Chiral cysteine-copper ion-based assemblies for improved phototherapy.

Phototherapy, encompassing photothermal therapy and photodynamic therapy, is gaining attention as an appealing cancer treatment modality. To enhance its clinical implementation, a comprehensive exploration of the pivotal factors influencing phototherapy is warranted. In this study, the L/d-cysteine (Cys)-copper ion (Cu2+) chiral nanoparticles, through the assembly of L/d-Cys-Cu2+ coordination complexes, were constructed. We found that these nanoparticles interacted with chiral liposomes in a chirality-dependent manner, with d-Cys-Cu2+ nanoparticles exhibiting more than three times stronger binding affinity than l-Cys-Cu2+ nanoparticles. Furthermore, we demonstrated that the d-Cys-Cu2+ nanoparticles were more efficiently internalized by Hela cells in contrast with l-Cys-Cu2+. On this basis, indocyanine green (ICG), acting as both photothermal and photodynamic agent, was encapsulated into L/d-Cys-Cu2+ nanoparticles. Experimental results showed that the l-Cys-Cu2+-ICG and d-Cys-Cu2+-ICG nanoparticles displayed almost identical photothermal performance and singlet oxygen (1O2) generation capability in aqueous solution. However, upon laser irradiation, the d-Cys-Cu2+-ICG nanoparticles achieved enhanced anti-tumor effects compared to l-Cys-Cu2+-ICG due to their chirality-promoted higher cellular uptake efficiency. These findings highlight the crucial role of chirality in phototherapy and provide new perspectives for engineering cancer therapeutic agents.

Evaluating Social Determinants of Health in a Mobile Integrated Healthcare-Community Paramedicine Program.

In 2018, the University of Maryland Medical Center and the Baltimore City Fire Department implemented a community paramedicine program to help medically or socially complex patients transition from hospital to home and avoid hospital utilization. This study describes how patients' social determinants of health (SDoH) needs were identified, and measures the association between needs and hospital utilization. SDoH needs were categorized into ten domains. Multinomial logistic regression was used to measure association between identified SDoH domains and predicted risk of readmission. Poisson regression was used to measure association between SDoH domains and actual 30-day hospital utilization. The most frequently identified SDoH needs were in the Coordination of Healthcare (37.7%), Durable Medical Equipment (18.8%), and Medication (16.3%) domains. Compared with low-risk patients, patients with an intermediate risk of readmission were more likely to have needs within the Coordination of Healthcare (RRR [95% CI] 1.12 [1.01, 1.24], p = 0.032) and Durable Medical Equipment (RRR = 1.13 [1.00, 1.27], p = 0.046) domains. Patients with the highest risk for readmission were more likely to have needs in the Utilities domain (RRR = 1.76 [0.97, 3.19], p = 0.063). Miscellaneous domain needs, such as requiring a social security card, were associated with increased 30-day hospital utilization (IRR = 1.23 [0.96, 1.57], p = 0.095). SDoH needs within the Coordination of Healthcare, Durable Medical Equipment, and Utilities domains were associated with higher predicted 30-day readmission, while identification documentation and social services needs were associated with actual readmission. These results suggest where to allocate resources to effectively diminish hospital utilization.

Evaluating the Impact of a Mobile Integrated Health‒Community Paramedicine Program on Health-Related Social Needs and Hospital Readmissions.

OBJECTIVE: Evaluate a mobile integrated health-community paramedicine program's effect on addressing health-related social needs and their association with hospital readmissions. METHODS: This observational study enrolled 1,003 patients from 5/4/2018-7/23/21. Descriptive statistics summarize social needs. A Poisson regression model examined the association of interventions for social needs with 30-day readmissions. RESULTS: Patients who had their medication-related needs fully addressed had a 65% lower rate of total 30-day readmission compared with patients who had no such needs fully addressed (IRR=0.35, 95% CI 0.18-0.68, P=.002). No variables reached statistical significance related to unplanned 30-day readmissions, aside from the HOSPITAL Score. CONCLUSIONS: Assisting patients with medication-related needs is associated with reductions in overall 30-day readmissions. Interventions within most domains were not associated with reductions in overall or unplanned 30-day readmissions. This program had greater success addressing needs with one-step interventions, suggesting additional time and resources may be necessary to address complex social needs.

Impact of a mobile integrated healthcare and community paramedicine program on improving medication adherence in patients with heart failure and chronic obstructive pulmonary disease after hospital discharge: A pilot study.

