Balance Recovery Response in Community-Dwelling Adults with Unilateral Transtibial Amputation and the Potential Benefits of a Weight-Shifting Balance Training Intervention

Previous studies have shown that individuals with various physical, sensory and neuromuscular impairments are at higher risks of falls. Individuals with unilateral transtibial amputation (UTTA) suffered from all these impairments, and tripping not surprisingly caused a considerable number of falls in this population. To study falls, researchers have to put participants in a well-protected environment and reproduce tripping fall scenarios. Furthermore, the perturbation delivery needs to be precise in terms of temporo-spatial timing. These features would ensure the quality of responses elicited and reproducibility of the results. Thus, in Chapter 2, we developed a treadmill-based perturbation delivery protocol and confirmed that by referencing ground reaction force, the system was able to consistently and precisely deliver perturbations in early stance phase to elicit tripping falls.Because tripping usually arrests only one side of the limb, individuals with UTTA may respond differently when encountering trips with their prosthetic versus non- prosthetic limb. Understanding the biomechanical differences in fall recovery response between these two tripping conditions will facilitate ideas for patient-specific intervention targeting tripping fall prevention. Therefore, in Chapter 3, we utilized the protocol developed in Chapter 2 to deliver destabilizing perturbations to the participants in order to examine the limb-to-limb differences during fall recovery. We found that while the gross fall recovery strategies (i.e. the stepping response) were similar, there existed key biomechanical differences. Perturbation during a static standing condition was typically arrested with the perturbed limb making the recovery step. Dynamic perturbation condition was recovered with the contralateral (non-perturbed) limb making the first recovery step followed by the ipsilateral limb making the reciprocal second recovery step. We observed that certain defined response times were longer when the recover step was executed by the prosthetic limb in both static and dynamic perturbation conditions, suggesting the impaired sensory detection or motor execution of the prosthetic limb. Currently, clinical practitioners are encouraged to include balance training in post amputation rehabilitation. A balance training that focuses on weight-shifting may prepare individuals with lower limb loss the essential ability to make successful recovery step when encountering destabilizing scenarios. However, it is currently unknown if a training program focusing solely on balance control can improve fall recovery response. Hence, in Chapter 4, we examined the effects of a 2-day weight-shifting balance training using protocols developed in Chapters 2 and 3. We found that certain biomechanical variables relevant to weight-shifting and weight-bearing during fall recovery were altered by the training. For instance, the duration for unloading the prosthetic limb before taking the recovery step during static perturbation condition were improved after training. Another example was that when the prosthetic limb was perturbed, the duration of the first recovery step increased; meanwhile, when the non-prosthetic limb was perturbed, the duration of the second recovery step increased. These two durations were the non- prosthetic limb executing the recovery step in which the prosthetic limb providing the stance support, and the stance time increased. Overall, our findings suggest that sensorimotor deficits related to UTTA may lead to longer duration of step time when the prosthetic limb executed the recovery step. This is a promising direction to intervene in the future. Our balance training protocol appears to improve components that were related to participants’ weight-shifting ability. Whilst for altering the global fall recovery responses, we concluded that a more perturbation-based approach may be required and should be investigated in the future

Uniformly Distributed Graphene Domain Grows on Standing Copper via Low-Pressure Chemical Vapor Deposition

Uniformly distributed graphene domains were synthesized on standing copper foil by a low-pressure chemical vapor deposition system. This method improved the distribution of the graphene domains at different positions on the same piece of copper foil along the forward direction of the gas flow. Scanning electron microscopy (SEM) showed the average size of the graphene domains to be about ~20 m. This results show that the sheet resistance of monolayer graphene on a polyethylene terephthalate (PET) substrate is about ~359 /□ whereas that of the four-layer graphene films is about ~178 /□, with a transmittance value of 88.86% at the 550 nm wavelength. Furthermore, the sheet resistance can be reduced with the addition of HNO3 resulting in a value of 84 /□. These values meet the absolute standard for touch sensor applications, so we believe that this method can be a candidate for some transparent conductive electrode applications

Panax notoginseng Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Panax notoginseng (PN) is a traditional Chinese herb experimentally proven to have anti-inflammatory effects, and it is used clinically for the treatment of atherosclerosis, cerebral infarction, and cerebral ischemia. This study aimed to determine the anti-inflammatory effects of PN against bleomycin-induced pulmonary fibrosis in mice. First, in an in vitro study, culture media containing lipopolysaccharide (LPS) was used to stimulate macrophage cells (RAW 264.7 cell line). TNF-α and IL-6 levels were then determined before and after treatment with PN extract. In an animal model (C57BL/6 mice), a single dose of PN (0.5 mg/kg) was administered orally on Day 2 or Day 7 postbleomycin treatment. The results showed that TNF-α and IL-6 levels increased in the culture media of LPS-stimulated macrophage cells, and this effect was significantly inhibited in a concentration-dependent manner by PN extract. Histopathologic examination revealed that PN administered on Day 7 postbleomycin treatment significantly decreased inflammatory cell infiltrates, fibrosis scores, and TNF-α, TGF-β, IL-1β, and IL-6 levels in bronchoalveolar lavage fluid when compared with PN given on Day 2 postbleomycin treatment. These results suggest that PN administered in the early fibrotic stage can attenuate pulmonary fibrosis in an animal model of idiopathic pulmonary fibrosis

