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The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a 'second space age'. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, and encompass multi-omic, single-cell and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics, as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this Perspective, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration, Japan Aerospace Exploration Agency, European Space Agency and other space agencies, and detail the entrance of the commercial spaceflight sector (including SpaceX, Blue Origin, Axiom and Sierra Space) into aerospace medicine and space biology, the first aerospace medicine biobank, and various upcoming missions that will utilize these tools to ensure a permanent human presence beyond low Earth orbit, venturing out to other planets and moons.
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Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiological and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.
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BACKGROUND: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. METHODS: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. RESULTS: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. CONCLUSIONS: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).
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COVID-19/terapia , Progressão da Doença , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/complicações , COVID-19/imunologia , COVID-19/mortalidade , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Imunização Passiva , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Método Simples-Cego , Falha de Tratamento , Adulto Jovem , Soroterapia para COVID-19RESUMO
Silica-supported amine absorbents, including materials produced by tethering aminosilanes or infusion of poly(ethyleneimine), represent a promising class of materials for CO2 capture applications, including direct air and point source capture. Various silica surface treatments and functionalization strategies are explored to enhance stability and CO2 uptake in amine-based solid sorbent systems. Here, the synthesis and characterization of novel vinyltrimethoxysilane-treated Santa Barbara Amorphous-15 (SBA-15) supports and the corresponding enhancement in CO2 uptake compared to various SBA-15-based control supports are presented. The relationship between CO2 diffusion and amine efficiency in these systems is explored using a previously reported kinetic model. The synthesized materials are characterized with CO2 and H2O isotherms, diffuse reflectance infrared Fourier transform spectroscopy, 1H T1-T2 relaxation correlation NMR, and rapid thermal cycling experiments. The novel support materials are shown to enable high amine efficiencies, approaching a fourfold improvement over standard SBA-15-supported amines, while simultaneously exhibiting excellent stability when cycled rapidly under humid conditions. As the poly(ethyleneimine) loadings are held constant across the various samples, enhancements in CO2 uptake are attributed to differences in the way the poly(ethyleneimine) interacts with the support surface.
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ConspectusSolid-supported amines are a promising class of CO2 sorbents capable of selectively capturing CO2 from diverse sources. The chemical interactions between the amine groups and CO2 give rise to the formation of strong CO2 adducts, such as alkylammonium carbamates, carbamic acids, and bicarbonates, which enable CO2 capture even at low driving force, such as with ultradilute CO2 streams. Among various solid-supported amine sorbents, oligomeric amines infused into oxide solid supports (noncovalently supported) are widely studied due to their ease of synthesis and low cost. This method allows for the construction of amine-rich sorbents while minimizing problems, such as leaching or evaporation, that occur with supported molecular amines.Researchers have pursued improved sorbents by tuning the physical and chemical properties of solid supports and amine phases. In terms of CO2 uptake, the amine efficiency, or the moles of sorbed CO2 per mole of amine sites, and uptake rate (CO2 capture per unit time) are the most critical factors determining the effectiveness of the material. While structure-property relationships have been developed for different porous oxide supports, the interaction(s) of the amine phase with the solid support, the structure and distribution of the organic phase within the pores, and the mobility of the amine phase within the pores are not well understood. These factors are important, because the kinetics of CO2 sorption, particularly when using the prototypical amine oligomer branched poly(ethylenimine) (PEI), follow an unconventional trend, with rapid initial uptake followed by a very slow, asymptotic approach to equilibrium. This suggests that the uptake of CO2 within such solid-supported amines is mass transfer-limited. Therefore, improving sorption performance can be facilitated by better understanding the amine structure and distribution within the pores.In this context, model solid-supported amine sorbents were constructed from a highly ordered, mesoporous silica SBA-15 support, and an array of techniques was used to probe the soft matter domains within these hybrid materials. The choice of SBA-15 as the model support was based on its ordered arrangement of mesopores with tunable physical and chemical properties, including pore size, particle lengths, and surface chemistries. Branched PEIâthe most common amine phase used in solid CO2 sorbentsâand its linear, low molecular weight analogue, tetraethylenepentamine (TEPA), were deployed as the amine phases. Neutron scattering (NS), including small angle neutron scattering (SANS) and quasielastic neutron scattering (QENS), alongside solid-state NMR (ssNMR) and molecular dynamics (MD) simulations, was used to elucidate the structure and mobility of the amine phases within the pores of the support. Together, these tools, which have previously not been applied to such materials, provided new information regarding how the amine phases filled the support pores as the loading increased and the mobility of those amine phases. Varying pore surface-amine interactions led to unique trends for amine distributions and mobility; for instance, hydrophilic walls (i.e., attractive to amines) resulted in hampered motions with more intimate coordination to the walls, while amines around hydrophobic walls or walls with grafted chains that interrupt amine-wall coordination showed recovered mobility, with amines being more liberated from the walls. By correlating the structural and dynamic properties with CO2 sorption properties, novel relationships were identified, shedding light on the performance of the amine sorbents, and providing valuable guidance for the design of more effective supported amine sorbents.