Background: The mobile integrated health-community paramedicine (MIH-CP) program affiliated with the University of Maryland Medical Center focuses on improving patient transitions from hospital to home by addressing both medical and social determinants of health. Until recently, only self-contained health systems could integrate inpatient and outpatient medication data. Without some means to track patients in transition, there is a significant risk of medication-related problems and errors. Objective: To evaluate the impact of the MIH-CP program on medication adherence among patients with congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD). Methods: This is a pilot observational study designed to compare adherence to drug regimens prescribed at hospital discharge (measured by the proportion of days covered [PDC]) between patients enrolled in the MIH-CP program and a propensity-matched control group. Propensity scores were calculated using 11 demographic, diagnostic, third-party payer, and patient care-associated variables. Discharge medication details were obtained from electronic medical records. PDC for each of the medications were calculated from pharmacy claims data. Results: Eighty-three patients were included in the study; forty-three patients were placed in the intervention group and 40 were propensity-matched controls. After adjusting for age, sex, and third-party payer, findings indicated that medication adherence was higher among patients enrolled in the MIH-CP program compared with control during the first 30 days post-discharge, specifically among patients diagnosed with CHF (8% difference in PDC, 95% confidence interval [CI], -0.12-0.28%) and COPD (14% difference, 95% CI, -0.15-0.43%), although neither result achieved statistical significance. The differences in medication adherence between patients who were enrolled and those who were not enrolled in the MIH-CP program diminished after 30 days post-discharge. Conclusion: This pilot study demonstrated a trend toward improved medication adherence among patients enrolled in the MIH-CP program. Future research involving a larger patient cohort will be required to confirm these preliminary findings.

Carthamus tinctorius L.: A natural neuroprotective source for anti-Alzheimer's disease drugs.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multicausal neurodegenerative disease clinically characterized by generalized dementia. The pathogenic process of AD not only is progressive and complex but also involves multiple factors and mechanisms, including ß-amyloid (Aß) aggregation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. As the first-line treatment for AD, cholinesterase inhibitors can, to a certain extent, relieve AD symptoms and delay AD progression. Nonetheless, the current treatment strategies for AD are far from meeting clinical expectations, and more options for AD treatment should be applied in clinical practice. AIM OF THE REVIEW: The aim of this review was to investigate published reports of C. tinctorius L. and its active constituents in AD treatment through a literature review. MATERIALS AND METHODS: Information was retrieved from scientific databases including Web of Science, ScienceDirect, Scopus, Google Scholar, Chemical Abstracts Services and books, PubMed, dissertations and technical reports. Keywords used for the search engines were "Honghua" or "Carthamus tinctorius L." or "safflower" in conjunction with "(native weeds OR alien invasive)"AND "Chinese herbal medicine". RESULTS: A total of 47 literatures about C. tinctorius L. and its active constituents in AD treatment through signaling pathways, immune cells, and disease-related mediators and systematically elucidates potential mechanisms from the point of anti-Aß aggregation, suppressing tau protein hyperphosphorylation, increasing cholinergic neurotransmitters levels, inhibiting oxidative stress, anti-neuroinflammation, ameliorating synaptic plasticity, and anti-apoptosis. CONCLUSIONS: Chinese herbal medicine (CHM) is a treasure endowed by nature to mankind. Emerging studies have confirmed that CHM and its active constituents play a positive role in AD treatment. Carthamus tinctorius L., the most commonly used CHM, can be used with medicine and food, with the effect of activating blood circulation and eliminating blood stasis. In the paper, we have concluded that the existing therapeutic mechanisms of C. tinctorius L. and summarized the potential mechanisms of C. tinctorius L. and its active constituents in AD treatment through a literature review.

Potential Mechanisms of White Peony against Primary Sjögren's Syndrome Based on Network Pharmacology and Molecular Docking.

