ABSTRACT
BACKGROUND: Tildrakizumab is a humanized anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes real-world effectiveness and safety of tildrakizumab through 64 weeks of treatment. METHODS: In this Phase 4, multicenter, uncontrolled, open-label trial (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at weeks 0 and 4 and every 12 weeks thereafter through week 52. Effectiveness was assessed from body surface area (BSA) affected and static Physician Global Assessment (sPGA) through week 64 and Psoriasis Area and Severity Index (PASI) through week 52. Adverse events are reported. RESULTS: Of 55 patients enrolled, 45 completed the study and 36 received all doses of tildrakizumab. From baseline to week 64, mean +/- standard deviation BSA decreased by 83.1% (from 14.5 +/- 11.5 to 2.1 +/- 3.6) and sPGA by 67.6% (from 3.2 +/- 0.6 to 1.0 +/- 1.0); sPGA x BSA decreased by 89.6% (from 47.0 +/- 41.5 to 4.6 +/- 9.4; all P<0.001). PASI scores decreased compared to baseline at weeks 4, 16, 28, and 52 (P<0.001). For PASI responses at week 52 compared with baseline, 87.0% achieved greater than or equal to 75% improvement, 56.5% achieved greater than or equal to 90% improvement, and 32.6% achieved 100% improvement. Of 85 treatment-emergent adverse events in 34/55 patients, none were considered related to tildrakizumab treatment. CONCLUSIONS: Tildrakizumab treatment was effective in adult patients with moderate-to-severe plaque psoriasis in real-world settings, with no new safety signals. J Drugs Dermatol. 2024;23(8):612-618. doi:10.36849/JDD.8217.
Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Severity of Illness Index , Humans , Psoriasis/drug therapy , Psoriasis/diagnosis , Female , Male , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Middle Aged , Treatment Outcome , Adult , Interleukin-23 Subunit p19/antagonists & inhibitors , Interleukin-23 Subunit p19/immunology , AgedABSTRACT
Heat stress (HS) impacts the nuclear proteome and, subsequently, protein activities in different nuclear compartments. In Arabidopsis thaliana, a short exposure to 37 °C leads to loss of the standard tripartite architecture of the nucleolus, the most prominent nuclear substructure, and, consequently, affects the assembly of ribosomes. Here, we report a quantitative label-free LCâMS/MS (Liquid Chromatography coupled to tandem Mass Spectrometry) analysis to determine the nuclear proteome of Arabidopsis at 22 °C, HS (37 °C for 4 and 24 h), and a recovery phase. This analysis identified ten distinct groups of proteins based on relative abundance changes in the nucleus before, during and after HS: Early, Late, Transient, Early Persistent, Late Persistent, Recovery, Early-Like, Late-Like, Transient-Like and Continuous Groups (EG, LG, TG, EPG, LPG, RG, ELG, LLG, TLG and CG, respectively). Interestingly, the RNA polymerase I subunit NRPA3 and other main nucleolar proteins, including NUCLEOLIN 1 and FIBRILLARIN 1 and 2, were detected in RG and CG, suggesting that plants require increased nucleolar activity and likely ribosome assembly to restore protein synthesis after HS.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Heat-Shock Response , Proteomics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Proteomics/methods , Cell Nucleus/metabolism , Proteome/metabolism , Proteome/analysis , Tandem Mass Spectrometry , Kinetics , Chromatography, Liquid/methods , Nuclear Proteins/metabolismABSTRACT
BACKGROUND: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes final primary results of a 64-week real-world study of the effect of tildrakizumab on patients' health-related quality of life (HRQoL). MATERIALS AND METHODS: In this open-label phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52. The primary endpoint was improvement from baseline in HRQoL measured by Psychological General Well-Being Index (PGWBI) total score at weeks 28 and 52. Secondary HRQoL endpoints included change from baseline in Dermatology Life Quality Index (DLQI) score through week 64. Missing data were not imputed. RESULTS: Of 55 patients enrolled, 45 were assessed at week 64. Mean ± standard deviation (SD) total PGWBI score improved from 78.1 ± 14.1 at baseline to 85.2 ± 12.0 at week 52 (p < .001). Mean ± SD DLQI score improved from 9.4 ± 5.2 at baseline to 2.0 ± 2.6 (p < .001) at week 64 with 62.2% of patients having a DLQI score of 0 or 1 at week 64. CONCLUSIONS: Tildrakizumab improved long-term HRQoL in patients with psoriasis in a real-world setting.
Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Quality of Life , Severity of Illness Index , Humans , Psoriasis/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Male , Female , Middle Aged , Adult , Treatment Outcome , Interleukin-23 Subunit p19/antagonists & inhibitors , Interleukin-23 Subunit p19/immunology , Dermatologic Agents/therapeutic useABSTRACT
INTRODUCTION: Plaque psoriasis is a chronic condition that may impact patients' work productivity. Tildrakizumab, an interleukin-23 p19 inhibitor, is approved for treatment of moderate-to-severe plaque psoriasis in adults. However, the effect of tildrakizumab treatment on work productivity in patients with psoriasis is not well characterized. METHODS: In this multicenter, open-label, uncontrolled phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52. Patients completed the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI:PSO) at baseline and every 12 weeks from week 16 through week 64. The following four domains of the WPAI:PSO were examined: absenteeism (percentage of time missed from work due to psoriasis), presenteeism (percentage reduction of productivity while at work due to psoriasis), total activity impairment (percentage impairment in activities other than work due to psoriasis), and total work productivity impairment (total percentage of work impairment from both absenteeism and presenteeism due to psoriasis). Missing data were not imputed. RESULTS: Of the 55 patients enrolled, 31 patients completed all domains of the WPAI:PSO at week 64. From baseline to week 64, respectively, mean ± standard deviation (SD) scores improved for presenteeism (20.5 ± 21.7 to 2.6 ± 5.8; P < 0.001), total activity impairment (29.5 ± 26.6 to 4.4 ± 9.4; P < 0.001), and total work productivity impairment (20.9 ± 22.2 to 2.6 ± 5.8; P < 0.001). The mean ± SD score for absenteeism decreased from 1.1 ± 5.7 at baseline to 0.0 ± 0.0 at week 64, but this change was not statistically significant. CONCLUSION: Tildrakizumab treatment mitigated work productivity loss due to psoriasis as measured by the presenteeism, total activity impairment, and total work productivity impairment domains of the WPAI:PSO. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03718299.
ABSTRACT
BACKGROUND: Tildrakizumab is an antiinterleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. This analysis evaluated real-world effectiveness and safety of tildrakizumab for 28 weeks. METHODS: In this Phase 4 study (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg subcutaneously at week 0, week 4, and every 12 weeks thereafter. Clinical improvement was assessed from Psoriasis Area and Severity Index (PASI) score change from baseline; disease activity from body surface area (BSA) percentage affected, static Physician's Global Assessment (sPGA), and sPGA x BSA; and safety from adverse events (AEs). RESULTS: At week 28, 52/55 enrolled patients were assessed. Mean (standard deviation [SD]) PASI score decreased significantly (P<0.001) from 11.6 (7.1) at baseline to 1.8 (3.0; 82.1% improvement) at week 28; 55.8% of patients achieved PASI 90 response. From baseline to week 28, mean (SD) BSA decreased significantly from 14.5% (11.5%) to 2.9% (6.4%), sPGA from 3.2 (0.6) to 1.2 (0.9), and BSA x sPGA from 47.0 (41.5) to 6.8 (20.3; all P<0.001). Serious AEs were infrequent. No treatment-emergent AEs were considered related to tildrakizumab. Conclusions: Real-world tildrakizumab treatment significantly improved clinical status and reduced disease activity, with no new safety concerns. Heim J, Gabriel Vasquez J, Schenkel B, et al. Real-world effectiveness and safety of tildrakizumab in patients with moderate- to-severe psoriasis: week 28 interim analysis of a phase 4 study. J Drugs Dermatol. 2023;22(8):754-760. doi:10.36849/JDD.7471.
Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Adult , Humans , Treatment Outcome , Double-Blind Method , Antibodies, Monoclonal, Humanized/adverse effects , Psoriasis/diagnosis , Psoriasis/drug therapy , Psoriasis/chemically induced , Severity of Illness IndexABSTRACT
BACKGROUND: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. Little real-world evidence is available regarding the effects of tildrakizumab on patients' health-related quality of life (HRQoL) and patient-reported symptoms. OBJECTIVE: This real-world study of tildrakizumab evaluated changes in HRQoL and clinical symptoms in patients with psoriasis. MATERIALS AND METHODS: In this Week (W)28 interim analysis of a 64-week Phase 4 study (NCT03718299), patients received tildrakizumab 100 mg at W0, W4, and every 12 weeks thereafter. Endpoints were improvement from baseline in Psychological General Well-Being Index (PGWBI), Dermatology Life Quality Index (DLQI), and Itch-, Pain-, and Scaling-Numerical Rating Scale scores through W28. RESULTS: Of 55 patients enrolled, 53 were assessed at W28. Mean (standard deviation [SD]) total PGWBI score improved from baseline to W28 (change, 3.7 [12.4]; p = .033), as did the positive well-being (1.0 [2.9]; p = .018) and general health (1.5 [2.2]; p < .001) domain scores. Mean (SD) DLQI score improved by -3.9 (4.3) at W4 and by -7.6 (5.1) at W28 (p < .001). Patient-reported symptoms improved starting at W4 (p < .001). CONCLUSION: Tildrakizumab treatment improved HRQoL and patient-reported symptoms in patients with psoriasis in a real-world setting. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03718299.
