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OBJECTIVE: To promote antimicrobial stewardship, many institutions have implemented a policy of reflexing to a urine culture based on a positive urinalysis result. The rehabilitation patient population, including individuals with brain and spinal cord injuries, may have atypical presentations of urinary tract infections. The study objective is to determine the effects of implementing a urine culture reflex policy in this specific patient population. DESIGN: In an inpatient rehabilitation unit, 348 urinalyses were analyzed from August 2019 to June 2021. Urinalysis with greater than or equal to 10 white blood cells per high power field was automatically reflexed to a urine culture in this prospective study. Primary outcome was return to acute care related to urinary tract infection. Secondary outcomes included adherence to reflex protocol, antibiotic utilization and appropriateness, adverse outcomes related to antibiotic use, and reduction in urine cultures processed and the associated reduction in healthcare costs. RESULTS: There was no statistically significant difference before and after intervention related to the primary outcome. Urine cultures processed were reduced by 58% after intervention. CONCLUSIONS: Urine culture reflex policy is likely an effective intervention to reduce the frequency of urine cultures without significantly affecting the need to transfer patients from inpatient rehabilitation back to the acute care setting.
Assuntos
Urinálise , Infecções Urinárias , Humanos , Projetos Piloto , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Gestão de Antimicrobianos , Adulto , Antibacterianos/uso terapêutico , Pacientes Internados , Centros de Reabilitação , IdosoRESUMO
Optimization of flow cytometry assays for extracellular vesicles (EVs) often fail to include appropriate reagent titrations - the most critically antibody titration is either not performed or is incomplete. Using nonoptimal antibody concentration is one of the main sources of error leading to a lack of reproducible data. Antibody titration for the analysis of antigens on the surface of EVs is challenging for a variety of technical reasons. Using platelets as surrogates for cells and platelet-derived particles as surrogates for EV populations, we demonstrate our process for antibody titration, highlighting some of the key analysis parameters that may confound and surprise new researchers moving into the field of EV research. Additional care must be exercised to ensure instrument and reagent controls are utilized appropriately. Complete graphical analysis of positive and negative signal intensities, concentration, and separation or stain index data is highly beneficial when paired with visual analysis of the cytometry data. Using analytical flow cytometry procedures optimized for cells for EV analysis can lead to misleading and nonreproducible results.
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Vesículas Extracelulares , Plaquetas , Citometria de Fluxo/métodos , CorantesRESUMO
Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a behavioral phenomenon termed "incubation of craving." Mechanistic studies of incubation of craving have focused on specific neurobiological targets within preselected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now allow unbiased brain-wide cellular resolution mapping of regions and circuits engaged during learned behaviors. However, these whole-brain imaging approaches were developed for mouse brains, while incubation of drug craving has primarily been studied in rats, and incubation of food craving has not been demonstrated in mice. Here, we established a mouse model of incubation of palatable food craving and examined food reward seeking after 1, 15, and 60 abstinence days. We then used the neuronal activity marker Fos with intact-brain mapping procedures to identify corresponding patterns of brain-wide activation. Relapse to food seeking was significantly higher after 60 abstinence days than after 1 or 15 days. Using unbiased ClearMap analysis, we identified increased activation of multiple brain regions, particularly corticostriatal structures, following 60 but not 1 or 15 abstinence days. We used orthogonal SMART2 analysis to confirm these findings within corticostriatal and thalamocortical subvolumes and applied expert-guided registration to investigate subdivision and layer-specific activation patterns. Overall, we 1) identified brain-wide activity patterns during incubation of food seeking using complementary analytical approaches and 2) provide a single-cell resolution whole-brain atlas that can be used to identify functional networks and global architecture underlying the incubation of food craving.
