Miracle-dz/UniFAR-FTUs huggingface dataset:
Wine polyphenols and promotion of cardiac health

Wine polyphenols are considered to have beneficial effects on CHD and atherosclerosis. The consumption of red wine is high in Italy and France, approximately four times greater than that in the UK. This disparity in red wine consumption is thought to be the reason for the ‘French paradox’, where France was shown to have a coronary mortality rate close to that of China or Japan despite saturated fat intakes and cholesterol levels similar to the UK and USA. In the present review, we discuss the effects of wine and some of its polyphenol constituents on early pathological indicators of CHD such as plasma lipids, the endothelium and vasculature, platelets and serum antioxidant activity. The review also examines whether the polyphenols or the alcohol in wine is responsible for the effects on markers of heart disease. The present review concludes that red wine polyphenols have little effect on plasma lipid concentrations but wine consumption appears to reduce the susceptibility of LDL to oxidation and increase serum antioxidant capacity. However, these effects do depend on the amount of wine and period of supplementation. Authors who have examined specific polyphenols suggest that some phenolics appear to have endothelium-dependent vaso-relaxing abilities and some a positive effect on NO concentrations. Red wine phenolics also have an inhibitory effect on platelet aggregation, and individual phenolics also have a similar effect in vitro, although it should be noted that there are often discrepancies as large as ten-fold between the concentrations of polyphenolics tested in vitro and their measured levels in vivo. Evidence suggests that alcohol has a positive synergistic effect with wine polyphenols on some atherosclerotic risk factors. Thus evidence that wine drinking is beneficial for cardiac health continues to accumulate but more research is required to understand fully and exactly the functions of red wine polyphenols.
Adaptive Tracking Controller Design of Nonlinear Systems With Time Delays and Unknown Dead-Zone Input

This paper focuses on the tracking control problem for a class of nonlinear system with time delays and dead-zone input. The nonsymmetric dead-zone input case is considered without the knowledge of the dead zone parameters. The time delay uncertainties are bounded by a nonlinear function with unknown coefficients. By constructing a novel Lyapunov functional, we design a simple and smooth adaptive state feedback controller. It is shown that the solution of the resulting closed-loop error system converges to an adjustable region exponentially. Finally, numerical examples are included to show the effectiveness of the theoretical results.
Improving emergency department efficiency by patient streaming to outcomes-based teams.

OBJECTIVE To describe the process and results of a process redesign based on task analysis and lean thinking approaches aimed at improving emergency department (ED) efficiency. METHODS Before-and-after study comparing 12-month periods before and after the process redesign for total episodes of ambulance bypass, waiting times (overall and by triage category) and total ED time (overall and by triage category). Time data were analysed using non-parametric methods. RESULTS The years were broadly comparable, with the exception that there was an 8.4% increase in total hours of care delivered (a marker of ED workload) in the year after the change. Episodes of ambulance bypass reduced by 55% (120 v 54). There were statistically significant waiting times reductions for triage categories 3 and 5 (median reductions 5 and 11 minutes respectively). There was an increase in total ED time for triage category 3 (median increase 7 min) and a decrease for categories 4 and 5 (median reduction 14 and 18 min, respectively). CONCLUSION ED process redesign based on task analysis and lean thinking approaches can result in improved ED efficiency.
Development of the upper lip: Morphogenetic and molecular mechanisms

The vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross‐regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis. Developmental Dynamics 235:1152–1166, 2006. © 2005 Wiley‐Liss, Inc.
The patient-physician relationship. JAMA focuses on the center of medicine.

The patient-physician relationship is under siege. I believe there are two sources that underlie the distress experienced by many patients and physicians in their interactions with each other. First, there is an intensification of the tension between the science and the art of medicine. Second, there are severe strains related to the rapid changes in the economics of medical practice. Concern about tensions between the science and the art of medicine is hardly new. In the first paragraph of his landmark 1927JAMAarticle, Francis Peabody noted that the most common criticism of young physicians of that era was that "they are too 'scientific' and do not know how to take care of patients. "2A physician can hardly be "too scientific" in the sense of having an understanding of a disease and the knowledge necessary to diagnose and treat it successfully. What Dr Peabody meant almost 70 years ago,
A Conceptual Model of the Factors Affecting the Recreation and Leisure Participation of Children with Disabilities