Subject(s)
Psoriasis , Quality of Life , Adult , Humans , Treatment Outcome , Psoriasis/diagnosis , Patient Reported Outcome Measures , Severity of Illness IndexABSTRACT
BACKGROUND: Procedural anxiety was anticipated in children 5-11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway. METHODS: The Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child's support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5-11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message. RESULTS: Between 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs. CONCLUSION: A tailored COVID-19 vaccination program for children 5-11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Child , Child, Preschool , Victoria/epidemiology , Australian Aboriginal and Torres Strait Islander Peoples , COVID-19/prevention & control , VaccinationABSTRACT
La sobredentadura retenida por dos implantes es una opción para la rehabilitación del edentulismo, pero no se ha estudiado a profundidad su efecto sobre el mantenimiento de la altura del reborde alveolar posterior. El objetivo de este trabajo fue determinar los cambios en altura del reborde alveolar posterior mandibular después de 7 años del uso de una sobredentadura mandibular. Este estudio descriptivo consideró 17 pacientes. Cada paciente había recibido una sobredentadura mandibular retenida por dos implantes no ferulizados cargados de forma inmediata y unidos mediante ajustes en bola. Se realizaron mediciones en dos radiografías panorámicas (una tomada antes de la inserción de la sobredentadura [T0] y otra siete años después [T7]),para los trazos, el área se expresó como un triángulo posterior formado por el gonion, el borde inferior del agujero mental y un punto que fue el centro del triángulo gonion - foramen mental - muesca sigmoidea. El área medida se comparó con el área triangular en el mismo lado.Los resultados en mm con significancia estadística (p< 0.05) fueron: área de referencia ósea X( [T0]:494.3- [T7]:431.6) área de referencia ósea izquierda ([T0]:502.0 -[T7]:405.3) y el índice de área posterior([T0]:1.4-[T7]:1.2).Los resultados en mm sin significancia estadísticas(p>0.05)indicaron: área de referencia ósea X derecha([T0]:486.1 - [T7]:458.0), área de referencia en Y izquierda ([T0]:354.8-[T7]:360.6), derecha ([T0]:361.9-[T7]:375.6) y promedio de longitud del reborde maxilar ([T0]:35.4-[T7]:36.9). La reabsorción del reborde alveolar posterior a los 7 años estuvo dentro de los parámetros normales, no existiría ningún efecto nocivo de la sobredentadura sobre este reborde. (AU)
The overdenture retained by two implants is an option for the rehabilitation of edentulism, but its effect on the maintenance of the posterior alveolar ridge has not been studied in depth.The objective of this work was to determine the changes in height of the mandibular posterior alveolar ridge after 7 years of the use of a mandibular overdenture. This descriptive study considered 17 patients. Each patient had received a mandibular overdenture retained by two non-splinted implants immediately loaded and joined by ball adjustments. Measurements were made in two panoramic radiographs (one taken before the insertion of the overdenture [T0] and another seven years later [T7]), for the lines the area was expressed as a posterior triangle formed by the gonion, the lower edge of the mental hole and a point that was the center of the gonion triangle - mental foramen - sigmoid notch. The measured area was compared to the triangular area on the same side. The results in mm with statistical significance (p< 0.05) were: bone reference area X( [T0]:494.3- [T7]:431.6) left bone reference area ([T0]:502.0 -[T7]: 405.3) and the posterior area index ([T0]:1.4-[T7]:1.2). The results in mm without statistical significance (p>0.05) indicated: right X bone reference area ([T0]:486.1 - [T7]:458.0), left Y reference area ([T0]:354.8-[T7]:360.6), right ([T0]:361.9-[T7]:375.6) and average ridge length maxilla ([T0]:35.4-[T7]:36.9). The resorption of the alveolar ridge after 7 years was within normal parameters, there would be no harmful effect of the overdenture on this ridge. (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Alveolar Process , Dental Prosthesis, Implant-Supported , Dental Implant-Abutment Design , Denture, Overlay , Radiography, Panoramic , Epidemiology, DescriptiveABSTRACT
