Heel-to-toe drop effects on biomechanical and muscle synergy responses during uphill walking.

Uphill walking is a common task encountered in daily life, with steeper inclines potentially imposing greater biomechanical and neuromuscular demands on the human body. The heel-to-toe drop (HTD) in footwear may influence the biomechanical and neuromuscular pattern of uphill walking; but the impact remains unclear. Adjustments in HTD can modulate biomechanical and neuromuscular patterns, mitigating the demands and optimizing the body's response to different inclinations. We hypothesize that adjustments in HTD can modulate biomechanical and neuromuscular patterns, mitigating the demands and optimizing the body's response to different inclinations. Nineteen healthy men walked on an adjustable slope walkway, with varied inclinations (6°, 12°, 20°) and HTD shoes (10mm, 25mm, 40 mm), while the marker positions, ground reaction forces and electromyography data were collected. Our study reveals that gait temporo-spatial parameters are predominantly affected by inclination over HTD. Inclination has a more pronounced effect on kinematic variables, while both inclination and HTD significantly modulate kinetic and muscle synergy parameters. This study demonstrates that an increase in the inclination leads to changes in biomechanical and neuromuscular responses during uphill walking and the adjustment of HTD can modulate these responses during uphill walking. However, the present study suggests that an increased HTD may lead to elevated loads on the knee joint and these adverse effects need more attention.

The Scheduling Mode of Anesthesia Nurses Affects Postanesthesia Care Unit Efficiency: A Single-Center Retrospective Study From China.

PURPOSE: Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. DESIGN: A retrospective observational cohort study. METHODS: We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. FINDINGS: The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). CONCLUSIONS: The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.

Momordica charantia Bioactive Components: Hypoglycemic and Hypolipidemic Benefits Through Gut Health Modulation.

Momordica charantia (MC), a member of the Cucurbitaceae family, is well known for its pharmacological activities that exhibit hypoglycemic and hypolipidemic properties. These properties are largely because of its abundant bioactive compounds and phytochemicals. Over the years, numerous studies have confirmed the regulatory effects of MC extract on glycolipid metabolism. However, there is a lack of comprehensive reviews on newly discovered MC-related components, such as insulin receptor-binding protein-19, adMc1, and MC protein-30 and triterpenoids 3ß,7ß,25-trihydroxycucurbita-5,23(E)-dien-19-al, and the role of MC in gut microbiota and bitter taste receptors. This review offers an up-to-date overview of the recently reported chemical compositions of MC, including polysaccharides, saponins, polyphenolics, peptides, and their beneficial effects. It also provides the latest updates on the role of MC in the regulation of gut microbiota and bitter taste receptor signaling pathways. As a result, this review will serve as a theoretical basis for potential applications in the creation or modification of MC-based nutrient supplements.

Toxoplasma gondii infection positively associated with schizophrenia: Evidences from UK Biobank cohort and case-controlled studies.

Toxoplasma gondii (T. gondii) is an opportunistic pathogen affecting about 1/3 of world population. While often asymptomatic in immunocompetent individuals, it can lead to severe toxoplasmosis in immunocompromised patients. Recent research has unveiled a potential link between T. gondii infection and neuropsychiatric diseases. We implemented both a cohort study and a case control study to further identify this association. In the cohort study, we analyzed data from the UK Biobank database, which included 8814 individuals tested for T. gondii SAG1 antibodies and free of neuropsychiatric disorders at baseline. Among them, 22.52% (n = 1985) tested positive for SAG1 antibody. Over an average follow-up period of 12.26 years, Cox proportional hazards models and logistic regression analysis revealed a significant association between the SAG1 seropositivity at baseline and the incidence of schizophrenia (HR: 5.89; 95% CI: 1.69-20.53). In our case-control study, 239 patients diagnosed with schizophrenia and 455 healthy individuals were involved. Using the modified agglutination test (MAT) to detect T. gondii antibodies, logistic regression analysis showed a higher prevalence of T. gondii infection among schizophrenia patients (10.04%) compared to healthy controls (3.74%). T. gondii infection emerged as a significant risk factor for schizophrenia (OR: 3.33; 95% CI: 1.68-6.61). However, our investigations did not reveal a robust association between T. gondii infection and other neuropsychiatric conditions, including Alzheimer's disease, dementia, anxiety, depression, neurodegenerative disorders, and peripheral neurological disorders such as neurological and plexus disorders.