Background: Multiple system and organ damage occurs with the continuous progression of primary Sjögren's syndrome (pSS), and the lack of specific drugs against this disease is a huge challenge. White peony (WP), a widely used traditional Chinese herb, has been confirmed to have a therapeutic value in pSS. However, the specific mechanisms of WP in the treatment of pSS are unknown. Methods: The active ingredients and their targets in WP were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and disease-related targets were collected from GeneCards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). The overlapping targets were acquired by taking the intersection. A protein-protein interaction (PPI) network was structured using the STRING database. A disease-drug-ingredient-target (D-D-I-T) network was built using Cytoscape software. By filtering twice, core targets were acquired. Gene Ontology (GO) and Kyoto Encyclopedia Gene and Genome (KEGG) pathway enrichment analysis were accompanied by R packages. Finally, molecular docking was used to verify the abovementioned results. Results: In total, we screened 88 WP-related targets, 1480 pSS-related targets, and 32 overlapping targets. D-D-I-T Network analysis displayed six main active ingredients of WP, which played a significant therapeutic role in pSS. Further topological analysis selected seven core target genes, including IL-6, TNF, PPARγ, AKT1, CASP3, NOS3, and JUN. GO and KEGG analysis were used to elucidate pharmacological mechanisms, mainly acting in the AGE-RAGE signaling pathway. Molecular docking proved that paeoniflorin bound well with core targets. Conclusion: Our study revealed that IL-6, TNF, AKT1, CASP3, NOS3, and JUN may be pathogenic target genes, and PPARγ may be a protective target gene. The main active ingredients of WP mainly played a therapeutic role via the AGE-RAGE signaling pathway. These findings provide a fundamental and theoretical basis for the clinical application of WP.

Analysis of an Alternative Model of Definitive Care For Low-Acuity Emergency Calls: A Natural Experiment.

BACKGROUND: Emergency medical services (EMS) diversion strategies attempt to limit the impact of low-acuity care on emergency department (ED) crowding, but evidence supporting these strategies is scarce. OBJECTIVE: This study aims to measure the effect of a treat-in-place and alternative destination program on ED transports and EMS utilization. METHODS: We used a natural experiment study design to measure effects of a pilot prehospital diversion program on ED transport, number of EMS vehicles dispatched, and EMS time on task for low-acuity emergency calls in a midsized urban setting characterized by a high prevalence of health disparities, concentrated poverty, and limited access to primary care between October 2018 and January 2020. We also used direct variable cost to estimate the return on investment attributable to avoided ED visits. RESULTS: Of 3725 calls that met eligibility criteria, the program responded to 1084 (29.1%), with 56.7% of those resulting in an ED visit, compared with 64.6% of the 492 control calls that were eligible but were dispatched when program services were unavailable. Of 1084 calls receiving response, 213 (19.6%) were enrolled in the program, and 8.5% of those were transported by EMS to the ED. Adjusted results show EMS time on task was 23.4 min less for enrolled calls vs. controls. The program can achieve a positive return on investment by enrolling 2.9 patients/day. CONCLUSIONS: A prehospital diversion program reduced ED visits and EMS transport times. Improved targeting of patients for enrollment would further increase the intervention's efficacy and cost savings.

The Orphan Crop Crassocephalum crepidioides Accumulates the Pyrrolizidine Alkaloid Jacobine in Response to Nitrogen Starvation.

Crassocephalum crepidioides is an African orphan crop that is used as a leafy vegetable and medicinal plant. Although it is of high regional importance in Sub-Saharan Africa, the plant is still mainly collected from the wild and therefore efforts are made to promote its domestication. However, in addition to beneficial properties, there was first evidence that C. crepidioides can accumulate the highly toxic pyrrolizidine alkaloid (PA) jacobine and here it was investigated, how jacobine production is controlled. Using ecotypes from Africa and Asia that were characterized in terms of their PA profiles, it is shown that the tetraploid C. crepidioides forms jacobine, an ability that its diploid close relative Crassocephalum rubens appears to lack. Evidence is provided that nitrogen (N) deficiency strongly increases jacobine in the leaves of C. crepidioides, that this capacity depends more strongly on the shoot than the root system, and that homospermidine synthase (HSS) activity is not rate-limiting for this reaction. A characterization of HSS gene representation and transcription showed that C. crepidioides and C. rubens possess two functional versions, one of which is conserved, that the HSS transcript is mainly present in roots and that its abundance is not controlled by N deficiency. In summary, this work improves our understanding of how environmental cues impact PA biosynthesis in plants and provides a basis for the development of PA-free C. crepidioides cultivars, which will aid its domestication and safe use.

The effect of a mobile integrated health program on health care cost and utilization.

