a suitable alternative to a lab-based assay for measuring L-lactate in transported cattle, due to variability across sampling time points and weak correlation with the traditional enzymatic method.

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Exploring early time points of vimentin assembly in flow by fluorescence fluctuation spectroscopy

Lab on a Chip ◽

10.1039/d0lc00985g ◽

2021 ◽

Vol 21 (4) ◽

pp. 735-745

Author(s):

Eleonora Perego ◽

Sarah Köster

Keyword(s):

Reaction Kinetics ◽

Photon Counting ◽

Early Time ◽

Fluorescence Fluctuation Spectroscopy ◽

Microfluidic Mixing ◽

Time Points ◽

Photon Counting Histogram ◽

Kinetics Of

The combination of photon counting histogram and microfluidic mixing reveals early time points in reaction kinetics of biomolecule aggregation.

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High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in long-term care facilities

Communications Medicine ◽

10.1038/s43856-021-00015-1 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Pablo M. De Salazar ◽

Nicholas B. Link ◽

Karuna Lamarca ◽

Mauricio Santillana

Keyword(s):

Long Term Care ◽

Mitigation Strategies ◽

Key Factors ◽

Modeling Framework ◽

High Coverage ◽

Term Care ◽

Early Effect ◽

Care Facilities ◽

The Relationship

Abstract Background Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies. Methods We evaluate the early effect of the administration of BNT162b2-mRNA vaccine to individuals older than 64 years residing in LTCFs in Catalonia, Spain. We monitor all the SARS-CoV-2 documented infections and deaths among LTCFs residents once more than 70% of them were fully vaccinated (February–March 2021). We develop a modeling framework based on the relationship between community and LTCFs transmission during the pre-vaccination period (July–December 2020). We compute the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction in the detected transmission for all the LTCFs. We compare the true observations with the counterfactual predictions. Results We estimate that once more than 70% of the LTCFs population are fully vaccinated, 74% (58–81%, 90% CI) of COVID-19 deaths and 75% (36–86%, 90% CI) of all expected documented infections among LTCFs residents are prevented. Further, detectable transmission among LTCFs residents is reduced up to 90% (76–93%, 90% CI) relative to that expected given transmission in the community. Conclusions Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic conditional on key factors such as vaccine escape, roll out and coverage.

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A Pilot Study to Investigate the Efficacy of Nicotine Oral Soluble Film, Lozenge and Gum in Relief of Acute Smoking Cue-provoked Craving for Cigarette in Low Dependence Smokers

The Journal of Smoking Cessation ◽

10.1017/jsc.2014.5 ◽

2014 ◽

Vol 10 (2) ◽

pp. 87-95 ◽

Cited By ~ 1

Author(s):

Daniel Du ◽

James Borders ◽

Alex Selmani ◽

William Waverczak

Keyword(s):

Pilot Study ◽

Early Time ◽

Controlled Study ◽

Nicotine Gum ◽

Open Label ◽

Time Points ◽

Smoking Cues ◽

Significant Difference ◽

Nicotine Lozenge

Introduction: A new nicotine film that releases nicotine quickly may lead to faster craving relief.Aims: This study compares the efficacy of 2.5 mg nicotine film with 2 mg nicotine lozenge and 2 mg nicotine gum on relieving provoked craving in low dependence smokers.Methods: A randomised, open-label, active comparators controlled study was conducted in 120 subjects. Subjects were abstinent from smoking for 4 hours prior to being provoked with smoking cues. After post-provocation craving assessment, subjects were administered one dose of the 3 treatments: nicotine film, lozenge, or gum. Craving intensity was then assessed at 50 seconds, 3, 5, 7, 15, 20, 25 and 30 minutes after administration.Results/Findings: Three treatments reduced craving with similar maximum effects. The effect was maintained up to 30 minutes. Nicotine film significantly reduced more craving than lozenge at 50 seconds, 3 and 5 minutes. It also significantly reduced more craving than gum at 50 seconds and 3 minutes. There was no significant difference between lozenge and gum.Conclusions: Nicotine film, lozenge and gum have similar maximum craving relief. Nicotine film significantly reduced more craving than lozenge and gum at early time points. Nicotine film may be particularly useful to provide acute craving relief.

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Variability of Burnout and Stress Measures in Pediatric Residents: An Exploratory Single-Center Study From the Pediatric Resident Burnout–Resilience Study Consortium

Journal of Evidence-Based Integrative Medicine ◽

10.1177/2515690x18804779 ◽

2018 ◽

Vol 23 ◽

pp. 2515690X1880477

Author(s):

Suzanne Reed ◽

Kathi J. Kemper ◽

Alan Schwartz ◽

Maneesh Batra ◽

Betty B. Staples ◽

...

Keyword(s):

Compassionate Care ◽

Short Term ◽

Cross Sectional ◽

Pediatric Residents ◽

Time Points ◽

Single Center Study ◽

Risk Period ◽

Resident Burnout ◽

Relationship Of ◽

The Relationship

Residency is a high-risk period for physician burnout. We aimed to determine the short-term stability of factors associated with burnout, application of these data to previous conceptual models, and the relationship of these factors over 3 months. Physician wellness questionnaire results were analyzed at 2 time points 3 months apart. Associations among variables within and across time points were analyzed. Logistic regression was used to predict burnout and compassionate care. A total of 74% of residents completed surveys. Over 3 months, burnout ( P = .005) and empathy ( P = .04) worsened. The most significant cross-sectional relationship was between stress and emotional exhaustion (time 1 r = 0.61, time 2 r = 0.68). Resilience was predictive of increased compassionate care and decreased burnout ( P < .05). Mindfulness was predictive of decreased burnout ( P < .05). Mitigating stress and fostering mindfulness and resilience longitudinally may be key areas of focus for improved wellness in pediatric residents. Larger studies are needed to better develop targeted wellness interventions.