Research advances in the molecular classification of gastric cancer.

Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.

Radiomics analysis for prediction of lymph node metastasis after neoadjuvant chemotherapy based on pretreatment MRI in patients with locally advanced cervical cancer.

Background: This study aims to develop and validate a pretreatment MRI-based radiomics model to predict lymph node metastasis (LNM) following neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC). Methods: Patients with LACC who underwent NACT from two centers between 2013 and 2022 were enrolled retrospectively. Based on the lymph node (LN) status determined in the pathology reports after radical hysterectomy, patients were categorized as LN positive or negative. The patients from center 1 were assigned as the training set while those from center 2 formed the validation set. Radiomics features were extracted from pretreatment sagittal T2-weighted imaging (Sag-T2WI), axial diffusion-weighted imaging (Ax-DWI), and the delayed phase of dynamic contrast-enhanced sagittal T1-weighted imaging (Sag-T1C) for each patient. The K-best and least absolute shrinkage and selection operator (LASSO) methods were employed to reduce dimensionality, and the radiomics features strongly associated with LNM were selected and used to construct three single-sequence models. Furthermore, clinical variables were incorporated through multivariate regression analysis and fused with the selected radiomics features to construct the clinical-radiomics combined model. The diagnostic performance of the models was assessed using receiver operating characteristic (ROC) curve analysis. The clinical utility of the models was evaluated by the area under the ROC curve (AUC) and decision curve analysis (DCA). Results: A total of 282 patients were included, comprising 171 patients in the training set, and 111 patients in the validation set. Compared to the Sag-T2WI model (AUC, 95%CI, training set, 0.797, 0.722-0.782; validation set, 0.648, 0.521-0.776) and the Sag-T1C model (AUC, 95%CI, training set, 0.802, 0.723-0.882; validation set, 0.630, 0.505-0.756), the Ax-DWI model exhibited the highest diagnostic performance with AUCs of 0.855 (95%CI, 0.791-0.919) in training set, and 0.753 (95%CI, 0.638-0.867) in validation set, respectively. The combined model, integrating selected features from three sequences and FIGO stage, surpassed predictive ability compared to the single-sequence models, with AUC of 0.889 (95%CI, 0.833-0.945) and 0.859 (95%CI, 0.781-0.936) in the training and validation sets, respectively. Conclusions: The pretreatment MRI-based radiomics model, integrating radiomics features from three sequences and clinical variables, exhibited superior performance in predicting LNM following NACT in patients with LACC.

The impact of digital literacy on personal health: Evidence from the China family panel study.

BACKGROUND: In the digital era, digital literacy is a fundamental indicator of a nation's quality and plays a crucial role in public health. Exploring the theoretical mechanisms and effects of digital literacy on individuals' health is of great practical importance, advancing the initiatives of 'Digital China' and 'Healthy China'. METHODS: The study utilised three-period survey panel data from the China Family Panel Study spanning 2016, 2018, and 2020 to measure and evaluate levels of digital literacy, physical health, mental health, healthy lifestyle, and integrated health among the participants. Subsequently, a series of empirical analyses were conducted to examine the general impact, heterogeneous effects and transmission pathways of digital literacy on various types of health levels. RESULTS: Digital literacy significantly enhances all aspects of respondents' health, and this conclusion remains valid even after conducting robustness tests and addressing endogeneity through variable substitution and selecting instrumental variables using the 2SLS method. Furthermore, examining heterogeneity by considering individual traits and the makeup of digital literacy reveals that the impact of digital literacy on individuals' health varies according to age, cultural background, personal income, and the components of digital literacy. Pathway analyses also demonstrate that medical accessibility, information access, social network, and planned behaviour are key routes through which digital literacy enhances the health of the population. CONCLUSIONS: It is imperative for the government to actively promote the advancement of the digital healthcare industry, while individuals should strive to enhance their digital literacy. By collectively focussing on these efforts, national health can be significantly improved.