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BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
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Cannabis , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Depressão/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/complicações , PsicopatologiaRESUMO
BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
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Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.
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Medo , Transtornos de Estresse Pós-Traumáticos , Humanos , Estudos Longitudinais , Medo/fisiologia , Tonsila do Cerebelo , Giro do Cíngulo/patologia , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/patologiaRESUMO
Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.
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PURPOSE: To investigate the clinical effectiveness of endoscopic iliopsoas tendon release (IPR) at the lesser trochanter (LT) in patients with iliopsoas impingement (IPI) after total hip arthroplasty (THA). METHODS: Between November 2017 and March 2021, a consecutive series of 36 patients were treated with endoscopic IPR for diagnosed IPI. Patients included had acetabular cup position confirmed by functional imaging (OPS, Corin, Pymble, NSW), typical clinical symptoms of IPI, and a positive response to diagnostic injection. Clinical assessment included validated patient-reported outcome measures (PROMs) along with hip flexion strength and active range of motion at different time marks up to 2-year follow-up, as well as surgical complications. RESULTS: Overall, 36 consecutive patients (11 males) with a mean age of 62 ± 12 years were included. All patients had failed nonoperative management. Dynamic computed tomography assessment was available in 89% of the patients, edge loading was reported in 10%, and variable cup overhang was reported in 50%. Clinically, PROMs were significantly improved at every time mark when compared with preoperative values (P < .001), showing the biggest improvement within the first 4 weeks after surgery. At the 6-month follow-up, peak isometric hip flexion strength on the operated side was 20% lower than the contralateral side (P < .001). Failure rate of the procedure was 2.8% (1 case). Linear regression showed no association between cup overhang and clinical outcomes. CONCLUSIONS: Endoscopic IPR at the LT is a safe and reproducible technique associated with significant and immediate improvement in pain, functional outcomes, and high patient satisfaction. With minimal short-term weakness, no complications, and only a single revision, even in cases with cup malposition and/or edge loading, we believe that endoscopic IPR can be considered as one of the first-line operative options in patients with symptomatic IPI, irrespective of component position. LEVEL OF EVIDENCE: Level IV, case series.
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Artroplastia de Quadril , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Artroplastia de Quadril/efeitos adversos , Tenotomia/métodos , Seguimentos , Músculos Psoas , Quadril/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Articulação do Quadril/cirurgiaRESUMO
BACKGROUND: Hip periprosthetic fractures (PPFs) after primary total hip arthroplasty are increasing with the number of primary implants and aging population. Mortality has been reported up to 34% at 1-year. The aim of this study was to evaluate the association of Clinical Frailty Scale (CFS) and 1-year mortality, complication rate, and length of stay (LOS) in surgically managed hip PPFs. METHODS: This was a retrospective study of prospectively collected data from January 2008 to January 2021. A total of 282 surgically managed hip PPFs were identified. Mean age was 79 years (range, 42 to 106). Preoperative scores were analyzed through linear regression to identify significant association with mortality, complication and LOS. Receiver operating characteristic curve and Area Under the Curve (AUC) were generated to evaluate the quality of the models and the discriminatory ability of each clinical score. Significance was considered at P values < .05. RESULTS: Mortality was 7.8% at 3-months and 15.7% at 1-year. Complication rate requiring surgery was 19.5% and mean LOS was 8.9 ± 7 days. The CFS was significantly associated with 3-month (odds ratio 2.23, P < .001) and 1-year mortality (odds ratio 2.01, P < .001). The receiver operating characteristic curve test for 1-year mortality showed a greater AUC for the CFS when compared with American Society for Anesthesiologists score and age-adjusted Charlson Comorbidity Index (AUC 0.80 versus 0.68 versus 0.72, respectively). CONCLUSIONS: Frailty is a syndrome with increased risk of mortality after surgically managed PPF. The CFS can be easily assessed at the time of admission and could be considered as a strong and reliable predictor of 1-year mortality with a greater AUC than the conventionally used American Society for Anesthesiologists score.