B-Cell Lymphoma 6 (BCL6) Is a Host Restriction Factor That Can Suppress HBV Gene Expression and Modulate Immune Responses

Hepatitis B virus (HBV) infection causes acute and chronic liver inflammation. Recent studies have demonstrated that some viral antigens can suppress host innate and adaptive immunity, and thus lead to HBV liver persistency. However, the cellular factors that can help host cells to clear HBV during acute infection remain largely unknown. Here, we used HBV-cleared and HBV-persistent mouse models to seek for cellular factors that might participate in HBV clearance. HBV replicon DNA was delivered into the mouse liver by hydrodynamic injection. RNA-Seq analysis was conducted to identify immune-related genes that were differentially expressed in HBV-persistent and HBV-cleared mouse models. A cellular factor, B cell lymphoma 6 (BCL6), was found to be significantly upregulated in the liver of HBV-cleared mice upon HBV clearance. Co-expression of BCL6 and a persistent HBV clone rendered the clone largely cleared, implicating an important role of BCL6 in controlling HBV clearance. Mechanistic studies demonstrated that BCL6 functioned as a repressor, binding to and suppressing the activities of the four HBV promoters. Correspondingly, BCL6 expression significantly reduced the levels of HBV viral RNA, DNA, and proteins. BCL6 expression could be stimulated by inflammatory cytokines such as TNF-α; the BCL6 in turn synergized TNF-α signaling to produce large amounts of CXCL9 and CXCL10, leading to increased infiltrating immune cells and elevated cytokine levels in the liver. Thus, positive feedback loops on BCL6 expression and immune responses could be produced. Together, our results demonstrate that BCL6 is a novel host restriction factor that exerts both anti-HBV and immunomodulatory activities. Induction of BCL6 in the liver may ultimately assist host immune responses to clear HBV

The role of head-up cardiopulmonary resuscitation in sudden cardiac arrest: a systematic review and meta-analysis

BACKGROUND: Head-up cardiopulmonary resuscitation (HU-CPR) is an experimental treatment for sudden cardiac arrest (SCA), where cardiopulmonary resuscitation (CPR) is performed in a ramped position. We evaluated whether HU-CPR improved survival and surrogate outcomes as compared to standard CPR (S-CPR). METHODS: Studies reporting on HU-CPR in SCA were searched for in PubMed, Embase and Cochrane Library from inception to May 1st 2021. Outcomes included neurologically-intact survival, 24-hour-survival, intracranial pressure (ICP), cerebral perfusion pressure (CerPP) and brain blood flow (BBF). Risk of bias was assessed using the GRADE assessment tool and Newcastle Ottawa Scale. Fixed- and random-effects models were used to estimate the pooled effects of HU-CPR at 30 degrees. RESULTS: Thirteen articles met the criteria for inclusion (11 animal-only studies, one before-and-after human-only study, one study that utilized human- and animal-cadavers). Among animal studies, the most common implementation of HU-CPR was a 30-degree upward tilt of the head and thorax (n=7), while four studies investigated controlled sequential elevation (CSE). Two animal studies reported improved cerebral performance category (CPC) scores at 24-hour. The pooled effect on 24-hour survival was not statistically significant (P=0.37). The lone human study reported doubled return of spontaneous circulation (ROSC) (17.9% versus 34.2%, P<0.0001). The pooled effect on ROSC in three porcine studies was OR =3.63 (95% CI: 0.72–18.39). Pooled effects for surrogate physiological outcomes of intracranial cranial pressure (MD −14.08, 95% CI: −23.21 to −4.95, P=0.003), CerPP (MD 14.39, 95% CI: 3.07–25.72, P=0.01) and BBF (MD 0.14, 95% CI: 0.02–0.27, P=0.03), showed statistically significant benefit. DISCUSSION: Overall, HU-CPR improved neurologically-intact survival at 24-hour, ROSC and physiological surrogate outcomes in animal models. Despite promising preclinical data, and one human observational study, clinical equipoise remains surrounding the role of HU-CPR in SCA, necessitating clarification with future randomized human trials

High levels of serum macrophage migration inhibitory factor and interleukin 10 are associated with a rapidly fatal outcome in patients with severe sepsis

