Miracle-dz/UniFAR-FTUs huggingface dataset:
Curcumin‐loaded poly(ε‐caprolactone) nanofibres: Diabetic wound dressing with anti‐oxidant and anti‐inflammatory properties

1 Curcumin is a naturally occurring poly‐phenolic compound with a broad range of favourable biological functions, including anti‐cancer, anti‐oxidant and anti‐inflammatory activities. The low bioavailability and in vivo stability of curcumin require the development of suitable carrier vehicles to deliver the molecule in a sustained manner at therapeutic levels. 2 In the present study, we investigated the feasibility and potential of poly(caprolactone) (PCL) nanofibres as a delivery vehicle for curcumin for wound healing applications. By optimizing the electrospinning parameters, bead‐free curcumin‐loaded PCL nanofibres were developed. 3 The fibres showed sustained release of curcumin for 72 h and could be made to deliver a dose much lower than the reported cytotoxic concentration while remaining bioactive. Human foreskin fibroblast cells (HFF‐1) showed more than 70% viability on curcumin‐loaded nanofibres. 4 The anti‐oxidant activity of curcumin‐loaded nanofibres was demonstrated using an oxygen radical absorbance capacity (ORAC) assay and by the ability of the fibres to maintain the viability of HFF‐1 cells under conditions of oxidative stress. 5 The curcumin‐loaded nanofibres also reduced inflammatory induction, as evidenced by low levels of interleukin‐6 release from mouse monocyte–macrophages seeded onto the fibres following stimulation by Escherichia coli‐derived lipopolysaccharide. 6 The in vivo wound healing capability of the curcumin loaded PCL nanofibres was demonstrated by an increased rate of wound closure in a streptozotocin‐induced diabetic mice model. 7 These results demonstrate that the curcumin‐loaded PCL nanofibre matrix is bioactive and has potential as a wound dressing with anti‐oxidant and anti‐inflammatory properties.
Kruppel-like Factor 4 Is a Mediator of Proinflammatory Signaling in Macrophages*

Activation of macrophages is important in chronic inflammatory disease states such as atherosclerosis. Proinflammatory cytokines such as interferon-γ (IFN-γ), lipopolysaccharide (LPS), or tumor necrosis factor-α can promote macrophage activation. Conversely, anti-inflammatory factors such as transforming growth factor-β1 (TGF-β1) can decrease proinflammatory activation. The molecular mediators regulating the balance of these opposing effectors remain incompletely understood. Herein, we identify Kruppel-like factor 4 (KLF4) as being markedly induced in response to IFN-γ, LPS, or tumor necrosis factor-α and decreased by TGF-β1 in macrophages. Overexpression of KLF4 in J774a macrophages induced the macrophage activation marker inducible nitric-oxide synthase and inhibited the TGF-β1 and Smad3 target gene plasminogen activator inhibitor-1 (PAI-1). Conversely, KLF4 knockdown markedly attenuated the ability of IFN-γ, LPS, or IFN-γ plus LPS to induce the iNOS promoter, whereas it augmented macrophage responsiveness to TGF-β1 and Smad3 signaling. The KLF4 induction of the iNOS promoter is mediated by two KLF DNA-binding sites at –95 and –212 bp, and mutation of these sites diminished induction by IFN-γ and LPS. We further provide evidence that KLF4 interacts with the NF-κB family member p65 (RelA) to cooperatively induce the iNOS promoter. In contrast, KLF4 inhibited the TGF-β1/Smad3 induction of the PAI-1 promoter independent of KLF4 DNA binding through a novel antagonistic competition with Smad3 for the C terminus of the coactivator p300/CBP. These findings support an important role for KLF4 as a regulator of key signaling pathways that control macrophage activation.
Maternal serum inhibin levels in twin and singleton pregnancies conceived by assisted reproduction.