OBJECTIVE: To measure the effect of a mobile integrated health community paramedicine (MIH-CP) transitional care program on hospital utilization, emergency department visits, and charges. DATA SOURCES: Retrospective secondary data from the electronic health record and regional health information exchange were used to analyze patients discharged from a large academic medical center and an affiliated community hospital in Baltimore, Maryland, May 2018-October 2019. STUDY DESIGN: We performed an observational study comparing patients enrolled in an MIH-CP program to propensity-matched controls. Propensity scores were calculated using measures of demographics, clinical characteristics, social determinants of health, and prior health care utilization. The primary outcome is inpatient readmission within 30 days of discharge. Secondary outcomes include excess days in acute care 30 days after discharge and emergency department visits, observation hospitalizations, and total health care charges within 30 and 60 days of discharge. DATA COLLECTION: Included patients were over 18 years old, discharged to home from internal/family medicine services, and live in eligible ZIP codes. The intervention group was enrolled in the MIH-CP program; controls met inclusion criteria but were not enrolled during the study period. PRINCIPAL FINDINGS: The adjusted model showed no difference in 30-day inpatient readmission between 464 enrolled patients and propensity-matched controls (adjusted incidence rate ratio = 1.19, 95% confidence interval [CI] [0.89, 1.60]). There was a higher rate of observation hospitalizations within 30 days of index discharge for MIH-CP patients (adjusted incidence rate ratio = 1.78, 95% CI = [1.01, 3.14]). This difference did not persist at 60 days, and there were no differences in other secondary outcomes. CONCLUSIONS: We found no significant difference in short-term health care utilization or charges between patients enrolled in an MIH-CP transitional care program and propensity-matched controls. This highlights the importance of well-controlled, robust evaluations of effectiveness in novel care-delivery systems.

Application of care bundles in bowel preparation for colonoscopy in children.

BACKGROUND: To explore the value of care bundles (CBs) in bowel preparation for colonoscopy in children. METHODS: Children who underwent electronic fiberoptic colonoscopy or enteroscopic surgery in our hospital from September 2016 to October 2017 were enrolled as the conventional nursing (CN) group and children who received such procedures from November 2017 to December 2018 were enrolled as the care bundle group. Polyethylene glycol electrolyte lavage solution (PEG-ELS) was used for bowel preparation in all children. The CBs included nurse education, risk evaluation of inadequate bowel preparation, education of children and families, and observation and assessment during preparation. The quality of bowel preparation, tolerance and safety, families' anxiety score, and degree of satisfaction with hospitalization were compared between these two groups. RESULTS: Eighty-two children were enrolled in this study, with 42 cases in the CB group and 40 cases in the CN group. Symptoms of distension, abdominal pain, vomiting, and fatigue, along with intragastric feeding, were compared between the two groups. An additional enema was performed in 2 cases in the CB group and in 12 cases in the CN group, demonstrating a significant difference between the groups. The Aronchick score and anxiety score of families were 1.24±0.85 vs. 2.35±1.76 (t=-3.477, P=0.001) and 3.28±0.85 vs. 5.45±1.78 (t=-3.473, P=0.001) in the CN group and CB group, respectively. The satisfaction rate was 97.62% vs. 85.00% (χ2=6.764, P<0.001). CONCLUSIONS: Implementation of the care bundles in the bowel preparation of children planning to receive colonoscopy can improve the quality of preparation and the satisfaction with hospitalization while alleviating the anxiety of patients and their families.

Iodine-based Dual-Energy CT of Traumatic Hemorrhagic Contusions: Relationship to In-Hospital Mortality and Short-term Outcome.