Population-based cohort study of Toxoplasma gondii P22 antibody positivity correlation with anxiety.

BACKGROUND: Accumulating evidence suggests that latent infection with Toxoplasma gondii (T. gondii) is associated with a variety of neuropsychiatric and behavioral conditions. This research aims to explore the potential correlation between T. gondii antibody positivity and neuropsychiatric disorders through a comprehensive prospective cohort study. METHODS: The cohort study utilized the UK Biobank database to recruit 8814 individuals with no prior diagnosis of neuropsychiatric disorders. Cox proportional hazards models were employed to investigate the associations between T. gondii P22 antibody seropositivity (P22+) and the development of various types of neuropsychiatric disorders. RESULTS: Of the population, 14.65 % tested positive for T. gondii P22 antibody. The presence of T. gondii P22 antibody showed a slight inverse association with epilepsy (HR: 0.28; 95 % CI: 0.10-0.77), while it was positively associated with an increased risk of developing anxiety disorders (HR: 1.38; 95 % CI: 1.04-1.83). LIMITATIONS: The study sample consisted mostly of white British individuals aged 40 to 69 years old. Although we adjusted for potential confounders, there may be other unmeasured and residual confounding factors that could have influenced our reported associations. CONCLUSIONS: The findings suggested an increased risk of anxiety and potential evidence of epilepsy associated with T. gondii P22+. However, our analysis did not reveal an increased risk of several other neuropsychiatric conditions including Alzheimer's disease, dementia, substance abuse disorders, depression, and neurodegenerative disorders, associated with P22 antibody seropositivity.

The effects of probiotics supplementation on Helicobacter pylori standard treatment: an umbrella review of systematic reviews with meta-analyses.

Helicobacter pylori infection, a worldwide health issue, is typically treated with standard antibiotic therapies. However, these treatments often face resistance and non-compliance due to side effects. In this umbrella review, we aimed to comprehensively assess the impact of probiotics supplementation in different preparations on Helicobacter pylori standard treatment. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials in the Cochrane Library from inception to June 1, 2023, to identify systematic reviews with meta-analyses that focused on eradication rates, total side effects and other outcomes of interest. The most comprehensive meta-analysis was selected for data extraction. AMSTAR 2 was used to assess quality of meta-analyses. Overall, 28 unique meta-analyses based on 534 RCTs were included. The results suggests that probiotics supplementation with pooled probiotic strains was significantly associated with improved eradication rates (RR 1.10, 95% CI 1.06-1.14) and reduced risk of total side effects (RR 0.54, 95% CI 0.42-0.70) compared with standard therapy alone. Single-strained or multi-strained preparation of probiotics supplementation showed similar results. Despite Bifidobacterium spp. showing the highest potential for eradication, the study quality was critically low for most meta-analyses, necessitating further high-quality research to explore the optimal probiotic strains or their combinations for Helicobacter pylori treatment.aq_start?>Kindly check and confirm the edit made in article title.

Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2.

Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by an inducible genetic knockout of nf2a/b, the zebrafish homolog of human NF2. Analysis of nf2a and nf2b expression reveals ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displays lower expression levels. Induction of nf2a/b knockout at early stages increases the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggers the development of a spectrum of tumors, including vestibular schwannomas, spinal schwannomas, meningiomas, and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.

Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities.

White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low-grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity-related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.

Association of high-density lipoprotein cholesterol with sarcopenia in Chinese community-dwelling middle-aged and older adults: Evidence from 4-year longitudinal study from the CHARLS.

