Abstract Background Movement and muscle activity of the hip have been shown to affect movement of the lower extremity, and been related to injury. The purpose of this study was to determine if ...increased hip strength affects lower extremity mechanics during running. Methods Within subject, repeated measures design. Fifteen healthy women volunteered. Hip abduction and external rotation strength were measured using a hand-held dynamometer. Three-dimensional biomechanical data of the lower extremity were collected during running using a high-speed motion capture system. Measurements were made before, at the mid-point, and after a 6-week strengthening program using closed-chain hip rotation exercises. Joint range of motion (rearfoot eversion, knee abduction, hip adduction, and internal rotation), eversion velocity, eversion angle at heel strike, and peak joint moments (rearfoot inversion, knee abduction, hip abduction, and external rotation) were analyzed using repeated measures analysis of variance ( P ⩽ 0.05). The independent variable was time (pre-, week 3, and week 6). A separate analysis of variance was conducted with the dependent variables of peak hip abduction and external rotation strength. Findings Hip abduction ( P = 0.009) and external rotation strength ( P < 0.0005) increased by 13% and 23%, respectively. Eversion range of motion decreased ( P = 0.05), hip adduction range of motion increased ( P = 0.05), and a trend of decreased hip internal rotation range of motion ( P = 0.08) were found. Rearfoot inversion moment ( P = 0.02) and knee abduction moment ( P = 0.05) decreased by 57% and 10%, respectively. Interpretation The hip abductors and external rotators were strengthened, leading to an alteration of lower extremity joint loading which may reduce injury risk. These exercises could be used in the rehabilitation, or prevention, of lower extremity injuries.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In ...human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell–cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epithelial ovarian cancer (EOC) is the most common form of ovarian cancer. The poor prognosis generally associated with this disease has led to the search for improved therapies such as ...ferroptosis-inducing agents. Ferroptosis is a form of regulated cell death that is dependent on iron and is characterized by lipid peroxidation. Precise mapping of lipids and iron within tumors exposed to ferroptosis-inducing agents may provide insight into processes of ferroptosis in vivo and ultimately assist in the optimal deployment of ferroptosis inducers in cancer therapy. In this work, we present a method for combining matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) with secondary ion mass spectrometry (SIMS) to analyze changes in spatial lipidomics and metal composition, respectively, in ovarian tumors following exposure to a ferroptosis inducer. Tumors were obtained by injecting human ovarian cancer tumor-initiating cells into mice, followed by treatment with the ferroptosis inducer erastin. SIMS imaging detected iron accumulation in the tumor tissue, and sequential MALDI-MS imaging of the same tissue section displayed two chemically distinct regions of lipids. One region was associated with the iron-rich area detected with SIMS, and the other region encompassed the remainder of the tissue section. Bulk lipidomics confirmed the lipid assignments putatively assigned from the MALDI-MS data. Overall, we demonstrate the ability of multimodal MSI to identify the spatial locations of iron and lipids in the same tissue section and associate these regions with clinical pathology.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Autophagy is regulated by nutrient and energy status and plays an adaptive role during nutrient deprivation and ischemic stress. Metabolic syndrome (MetS) is a hypernutritive state characterized by ...obesity, dyslipidemia, elevated fasting blood glucose levels, and insulin resistance. It has also been associated with impaired autophagic flux and larger-sized infarcts. We hypothesized that diet-induced obesity (DIO) affects nutrient sensing, explaining the observed cardiac impaired autophagy. We subjected male friend virus B NIH (FVBN) mice to a high-fat diet, which resulted in increased weight gain, fat deposition, hyperglycemia, insulin resistance, and larger infarcts after myocardial ischemia-reperfusion. Autophagic flux was impaired after 4 wk on a high-fat diet. To interrogate nutrient-sensing pathways, DIO mice were subjected to overnight fasting, and hearts were processed for biochemical and proteomic analysis. Obese mice failed to upregulate LC3-II or to clear p62/SQSTM1 after fasting, although mRNA for LC3B and p62/SQSTM1 were appropriately upregulated in both groups, demonstrating an intact transcriptional response to fasting. Energy- and nutrient-sensing signal transduction pathways AMPK and mammalian target of rapamycin (mTOR) also responded appropriately to fasting, although mTOR was more profoundly suppressed in obese mice. Proteomic quantitative analysis of the hearts under fed and fasted conditions revealed broad changes in protein networks involved in oxidative phosphorylation, autophagy, oxidative stress, protein homeostasis, and contractile machinery. In many instances, the fasting response was quite discordant between lean and DIO mice. Network analysis implicated the peroxisome proliferator-activated receptor and mTOR regulatory nodes. Hearts of obese mice exhibited impaired autophagy, altered proteome, and discordant response to nutrient deprivation.
Recent evidence has suggested physical therapist involvement in care transitions after hospitalization is associated with reduced rates of hospital readmissions. However, little is known about how ...physical therapists participate in care transitions for older adults, the content of care communications, and the facilitators and barriers of implementing evidence-based care transition strategies into practice. Thus, the purpose of this article is to evaluate participation in care transition activities known to influence readmission risk among older adults, and understand perceptions of and barriers to participation in these activities.
We developed a survey questionnaire to quantify hospital-based physical therapist participation in care transitions and validated it using cognitive interviewing. It was introduced to a cross-sectional national sample of physical therapists who participate in the Academy of Acute Care Physical Therapy electronic discussion board using a SurveyMonkey tool.