BackgroundTraumatic hemorrhagic contusions are associated with iodine leak; however, quantification of leakage and its importance to outcome is unclear.PurposeTo identify iodine-based dual-energy CT variables that correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.Materials and MethodsIn this retrospective study, consecutive patients with contusions from May 2016 through January 2017 were analyzed. Two radiologists evaluated CT variables from unenhanced admission head CT and follow-up head dual-energy CT scans obtained after contrast material-enhanced whole-body CT. The outcomes evaluated were in-hospital mortality, Rancho Los Amigos scale (RLAS) score, and disability rating scale (DRS) score. Logistic regression and linear regression were used to develop prediction models for categorical and continuous outcomes, respectively.ResultsThe study included 65 patients (median age, 48 years; interquartile range, 25-65.5 years); 50 were men. Dual-energy CT variables that correlated with mortality, RLAS score, and DRS score were iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusion. The single-energy CT variable that correlated with mortality, RLAS score, and DRS score was hematoma volume at follow-up CT. Multiple logistic regression analysis after inclusion of clinical variables identified two predictors that enabled determination of mortality: postresuscitation Glasgow coma scale (P-GCS) (adjusted odds ratio, 0.42; 95% confidence interval [CI]: 0.2, 0.86; P = 0.01) and iodine quantity in pseudohematoma (adjusted odds ratio, 1.4 per milligram; 95% CI: 1.02 per milligram, 1.9 per milligram; P = 0.03), with a mean area under the receiver operating characteristic curve of 0.96 ± 0.05 (standard error). For RLAS, the predictors were P-GCS (mean coefficient, 0.32 ± 0.06; P < .001) and iodine quantity in contusion (mean coefficient, -0.04 per milligram ± 0.02; P = 0.01). Predictors for DRS were P-GCS (mean coefficient, -1.15 ± 0.27; P < .001), age (mean coefficient, 0.13 per year ± 0.04; P = .002), and iodine quantity in contusion (mean coefficient, 0.19 per milligram ± 0.07; P = .02).ConclusionIodine-based dual-energy CT variables correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Talbott and Hess in this issue.

Oxyresveratrol protects human lens epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis by activation of Akt/HO-1 pathway.

Oxidative stress induced by hydrogen peroxide (H2O2) triggers human lens epithelial cell (HLEC) apoptosis and initiates cataract formation. Oxyresveratrol (Oxy) was reported to possess antioxidant and free radical scavenging activities. Herein, we investigated the effects of Oxy on H2O2-induced oxidative stress and apoptosis in HLECs and the associated mechanisms. Cell viability was detected by MTT assay. The oxidative damage was assessed by measuring the activities of superoxide dismutases-1 (SOD-1), catalase (CAT), glutathione reductase (GSH), and malondialdehyde (MDA). Apoptosis was analyzed by flow cytometry analysis. The changed expressions of heme oxygenase-1 (HO-1) and protein kinase B (Akt) pathways were evaluated by qRT-PCR and western blot. We found that exposure to H2O2 dose-dependently reduced cell viability, and induced oxidative stress and apoptosis in HLECs, which were reversed by pretreatment with Oxy. Oxy increased p-Akt and HO-1 expressions in H2O2-stimulated HLECs. Akt and HO-1 expressions form a regulatory axis and Oxy activated the Akt/HO-1 pathway in H2O2-stimulated HLECs. Inhibition of the Akt/HO-1 pathway by LY294002 or ZnPP attenuated the effects of Oxy on oxidative stress and apoptosis in H2O2-stimulated HLECs. In conclusion, Oxy protected H2O2-induced oxidative stress and apoptosis through activating the Akt/HO-1 pathway, suggesting the protective effect of Oxy against H2O2-induced cataract.

Meta-analysis of Exercise Training on Vascular Endothelial Function in Cancer Survivors.

Cancer and cardiovascular disease (CVD) are leading causes of morbidity and mortality in the United States. Vascular endothelial dysfunction, an important contributor in the development of CVD, improves with exercise training in patients with CVD. However, the role of regular exercise to improve vascular function in cancer survivors remains equivocal. We performed a meta-analysis to determine the effect of exercise training on vascular endothelial function in cancer survivors. We searched PubMed (1975 to 2016), EMBASE CINAHL (1937 to 2016), OVID MEDLINE (1948 to 2016), and Cochrane Central Registry of Controlled Trials (1991 to 2016) using search terms: vascular function, endothelial function, flow-mediated dilation [FMD], reactive hyperemia, exercise, and cancer. Studies selected were randomized controlled trials of exercise training on vascular endothelial function in cancer survivors. We calculated pooled effect sizes and performed a meta-analysis. We identified 4 randomized controlled trials (breast cancer, n=2; prostate cancer, n=2) measuring vascular endothelial function by FMD (n=3) or reactive hyperemia index (n=1), including 163 cancer survivors (exercise training, n=82; control, n=81). Aerobic exercise training improved vascular function (n=4 studies; standardized mean difference [95% CI]=0.65 [0.33, 0.96], I2=0%; FMD, weighted mean difference [WMD]=1.28 [0.22, 2.34], I2=23.2%) and peak exercise oxygen uptake (3 trials; WMD [95% CI]=2.22 [0.83, 3.61] mL/kg/min; I2=0%). Our findings indicate that exercise training improves vascular endothelial function and exercise capacity in breast and prostate cancer survivors.