Controversy has existed as to whether monensin will provide equal or differential benefits in a higher-energy, lower-roughage close-up diet versus a higher-roughage, lower-energy diet. Our objective was to determine the rumen effects of a controlled-energy, high-fiber diet balanced to meet but not greatly exceed energy requirements during the dry period or a traditional 2-group approach of higher-energy close-up diet. The effects of added monensin in each diet type were determined. Multiparous Holstein cows (n = 17) were fitted surgically with ruminal cannulas. During the first 4 wk of the dry period, all cows were fed a controlled-energy, high-fiber diet (CE) as a total mixed ration for ad libitum intake. During the last 3 wk before calving, half of the cows were switched to a higher-energy, close-up diet until calving (CU), whereas the other half continued to receive the CE diet. Within each dietary group, half of the cows received monensin (MON) supplementation in the diet (24.2 g/t of total dry matter) and half did not (CON). After calving, all cows received the same lactation diet containing monensin (15.4 g/t of dietary dry matter). At 14 d prepartum, dry matter intake was not different across treatments. The weight of rumen contents was greater for cows fed CE. Rumen liquid dilution rate, solids passage rate, pH, total volatile fatty acid (VFA) concentrations, molar proportions of acetate and propionate, and papillae length did not differ among diets. Butyrate percentage tended to be greater for cows fed CE. Postpartum, dry matter intake, mass of rumen contents, solids passage rate, pH, total VFA concentration, molar percentages of propionate and butyrate, and papillae length did not differ among treatments. Liquid dilution rate (16.6, 10.7, 16.0, and 18.2%/h for CE + CON, CE + MON, CU + CON, and CU + MON, respectively) was affected by a diet × monensin interaction. Cows on the CE + CON diet had a greater ruminal proportion of acetate than did cows fed CU + CON, whereas cows fed monensin on either diet were intermediate (diet × monensin interaction). Addition of MON to the CU diet decreased the proportion of propionate (diet × monensin interaction). Cows fed CE had greater mass of rumen contents before parturtition but the high inclusion of wheat straw in the CE diet did not negatively affect rumen papillae length. Monensin inclusion differentially affected liquid passage rate and VFA concentrations.
Subject(s)
Monensin , Propionates , Animals , Cattle , Female , Butyrates , Diet/veterinary , Dietary Fiber , Monensin/pharmacology , RumenABSTRACT
Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.
Subject(s)
Arabidopsis , RNA Precursors , Arabidopsis/genetics , Arabidopsis/metabolism , Heat-Shock Response , RNA Precursors/genetics , RNA Precursors/metabolism , RNA Processing, Post-Transcriptional , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism , Ribosomes/genetics , Ribosomes/metabolismABSTRACT
After 43 years of dormancy, Taal Volcano violently erupted in January 2020 forming a towering eruption plume. The fall deposits covered an area of 8605 km2, which includes Metro Manila of the National Capital Region of the Philippines. The tephra fall caused damage to crops, traffic congestion, roof collapse, and changes in air quality in the affected areas. In a tropical region where heavy rains are frequent, immediate collection of data is crucial in order to preserve the tephra fall deposit record, which is readily washed away by surface water runoff and prevailing winds. Crowdsourcing, field surveys, and laboratory analysis of the tephra fall deposits were conducted to document and characterize the tephra fall deposits of the 2020 Taal Volcano eruption and their impacts. Results show that the tephra fall deposit thins downwind exponentially with a thickness half distance of about 1.40 km and 9.49 km for the proximal and distal exponential segments, respectively. The total calculated volume of erupted fallout deposit is 0.057 km3, 0.042 km3, or 0.090 km3 using the exponential, power-law, and Weibull models, respectively, and all translate to a VEI of 3. However, using a probabilistic approach (Weibull method) with 90% confidence interval, the volume estimate is as high as 0.097 km3. With the addition of the base surge deposits amounting to 0.019 km3, the volume translates to a VEI of 4, consistent with the classification for the observed height and umbrella radius of the 2020 main eruption plume. VEI 4 is also consistent with the calculated median eruption plume height of 17.8 km and sub-plinian classification based on combined analysis of isopleth and isopach data. Phreatomagmatic activity originated from a vent located in Taal Volcano's Main Crater Lake (MCL), which contained 42 million m3 of water. This eruptive style is further supported by the characteristics of the ash grain components of the distal 12 January 2020 tephra fall deposits, consisting dominantly of andesitic vitric fragments (83-90%). Other components of the fall deposits are lithic (7-11%) and crystal (less than 6%) grains. Further textural and geochemical analysis of these tephra fall deposits contributes to better understand the volcanic processes that occurred at Taal Volcano, one of the 16 Decade Volcanoes identified by the International Association of Volcanology and Chemistry of the Earth's Interior (IAVCEI) because of its destructive nature and proximity to densely populated areas. The crowdsourcing initiative provided a significant portion of the data used for this study while at the same time educating and empowering the community to build resilience. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00445-022-01534-y.