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Fissura , Metanfetamina , Animais , Camundongos , Encéfalo , Fissura/fisiologia , Sinais (Psicologia) , Comportamento de Procura de Droga/fisiologia , Alimentos , Recidiva , AutoadministraçãoRESUMO
PURPOSE: Fatal pedestrian collisions are over-represented at night and poor conspicuity is believed to be a leading causative factor. Retro-reflective clothing enhances pedestrian conspicuity, particularly when placed in a biological motion or "biomotion" configuration. In this study, we explored how various retro-reflective clothing configurations affected the ability to judge the direction of a pedestrian walking across the road, which has important implications for collision avoidance. METHODS: Participants included 21 young drivers (mean age 21.6⯱â¯2.0â¯years) with normal vision. A closed-road circuit was used to assess the accuracy of drivers' judgement of the direction of walking of a pedestrian at night-time wearing one of five different clothing configurations: four with retro-reflective materials placed in different locations (Biomotion, Legsâ¯+â¯Torso, Torso Only, Legs Only), and a control wearing only black clothing (Street). Participants were seated in a stationary vehicle with low beam headlamps, 135â¯m from a pedestrian, who walked across the road from both sides, in different directions (towards the car, straight across the road, or away from the car). Outcome measures included drivers' response accuracy and confidence ratings for judging pedestrian walking direction. RESULTS: Accuracy in judging pedestrian walking direction differed significantly across the clothing configurations (pâ¯<â¯0.001). Response accuracy was significantly higher for the Biomotion configuration (80% correct), compared to the other retro-reflective (Legsâ¯+â¯Torso 64%; Torso Only 53%; Legs Only 50%) and Street configurations (33%). Similar trends were noted for confidence ratings across the clothing conditions, yet the relationship between confidence ratings and response accuracy within each clothing configurations was poor. CONCLUSIONS: The use of retro-reflective clothing in a biomotion configuration facilitated the highest accuracy and confidence in drivers' judgment of pedestrian walking direction, compared to other configurations. These findings highlight the importance of using biomotion clothing for pedestrians at night, to not only facilitate drivers' earlier recognition of pedestrians, but also increase their accuracy in determining the walking direction of pedestrians as they cross the road. Practical applications: The use of clothing incorporating retro-reflective material in a biomotion configuration for pedestrians crossing roads at night provides enhanced cues for drivers regarding the presence and walking direction of pedestrians.
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Acidentes de Trânsito/prevenção & controle , Condução de Veículo/psicologia , Vestuário , Julgamento , Pedestres/estatística & dados numéricos , Feminino , Humanos , Masculino , Queensland , Percepção Visual , Caminhada , Adulto JovemRESUMO
PURPOSE: To evaluate the wear resistance of a recently developed three-dimensional (3D) printed denture teeth resin compared to three commercially available prefabricated denture teeth. MATERIALS AND METHODS: A total of 88 maxillary first molar denture teeth were evaluated: C (Classic; Dentsply Sirona, York, PA), DCL (SR Postaris DCL; Ivoclar Vivadent, Schaan, Liechtenstein), IPN (Portrait IPN; Dentsply Sirona, York, PA), and F (Denture Teeth A2 Resin 1 L; Formlabs, Somerville, MA). The 3D printed denture tooth specimens were fabricated from a methacrylate-based photopolymerizing resin using stereolithography (SLA). Denture teeth were subjected to a three-body wear test with a poly(methylmethacrylate) (PMMA) abrasive slurry. A Leinfelder-style four station wear apparatus with custom bullet-shaped milled zirconia styli was utilized with a load force of 36-40 N at 1.7 Hz for 200,000 cycles. Maximum depth of wear was measured using a lab grade scanner and analyzing software program. Data were analyzed using a one-way ANOVA followed by the Tukey's Multiple Comparisons post hoc test (α = 0.05). RESULTS: A statistically significant difference in depth of wear was found between denture tooth materials (p < 0.001). The mean vertical depth of wear for the 3D printed denture teeth (0.016 ± 0.010 mm) was statistically significantly less than the prefabricated denture teeth. The highly cross-linked denture teeth, DCL (0.036 ± 0.011 mm) and IPN (0.035 ± 0.014 mm), exhibited statistically significantly less wear than the conventional acrylic denture teeth. The conventional acrylic denture teeth demonstrated the greatest wear (0.058 ± 0.014 mm). No significant difference in depth of wear was found between DCL and IPN (p > 0.001). CONCLUSIONS: Denture tooth material significantly influences the depth of wear. The 3D printed denture teeth demonstrated superior wear resistance compared to the commercially available prefabricated denture teeth when opposed to zirconia. Denture teeth fabricated with SLA technology may have a promising future in prosthetic dentistry.
