Choe, KH, Coburn, JW, Costa, PB, and Pamukoff, DN. Hip and knee kinetics during a back-squat and deadlift. J Strength Cond Res 35(5): 1364-1371, 2021-The back-squat and deadlift are performed to ...improve hip and knee extensor function. The purpose of this study was to compare lower extremity joint kinetics (peak net joint moments NJMs and positive joint work PJW) between the back-squat and deadlift. Twenty-eight resistance-trained subjects (17 men: 23.7 ± 4.3 years, 1.76 ± 0.09 m, 78.11 ± 10.91 kg; 11 women: 23.0 ± 1.9 years, 1.66 ± 0.06 m, 65.36 ± 7.84 kg) were recruited. One repetition maximum (1RM) testing and biomechanical analyses occurred on separate days. Three-dimensional biomechanics of the back-squat and deadlift were recorded at 70 and 85% 1RM for each exercise. The deadlift demonstrated larger hip extensor NJM than the back-squat {3.59 (95% confidence interval CI: 3.30-3.88) vs. 2.98 (95% CI: 2.72-3.23) Nm·kg-1, d = 0.81, p < 0.001}. However, the back-squat had a larger knee extensor NJM compared with the deadlift (2.14 95% CI: 1.88-2.40 vs. 1.18 95% CI: 0.99-1.37 Nm·kg-1, d = 1.44 p < 0.001). More knee PJW was performed during the back-squat compared with the deadlift (1.85 95% CI: 1.60-2.09 vs. 0.46 95% CI: 0.35-0.58 J·kg-1, d = 2.10, p < 0.001). However, there was more hip PJW during the deadlift compared with the back-squat (3.22 95% CI: 2.97-3.47 vs. 2.37 95% CI: 2.21-2.54 J·kg-1, d = 1.30, p < 0.001). Larger hip extensor NJM and PJW during the deadlift suggest that individuals targeting their hip extensors may yield greater benefit from the deadlift compared with the back-squat. However, larger knee extensor NJM and PJW during the back-squat suggest that individuals targeting their knee extensor muscles may benefit from incorporating the back-squat compared with the deadlift.
Frontal and sagittal plane landing biomechanics differ between sexes but reported values don’t account for simultaneous segment or joint motion necessary for a coordinated landing. Frontal and ...sagittal plane coordination patterns, angles, and moments were compared between 28 males and 28 females throughout the landing phase of a drop vertical jump. Females landed with less isolated thigh abduction (p = 0.018), more in-phase motion (p < 0.001), and more isolated shank adduction (p = 0.028) between the thigh and shank in the frontal plane compared with males. Females landed with less in-phase (p = 0.012) and more anti-phase motion (p = 0.019) between the thigh and shank in the sagittal plane compared with males. Females landed with less isolated knee flexion (p = 0.001) and more anti-phase motion (p < 0.001) between the sagittal and frontal plane knee coupling compared with males. Waveform and discrete metric analyses revealed females land with less thigh abduction from 20 % to 100 % and more shank abduction from 0 to 100 % of landing, smaller knee adduction at initial contact (p = 0.002), greater peak knee abduction angles (p = 0.015), smaller knee flexion angles at initial contact (p = 0.035) and peak (p = 0.034), greater peak knee abduction moments (p = 0.024), greater knee abduction angles from 0 to 13 % and 19 to 30 %, greater knee abduction moments from 19 to 25 %, and smaller knee flexion moments from 3 to 5 % of landing compared with males. Females utilize greater frontal plane motion compared with males, which may be due to different inter-segmental joint coordination and smaller sagittal plane angles. Larger knee abduction angles and greater knee adduction motion in females are due to aberrant shank abduction rather than thigh adduction.
Force attenuation during landing requires coordinated motion of the ankle, knee, hip, and trunk, and strategies may differ between sexes. Sagittal plane coordination of the ankle/knee, knee/hip, and ...knee/trunk, and lower extremity and trunk kinematics and kinetics was compared throughout landing between 28 males and 28 females. Coordination was assessed with a modified vector coding technique and binning analysis. Total support moments (TSM), each joint's percent contribution, and timing of the TSM were compared. Females landed with less isolated knee flexion in the ankle/knee, knee/hip, and knee/trunk couplings, but more simultaneous ankle/knee flexion, less simultaneous knee flexion/hip extension, and more simultaneous trunk/knee flexion. Females landed with larger plantarflexion angles from 0-16% and smaller trunk flexion angles from 0-78%. In females, absolute TSM were larger from 0-6% and smaller from 42-100%, and normalized TSM were larger from 0-8% and 26-42%. Females had greater ankle contribution to the TSM from 14-15% and 29-35%, smaller absolute peak TSM, and the peak TSM occurred earlier. Females compensated for less isolated knee flexion with greater simultaneous ankle/knee flexion early in landing and knee/trunk flexion later in landing. Coordination and TSM differences may influence force attenuation strategies and have implications for knee injury disparity between sexes.