BACKGROUND To investigate whether second trimester serum inhibin levels differ in pregnancies conceived by assisted reproduction technology (ART). METHODS In Israel, serum samples from twin pregnancies were obtained for inhibin testing from women either referred for routine ultrasound monitoring, follow up after multi-fetal reduction or amniocentesis, largely for advanced maternal age. In the UK, inhibin had been tested prospectively in singleton and twin pregnancies of women having routine Down's syndrome (DS) screening. Results were available from 207 ART pregnancies: 170 singletons and 37 twins. This includes 15 twins from Israel, known to have been reduced from triplets to twins. Comparison was made with 4384 spontaneous pregnancies: 4334 singletons and 50 twins. Results were expressed in multiples of the gestation-specific median (MoM) for normal spontaneous pregnancies. RESULTS In ART singletons, the median maternal inhibin level was higher (1.11 MoM) than in spontaneous singletons (0.99 MoM, P < 0.001, two-tail Wilcoxon Rank Sum Test). In twins, there was no material difference between ART and spontaneous pregnancies with medians of 1.98 and 2.18 MoM, respectively (P = 0.62). There was no effect of multi-fetal reduction, with medians of 1.76 and 1.81 MoM in reduced and non-reduced twins, respectively (P = 0.46). CONCLUSION It appears that serum inhibin levels are increased on average in ART singletons but not in ART twin pregnancies. More data will be needed before deciding whether risk calculation parameters need to be altered when using inhibin for DS screening in pregnancy.
Carotid Endarterectomy and Intraoperative Emboli Detection

Carotid endarterectomy (CEA) performed with continuous transcranial Doppler (TCD) monitoring provides a unique opportunity to determine the number of cerebral microemboli and to relate their occurrence to the surgical technique. The purpose of this study was to assess in CEA the impact of cerebral microembolism on clinical outcome and brain morphology. We also evaluated the influence of the audible TCD signal on the surgeon and his/her technique. In a prospective series of 301 endarterectomies, brain function was monitored with electroencephalography and TCD ultrasonography. Preoperative and intraoperative risk factors were entered in a logistic regression analysis program to assess their correlation with cerebral outcome. To evaluate the impact of cerebral microembolism on brain morphology, we compared preoperative and postoperative magnetic resonance (MR) images of the brain in a subgroup of 40 patients. Microemboli (> 10) observed during the dissection phase of the operation were related to intraoperative (P < 0.002) and postoperative (P < 0.02) cerebral complications. Microemboli that occurred during shunting were also related to intraoperative complications (P < 0.007). Finally, the phenomenon of > 10 microemboli during dissection was significantly (P < 0.005) related to new hyperintensive lesions on the postoperative T2‐weighted MR images. The presence of microembolism (> 10) during the dissection phase of carotid endarterectomy shows a statistically significant relationship with perioperative cerebral complications and with new ischemic lesions on MR images of the brain. Microembolism during shunting is also related to intraoperative complications. Surgeons can be guided by the audio Doppler and emboli signals by changing their technique, which may result in a decline of the intraoperative stroke rate.
Invasion of Vero cells and induction of apoptosis in macrophages by pathogenic Leptospira interrogans are correlated with virulence

Interactions of virulent Leptospira interrogans serovar icterohaemorrhagiae strain Verdun with Vero cells (African green monkey kidney fibroblasts) and a monocyte-macrophage-like cell line (J774A.1) were assayed by a double-fluorescence immunolabelling method. Infectivity profiles were investigated according to (i) the duration of contact between leptospires and eukaryotic cells and (ii) the number of in vitro passages after primary isolation from lethally infected guinea pigs. Comparative experiments were conducted with the corresponding high-passage avirulent variant and the saprophytic leptospire Leptospira biflexa Patoc I. In Vero cells, virulent leptospires were quickly internalized from 20 min postinfection, whereas avirulent and saprophytic strains remained extracellularly located. In addition, the virulent strain demonstrated an ability to actively invade the monocyte-macrophage-like J774A.1 cells during the early stages of contact and to induce programmed cell death, as shown by the detection of oligonucleosomes in a quantitative sandwich enzyme immunoassay. In both cellular systems, subsequent in vitro subcultures demonstrated a progressive decrease of the invasiveness, pointing out the necessity of using primocultures of Leptospira for virulence studies. Invasiveness of virulent leptospires was significantly inhibited with monodansylcadaverine, indicating that internalization was dependent on receptor-mediated endocytosis. Invasion of epithelial cells and induction of apoptosis in macrophages may be related to the pathogenicity of Leptospira, and both could contribute to its ability to survive in the host and to escape from the immune response.
Neural mechanisms of evoked oscillations: Stability and interaction with transient events