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BACKGROUND: We investigated if the use of augmented tibial fixation with stems in primary total knee arthroplasty (TKA) in obese patients was associated with a difference in reason for revision, type of revision, or overall revision rate. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry compared reason for revision, rate, and type of revision between primary TKA using stemmed tibial prostheses to nonstemmed prostheses, stratified by body mass index (BMI) and obesity. The cumulative percent revision was obtained using the Kaplan-Meier method, and Cox proportional hazards models estimated hazard ratios (HRs) adjusted for age and sex with 95% confidence intervals (CIs). All tests were 2-tailed at 5% statistical significance (P < .05). There were 66,508 procedures available for analyses. RESULTS: Obese class 2 (BMI 35 to 39.99) had higher rates of revision in the stemmed group compared to the nonstemmed group (HR 1.44, 95% CI 1.00, 2.05, P = .047). There was no significant difference in revision rates between stemmed and nonstemmed tibial prostheses in any other BMI group. Primary TKA in obese patients (BMI ≥30) with a stem extension had a significantly higher rate of minor revisions compared to no stem extension (HR 1.31, 95% CI 1.03, 1.66, P = .025). There was no significant difference between stemmed and nonstemmed groups for major revision in obese patients and for minor or major revision in nonobese patients. CONCLUSION: Using a tibial stem during primary TKA in obese patients is not associated with a lower rate of revision.
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Artroplastia do Joelho , Prótese do Joelho , Humanos , Artroplastia do Joelho/métodos , Reoperação , Austrália/epidemiologia , Obesidade/complicações , Sistema de Registros , Falha de Prótese , Resultado do TratamentoRESUMO
BACKGROUND: We compared revision rates and reasons for revision for primary total knee arthroplasty (TKA) performed for osteoarthritis with and without tibial stem extensions. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry were used to compare all-cause revision, reason, and type of revision between primary TKA using stemmed tibial prostheses and non-stemmed prostheses. RESULTS: All-cause revision for TKA with stem extension was higher for the first 6 months (hazard ratio [HR] 1.47; 95% confidence interval [CI]1.19 to 1.82; P < .001); while after 1.5 years TKA with stem extension had a lower rate of revision (HR 0.84; 95% CI 0.73 to 0.97; P = .01). Stemmed components were more likely to be revised for infection between 3 months and 1.5 years after surgery (HR 1.39; 95% CI 1.05 to 1.83; P = .02). The revision rate for aseptic loosening was lower in the stemmed group beyond 2 years (HR = 0.45; 95% CI 0.31 to 0.63; P < .001). Insert-only revision was higher in the stemmed group at all times (HR = 1.42; 95% CI 1.21 to 1.66, P < .001). Isolated tibial component revision was lower in the stemmed group at all times (HR 0.47; 95% CI 0.29 to 0.74; P = .001). Aseptic loosening for tibial component-only revision was significantly lower in the stemmed group at all times (HR 0.23; 95% CI 0.11 to 0.50; P < .001). CONCLUSIONS: Patients undergoing primary stemmed TKA have lower rates of all-cause revision beyond 1.5 years and tibial component-only revision at all times. Further investigation is required to preoperatively select patients that benefit from augmentation with stems.