ABSTRACT
In all eukaryotic cells, the most abundant modification of ribosomal RNA (rRNA) is methylation at the ribose moiety (2'-O-methylation). Ribose methylation at specific rRNA sites is guided by small nucleolar RNAs (snoRNAs) of C/D-box type (C/D snoRNA) and achieved by the methyltransferase Fibrillarin (FIB). Here we used the Illumina-based RiboMethSeq approach for mapping rRNA 2'-O-methylation sites in A. thaliana Col-0 (WT) plants. This analysis detected novel C/D snoRNA-guided rRNA 2'-O-methylation positions and also some orphan sites without a matching C/D snoRNA. Furthermore, immunoprecipitation of Arabidopsis FIB2 identified and demonstrated expression of C/D snoRNAs corresponding to majority of mapped rRNA sites. On the other hand, we show that disruption of Arabidopsis Nucleolin 1 gene (NUC1), encoding a major nucleolar protein, decreases 2'-O-methylation at specific rRNA sites suggesting functional/structural interconnections of 2'-O-methylation with nucleolus organization and plant development. Finally, based on our findings and existent database sets, we introduce a new nomenclature system for C/D snoRNA in Arabidopsis plants.
Subject(s)
Arabidopsis/genetics , RNA, Plant/chemistry , RNA, Plant/genetics , RNA, Ribosomal/chemistry , RNA, Ribosomal/genetics , RNA, Small Nucleolar/genetics , MethylationABSTRACT
Generalized fear is one purported mechanism of anxiety that is a target of clinical and basic research. Impaired fear discrimination has been primarily examined from the perspective of increased fear learning, rather than how learning about non-threatening stimuli affects fear discrimination. To address this question, we tested how three Safety Conditioning protocols with varied levels of salience allocated to the safety cue compared to classic Fear Conditioning in their impact on subsequent innate anxiety, and differential fear learning of new aversive and neutral cues. Using a high anxiety strain of mice (129SvEv, Taconic), we show that Fear Conditioned animals show little exploration of the anxiogenic center of an open field 24 h later, and poor discrimination during new differential conditioning 7 days later. Three groups of mice underwent Safety Conditioning, (i) the safety tone was unpaired with a shock, (ii) the safety tone was unpaired with the shock and co-terminated with a house light signaling the end of the safety period, and (iii) the safety tone was unpaired with the shock and its beginning co-occurred with a house light, signaling the start of a safety period. Mice from all Safety Conditioning groups showed higher levels of open field exploration than the Fear Conditioned mice 24 h after training. Furthermore, Safety Conditioned animals showed improved discrimination learning of a novel non-threat, with the Salient Beginning safety conditioned group performing best. These findings indicate that high anxiety animals benefit from salient safety training to improve exploration and discrimination of new non-threating stimuli.
Subject(s)
Anxiety/physiopathology , Conditioning, Classical/physiology , Discrimination Learning/physiology , Emotional Regulation/physiology , Fear/physiology , Safety , Animals , Behavior, Animal/physiology , Disease Models, Animal , Male , Mice , Mice, 129 StrainABSTRACT
Our objectives were to evaluate the effects of prepartum monensin supplementation and dry-period nutritional strategy on the postpartum productive performance of cows fed monensin during lactation. A total of 102 Holstein cows were enrolled in the experiment (32 primiparous and 70 multiparous). The study was a completely randomized design, with randomization restricted to balance for parity, body condition score, and expected calving date. A 2 × 2 factorial arrangement of prepartum treatments was used; the variables of interest were prepartum feeding strategy [controlled-energy diet throughout the dry period (CE) vs. controlled-energy diet from dry-off to 22 d before expected parturition, followed by a moderate-energy close-up diet from d 21 before expected parturition through parturition (CU)] and prepartum monensin supplementation [0 g/t (control, CON) or 24.2 g/t (MON); Rumensin; Elanco Animal Health, Greenfield, IN]. Lactation diets before and after the dry period contained monensin at 15.4 g/t. During the close-up period, cows fed CU had greater DM and NEL intakes than cows fed CE. Calf BW at birth tended to be greater for cows fed CU than for those fed CE but was not affected by MON supplementation. Diet did not affect calving difficulty score, but cows supplemented with MON had an increased calving difficulty score. We found a tendency for a MON × parity interaction for colostral IgG concentration, such that multiparous MON cows tended to have lower IgG concentration than CON cows, but colostral IgG concentration for primiparous MON and CON cows did not differ. Postpartum milk yield did not differ between diets but tended to be greater for cows supplemented with MON. Milk fat and lactose content were greater for cows fed CU than for those fed CE, and lactose content and yield were increased for cows supplemented with MON. Solids-corrected and fat-corrected milk yields were increased by MON supplementation, but were not affected by diet. Overall means for postpartum DMI did not differ by diet or MON supplementation. The CU diet decreased the concentration of nonesterified fatty acids during the close-up period but increased it postpartum. Neither diet nor monensin affected ß-hydroxybutyrate or liver composition. Overall, postpartum productive performance differed little between prepartum dietary strategies, but cows fed MON had greater energy-corrected milk production. In herds fed monensin during lactation, monensin should also be fed during the dry period.