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Yo el Supremo, de Roa Bastos. Sobre el poder y el derecho en el mito del Doctor Francia

Interpretatio. Revista de Hermenéutica ◽

10.19130/irh.2021.2.345523 ◽

2021 ◽

Vol 6 (2) ◽

pp. 17-34

Author(s):

Jesús Antonio de la Torre Rangel ◽

Keyword(s):

Latin American ◽

The Novel ◽

What Is Said ◽

Historic Data ◽

Literature And Law ◽

The Law ◽

The Relationship

The importance of the relationship between literature and law, in general, is highlighted; and it is pointed out through examples set by some novels and their treatment of Rights. The text is dedicated, especially, to show how the law is manifested in Roa Bastos’s Yo el supremo, a masterpiece of Latin American letters. The famous and enigmatic Doctor Francia —theologian and jurist—, in his Perpetual Dictatorship in Paraguay, dictates and practices the Law. It expresses what the novel says about the Law and offers historic data that support what is said.

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F-actin serves as a template for cytokeratin organization in cell free extracts

Journal of Cell Science ◽

10.1242/jcs.115.7.1373 ◽

2002 ◽

Vol 115 (7) ◽

pp. 1373-1382 ◽

Cited By ~ 2

Author(s):

Kari L. Weber ◽

William M. Bement

Keyword(s):

Time Course ◽

Early Time ◽

Dynamic Imaging ◽

Actin Network ◽

Intact Cells ◽

Time Points ◽

Egg Extracts ◽

Actin Cables

The microtubule, F-actin, and intermediate filament systems are often studied as isolated systems, yet the three display mutual interdependence in living cells. To overcome limitations inherent in analysis of polymer-polymer interactions in intact cells, associations between these systems were assessed in Xenopus egg extracts. In both fixed and unfixed extract preparations, cytokeratin associated with F-actin cables that spontaneously assembled in the extracts. Time-course experiments revealed that at early time points cytokeratin cables were invariably associated with F-actin cables,while at later time points they could be found without associated F-actin. In extract samples where F-actin assembly was prevented, cytokeratin formed unorganized aggregates rather than cables. Dynamic imaging revealed transport of cytokeratin by moving F-actin as well as examples of cytokeratin release from F-actin. Experimental alteration of F-actin network organization by addition of α-actinin resulted in a corresponding change in the organization of the cytokeratin network. Finally, pharmacological disruption of the F-actin network in intact, activated eggs disrupted the normal pattern of cytokeratin assembly. These results provide direct evidence for an association between F-actin and cytokeratin in vitro and in vivo, and indicate that this interaction is necessary for proper cytokeratin assembly after transition into the first mitotic interphase of Xenopus.

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An in vitro transcription analysis of early responses of the human immunodeficiency virus type 1 long terminal repeat to different transcriptional activators

Molecular and Cellular Biology ◽

10.1128/mcb.11.4.1883-1893.1991 ◽

1991 ◽

Vol 11 (4) ◽

pp. 1883-1893

Author(s):

Y C Li ◽

J Ross ◽

J A Scheppler ◽

B R Franza

Keyword(s):

Human Immunodeficiency Virus ◽

Protein Synthesis ◽

Early Time ◽

In Vitro Transcription ◽

Jurkat Cells ◽

Time Points ◽

Immunodeficiency Virus ◽

Hiv 1

In this report we introduce a simple, fast, and reliable method to prepare whole cell or nuclear extracts from small numbers of cells. These extracts were used to study transcriptional activation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in vitro. Our results revealed that the time courses of activation of extracts derived from cells stimulated with the mitogenic lectin phytohemagglutinin (PHA) or with the tumor promoter phorbol 12-myristate 13-acetate (PMA) are different. PMA induces a rapid onset of increased in vitro transcription from the HIV-1 LTR, while PHA causes a slow and sustained response. The biochemical relevance of protein synthesis inhibition by cycloheximide treatment of cells was investigated. In these studies, PMA induction of a change in in vitro transcriptional activity is not dependent on protein synthesis. Cycloheximide alone is insufficient to induce activation. Oligonucleotide-mediated site-directed mutagenesis demonstrated that mutation of the TATA box in the LTR ablated initiation of both basal-level transcription and activation by extracts from cells stimulated with PMA. Surprisingly, mutation of both kappa B sites in the LTR reduced but did not eliminate the in vitro response to extracts prepared at early time points after PHA or PMA stimulation of Jurkat cells. The reduction was greater in extracts derived from cells treated with PMA. Deletion analysis of the HIV-1 LTR revealed at least one region (-464 to -252) capable of suppressing in vitro transcription in extracts from Jurkat cells stimulated by PMA. This result is consistent with early studies of the HIV-1 LTR in transient transfection assays. We therefore have been able to observe distinct regulatory events at early time points after cells are exposed to agents known to induce transcription of both the HIV-1 LTR reporter gene constructs and the HIV-1 provirus itself.

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