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Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Falha de Prótese , Sistema de Registros , Reoperação , Humanos , Artroplastia do Joelho/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Austrália , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Desenho de Prótese , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Secondary patella resurfacing is often performed for dissatisfaction following primary knee arthroplasty where the native patella was retained. The purpose of this meta-analysis was to evaluate outcomes of secondary patella resurfacing. METHODS: The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting on patients who underwent secondary patella resurfacing after previous primary knee arthroplasty with retention of the native patella were considered eligible. The risk of bias was assessed using the Methodological Index for Non-Randomized studies tool. A random-effects model and the inverse-variance weighting method was used for meta-analysis. There were sixteen retrospective studies including 604 knees (594 patients) with a mean follow up of 42 months (range, 2 to 197). RESULTS: An overall improvement in patient-reported outcomes (PROMs) was achieved in 53% of cases from pooled data available for 293 knees [95% Confidence Interval (CI) (0.44, 0.62), I2=68% - moderate heterogeneity]. The pooled proportion of patients satisfied with the procedure was 59% [95% CI (48, 68), I2 = 70% - moderate heterogeneity] in a sample size of 415. There was a minimal rate (2%) of complication incidence when performing secondary patella resurfacing and a pooled rate of revision surgery of 10%. CONCLUSIONS: An improvement in pain, satisfaction, and PROMs was achieved in slightly more than half of the patients following secondary patella resurfacing. However, studies lacked standardized objective selection criteria for the procedure and the available data was predominantly retrospective, with high heterogeneity and variation in outcome reporting.
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Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Patela/cirurgia , Estudos Retrospectivos , Dor/cirurgia , Reoperação , Resultado do Tratamento , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgiaRESUMO
PURPOSE: This study aimed to optimize cement application techniques in fully cemented primary total knee arthroplasty (TKA) by comparing the effects of two different approaches: cement on bone surface (CoB) versus cement on bone surface and implant surface (CoBaI) on the short-term presence of radiolucent lines (RLL) as indicators of potential complications. METHODS: In this monocentric study, a total of 379 fully cemented primary TKAs (318 patients) were included. The two study groups were differentiated by the technique of cement application: CoB group (cement applied only on bone surface) and CoBaI group (cement applied on both bone surface and implant surface). The presence of RLL or osteolysis was evaluated using the updated Knee Society Radiographic Evaluation System. RESULTS: In the whole study population, RLL were present in 4.7% of cases, with a significantly higher incidence in the CoBaI group (10.5%) at the 4-week follow-up. At the 12-month follow-up, RLL were observed in 29.8% of TKAs in the CoBaI group, while the incidence was lower in the CoB group (24.0%) (not statistically significant). There were two revisions in each group, none of which were due to aseptic loosening. CONCLUSION: The findings of this study suggest that the application of bone cement on bone surface only (CoB) may be more beneficial than applying it on both bone surface and implant surface (CoBaI) in terms of short-term presence of RLL in fully cemented primary TKA. Long-term results, especially with regard to aseptic loosening, will be of interest and may provide valuable guidance for future directions in bone cement applications in TKA.
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Artroplastia do Joelho , Prótese do Joelho , Humanos , Artroplastia do Joelho/métodos , Cimentos Ósseos , Seguimentos , RadiografiaRESUMO
Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.
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A variety of amine-impregnated porous solid sorbents for direct air capture (DAC) of CO2 have been developed, yet the effect of amine-solid support interactions on the CO2 adsorption behavior is still poorly understood. When tetraethylenepentamine (TEPA) is impregnated on two different supports, commercial γ-Al2O3 and MIL-101(Cr), they show different trends in CO2 sorption when the temperature (-20 to 25 °C) and humidity (0-70% RH) of the simulated air stream are varied. In situ IR spectroscopy is used to probe the mechanism of CO2 sorption on the two supported amine materials, with weak chemisorption (formation of carbamic acid) being the dominant pathway over MIL-101(Cr)-supported TEPA and strong chemisorption (formation of carbamate) occurring over γ-Al2O3-supported TEPA. Formation of both carbamic acid and carbamate species is enhanced over the supported TEPA materials under humid conditions, with the most significant enhancement observed at -20 °C. However, while equilibrium H2O sorption is high at cold temperatures (e.g., -20 °C), the effect of humidity on a practical cyclic DAC process is expected to be minimal due to slow H2O uptake kinetics. This work suggests that the CO2 capture mechanisms of impregnated amines can be controlled by adjusting the degree of amine-solid support interaction and that H2O adsorption behavior is strongly affected by the properties of the support materials. Thus, proper selection of solid support materials for amine impregnation will be important for achieving optimized DAC performance under varied deployment conditions, such as cold (e.g., -20 °C) or ambient temperature (e.g., 25 °C) operations.