The anterior cruciate ligament (ACL) is commonly injured, especially in individuals under the age of 25. ACL reconstruction (ACLR) is the most common treatment after ACL injury, followed by physical ...therapy. However, successful surgery and completion of rehabilitation, individuals still demonstrate quadriceps weakness and asymmetries during locomotion. To improve these deficits, an intervention that improves quadriceps strength and lower extremity biomechanics during locomotion is required. First, we aimed to complete a systematic review of the literature to determine the efficacy of resistance training in improving outcomes after ACLR. Second, we aimed to identify if a history of resistance training positively influences limb symmetry in individuals with ACLR during locomotion. We hypothesized that due to the strength adaptations of resistance training, individuals with ACLR who resistance train will move more symmetrically than those who do not. Lastly, we aimed to evaluate the relationship between lower extremity LBM and limb symmetry in individuals with ACLR during locomotion. We hypothesized that lower extremity lean body mass (LBM) would be positively associated with limb symmetry.From our systematic review, we can conclude that resistance training should be used by clinicians in rehabilitation after ACL reconstruction due to the improvements in muscle size and strength. Secondly, we found that during walking, the resistance trained group demonstrated greater LSI for knee range of motion (d=1.20), peak knee flexion angle (d=1.05), and peak knee extensor moment (d=1.51). We found similar results during running, as the resistance trained group demonstrated greater LSI for knee range of motion (d=1.13), peak knee flexion angle (d=1.32), and peak knee extensor moment (d=1.17). During the sit to stand task, the resistance trained group demonstrated greater LSI for peak vertical GRF (d=1.12) and peak knee extensor moment (d=0.71). Lastly, lower extremity LBM was positively associated with knee range of motion LSI (F1,21= 6.16, p=0.022) during walking. For running, lower extremity LBM was positively associated with knee range of motion LSI (F1,21= 4.726, p=0.042), peak knee flexion angle LSI (F1,21= 9.200, p=0.007) and knee extensor moment LSI (F1,21= 8.124, p=0.020). For the sit to stand task, lower extremity LBM was positively associated peak knee extensor moment LSI (F1,21= 6.673, p=0.018).Our results demonstrate that resistance training is effective in improving muscle strength after surgery. Additionally, individuals who have had ACLR who resistance train after surgery move more symmetrically than those who do not during functional tasks. An adaptation of resistance training is increased lower extremity LBM, which is positively associated with limb symmetry index during locomotion. Therefore, individuals should resistance train after ACLR to increase the odds of moving symmetrically, which has implications for knee osteoarthritis. Furthermore, clinicians should incorporate resistance training and interventions to improve lower extremity LBM after ACLR. Future aims should prospectively investigate the effects of resistance training after ACLR.
Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in ...humans due to patient-to-patient variability. Here, we show that a small airway-on-a-chip device lined by living human bronchiolar epithelium from normal or COPD patients can be connected to an instrument that “breathes” whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro. This technology enables true matched comparisons of biological responses by culturing cells from the same individual with or without smoke exposure. These studies led to identification of ciliary micropathologies, COPD-specific molecular signatures, and epithelial responses to smoke generated by electronic cigarettes. The smoking airway-on-a-chip represents a tool to study normal and disease-specific responses of the human lung to inhaled smoke across molecular, cellular and tissue-level responses in an organ-relevant context.
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•Smoking lung airway chip recapitulated clinical oxidative stress molecular profiles•New smoke-induced ciliary micropathologies were identified•This technology supported study of potential toxic effects of electronic cigarettes•COPD-specific responses were reproduced in vitro and novel biomarkers were identified
Benam et al. describe a microengineered in vitro model system that permits analysis of the effects of whole smoke, from both conventional tobacco and electronic cigarettes, delivered under physiologically relevant flow conditions that mimic breathing on the pathophysiology of differentiated human mucociliated bronchiolar epithelium cultured in a microfluidic small airway-on-a-chip.