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Desgaste de Restauração Dentária , Dentaduras , Teste de Materiais , Impressão Tridimensional , Propriedades de Superfície , ZircônioRESUMO
PURPOSE: to estimate the prevalence of depression at 4-week postpartum using the Edinburgh postpartum Depression Scale (EPDS) in women who delivered in a public maternity hospital in Argentina. METHODS: This prospective cohort study was carried out from March to August 2016 in northwest Argentina. Eligibility included delivering a singleton live birth 28 weeks of gestational age or over, 18 years or older and resided within 1h from the maternity hospital. Women were excluded if they or their newborn were in the intensive care unit. We defined a positive screening as an EPDS score of 10 or higher or a positive response to item 10, which indicates thoughts of self-harm. RESULTS: A total of 587 women were enrolled and 539 women completed the home visit interview and the EPDS. A total of 167 (31.0%, 95% CI 27.1-35.1) mothers screened positive in the EPDS using a score ≥ 10 and 99 (18.4%, 95% CI 15.1-21.6%) using a score ≥ 13, which indicate increased severity of depressive symptoms. In both cases, the 23 (4.3%) women that responded as having thoughts of self-harm were included. CONCLUSION: Nearly a third of women who participated had depressive symptoms at four weeks postpartum in a public hospital in Tucumán, Argentina. Socio-demographic, particularly personal psychiatric history, factors and social and cultural influences can impact results. Our results highlight the need for improved screening and better diagnostic tool for women with postpartum depression in Argentina and to investigate the impact of postpartum depressive symptoms on women's health and their families.
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Depressão Pós-Parto/psicologia , Cuidado Pós-Natal/psicologia , Período Pós-Parto/psicologia , Ideação Suicida , Adulto , Argentina , Depressão , Feminino , Humanos , Recém-Nascido , Mães/psicologia , Gravidez , Prevalência , Estudos Prospectivos , Comportamento Autodestrutivo/psicologia , Adulto JovemRESUMO
Disc degeneration is a common medical affliction whose origins are not fully understood. An improved understanding of its underlying mechanisms could lead to the development of more effective treatments. The aim of this paper was to investigate the effect of (1) degeneration, (2) circumferential region and (3) strain rate on the microscale mechanical properties (toe region modulus, linear modulus, extensibility, phase angle) of individual fibre bundles in the anulus fibrosus lamellae of the human intervertebral disc. Healthy and degenerate fibre bundles excised from different circumferential regions in the outer anulus (posterolateral, lateral, anterolateral, anterior) were tensile tested at slow (0.1%/s), medium (1%/s) and fast (10%/s) strain rates using a micromechanical testing system. Our preliminary results showed that neither degeneration nor circumferential region significantly affected the fibre bundles' mechanical behaviour. However, when the fibre bundles were tested at higher strain rates, this resulted in significantly higher linear moduli and lower phase angles. These findings, compared with data from other studies investigating single and multiple lamellae sections, suggest that degeneration has minimal effect on outer anulus mechanics irrespective of structural level, and the inter- and intra-lamellar arrangement and continuity of the fibre bundles may influence the lamellae's regional behaviour and viscoelasticity.
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Anel Fibroso/fisiologia , Disco Intervertebral/fisiologia , Vértebras Lombares/fisiologia , Região Lombossacral/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Humanos , Pessoa de Meia-Idade , Estresse Mecânico , Resistência à Tração , Viscosidade , Adulto JovemRESUMO
OBJECTIVES: The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). STUDY DESIGN AND SETTING: Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic sources (clinical study reports [CSRs] and individual participant data [IPD]). RESULTS: We found 21 gabapentin RCTs (74 reports, 6 IPD) and 7 quetiapine RCTs (50 reports, 1 IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains "pain intensity" (gabapentin) and "depression" (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD] = -0.45; 95% confidence interval [CI]: -0.63 to -0.27) to ineffective (SMD = -0.06; 95% CI: -0.24 to 0.12). We could change the effect for depression from a medium effect (SMD = -0.55; 95% CI: -0.85 to -0.25) to a small effect (SMD = -0.26; 95% CI: -0.41 to -0.1). CONCLUSIONS: Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.
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Viés , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Aminas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Gabapentina , Humanos , Metanálise como Assunto , Neuralgia/tratamento farmacológico , Fumarato de Quetiapina/uso terapêutico , Resultado do Tratamento , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
Reconstruction of the eyelid remains challenging due to the unique properties of the tarsal plate, which is a fibrocartilagenous structure within the eyelid providing structural support and physical form. There are no previous studies investigating the biomechanical properties of tarsus tissue, which is vital to the success of bioengineered tarsal substitutes. We therefore aimed to determine the biomechanical properties of human tarsus tissue, and used a CellScale BioTester 5000 (CellScale, Waterloo, Canada) to perform uniaxial tensile tests on ten samples of healthy eyelid tarsus. All samples were tested 'fresh' within two hours of harvest. A tensile preload of 50 mN was applied for 10 min before the sample was subjected to uniaxial tension under linear ramp displacement control. Maximum strain was 30% of the original tissue length and thirty dynamic cycles were performed at a strain rate of 1%/s using a triangular waveform. Of the samples tested, the mean (SD) width was 5.51 mm (1.45 mm) whilst mean thickness was 1.6mm (0.51 mm). The mean toe modulus was 0.14 (0.10) MPa, elastic modulus was 1.73 (0.61) MPa, with an extensibility of 15.8 (2.1)%, and phase angle of 6.4° (2.4)°. After adjusting for the initial tissue slack, the maximum strain ranged from 23.8% to 30.0%. At maximum strain, it was observed that the linear region of the stress-strain curve was reached without the sample slipping out of the clamps. Our results establish a benchmark for native tarsus tissue, which can be used when evaluating tissue engineered tarsal substitutes in the future.