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Short-interfering RNA (siRNA) oligonucleotide therapeutics that modify gene expression by accessing RNA-interference (RNAi) pathways have great promise for the treatment of a range of disorders; however, their application in clinical settings has been limited by significant challenges in cellular delivery. Herein, we report a structure-function study using a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) to determine the impact of peptide sequence on (1) siRNA-binding efficiency, (2) cellular delivery and knockdown efficiency, and (3) the endocytic uptake mechanism. Nine cyclic peptides of the general sequence Ac-C[XZ]4CG-NH2 in which X residues are hydrophobic/aromatic (Phe, Tyr, Trp, or Leu) and Z residues are charged/hydrophilic (Arg, Lys, Ser, or Glu) are assessed along with one acyclic peptide, Ac-(WR)4G-NH2. Cyclization is enforced by intramolecular disulfide bond formation between the flanking Cys residues. Binding analyses indicate that strong cationic character and the presence of aromatic residues that are competent to participate in CH-π interactions lead to CAP sequences that most effectively interact with siRNA. CAP-siRNA binding increases in the following order as a function of CAP hydrophobic/aromatic content: His < Phe < Tyr < Trp. Both cationic charge and disulfide-constrained cyclization of CAPs improve uptake of siRNA in vitro. Net neutral CAPs and an acyclic peptide demonstrate less-efficient siRNA translocation compared to the cyclic, cationic CAPs tested. All CAPs tested facilitated efficient siRNA target gene knockdown of at least 50% (as effective as a lipofectamine control), with the best CAPs enabling >80% knockdown. Significantly, gene knockdown efficiency does not strongly correlate with CAP-siRNA internalization efficiency but moderately correlates with CAP-siRNA-binding affinity. Finally, utilization of small-molecule inhibitors and targeted knockdown of essential endocytic pathway proteins indicate that most CAP-siRNA nanoparticles facilitate siRNA delivery through clathrin- and caveolin-mediated endocytosis. These results provide insight into the design principles for CAPs to facilitate siRNA delivery and the mechanisms by which these peptides translocate siRNA into cells. These studies also demonstrate the nature of the relationships between peptide-siRNA binding, cellular delivery of siRNA cargo, and functional gene knockdown. Strong correlations between these properties are not always observed, which illustrates the complexity in the design of optimal next-generation materials for oligonucleotide delivery.
Assuntos
Peptídeos Penetradores de Células , Peptídeos Cíclicos , Peptídeos Cíclicos/química , RNA Interferente Pequeno/química , Técnicas de Silenciamento de Genes , Peptídeos Penetradores de Células/química , Oligonucleotídeos , DissulfetosRESUMO
Chronic sleep restriction, common in today's 24/7 society, causes cumulative neurobehavioural impairment, but the dynamics of the build-up and dissipation of this impairment have not been fully elucidated. We addressed this knowledge gap in a laboratory study involving two, 5-day periods of sleep restriction to 4 hr per day, separated by a 1-day dose-response intervention sleep opportunity. We measured sleep physiological and waking neurobehavioural responses in 70 healthy adults, each randomized to one of seven dose-response intervention sleep doses ranging from 0 to 12 hr, or a non-sleep-restricted control group. As anticipated, sleep physiological markers showed homeostatic dynamics throughout the study, and waking neurobehavioural impairment accumulated across the two sleep restriction periods. Unexpectedly, there was only a slight and short-lived effect of the 1-day dose-response intervention sleep opportunity. Whether the dose-response intervention sleep opportunity involved extension, further restriction or total deprivation of sleep, neurobehavioural functioning during the subsequent second sleep restriction period was dominated by prior sleep-wake history. Our findings revealed a profound and enduring influence of long-term sleep-wake history as a fundamental aspect of the dynamic regulation of the neurobehavioural response to sleep loss.
RESUMO
A Zr-catalyzed synthesis of tetrasubstituted 1,3-diacylpyrroles is reported that employs the direct use of N-acyl α-aminoaldehydes with 1,3-dicarbonyl compounds. The products were formed in up to 88% yield and shown to be hydrolytically and configurationally stable under the reaction conditions (THF/1,4-dioxane and H2O). The N-acyl α-aminoaldehydes were readily prepared from the corresponding α-amino acids. The reaction tolerates a wide array of substrate types including alkyl-, aryl-, heteroaryl-, and heteroatom-containing groups on the aminoaldehyde side chain. A variety of 1,3-dicarbonyls proved amenable to the reaction along with an aldehyde derived from a l,l-dipeptide, an aldehyde generated in situ, and an N-acylated glucosamine.