There is increasing evidence that early event‐related potentials are a result of phase alignment of ongoing background oscillations of the electroencephalogram rather than additive amplitude modulation. Steady state visual‐evoked potentials (ssVEPs) can be recorded using an intensity modulated stimulus, resulting in an evoked brain response at a known frequency, i.e. the stimulation frequency. Given this property, the ssVEP is ideally suited for examining the relationship between single‐trial fluctuations in phase/amplitude and the evoked brain potential resulting from averaging across trials. To address this issue, the current study investigated the contribution of single trial power and intertrial phase locking to ssVEP generation by presenting a peripheral flicker. Further, transient stimuli were presented during flicker and at three increasing latency lags following flicker offset to examine (1) to what extent a stimulus can disturb the ssVEP oscillation and (2) how phase alignment during P1‐N1‐P2 time windows is affected during presence of evoked oscillations. The former assessment evaluates the stability of ssVEPs and the latter the phase alignment processes to transient stimuli under experimentally induced background oscillations. We observed that ssVEPs are a result of phase alignment rather than single trial amplitude modulation. In addition, ssVEP oscillations were not disturbed by transient stimuli. Finally, phase alignment in P1‐N1‐P2 time windows was distorted during and shortly after steady state stimulation. We conclude that ssVEPs represent strongly phase locked oscillations sharing the same generation mechanisms as early evoked potentials. Hum Brain Mapp, 2007. © 2007 Wiley‐Liss, Inc.
Mechanochemotransduction During Cardiomyocyte Contraction Is Mediated by Localized Nitric Oxide Signaling

Nitric oxide exposed to mechanical stress reveals the chemical cues involved in altering Ca2+ signals that lead to arrhythmias. Pulling Harder on the Heartstings To eject blood, a beating heart must contract against afterload, the buildup of mechanical tension in the left ventricle, which imposes mechanical stress. Calcium signaling increases in cardiomyocytes in a beating heart to enhance the strength of the muscular contraction to cope with afterload. However, this increase in calcium signaling can lead to arrhythmias. Jian et al. analyzed cardiomyocytes embedded in a gel matrix that imposed mechanical strain resembling afterload and found that nitric oxide generated near ryanodine receptors, a group of intracellular calcium channels, contributed to the afterload-induced increase in calcium signaling. These results identify potential therapeutic targets for treating various heart diseases that are caused by excessive mechanical stress or dysregulated Ca2+ signaling. Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca2+ dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca2+ transient, which enhanced contractility to counter mechanical load but also caused spontaneous Ca2+ sparks during diastole that could be arrhythmogenic. The increases in the Ca2+ transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2+ in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2+ sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca2+-calmodulin–dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca2+ sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca2+ sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2+ sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress–induced Ca2+ dysregulation, arrhythmias, and cardiomyopathy.
The discipline of innovation.

Some innovations spring from a flash of genius. But as Peter Drucker points out in this HBR Classic, most result from a conscious, purposeful search for opportunities. For managers seeking innovation, engaging in disciplined work is more important than having an entrepreneurial personality. Writing originally in the May-June 1985 issue, Drucker describes the major sources of opportunities for innovation. Within a company or industry, opportunities can be found in unexpected occurrences, incongruities of various kinds, process needs, or changes in an industry or market. Outside a company, opportunities arise from demographic changes, changes in perception, or new knowledge. These seven sources overlap, and the potential for innovation may well lie in more than one area at a time. Innovations based on new knowledge, of course, tend to have the greatest effect on the marketplace. But it often takes decades before the ideas are translated into actual products, processes, or services. The other sources of innovation are easier and simpler to handle, yet they still require managers to look beyond established practices. Drucker emphasizes that in seeking opportunities, innovators need to look for simple, focused solutions to real problems. The greatest praise an innovation can receive is for people to say, "This is obvious! " Grandiose ideas designed to revolutionize an industry rarely work. Innovation, like any other endeavor, takes talent, ingenuity, and knowledge. But Drucker cautions that if diligence, persistence, and commitment are lacking, companies are unlikely to succeed at the business of innovation.
Silver enhances the in vitro antifungal activity of the saponin, CAY‐1