Participation in everyday activities is considered to be a vital part of children's development, which is related to their quality of life and future life outcomes. Research studies indicate that children with disabilities are at risk for lower participation in ordinary activities at home and in the community. This article presents a conceptual model of 11 environmental, family, and child factors that are thought to influence children's participation in recreation and leisure activities. The article outlines the existing evidence for the influence of these factors on one another and on children's participation. The review encompasses four bodies of literature: the participation of children or adults with disabilities, the risk and resilience of children facing adversity, the determinants of leisure and recreation activities, and the factors influencing physical activity and exercise. The proposed model is expected to be a useful tool for guiding future research studies and for developing policies and programs for children with disabilities and their families.
Numerical Analysis and Optimization of Miniature Electrohydrodynamic Air Blowers

As the demand for advanced microelectronic devices of small form factor and high power density has increased, the capability of the miniaturized mechanical solutions for effective cooling has become critical. Electrohydrodynamic (EHD) air blowers have great potential as alternative cooling solutions over the traditional mechanical systems to meet the thermal management requirements with flexible design and considerable flow production for effective heat removal. In this paper, a numerical analysis and optimization of wire-to-plane EHD air blowers are performed based on 2-D developed models validated against previous data. For a range of blower heights from 2 to 10 mm, the location and length of the collecting plane located at the blower walls apart from the emitter wire electrode are investigated and optimized based on pumping efficiency using the ranges of fixed operating powers and voltages. Simple relations for each optimization method are presented to determine the optimal blower configuration. Results of flow rate and static pressure obtained by each optimized blower show good agreement with those predicted by EHD scaling laws previously presented.
Characterization of Structural Features That Mediate the Tethering of Caenorhabditis elegans Protein Kinase A to a Novel A Kinase Anchor Protein

Caenorhabditis elegans protein kinase A (PKAICE) is tethered to organelles in vivo. A unique A kinase anchor protein (AKAPCE) avidly binds the RI-like regulatory subunits (RCE) of PKAICE and stringently discriminates against RIIα and RIIβ subunits, the preferred ligands for classical AKAPs. We elucidated structural features that stabilize AKAPCE·RCE complexes and confer atypical R isoform specificity on the anchor protein. Three large aliphatic amino acids (Leu236, Ile248, and Leu252) in the tethering domain of AKAPCE(residues 236–255) are crucial for ligation of RCE. Their side chains apparently generate a precisely configured hydrophobic binding pocket that accommodates an apolar surface on RCEdimers. Basic residues (His254-Arg255-Lys256) at the C terminus of the tethering site set an upper limit on affinity for RCE. A central dipeptide (Phe243-Ser244) contributes critical and distinctive properties of the tethering site. Ser244 is essential for selective binding of RCE and exclusion of RII isoforms. The aromatic hydrophobic character of Phe243ensures maximal RCE binding activity, thereby supporting a “gatekeeper” function of Ser244. Substitution of Phe243-Ser244 with Leu-Val generated an RII-specific AKAP. RCE and RII subunits contain similar dimerization domains. AKAP-binding domains of RCE (residues 23–47) and RII differ markedly in size, amino acid sequence, and docking specificity. Four hydrophobic residues (Cys23, Val27, Ile32, and Cys44) in RCE are crucial for avid binding with AKAPCE, whereas side chains from Leu20, Leu35, Val36, Ile40, and Ile41 have little impact on complex formation. Tyr26 is embedded in the docking domain, but its aromatic ring is required for RCE-RCE dimerization. Residues 236–255 in AKAPCE also constitute a binding site for mammalian RIα. RIα (PKAIα) is tightly sequestered by AKAPCE in vitro (K D = ∼10 nm) and in the environment of intact cells. The tethering domain of AKAPCEprovides a molecular module for manipulating intracellular localization of RI and elucidating functions of anchored PKAI in eukaryotes.
The Contributions of Aspartyl Residues in the Acetylcholine Receptor γ and δ Subunits to the Binding of Agonists and Competitive Antagonists*