Less Exercise and More Drugs: How a Low-Income Population Manages Chronic Pain.

OBJECTIVES: To evaluate chronic pain management in a multistate, low-income Hispanic population, and to examine predictors of exercising and prescription pain medication (PPM) use. DESIGN: Online survey administered to a representative sample of Hispanic adults in June 2015. SETTING: Five southwestern states. PARTICIPANTS: Among all online panel members who were Hispanic (N=1007), aged 35 to 75 years from 5 states, representing 11,016,135 persons, the survey was completed by 516 members (51%). Among these, 102 participants were identified with chronic noncancer pain representing 1,140,170 persons. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Exercising or using PPM for chronic pain in past year. RESULTS: Most participants reported using PPM (58%) and exercise (54%) to manage pain. Compared with annual household incomes >$75,000, adjusted odds ratios [AORs] for exercising were .20 for <$10,000 (P=.12); .40 for $10,000 to $34,999 (P=.22); and .15 for $35,000 to $74,999 (P=.015). Conversely, AORs for PPM were over 4-fold higher for lower-income groups as follows: 14.2, 4.79, and 4.85, respectively (all P<.065). PPM users rated the importance of accessing a gym to manage pain lower (P=.01), while exercisers rated the feasibility of gym access to manage pain higher (P=.001). CONCLUSIONS: In a Hispanic population-based sample with chronic pain, lower-income groups tended to exercise less but use PPM more. Barriers to gym access and use may play a role in these disparities.

Bone marrow from blotchy mice is dispensable to regulate blood copper and aortic pathologies but required for inflammatory mediator production in LDLR-deficient mice during chronic angiotensin II infusion.

BACKGROUND: The blotchy mouse caused by mutations of ATP7A develops low blood copper and aortic aneurysm and rupture. Although the aortic pathologies are believed primarily due to congenital copper deficiencies in connective tissue, perinatal copper supplementation does not produce significant therapeutic effects, hinting additional mechanisms in the symptom development, such as an independent effect of the ATP7A mutations during adulthood. METHODS: We investigated if bone marrow from blotchy mice contributes to these symptoms. For these experiments, bone marrow from blotchy mice (blotchy marrow group) and healthy littermate controls (control marrow group) was used to reconstitute recipient mice (irradiated male low-density lipoprotein receptor -/- mice), which were then infused with angiotensin II (1,000 ng/kg/min) for 4 weeks. RESULTS: By using Mann-Whitney U test, our results showed that there was no significant difference in the copper concentrations in plasma and hematopoietic cells between these 2 groups. And plasma level of triglycerides was significantly reduced in blotchy marrow group compared with that in control marrow group (P < 0.05), whereas there were no significant differences in cholesterol and phospholipids between these 2 groups. Furthermore, a bead-based multiplex immunoassay showed that macrophage inflammatory protein (MIP)-1ß, monocyte chemotactic protein (MCP)-1, MCP-3, MCP-5, tissue inhibitor of metalloproteinases (TIMP)-1, and vascular endothelial growth factor (VEGF)-A production was significantly reduced in the plasma of blotchy marrow group compared with that in control marrow group (P < 0.05). More important, although angiotensin II infusion increased maximal external aortic diameters in thoracic and abdominal segments, there was no significant difference in the aortic diameters between these 2 groups. Furthermore, aortic ruptures, including transmural breaks of the elastic laminae in the abdominal segment and lethal rupture in the thoracic segment, were observed in blotchy marrow group but not in control marrow group; however, there was no significant difference in the incidence of aortic ruptures between these 2 groups (P = 0.10; Fisher's exact test). CONCLUSIONS: Overall, our study indicated that the effect of bone marrow from blotchy mice during adulthood is dispensable in the regulation of blood copper, plasma cholesterol and phospholipids levels, and aortic pathologies, but contributes to a reduction of MIP-1ß, MCP-1, MCP-3, MCP-5, TIMP-1, and VEGF-A production and triglycerides concentration in plasma. Our study also hints that bone marrow transplantation cannot serve as an independent treatment option.

Music to reduce pain and distress in the pediatric emergency department: a randomized clinical trial.