Subject(s)
Energy Metabolism , Monensin , Animals , Cattle , Diet/veterinary , Dietary Supplements , Female , Lactation , Milk , Monensin/pharmacology , Postpartum Period , PregnancyABSTRACT
INTRODUCTION: Burnout syndrome has increased dramatically in urology within recent years. A healthy lifestyle has been described as a protective factor. However, data on lifestyle is lacking among residents and urologists and remains to be elucidated. We aim to assess lifestyle among urology residents and young urologists across Europe. MATERIALS AND METHODS: Members of the European Society of Residents in Urology (ESRU) designed a 34-item online survey via surveymonkey.com. The survey was designed in accordance with Checklist for Reporting Results of Internet E-Surveys (CHERRIES) guidelines and was distributed via e-mail and social media in 23 European countries to urology residents and young urologists. The primary endpoint was reported as self-perceived health status. Secondary endpoints included questions on sleeping disorders, exercise and dietary habits. Data was analyzed SPSS software. RESULTS: A total of 412 residents and young urologists responded to the survey. The mean age of the respondents was 31.4±3.9 yr. The data on dietary intake demonstrate a mean of 2 or more cups/day of coffee and alcohol consumption 2-3 times/week. The intake of fruits and vegetables is very low, almost 60% of responders consume<1 portions of fruit/day and more than half (52%) eat<1 portion of vegetable/day. Overall, the majority of respondents reported to have a moderate to low satisfaction with lifestyle (59.65%) and low to moderate self-perceived health status (45.94%). Moreover, 46% of respondents reported to have some kind of sleep disturbance and 60% only slept 6hours/night or less with 53% reporting a moderate to very low quality of Sleep. Regular exercise of at least 30min twice weekly was only performed by 33% of the respondents. CONCLUSIONS: Residents and young urologists have unbalanced diet, tend to exercise too little and often suffer from sleep disturbances all of which increases the risk of burnout. Physicians, organizations and institutions should strive to promote healthy lifestyle, resiliency and support programs.
Subject(s)
Burnout, Professional/epidemiology , Internship and Residency , Life Style , Urologists/psychology , Urology/education , Adult , Europe , Female , Humans , Male , Self ReportSubject(s)
Delirium , Adolescent , Child , Child, Preschool , Critical Care , Hospitalization , Humans , PrevalenceABSTRACT
Resumen El paso de guardia en enfermería es una actividad fundamental para dar continuidad al cuidado de los pacientes, se realiza como cumplimiento obligatorio de una tarea en el quehacer laboral. Objetivo Describir la producción científica publicada entre 2007-2017, referente a la temática de paso de guardia de enfermería en los servicios de urgencias. Metodología Se desarrolló una revisión sistemática en seis bases de datos, se incluyeron estudios en idiomas inglés, español y portugués que estuvieran publicados en revistas indexadas con acceso a texto completo. Se realizó un análisis crítico de cada uno de los artículos con las Herramientas CASPe y STROBE, los resultados se ordenaron en una matriz que facilitó la obtención de información y categorías. Resultados De un total de 430 artículos, se incluyeron a la investigación únicamente 19, de los cuales 17 están escritos en idioma inglés y dos en español. Después del análisis de los artículos seleccionados se estructuraron dos categorías: Características del paso de guardia y Estandarización del proceso. Conclusiones Las brechas en la comunicación se perfilan como uno de los principales aspectos a tener en cuenta, para mejorar el paso de guardia. El lugar más recomendable para que se lleve a cabo el proceso debe ser en la habitación del paciente y verificado por los dos equipos de enfermería. En la actualidad es necesario realizar investigaciones para mejorar el nivel de evidencia de los estudios.
Abstract Nursing shift handover is an obligatory and a fundamental activity to ensure continuity in the process of patient care. Objective To describe the scientific production published between 2007-2017 regarding nursing shift handover within medical emergency services. Methodology A systematic review was conducted on six databases. Articles with full texts written in English, Spanish, and Portuguese, and published in indexed journals were included. A critical analysis on each article was conducted using the Critical Appraisal Skills Programme spanish, and the Strengthening the Reporting of Observational Studies in Epidemiology tools. Articles were clustered in a matrix of categories. Results From a total of 430 possible articles, 19 were included for this study - 17 written in English and 2 written in Spanish. From the corresponding analysis, two categories were structured: Nursing Shift Handover Characteristics, and Process Standardization. Conclusions Communication gaps seem to be one of the main issues to address while improving the nursing shift handover process. The patient room should be the place for the shift handover, and this process must be acknowledged by both nursing teams.