High mobility group box 1 (HMGB1) protein, a DNA binding protein that stabilizes nucleosomes and facilitates transcription, was recently identified as a late mediator of endotoxin lethality. High ...serum HMGB1 levels in patients with sepsis are associated with increased mortality, and administration of HMGB1 produces acute inflammation in animal models of lung injury and endotoxemia. Neutrophils occupy a critical role in mediating the development of endotoxemia-associated acute lung injury, but previously it was not known whether HMGB1 could influence neutrophil activation. In the present experiments, we demonstrate that HMGB1 increases the nuclear translocation of NF-kappaB and enhances the expression of proinflammatory cytokines in human neutrophils. These proinflammatory effects of HMGB1 in neutrophils appear to involve the p38 MAPK, phosphatidylinositol 3-kinase/Akt, and ERK1/2 pathways. The mechanisms of HMGB1-induced neutrophil activation are distinct from endotoxin-induced signals, because HMGB1 leads to a different profile of gene expression, pattern of cytokine expression, and kinetics of p38 activation compared with LPS. These findings indicate that HMGB1 is an effective stimulus of neutrophil activation that can contribute to development of a proinflammatory phenotype in diseases characterized by excessively high levels of HMGB1.
SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing ...effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.
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•mRNA vaccines induce robust type 1 CD4+ and CD8+ T cells in the spleen and lung•Vaccine-induced T cells readily exit the vasculature and enter the lung parenchyma•mRNA vaccines elicit strong long-lived plasma cell and memory B cell responses•mRNA vaccines induce antibodies with potent anti-SARS-CoV-2 neutralization activity
SARS-CoV-2 mRNA-based vaccines are among the most promising vaccine candidates against COVID-19. Laczkó et al. evaluate two nucleoside-modified mRNA vaccine candidates in mice and demonstrate that they induce potent T and B cell immune responses and high levels of neutralizing antibodies after administration of a single vaccine dose.
Chronic pancreatitis is a debilitating, life-altering disease; however, the long-term outcomes after operative intervention have not been established.
Patients who underwent operative intervention at ...a single institution between 2000 and 2020 for chronic pancreatitis were included, and survival was assessed using the National Death Index.
A total of 493 patients who underwent 555 operative interventions for chronic pancreatitis during 2 decades were included. Of these patients, 48.5% underwent total pancreatectomy ± islet autotransplantation, 21.7% underwent a duodenal preserving pancreatic head resection and/or drainage procedure, 16.2% underwent a pancreaticoduodenectomy, and 12.8% underwent a distal pancreatectomy. The most common etiology of chronic pancreatitis was idiopathic (41.8%), followed by alcohol (28.0%) and known genetic polymorphisms (9.9%). With a median follow-up of 83.9 months, median overall survival was 202.7 months, with a 5- and 10-year overall survival of 81.3% and 63.5%. One hundred sixty-five patients were deceased, and the most common causes of death included infections (16.4%, n=27), cardiovascular disease (12.7%, n=21), and diabetes-related causes (10.9%, n=18). On long-term follow-up, 73.1% (n=331) of patients remained opioid free, but 58.7% (n=266) had insulin-dependent diabetes. On multivariate Cox proportional hazards modeling, only persistent opioid use (hazard ratio 3.91 95% CI 2.45 to 6.24, p < 0.01) was associated with worse overall survival.
Our results represent the largest series to date evaluating long-term survival outcomes in patients with chronic pancreatitis after operative intervention. Our data give insight into the cause of death and allow for the development of mitigation strategies and long-term monitoring of comorbid conditions.
Background
The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in ...patients with early stage disease.
Methods
The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC. Exclusion criteria included neoadjuvant therapy, radiation, or those who suffered a 90-day mortality.
Results
Of the 1526 patients included in the study, 42.2% received AC and 57.8% underwent surgery alone. Patients who received AC were younger, had fewer comorbidities, and were more likely to have private insurance, compared with those treated with surgery alone. Patients who received AC had longer median overall survival (OS) compared with those who underwent surgery alone (105.7 months vs 72.0 months,
p
< 0.01). Subset analyses based on individual “good” prognostic features (size ≤ 1.0 cm, lymphovascular invasion negative, well/moderately differentiated, margin negative resection) demonstrated improved OS with AC. Following propensity score matching based on key clinicopathologic features, AC remained associated with improved median OS (83.7 months vs 59.8 months,
p
< 0.01). However, in the cohort with body/tail tumors (101.2 months vs 95.0 months,
p
= 0.19) and those with all “good” prognostic features (95.9 months vs 90.6 months,
p
= 0.15), AC was not associated with improved survival.
Conclusions
In resected, Stage IA PDAC, AC is associated with improved overall survival in the vast majority of patients; however, in select cohorts the role of AC is unclear. Further study is needed to tailor treatment to individual patients with PDAC.
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