Introduction There is inconsistent evidence on the associations between high-density lipoprotein cholesterol (HDL-C) and risk of sarcopenia. To determine the evidence existing between HDL-C and sarcopenia in Chinese middle-aged and older adults. Methods We used a panel study design of the China Health and Retirement Longitudinal Study (CHARLS), with 7,415 participants (mean age 57.5 years) from 2011, 2013, and 2015. HDL-C was measured by colormetric test of venous serum samples. Sarcopenia was defined as low muscle mass, plus low muscle strength, or low physical performance. Muscle mass was estimated by anthropometric measures. Muscle strength was measured by handgrip strength using dynamometer. Physical performance was measured by 5-time chair stand test, gait speed test, and short physical performance battery. Results With 961 (13.0%) sarcopenia cases, each 1-unit increase (1 SD = 15.4 mg/dL) of HDL-C levels was associated with 42% increased odds of incident sarcopenia [OR = 1.42, 95% confidence interval (CI) = 1.28 - 1.58] at 4 years follow up. Females with high HDL-C levels (HDL-C > 60 mg/dL) had a higher risk of sarcopenia [OR = 2.49, 95% CI = 1.76 - 3.52]. A J-shaped association between HDL-C and risk of sarcopenia in females. HDL-C was negatively associated with muscle mass [ = -0.23, 95% CI = -0.27 - -0.20] and hand grip strength [ = -0.05, 95% CI = -0.19 - 0.09]. Conclusion High HDL-C levels were associated with higher risk of sarcopenia among middle-aged and older Chinese adults, and appropriate control of its high levels informs the management of sarcopenia.

Burnout among Nurses: A Bibliometric Analysis of the Global Publications.

Objective: To investigate the current situation, trending subjects, and future directions in the field of burnout among nurses, and to serve as a resource for researchers conducting related research. Methods: The bibliometric analysis was carried out using R package "bibliometrix", bibliometric online analysis platform (https://bibliometric.com/) and VOSviewer (1.6.18). Results: The leading countries that had a significant impact on this field were the USA and China. University of Pennsylvania was the most influential institution. Journal of Nursing Management was the top productive journal. Critical care, oncology care, acute care, and infectious disease care were more likely to lead to symptoms of burnout among nurses. "Mental health", "job satisfaction", "stress", and "COVID-19" were the current hot topics in this field. Conclusion: Our study not only provides a thorough outline to assist researchers in understanding the leading countries, institutions, journals, and potential collaborators, but it also examines the current and upcoming trends in this field and inspires researchers to select research directions.

Transcriptome and volatile compounds analyses of floral development provide insight into floral scent formation in Paeonia lactiflora 'Wu Hua Long Yu'.

Herbaceous peony (Paeonia lactiflora) is a well-known ornamental plant in China, celebrated for its beautiful flowers that can emit fragrances. However, exact molecular mechanisms governing synthesis of floral volatiles within herbaceous peony remain unclear. To address this gap in knowledge, our study focused on analyzing the transcriptome and the levels of floral volatile compounds in P. lactiflora 'Wu Hua Long Yu' at different stages of flower development. Using gas chromatography-mass spectrometry (GC-MS), we obtained eighteen major volatile compounds, with monoterpenes being the dominant components among them. Our transcriptome analysis, based on pooled sequencing data, revealed the most differentially expressed genes (DEGs) existed between stages S1 and S3 of flower development. Among these DEGs, we identified 89 functional genes associated with the synthesis of volatile monoterpenes, with 28 of these genes showing a positive correlation with the release of monoterpenes. Specifically, key regulators of monoterpene synthesis in herbaceous peony appear to be 1-deoxy-D-xylulose 5-phosphate synthase (DXS), geranyl pyrophosphate synthase (GPPS), and terpene synthase (TPS). Additionally, our study identified some transcription factors (TFs) that may be involved in the biosynthesis of monoterpenes. These discoveries offer invaluable illumination into the intricate molecular underpinnings orchestrating the generation of floral fragrances in herbaceous peonies, and they offer a foundation for further research to identify and utilize candidate gene resources for this purpose.

Cuproptosis Related Gene DLD Associated with Poor Prognosis and Malignant Biological Characteristics in Lung Adenocarcinoma.