IMPORTANCE: Many medical procedures aimed at helping children cause them pain and distress, which can have long-lasting negative effects. Music is a form of distraction that may alleviate some of the pain and distress experienced by children while undergoing medical procedures. OBJECTIVE: To compare music with standard care to manage pain and distress. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted in a pediatric emergency department with appropriate sequence generation and adequate allocation concealment from January 1, 2009, to March 31, 2010. Individuals assessing the primary outcome were blind to treatment allocation. A total of 42 children aged 3 to 11 years undergoing intravenous placement were included. INTERVENTIONS: Music (recordings selected by a music therapist via ambient speakers) vs standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was behavioral distress assessed blinded using the Observational Scale of Behavioral Distress-Revised. The secondary outcomes included child-reported pain, heart rate, parent and health care provider satisfaction, ease of performing the procedure, and parental anxiety. RESULTS: With or without controlling for potential confounders, we found no significant difference in the change in behavioral distress from before the procedure to immediately after the procedure. When children who had no distress during the procedure were removed from the analysis, there was a significantly less increase in distress for the music group (standard care group = 2.2 vs music group = 1.1, P < .05). Pain scores among children in the standard care group increased by 2 points, while they remained the same in the music group (P = .04); the difference was considered clinically important. The pattern of parent satisfaction with the management of children's pain was different between groups, although not statistically significant (P = .07). Health care providers reported that it was easier to perform the procedure for children in the music group (76% very easy) vs the standard care group (38% very easy) (P = .03). Health care providers were more satisfied with the intravenous placement in the music group (86% very satisfied) compared with the standard care group (48%) (P = .02). CONCLUSIONS AND RELEVANCE: Music may have a positive impact on pain and distress for children undergoing intravenous placement. Benefits were also observed for the parents and health care providers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00761033.

Effect of L-carnitine on maturation, cryo-tolerance and embryo developmental competence of bovine oocytes.

In this study, the effects of the addition of L-carnitine in in vitro maturation (IVM) medium for bovine oocytes on their nuclear maturation and cryopreservation were investigated; they were matured in IVM medium supplemented with 0.0, 0.3, 0.6 and 1.2 mg/mL of L-carnitine (control, 0.3, 0.6 and 1.2 groups, respectively) and some of them were vitrified by Cryotop. Moreover, the effects of L-carnitine during in vitro fertilization (IVF) and in vitro culture (IVC) on the developmental potential and quality of IVF embryos were also examined. A significantly higher maturation rate of oocytes was obtained for 0.3 and 0.6 mg/mL groups compared with the control (P < 0.05). The blastocyst formation rate in the 0.6 group was significantly improved, whereas the rate in the 1.2 group was significantly decreased when compared with the control group (P < 0.05). No significant difference was found in embryo development between the control and the L-carnitine group after oocyte vitrification. Supplementation of IVF and IVC media with L-carnitine had no effect on development to the blastocyst stage of IVM oocytes treated with 0.6 mg/mL L-carnitine. In conclusion, the supplementation of L-carnitine during IVM of bovine oocytes improved their nuclear maturation and subsequent embryo development after IVF, but when they were vitrified the improving effects were neutralized.

[Experimental study of ginsenoside Rb1 on herpes simplex virus-1 infection for protecting nerves].

OBJECTIVE: To explore the action mechanism of ginsenoside Rb1 (GRb1) on protecting herpes simplex virus-1 (HSV-1) infected nerves by studying its inhibitory effects on abnormal changes of apoptosis and nerve growth factor (NGF) mRNA expression in HSV-1 infected human glioma cells U251. METHODS: The inhibitory effects of GRb1 on HSV-1 induced abnormal apoptosis of U251 cells were detected using MTT colorimetry and flow cytometry. The NGF mRNA expressions in different treatment groups were detected using semiquantitative RT-PCR. RESULTS: (1) In 400 microg/mL GRb1 + HSV-1 group, MTT value was higher than HSV-1 group at 24, 36, and 48 h after infection (P < 0.05). (2) Cytopathic effects (CPE) were observed in HSV-1 group at 36 h after infection. In 400 microg/mL GRb1 + HSV-1 group merges increased at 36 h after infection, but most cells were in normal shapes. (3) Results of flow cytometry showed that the cell apoptosis rate was lower in 400 microg/mL GRb1 + HSV-1 group than in the HSV-1 group at24 and 36 h after infection (P < 0.05). (4) Results of RT-PCR showed that in 400 microg/mL GRb1 + HSV-1 group, NGF mRNA expressions decreased at 6-12 h after infection (P < 0.05), but it increased at 24, 36, and 48 h after infection, and was obviously higher than that in the HSV-1 group (P < 0.05). CONCLUSIONS: GRb1 at an appropriate concentration could inhibit abnormal cell apoptosis and changes of NGF mRNA expressions in HSV-1 infection. Therefore, we inferred that GRb1 could protect nerves possibly through up-regulating NGF mRNA expressions and inhibiting apoptosis.