More than 90% of respondents agreed they routinely recommended a discharge location and provided recommendations for durable medical equipment for patients at the time of hospital discharge. Respondents did not routinely initiate communication with therapists in other care settings, or follow up with patients to determine whether recommendations were followed. A majority of respondents agreed their facilities would not consider many key care transition activities to count as productive time.This survey provides a novel insight into how hospital-based physical therapists participate in care transitions. Communications between rehabilitation providers across care settings are infrequent, even though those communications are recommended to help reduce readmissions. However, administrative barriers were elucidated in this study that may help explain lack of therapist involvement.
Physical therapists' communications across health care setting about older adults discharging from acute care hospitalization are infrequent, but may represent a meaningful intervention target for future studies. Future research is needed to evaluate best practices for hospital-based physical therapists during care transitions.
Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and ...downstream signaling regulate β-cell death.
We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling.
Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis.
Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids. Video Abstract.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Perceived discrimination is associated with racial cognitive health disparities. Links between discrimination and cognitive performance, like working memory, in everyday settings (i.e. ambulatory ...performance) require investigation. Depressive symptoms may be a mechanism through which discrimination relates to ambulatory working memory.
Discrimination, retrospective and momentary depressive symptoms/mood, and aggregated and momentary working memory performance among older Black and White adults were examined within the Einstein Aging Study.
Racially stratified analyses revealed that discrimination did not relate to Black or White adults' ambulatory working memory. Among Black adults, however, more frequent discrimination was associated with greater retrospectively reported depressive symptoms, which related to more working memory errors across two weeks (indirect effect
< 0.05). This path was not significant among White adults. Links between discrimination and momentary working memory were not explained by momentary reports of depressed mood for Black or White adults.
Depressive symptoms may play an important role in the link between discrimination and ambulatory working memory among Black adults across extended measurements, but not at the momentary level. Future research should address ambulatory cognition and momentary reports of discrimination and depression to better understand how to minimize cognitive health disparities associated with discrimination.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Sphagnum mosses dominate peatlands by employing harsh ecosystem tactics to prevent vascular plant growth and microbial degradation of these large carbon stores. Knowledge about Sphagnum‐produced ...metabolites, their structure and their function, is important to better understand the mechanisms, underlying this carbon sequestration phenomenon in the face of climate variability. It is currently unclear which compounds are responsible for inhibition of organic matter decomposition and the mechanisms by which this inhibition occurs. Metabolite profiling of Sphagnum fallax was performed using two types of mass spectrometry (MS) systems and 1H nuclear magnetic resonance spectroscopy (1H NMR). Lipidome profiling was performed using LC‐MS/MS. A total of 655 metabolites, including one hundred fifty‐two lipids, were detected by NMR and LC‐MS/MS—329 of which were novel metabolites (31 unknown lipids). Sphagum fallax metabolite profile was composed mainly of acid‐like and flavonoid glycoside compounds, that could be acting as potent antimicrobial compounds, allowing Sphagnum to control its environment. Sphagnum fallax metabolite composition comparison against previously known antimicrobial plant metabolites confirmed this trend, with seventeen antimicrobial compounds discovered to be present in Sphagnum fallax, the majority of which were acids and glycosides. Biological activity of these compounds needs to be further tested to confirm antimicrobial qualities. Three fungal metabolites were identified providing insights into fungal colonization that may benefit Sphagnum. Characterizing the metabolite profile of Sphagnum fallax provided a baseline to understand the mechanisms in which Sphagnum fallax acts on its environment, its relation to carbon sequestration in peatlands, and provide key biomarkers to predict peatland C store changes (sequestration, emissions) as climate shifts.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Our objective was to determine outcomes for complex ventral hernia repairs in a large cohort of patients utilizing an operative construct employing retrorectus placement of a narrow, ...macroporous polypropylene mesh with up to 45 suture fixation points for force distribution. No consensus exists on the optimal technique for repair of complex ventral hernias. Current trends emphasize large meshes with wide overlaps and minimal suture fixation, though reported complications and recurrence remain problematic. Methods A retrospective review was performed for all patients undergoing ventral hernia repair with retrorectus placement of midweight, uncoated, soft polypropylene mesh by a single surgeon (GAD) between the years of 2010 and 2015. Patient characteristics, operative history, operative data, and postoperative course were reviewed. Results A total of 101 patients with a mean age of 56 years and a mean body mass index of 29 m/kg2 (range 18–51 m/kg2 ) underwent hernia repair. Patients had a median of 3 prior abdominal operations (range 0–9), with 44 patients presenting with recurrent hernias. A total of 42 patients were Ventral Hernia Working Group grade 1, 40 grade 2, 17 grade 3, and 2 grade 4. There were no recurrences at a mean follow-up of almost 400 days for the 93 patients with long-term follow-up. The surgical site occurrence rate was 7.9% (3 surgical site infections, 2 seromas, 2 hematomas, and 4 instances of delayed wound healing in 8 patients). One patient required reoperation for hematoma drainage; 5 patients required readmission within 30 days. Conclusion An operative construct employing a retrorectus placement of a narrow, macroporous polypropylene mesh with up to 45 suture fixation points for force distribution can achieve significantly better outcomes across a spectrum of Ventral Hernia Working Group grade, risk-stratified patients compared to rates reported in the literature for current strategies that employ wide meshes with minimal fixation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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