PURPOSE: Cuproptosis plays a crucial role in the biological function of cells. The subject of this work was to analyze the effects of cuproptosis-related genes (CRGs) on the prognosis and biological function in lung adenocarcinoma (LUAD). METHODS: In this study, RNA sequencing and clinical data of LUAD samples were screened from public databases and our institution. A CRG signature was identified by least absolute shrinkage and selection operator and Cox regression. In addition, this study analyzed the correlation between prognostic CRGs and clinicopathological features. Finally, this study studied the effect of inhibiting dihydrolipoamide dehydrogenase (DLD) expression on cell biological function. RESULTS: There were 10 CRGs that showed differential expression between LUAD and normal tissues (p<0.05). A prognostic signature (DLD and lipoyltransferase 1 [LIPT1]) was constructed. Survival analysis suggested that patients with LUAD in the high-risk group had shorter overall survival (OS) (p<0.05). High expression of DLD and low expression of LIPT1 were significantly associated with shorter OS (p<0.05). Immunohistochemical analysis revealed that, in LUAD tissues, DLD was highly expressed, whereas LIPT1 was not detected. Finally, inhibition of DLD expression could significantly restrain cell proliferation, invasion and migration. CONCLUSION: Overall, this prognostic CRG signature may play a pivotal role in LUAD outcome, while oncogene DLD may be a future therapeutic candidate for LUAD.

A Compact Broadband Power Combiner for High-Power, Continuous-Wave Applications.

A compact broadband combiner with a high power capacity and a low insertion loss, which is especially useful for solid-state power sources where multi-way power synthesis is needed, was designed and experimentally investigated. The combiner could combine the microwave signals of sixteen terminals into a single one and was based on a radial-line waveguide whose circumferential symmetry benefited the amplitude and phase consistency of the combiner. Simulation and experimental results showed that the prototype device, designed for S-band applications, exhibited a reflection coefficient S1,1 < -20 dB in the range of 2.06-2.93 GHz, which corresponds to a relative bandwidth of approximately 34.6%. At 2.45 GHz, the phase imbalance was ±4.5° and the 16-way transmission coefficient was concentrated around -12.0~-12.3 dB. The insertion loss of the device at ambient and elevated temperatures was simulated and experimentally verified, which is of importance for the design of similar high-power microwave combiners. High-power tests proved that even without enforced wind or liquid cooling, the device can handle continuous power (CW) of at least 3.9 kW, which can be much enhanced by taking regular cooling measures. The combined features of the designed combiner suggest promising applications for power synthesis in high-power, solid-state RF sources.

Ultrasound Flow Imaging Study on Rat Brain with Ultrasound and Light Stimulations.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain's response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain's electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.

Does digital economy development affect urban environment quality: Evidence from 285 cities in China.

The impact of the digital economy (DE) on urban environmental quality (EQ) is a critical aspect of China's economic development. This study investigates the impact of DI on urban EQ using the data from prefecture-level cities spanning the period from 2011 to 2021 and updates some disparate conclusions of related studies. It is discovered that a non-linear correlation exists between DE and urban EQ. Currently, DE can effectively improve local city EQ. This conclusion remains valid even after robustness tests and endogeneity treatment. The impact of DE on improving EQ can be classified as the impact of technological innovation, industrial upgrading, resource allocation, infrastructure construction, environmental governance, and changes in public lifestyle. Heterogeneity analysis reveals that the influence of DE is particularly pronounced in cities located in central and eastern regions of China, those with higher levels of administrative management, resource-based urban areas, and those with more stringent environmental regulations.

Effect of midsole hardness and surface type cushioning on landing impact in heel-strike runners.

High loading impact associated with heel strikes causes running injuries. This study aimed to investigate how loading impact is affected by midsole hardness and running surface type. Twelve young rear-foot runners ran at a fixed speed along an 18 m runway wearing shoes with different midsole hardness (Asker C-45, C-50, C-55, C-60, from soft to hard) and on two different surfaces (rubber and concrete). We quantified vertical average loading rate (VALR) and vertical impact peak force (VIPF). We conducted midsole × surface repeated-measures ANOVA on loading impact measures, and one-sample t-tests to compare VALR with a threshold value (80 BW·s-1). Midsole hardness and surface type mainly affected VALR. Although no significant effect of these variables was observed for VIPF magnitude, there were effects on time to VIPF and steps with VIPF. Several combinations of midsole and surface hardness reduced VALR below 80 BW·s-1: Asker C-45 with both surfaces, and Asker C-50 with a rubber surface. The combination of softer midsole and surface effectively reduced loading rates as shown by increased time to VIPF and reduced VALR. Combining softer midsole and surface results in the greatest cushioning, which demonstrates the benefit of considering both factors in reducing running injuries.