The fungicidal properties of purified CAY‐1, dissolved silver ion and ethylenediamine tetraacetic acid (EDTA) separately were studied in vitro as were the abilities of silver and EDTA to enhance CAY‐1 fungicidal properties. Non‐germinated and germinating conidia of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium verticillioides (Fusarium moniliforme), Fusarium oxysporum and Fusarium solani were incubated separately with CAY‐1 (0–24.8 μg ml−1), silver (0–111.1 μg ml−1), and EDTA (0–2400 μg ml−1). Controls consisted of non‐germinated or germinated conidia in test medium. To assess combined activity, compounds, based on the sub‐lethal doses of each as defined in the initial experiments, were combined and tested in bioassays. Controls for the mixed sets consisted of non‐germinated or germinated conidia only or with the sub‐lethal CAY‐1 test concentrations. The minimum inhibitory concentrations (MICs) for CAY‐1 and silver, both separate and combined, were determined. Viability assays showed CAY‐1 activity only against the germinating conidia of A. flavus, A. niger and F. solani. Silver was active against the germinating conidia of all fungi and the non‐germinated conidia of F. oxysporum and F. solani. Combined silver and CAY‐1 produced significant viability loss at concentrations not effective separately. EDTA was not fungicidal separately and did not enhance CAY‐1 fungicidal properties. MIC data showed that CAY‐1 plus silver had an additive effect. Results indicate that dissolved silver was fungicidal in vitro and enhanced the fungicidal properties of CAY‐1 at concentrations ineffective when tested separately.
Judging a Book by Its Cover

Objectives: In certain health care facilities, the staff commonly wear uniforms for dementia care. Wearing uniforms are often believed to improve the well-being of institutionalized people with dementia (PwD) by facilitating orientation and preserving hygiene. However, when studied more thoroughly, it appears that their use counters to person centeredness. This study aims to investigate the impact of wearing uniforms on the quality of life (QoL) of institutionalized PwD. Method: A natural experimental design was operated in 4 special care units (SCUs) in France. Two SCUs served as an experimental group (caregivers wearing street clothes except when performing hands-on physical care; N = 13) and 2 served as a comparison group (caregivers wearing uniforms; N = 14). The QoL of PwD was measured using the QoL-Alzheimer’s Disease scale, and focus groups were carried out with caregivers. Results: Overall and significantly enhanced QoL scores were observed for the experimental street clothing staff group when compared to the uniform group. Caregivers also reported subjective impressions of overall beneficial outcomes for PwD when the caregivers were not wearing uniforms and reported feeling more at ease when interacting with them. Conclusion: Results are discussed in terms of intergroup relationships, living and working conditions, and ethical issues.
Autoclaves and their dangers and safety in laboratories