Resumo A passagem de plantão em enfermagem é uma atividade fundamental para dar continuidade ao cuidado dos pacientes, realiza-se como cumprimento obrigatório de uma tarefa no trabalho laboral. Objetivo Descrever a produção científica publicada entre 2007-2017, referente à temática de passagem de plantão de enfermagem nos serviços de urgências. Metodologia Desenvolveu-se uma revisão sistemática em seis bases de dados, incluíram-se estudos em idiomas inglês, espanhol e português que estiveram publicados em revistas indexadas com acesso a texto completo. Realizou-se uma análise crítica de cada um dos artigos com as Ferramentas CASPe e STROBE, os resultados ordenaram-se em uma matriz que facilitou a obtenção de informação e categorias. Resultados De um total de 430 artigos, incluíram-se à pesquisa unicamente 19, dos quais 17 estão escritos em idioma inglês e dois em espanhol. Depois da análise dos artigos selecionados estruturaram-se duas categorias: Caraterísticas da passagem de plantão e Padronização do processo. Conclusões Os abismos na comunicação perfilam-se como um dos principais aspectos a ter em conta, para melhorar a passagem de plantão. O lugar mais recomendável para se efetuar o processo deve ser no quarto do paciente e verificado pelas duas equipes de enfermagem. Na atualidade é necessário realizar pesquisas para melhorar o nível de evidência dos estudos.
ABSTRACT
The ability to learn that a stimulus no longer signals danger is known as extinction. A major characteristic of extinction is that it is context-dependent, which means that fear reduction only occurs in the same context as extinction training. In other contexts, there is re-emergence of fear, known as contextual renewal. The ability to properly extinguish fear memories and generalize safety associations to multiple contexts provides therapeutic potential, but little is known about the specific neural pathways that mediate fear renewal and extinction generalization. The ventral hippocampus (VH) is thought to provide a contextual gating mechanism that determines whether fear or safety is expressed in particular contexts through its projections to areas of the fear circuit, including the infralimbic (IL) and prelimbic (PL) cortices. Moreover, VH principal cells fire in large, overlapping regions of the environment, a characteristic that is ideal to support generalization; yet it is unclear how different projection cells mediate this process. Using a pathway-specific (intersectional) chemogenetic approach, we demonstrate that selective activation of VH cells projecting to PL attenuates fear renewal without affecting fear expression. These results have implications for anxiety disorders since they uncover a neural pathway associated with extinction generalization.
Subject(s)
Extinction, Psychological/physiology , Fear/physiology , Gyrus Cinguli/physiology , Hippocampus/physiology , Mental Recall/physiology , Prefrontal Cortex/physiology , Animals , Behavior, Animal/physiology , Genetic Techniques , Male , Mice , Mice, Inbred C57BLABSTRACT
Introducción: Las deficiencias congénitas en la visión del color afectan a un 8% de la población masculina y a un 0,5% de la femenina. El estudio de la visión del color es un proceso complejo debido a diversos factores: la propia psicofísica de la visión y la dificultad de establecer modelos matemáticos para su análisis, la vaga correlación de los resultados entre unos test y otros y la influencia de factores externos como la iluminación, la condición de los test o la experiencia del examinador y del paciente. En el presente documento se realiza una revisión simplificada de los principales test disponibles en la práctica clínica para evaluar la visión del color. Material y métodos: Tras realizar una filtrada revisión preliminar de la bibliografía relacionada con el estudio de la visión del color en el motor de búsqueda PubMed, se determinaron los test mayormente utilizados en la práctica clínica. Se realizó una interpretación atendiendo a su frecuencia de uso y el propósito para el que eran utilizados. A continuación, se procedió con un estudio bibliográfico de cada test en particular, atendiendo al diseño de los estímulos presentados, su población diana y su sensibilidad y especificidad. Resultados De las 95 publicaciones que mostró el buscador PubMed, en 41 de ellas los investigadores utilizaron test de colores en su metodología. De los 64 test de color utilizados, 19 eran diferentes (contando como distintos los test adaptados por grupos de investigación, 4, y aquellos realizados online, 2). El orden de empleo de los test es el siguiente: test de Ishihara (10,88%), Farnsworth-Munsell (7,04%), Farnsworth-Munsell 100 Hue (6,4%), Cambridge Colour Test (3,84%), Hardy-Rand-Rittler (3,2%), test propios desarrollados por los grupos (2,56%), el anomaloscopio (1,28%), los test online (1,28%) y, finalmente, Colour Assessment and Diagnosis (0,64%), Pflüger Trident Colour Plates (0,64%), Toothguide Training Box (0,64%), Lanthony Desaturated D-15 (0,64%), City University Test (0,64%), Universal Colour Discrimination Test (0,64%) y Rabin Cone Contrast Test (0,64%). Conclusiones El gold standard en cuanto a la evaluación de la visión del color es el anomaloscopio, instrumento incompatible con la práctica clínica diaria. Su manejo es relativamente complicado, exige disponibilidad de tiempo para su aplicación y es difícilmente comprensible por población infantil. Sin embargo, es posible alcanzar una fiel aproximación mediante la combinación de algunos de los test enumerados en este artículo. Los test expuestos son una buena alternativa para determinar la presencia de discromatopsias en ambientes cercanos a la práctica clínica diaria o en entornos menos controlados que un estudio clínico. El inconveniente principal del amplio elenco de test disponibles para el estudio de la visión del color es la dificultad para comparar los resultados entre test, ya que los datos publicados suelen tener unidades distintas, requiriendo experiencia para su correcta interpretación. En la actualidad, no existe unanimidad sobre qué test de color resulta ser el más completo; es recomendable utilizar al menos 2 para asegurar los diagnósticos y tener una información más completa sobre la percepción visual de los pacientes