The acetylcholine (ACh) receptors in muscle have the composition α2βγδ and contain two ACh binding sites. One is formed between an α subunit and the γ subunit, and the other is formed between an α subunit and the δ subunit. Among the residues in the ACh binding sites are αCys-192 and αCys-193. The negatively charged δAsp-180 is at an appropriate distance from αCys-192/193 also to be in the ACh binding site and to interact electrostatically with the positively charged ammonium group common to agonists and competitive antagonists. Mutation to Asn of either δAsp-180 or the aligned residue in the γ subunit, γAsp-174, decreased the affinities of three agonists, acetylcholine, tetramethylammonium, and succinyldicholine 170-560-fold. By contrast, these mutations decreased the affinities of three competitive antagonists, (+)-tubocurarine, hexamethonium, and dihydro-β-erythroidine, only 2-15-fold. Agonists, but not antagonists, promote the transitions of the receptor from the resting state to the higher affinity active and desensitized states, and the greater effects of the mutations of γAsp-174 and δAsp-180 on the apparent affinities of agonists could reflect the involvement of these residues in the conformational changes of the receptor corresponding to its transitions to higher affinity states. In these transitions, one possibility is that γAsp-174 and δAsp-180 move closer to bound agonist.
Cell Loss in Isolated Human Islets Occurs by Apoptosis

Purified islet allografts have largely failed to maintain long-term glucose homeostasis in human recipients, and the reasons for this are unclear. It is noteworthy, however, that islet isolation destroys or removes cellular and noncellular elements of the pancreas that could play an important role in supporting islet survival. The purpose of this study was to determine whether human islet isolation leads to the induction of programmed cell death. Human islets were enzymatically isolated from cadaveric donor pancreata using Liberase or Collagenase P, purified over a discontinuous BSA gradient, then cultured in RPMI 1640 at 37°C in 5% CO2 for ≤7 days. Islets were examined daily by routine histology and immunocytochemistry for islet hormones, DNA fragmentation [cell death; enzyme-linked immunosorbent assay (ELISA) and TUNEL assay] and for transglutaminase (TG) activity, two indicators of apoptosis. TG activity and DNA fragmentation increased by 1,000% and 1,890%, respectively (p < 0.05) This corresponded to the appearance of pyknotic nuclei on light microscopy, the presence of apoptotic bodies on electron microscopy, and the demonstration of TUNEL-positive cells. These were present primarily in a distribution that corresponded to the insulin-immunoreactive cells. At 5 days, 31.4 ± 2.2% of islet cells were TUNEL positive. In summary, apoptosis of islet cells appears soon after islet isolation, and involves primarily the &bgr; cell. This is the first report of apoptosis of islet cells after human islet isolation. The loss of &bgr;-cell mass could be implicated in the failure of islet transplantation and merits further investigation.
Prolonged survival of rat islet xenografts in mice after CD45RB monotherapy

Background. Pancreatic islet transplantation can correct the disordered glucose metabolism of type 1 diabetes, but the number of successful transplants has been low because of the need for long-term immunosuppression and the limited availability of human islets. New approaches, such as the use of tolerance-inducing treatment modalities and the use of islets of nonhuman sources, can possibly improve the success of islet transplantation. In the present study, the authors investigated the effect of anti-CD45RB treatment on the survival of islet xenografts. Methods. Chemically induced diabetic mice underwent xenografting with rat islets and were treated with CD45RB antibodies on days −1, 0, and 5. Immunohistology and real-time polymerase chain reaction were used to study the effect of the treatment in the xenografts. The effect of anti-CD45RB treatment in peripheral blood of normal mice was measured with flow cytometry. Results. In the treated mice, survival of the grafts was prolonged substantially. In the treated mice with functioning grafts, no lymphocytes were found infiltrating the transplanted islets on day 6; whereas in the untreated animals with functioning grafts, signs of rejection were evident. In the grafts of the treated animals, significantly less mRNA for interleukin (IL)-2, interferon-&ggr;, and IL-4 was found compared with the untreated mice. After CD45RB treatment, there was depletion or decrease of CD45RBbright cells from the peripheral blood. Conclusions. Our results show that a short course of anti-CD45RB monotherapy prolongs the survival of rat islet xenografts in C57BL/6 mice.
Selective iNOS Inhibition Prevents Hypotension in Septic Rats While Preserving Endothelium-Dependent Vasodilation

Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) mediates hypotension and metabolic derangements in sepsis. We hypothesized that selective iNOS-inhibition would prevent hypotension in septic rats without inhibiting endothelium-dependent vasodilation caused by the physiologically important endothelial NOS. Rats were exposed to lipopolysaccharide (LPS) for 6 h and the selective iNOS-inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL), the nonselective NOS-inhibitor NG-nitro-l-arginine methyl ester (L-NAME), or control. Mean arterial pressure (MAP) and vasodilation to acetylcholine (ACh, endothelium-dependent), sodium nitroprusside (SNP, endothelium-independent), and isoproterenol (ISO, endothelium-independent &bgr; agonist) were determined. Exhaled NO, nitrate/nitrite-(NOx) levels, metabolic data, and immunohistochemical staining for nitrotyrosine, a tracer of peroxynitrite-formation were also determined. In control rats, L-NAME increased MAP, decreased the response to ACh, and increased the response to SNP, whereas L-NIL did not alter these variables. LPS decreased MAP by 18% ± 1%, decreased vasodilation (ACh, SNP, and ISO), increased exhaled NO, NOx, nitrotyrosine staining, and caused acidosis and hypoglycemia. L-NIL restored MAP and vasodilation (ACh, SNP, and ISO) to baseline and prevented the changes in exhaled NO, NOx, pH, and glucose levels. In contrast, L-NAME restored MAP and SNP vasodilation, but did not alter the decreased response to ACh and ISO or prevent the changes in exhaled NO and glucose levels. Finally, L-NIL but not L-NAME decreased nitrotyrosine staining in LPS rats. In conclusion, L-NIL prevents hypotension and metabolic derangements in septic rats without affecting endothelium-dependent vasodilation whereas L-NAME does not.
TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: a systematic review and meta-analysis

Despite significant progress in improving access to antiretroviral therapy over the past decade, substantial numbers of people living with HIV (PLHIV) in all regions continue to experience severe illness and require hospitalization. We undertook a global review assessing the proportion of hospitalizations and in‐hospital deaths because of tuberculosis (TB) in PLHIV.
A Systematic Review of the Effect Of Proprioceptive and Balance Exercises on People With an Injured Or Reconstructed Anterior Cruciate Ligament

This systematic review investigated the effect of proprioceptive and balance exercise on outcomes following injury and surgical reconstruction of the anterior cruciate ligament (ACL). Five studies of high quality that offered empirical evidence by comparing one rehabilitation program to another were included in this review. There is some evidence that proprioceptive and balance exercise improves outcomes in individuals with ACL-deficient knees. Improvements in joint position sense, muscle strength, perceived knee joint function, and hop testing were reported following proprioceptive and balance exercise. Only one included study investigated proprioceptive exercise following ACL reconstruction. Benefits were noted in the proprioceptive group for measures of strength and proprioception; however, no benefits were noted for any measures of activity. No detrimental effects—such as increased passive joint laxity or decrease in strength—were noted when compared with standard rehabilitation programs for both ACL-deficient and ACL-reconstructed individuals. Further research is required to determine if proprioceptive and balance exercise improves long-term outcomes such as return to sport.
Support for healthy breastfeeding mothers with healthy term babies.

BACKGROUND There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended infants be exclusively breastfed until six months of age, with breastfeeding continuing as an important part of the infant's diet till at least two years of age. However, breastfeeding rates in many countries currently do not reflect this recommendation. OBJECTIVES To assess the effectiveness of support for breastfeeding mothers. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 October 2011). SELECTION CRITERIA Randomised or quasi-randomised controlled trials comparing extra support for healthy breastfeeding mothers of healthy term babies with usual maternity care. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. MAIN RESULTS Of the 67 studies that we assessed as eligible for inclusion, 52 contributed outcome data to the review (56,451 mother-infant pairs) from 21 countries. All forms of extra support analysed together showed an increase in duration of 'any breastfeeding' (includes partial and exclusive breastfeeding) (risk ratio (RR) for stopping any breastfeeding before six months 0.91, 95% confidence interval (CI) 0.88 to 0.96). All forms of extra support together also had a positive effect on duration of exclusive breastfeeding (RR at six months 0.86, 95% CI 0.82 to 0.91; RR at four to six weeks 0.74, 95% CI 0.61 to 0.89). Extra support by both lay and professionals had a positive impact on breastfeeding outcomes. Maternal satisfaction was poorly reported. AUTHORS' CONCLUSIONS All women should be offered support to breastfeed their babies to increase the duration and exclusivity of breastfeeding. Support is likely to be more effective in settings with high initiation rates, so efforts to increase the uptake of breastfeeding should be in place. Support may be offered either by professional or lay/peer supporters, or a combination of both. Strategies that rely mainly on face-to-face support are more likely to succeed. Support that is only offered reactively, in which women are expected to initiate the contact, is unlikely to be effective; women should be offered ongoing visits on a scheduled basis so they can predict that support will be available. Support should be tailored to the needs of the setting and the population group.