SUMMARY Using a laboratory downward displacement vertical autoclave with the help of thermocouples recorded on a 12 point multichannel strip recorder, the risk of failing to sterilize laboratory discard buckets has been demonstrated. The use of proper temperature and time controls can prevent this risk. A load in a bucket with perforated sides is more easily sterilized than in a solid bucket. Wire baskets, where appropriate, facilitate the sterilizing practice. The addition of water to a bucket does not reduce the time of heating up. It is desirable that sealed bottles of media should not be sterilized in simple downward displacement autoclaves, but if used, strict monitoring of temperatures and times is essential both in the heating up stage and especially in the cooling stage. The temperatures in bottles are slow to rise and very slow to fall. Bottles at high temperature 80–405° C. or over have a high internal pressure which can allow the bottles to explode when subjected to thermal shock if removed too early. It is suggested that all laboratory autoclaves should have a load temperature simulator or similar device to control the temperature of the load during the cycle automatically. For the sterilization of fluid media, it is suggested that, in addition to a simulator there should be accelerated cooling to reduce damage to the media and, what is more important, to rapidly bring down the temperature and thus the internal pressure in the bottles to a safe level. The opening of the sterilizer door or lid should be automatically controlled by the load temperature simulator.
Acute spondylolytic spondylolisthesis. Risk of progression and neurological complications.

Acute spondylolytic spondylolisthesis was diagnosed after major trauma in five patients. The level of injury was between the third and fourth lumbar vertebrae in one patient and between the fifth lumbar and first sacral vertebrae in four. The initial spondylolisthesis was grade I in four patients and grade III in one. Four of the patients were initially managed non-operatively. The deformity did not progress in a five-year-old boy with grade-I spondylolisthesis who had been managed with immobilization in a body cast. The deformity progressed in two of the adolescents who had been managed non-operatively; the progression was from grade I to grade III in one of these patients and from grade III to grade V (spondyloptosis) in the other, in whom a cauda equina syndrome also developed. The latter patient was subsequently managed with posterior reduction and arthrodesis followed by an anterior arthrodesis, and the neurological deficits resolved. The deformity also progressed, from grade I to grade II over three years, in a fifty-seven-year-old woman who had been managed non-operatively. One patient who had a grade-I deformity was managed with immediate operative stabilization followed by immobilization in a thoracolumbosacral orthosis; the deformity did not progress. Although minor or repetitive trauma is often associated with spondylolysis, high-energy trauma may produce a more severe form of spondylolysis with spondylolisthesis. These deformities are more unstable, with instability similar to that of a fracture-dislocation, and they have a greater propensity to progress than the usual form of spondylolytic spondylolisthesis. (ABSTRACT TRUNCATED AT 250 WORDS)
Hyperglycemia Diverts Dividing Osteoblastic Precursor Cells to an Adipogenic Pathway and Induces Synthesis of a Hyaluronan Matrix That Is Adhesive for Monocytes*

Background: Adipocytes accumulate in diabetic bone marrow. Results: Bone marrow stromal cells that divide in hyperglycemia divert from the osteoblast lineage to pathological adipogenesis and produce an extensive monocyte-adhesive hyaluronan matrix with consequent demineralization of trabecular bone. Conclusion: This mechanism diminishes the stromal cell population with an accumulation of metabolically stressed adipocytes. Significance: This provides new insights into diabetic osteopenia. Isolated rat bone marrow stromal cells cultured in osteogenic medium in which the normal 5.6 mm glucose is changed to hyperglycemic 25.6 mm glucose greatly increase lipid formation between 21–31 days of culture that is associated with decreased biomineralization, up-regulate expression of cyclin D3 and two adipogenic markers (CCAAT/enhancer binding protein α and peroxisome proliferator-activated receptor γ) within 5 days of culture, increase neutral and polar lipid synthesis within 5 days of culture, and form a monocyte-adhesive hyaluronan matrix through an endoplasmic reticulum stress-induced autophagic mechanism. Evidence is also provided that, by 4 weeks after diabetes onset in the streptozotocin-induced diabetic rat model, there is a large loss of trabecular bone mineral density without apparent proportional changes in underlying collagen matrices, a large accumulation of a hyaluronan matrix within the trabecular bone marrow, and adipocytes and macrophages embedded in this hyaluronan matrix. These results support the hypothesis that hyperglycemia in bone marrow diverts dividing osteoblastic precursor cells (bone marrow stromal cells) to a metabolically stressed adipogenic pathway that induces synthesis of a hyaluronan matrix that recruits inflammatory cells and establishes a chronic inflammatory process that demineralizes trabecular cancellous bone.