Music for pain and anxiety in children undergoing medical procedures: a systematic review of randomized controlled trials.

OBJECTIVE: The aim of this study was to conduct a systematic review of the efficacy of music therapy (MT) on pain and anxiety in children undergoing clinical procedures. METHODS: We searched 16 electronic databases of published and unpublished studies, subject bibliographies, reference lists of relevant articles, and trials registries. Two reviewers independently screened 4559 citations and reviewed the full manuscript of 393 studies. Nineteen studies met the inclusion criteria: randomized controlled trial, children aged 1 month to 18 years were examined, music was used as an intervention, and the study measured pain or anxiety. Music therapy was considered active if a music therapist was involved and music was used as a medium for interactive communication. Passive music therapy was defined as listening to music without the involvement of a music therapist. RESULTS: The 19 included trials involved 1513 subjects. The methodological quality of the studies was generally poor. Overall, MT showed a significant reduction in pain and anxiety (standardized mean difference [SMD] -0.35; 95% confidence interval [CI], -0.55 to -0.14; 9 studies; N = 704; I(2) = 42%). When analyzed by outcome, MT significantly reduced anxiety (SMD -0.39; 95% CI, -0.76 to -0.03; 5 studies; n = 284; I(2) = 52.4%) and pain (SMD -0.39; 95% CI, -0.66 to -0.11; 5 studies; N = 465; I(2) = 49.7%). There was no evidence of publication bias. CONCLUSIONS: Music is effective in reducing anxiety and pain in children undergoing medical and dental procedures. Music can be considered an adjunctive therapy in clinical situations that produce pain or anxiety.

Meditation practices for health: state of the research.

OBJECTIVES: To review and synthesize the state of research on a variety of meditation practices, including: the specific meditation practices examined; the research designs employed and the conditions and outcomes examined; the efficacy and effectiveness of different meditation practices for the three most studied conditions; the role of effect modifiers on outcomes; and the effects of meditation on physiological and neuropsychological outcomes. DATA SOURCES: Comprehensive searches were conducted in 17 electronic databases of medical and psychological literature up to September 2005. Other sources of potentially relevant studies included hand searches, reference tracking, contact with experts, and gray literature searches. REVIEW METHODS: A Delphi method was used to develop a set of parameters to describe meditation practices. Included studies were comparative, on any meditation practice, had more than 10 adult participants, provided quantitative data on health-related outcomes, and published in English. Two independent reviewers assessed study relevance, extracted the data and assessed the methodological quality of the studies. RESULTS: Five broad categories of meditation practices were identified (Mantra meditation, Mindfulness meditation, Yoga, Tai Chi, and Qi Gong). Characterization of the universal or supplemental components of meditation practices was precluded by the theoretical and terminological heterogeneity among practices. Evidence on the state of research in meditation practices was provided in 813 predominantly poor-quality studies. The three most studied conditions were hypertension, other cardiovascular diseases, and substance abuse. Sixty-five intervention studies examined the therapeutic effect of meditation practices for these conditions. Meta-analyses based on low-quality studies and small numbers of hypertensive participants showed that TM(R), Qi Gong and Zen Buddhist meditation significantly reduced blood pressure. Yoga helped reduce stress. Yoga was no better than Mindfulness-based Stress Reduction at reducing anxiety in patients with cardiovascular diseases. No results from substance abuse studies could be combined. The role of effect modifiers in meditation practices has been neglected in the scientific literature. The physiological and neuropsychological effects of meditation practices have been evaluated in 312 poor-quality studies. Meta-analyses of results from 55 studies indicated that some meditation practices produced significant changes in healthy participants. CONCLUSIONS: Many uncertainties surround the practice of meditation. Scientific research on meditation practices does not appear to have a common theoretical perspective and is characterized by poor methodological quality. Firm conclusions on the effects of meditation practices in healthcare cannot be drawn based on the available evidence. Future research on meditation practices must be more rigorous in the design and execution of studies and in the analysis and reporting of results.