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Pálpebras/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Módulo de Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Death receptor-dependent apoptosis is an important mechanism of growth control. It has been demonstrated that Ras association domain family protein 1A (RASSF1A) is a tumor suppressor protein involved in death receptor-dependent apoptosis. However, it is unclear how RASSF1A-mediated cell death is initiated. We have now detailed 14-3-3 dependent regulation of RASSF1A-mediated cell death. We demonstrate that basal association of RASSF1A with 14-3-3 was lost following stimulation with tumor necrosis factor alpha (TNFalpha) or TNFalpha related apoptosis inducing ligand (TRAIL). Subsequent to the loss of 14-3-3 association, RASSF1A associated with modulator of apoptosis (MOAP-1) followed by death receptor association with either TNFalpha receptor 1 (TNF-R1) or TRAIL receptor 1 (TRAIL-R1). 14-3-3 association required basal phosphorylation by the serine/threonine kinase, glycogen synthase kinase 3beta (GSK-3beta), on serine 175, 178, and 179. Mutation of these critical serines resulted in the loss of 14-3-3 association and earlier recruitment of RASSF1A to MOAP-1, TNF-R1, and TRAIL-R1. Furthermore, stable cells containing a triple serine mutant of RASSF1A [serine (S) 175 to alanine (A) [S175A], S178A, and S179A] resulted in increased basal cell death, enhanced Annexin V staining and enhanced cleavage of poly (ADP-ribose) polymerase (PARP) following TNFalpha stimulation when compared to stable cells containing wild type RASSF1A. RASSF1A-mediated cell death is, therefore, tightly controlled by 14-3-3 association.
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Proteínas 14-3-3/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Proteínas Reguladoras de Apoptose/metabolismo , Sítios de Ligação , Morte Celular , Linhagem Celular Tumoral , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Cinética , Modelos Biológicos , Dados de Sequência Molecular , Proteínas Mutantes/metabolismo , Fosforilação , Ligação Proteica , Receptores de Morte Celular/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Proteínas Supressoras de Tumor/químicaRESUMO
BACKGROUND: There are virtually no controlled data suggesting that concomitant psychotropic medications (CPMs) improve outcome in schizophrenia after the acute phase. Despite that, polypharmacy (with all of its disadvantages) is far more common than monotherapy. To our knowledge, there have been no published reports of prospective systematic investigations of the efficacy of unrestricted CPM use in nonacute schizophrenia. METHOD: This was a naturalistic, systematic study using a sample of 53 stabilized patients with DSM-IV-TR schizophrenia from 1 clinical practice setting including both private patients and patients from controlled research studies of the effectiveness of antipsychotics. Since there are meager controlled or systematic data on the effectiveness of CPM use with antipsychotics in nonacute schizophrenia, we tested the clinical strategy of CPM use by gradually tapering all CPMs (except antianxiety agents). The aim was to determine if the CPM improved outcome, had no effect, or worsened outcome using the Clinical Global Impressions-Improvement scale before and after taper, over at least 3 months and in some cases up to 18 months after discontinuation. Data were gathered from July 2002 to June 2005. RESULTS: For 21 patients undergoing 22 antidepressant tapers, no change was noted in 18 of 22 tapers, while in 3 improvement was noted and in 1 worsening was noted. For the 12 patients on treatment with mood stabilizers, no change was noted in 10 of 13 discontinuations, while in 3 mild worsening was noted. One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation. CONCLUSION: For most stabilized, chronic patients with schizophrenia, tapering adjunctive medications did not change outcome. This naturalistic study further defines the limits of efficacy of some concomitant classes of medications in patients with chronic schizophrenia who are already receiving adequate antipsychotic therapy.