SummaryObjectivesThe aim of this study was to delineate the association between high macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in the early phase of sepsis and rapidly fatal outcome.MethodsOne hundred and fifty-three adult subjects with the main diagnosis of severe sepsis (including septic shock) admitted directly from the emergency department of two tertiary medical centers and one regional teaching hospital between January 2009 and December 2011, were included prospectively. MIF and IL-10 levels were measured and outcomes were analyzed by Cox regression analysis according to the following outcomes: rapidly fatal outcome (RFO, death within 48h), late fatal outcome (LFO, death between 48h and 28 days), and survival at 28 days.ResultsAmong the three outcome groups, IL-10 levels were significantly higher in the RFO group (p < 0.001) and no significant differences were seen between the LFO and survivor groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml in both IL-10 and MIF was independently associated with RFO in patients with severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the RFO risk by a factor of 1.312 (95% confidence interval 1.094–1.575; p=0.003); this was the most significant factor leading to RFO in patients with severe sepsis.ConclusionsPatients with RFO exhibited simultaneously high MIF and IL-10 levels in the early phase of severe sepsis. Incremental increases in both IL-10 and MIF levels were associated with RFO in this patient group, and of the two, IL-10 was the most significant factor linked to RFO

The upper limits of risk ratios and recommendations for reporting risk ratios, odds ratios, and rate ratios

Background Relative measures, including risk ratios (RRs) and odds ratios (ORs), are reported in many epidemiological studies. RRs represent how many times a condition is likely to develop when exposed to a risk factor. The upper limit of RRs is the multiplicative inverse of the baseline incidence. Ignoring the upper limits of RRs can lead to reporting exaggerated relative effect sizes. Objectives This study aims to demonstrate the importance of such upper limits for effect size reporting via equations, examples, and simulations and provide recommendations for the reporting of relative measures. Methods Equations to calculate RRs and their 95% confidence intervals (CIs) were listed. We performed simulations with 10,000 simulated subjects and three population variables: proportions at risk (0.05, 0.1, 0.3, 0.5, and 0.8), baseline incidence (0.05, 0.1, 0.3, 0.5, and 0.8), and RRs (0.5, 1.0, 5.0, 10.0, and 25.0). Subjects were randomly assigned with a risk based on the set of proportions-at-risk values. A disease occurred based on the baseline incidence among those not at risk. The incidence of those at risk was the product of the baseline incidence and the RRs. The 95% CIs of RRs were calculated according to Altman. Results The calculation of RR 95% CIs is not connected to the RR upper limits in equations. The RRs in the simulated populations at risk could reach the upper limits of RRs: multiplicative inverse of the baseline incidence. The upper limits to the derived RRs were around 1.25, 2, 3.3, 10, and 20, when the assumed baseline incidence rates were 0.8, 0.5, 0.3, 0.2, and 0.05, respectively. We demonstrated five scenarios in which the RR 95% CIs might exceed the upper limits. Conclusions Statistical significance does not imply the RR 95% CIs not exceeding the upper limits of RRs. When reporting RRs or ORs, the RR upper limits should be assessed. The rate ratio is also subject to a similar upper limit. In the literature, ORs tend to overestimate effect sizes. It is recommended to correct ORs that aim to approximate RRs assuming outcomes are rare. A reporting guide for relative measures, RRs, ORs, and rate ratios, is provided. Researchers are recommended to report whether the 95% CIs of relative measures, RRs, ORs, and rate ratios, overlap with the range of upper limits and discuss whether the relative measure estimates may exceed the upper limits

Biological Properties of Acidic Cosmetic Water from Seawater

This current work was to investigate the biological effects of acidic cosmetic water (ACW) on various biological assays. ACW was isolated from seawater and demonstrated several bio-functions at various concentration ranges. ACW showed a satisfactory effect against Staphylococcus aureus, which reduced 90% of bacterial growth after a 5-second exposure. We used cultured human peripheral blood mononuclear cells (PBMCs) to test the properties of ACW in inflammatory cytokine release, and it did not induce inflammatory cytokine release from un-stimulated, normal PBMCs. However, ACW was able to inhibit bacterial lipopolysaccharide (LPS)-induced inflammatory cytokine TNF-α released from PBMCs, showing an anti-inflammation potential. Furthermore, ACW did not stimulate the rat basophilic leukemia cell (RBL-2H3) related allergy response on de-granulation. Our data presented ACW with a strong anti-oxidative ability in a superoxide anion radical scavenging assay. In mass spectrometry information, magnesium and zinc ions demonstrated bio-functional detections for anti-inflammation as well as other metal ions such as potassium and calcium were observed. ACW also had minor tyrosinase and melanin decreasing activities in human epidermal melanocytes (HEMn-MP) without apparent cytotoxicity. In addition, the cell proliferation assay illustrated anti-growth and anti-migration effects of ACW on human skin melanoma cells (A375.S2) indicating that it exerted the anti-cancer potential against skin cancer. The results obtained from biological assays showed that ACW possessed multiple bioactivities, including anti-microorganism, anti-inflammation, allergy-free, antioxidant, anti-melanin and anticancer properties. To our knowledge, this was the first report presenting these bioactivities on ACW