Introduction: Congenital colour vision deficiencies affect 8% of the male and 0.5% of the female population. The study of colour vision is a complex process due to several factors: the psychophysics of vision itself, the difficulty to establish mathematical models for its analysis, the vague correlation of results between different tests, and the influence of external factors such as lighting, the tests condition, or the experience of the examiner and the patient. In the present document, a simplified review was carried out on the main colour vision tests available in clinical practice. Material and methods: Once a filtered preliminary review was made of the bibliography related to the study of colour vision using the PubMed search tool, the most used tests in clinical practice were selected according to their frequency of use and the purpose for which they were applied. A bibliographic study was then carried out on each particular test according to the design of the shown stimuli, its target population, and its sensitivity and specificity. Results: From the 95 publications found using the PubMed search tool, in 41 of them, colour tests were used by researchers in their methodology. From the 64 colour tests used, 19 of them were different (with 4 of them being different tests adapted by research groups, and 2 of them carried out online). The most used tests were the following: Ishihara test (10.88%), Farnsworth-Munsell (7.04%), Farnsworth-Munsell 100 Hue (6.4%), Cambridge Colour Test (3.84%), Hardy-Rand-Rittler (3.2%), tests developed by the groups (2.56%), the Anomaloscope (1.28%), the online tests (1.28%) and, finally, Colour Assessment and Diagnosis (0.64%), Pflüger Trident Colour Plates (0.64%), Toothguide Training Box (0.64%), Lanthony Desaturated D-15 (0.64%), City University Test (0.64%), Universal Colour Discrimination Test (0.64%), and Rabin Cone Contrast Test (0.64%). Conclusions: The Anomaloscope is the "gold standard" in terms of colour vision testing, despite its incompatibility with daily clinical practice. It is fairly complex to use, difficult to understand for children, and its practice requires having the time available. Nevertheless, it is possible to reach an accurate approximation through the combination of some of the tests listed in this article. The above mentioned tests are a good alternative to determine the presence of dyschromatopsia in settings closer to daily clinical practice or in less controlled settings than a clinical study. The major drawback among the wide range of tests available for the study of colour vision is the difficulty to compare results between tests, since units of the reported data are usually different, and experience is required for its correct interpretation. Currently, there is no consensus on which colour test is the most complete. It is, therefore, advisable to use at least 2 tests in order to ensure diagnoses, and have more extensive information about the visual perception of patients
Subject(s)
Humans , Color Perception Tests/methods , Color Vision Defects/diagnosis , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To evaluate the clinical characteristics, prevalence and factors associated with delirium in critical patients from 5 to 14 years of age. DESIGN: An analytical, cross-sectional observational study was made. Delirium was assessed with the Pediatric-Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU) and motor classification was established with the Delirium Rating Scale Revised-98. SETTING: A pediatric Intensive Care Unit. PATIENTS: All those admitted over a one-year period were assessed during the first 24-72h, or when possible in deeply sedated patients. EXCLUSION CRITERIA: Patients in stupor or coma, with severe communication difficulty, subjected to deep sedation throughout admission, and those with denied consent. RESULTS: Twenty-nine of the 156 assessed patients suffered delirium (18.6%) and 55.2% were hypoactive. The neurocognitive alterations evaluated by the pCAM-ICU were similar in the three motor groups. Intellectual disability (OR=17.54; 95%CI: 3.23-95.19), mechanical ventilation (OR=18.80; 95%CI: 4.29-82.28), liver failure (OR=54.88; 95%CI: 4.27-705.33), neurological disease (OR=4.41; 95%CI: 1.23-15.83), anticholinergic drug use (OR=3.23; 95%CI: 1.02-10.26), different psychotropic agents (OR=4.88; 95%CI: 1.42-16.73) and tachycardia (OR=4.74; 95%CI: 1.21-18.51) were associated to delirium according to the logistic regression analysis. CONCLUSION: The frequency of delirium and hypoactivity was high. It is therefore necessary to routinely evaluate patients with standardized instruments. All patients presented with important neurocognitive alterations. Several factors related with the physiopathology of delirium were associated to the diagnosis; some of them are modifiable through the rationalization of medical care.