Chemically synthesized glycosides of hydroxylated flavylium ions as suitable models of anthocyanins: binding to iron ions and human serum albumin, antioxidant activity in model gastric conditions.
Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1) and its more water-soluble 7-O-β-d-glucopyranoside (P2), are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, they rapidly bind FeIII, weakly interact with FeII and promote its autoxidation to FeIII. Both pigments inhibit heme-induced lipid peroxidation in mildly acidic conditions (a model of postprandial oxidative stress in the stomach), the colorless (chalcone) forms being more potent than the colored forms. Finally, P1 and P2 are moderate ligands of human serum albumin (HSA), their likely carrier in the blood circulation, with chalcones having a higher affinity for HSA than the corresponding colored forms.


Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.
FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas. Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology criteria. Comprehensive genomic profiling was performed on available pretreatment archival tissue to explore additional molecular correlations with efficacy. Among 26 patients, the 6-month PFS rate was 16.0% [95% confidence interval (CI), 5.0-32.5], median PFS was 1.7 months (95% CI, 1.1-2.8), and objective response rate was 3.8%. However, 4 patients had durable disease control lasting longer than 1 year. Among these, 3 had tumors harboring activating point mutations at analogous positions of FGFR1 (K656E; n = 2) or FGFR3 (K650E; n = 1) in pretreatment tissue; an FGFR3-TACC3 fusion was detected in the other. Hyperphosphatemia was the most frequently reported treatment-related adverse event (all-grade, 76.9%; grade 3, 3.8%) and is a known on-target toxicity of FGFR inhibitors. FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3-TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted.


The functional potential and active populations of the pit mud microbiome for the production of Chinese strong-flavour liquor.
The popular distilled Chinese strong-flavour liquor (CSFL) is produced by solid fermentation in the ground pit. Microbes inhabiting in the pit mud (PM) on the walls of the fermentation pit are responsible for the production of caproic acid (CA) that determines the quality of CSFL to a large degree. However, little is known about the active microbial populations and metabolic potential of the PM microbiome. Here, we investigated the overall metabolic features of the PM microbiome and its active microbial components by combining metagenomics and MiSeq-sequencing analyses of the 16S rRNA genes from DNA and RNA (cDNA). Results showed that prokaryotes were predominant populations in the PM microbiome, accounting for 95.3% of total metagenomic reads, while eukaryotic abundance was only 1.8%. The dominant prokaryotic phyla were Firmicutes, Euryarchaeota, Bacteroidetes, Actinobacteria and Proteobacteria, accounting for 48.0%, 19.0%, 13.5%, 2.5% and 2.1% of total metagenomic reads respectively. Most genes encoding putative metabolic pathways responsible for the putative CA production via chain elongation pathway were detected. This indicated that the PM microbiome owned functional potential for synthesizing CA from ethanol or lactate. Some key genes encoding enzymes involved in hydrogenotrophic and acetoclastic methanogenesis pathways were detected in the PM metagenome, suggesting the possible occurrence of interspecies hydrogen transfer between CA-producing bacteria and methanogens. The 16S rDNA and 16S rRNA profiles showed that the Clostridial cluster IV, Lactobacillus, Caloramator, Clostridium, Sedimentibacter, Bacteroides and Porphyromonas were active populations in situ, in which Clostridial cluster IV and Clostridium were likely involved in the CA production. This study improved our understandings on the active populations and metabolic pathways of the PM microbiome involved in the CA synthesis in the CSFL fermentation.


[Seed rain, soil seed bank and seedling regeneration of Quercus aliena var. acureserrata in different slope directions on the middle Qinling Mountains, China].
We studied the seed rain, seed pool quantity and quality dynamics, and seedling develop-ment of natural Quercus aliena var. acureserrata forests in different slopes (sunny, semi-sunny, semi-shady and shady slope) of the middle Qinling Mountains, China. The results showed that seed rain of Q. aliena var. acureserrata generally began at mid-August, peaked from mid-late September to early October, and ended in mid-early November. The dissemination process, occurrence time, and composition of seed rain in four slopes were different. The seed rain intensity of the semi-sunny slope was the highest, which was 134.13 seeds·m-2, followed by sunny slope, semi-shady slope, and shady slope. The seed rain on the sunny slope occurred first, and the duration of the whole and peak period were the longest. The seed rain on the shady slope occurred at the latest, and the duration of the whole and peak period were the shortest. The seed viability and mature seeds proportion were semi-sunny slope > sunny slope > semi-shady slope > shady slope. From the end of the seed rain to the August of the next year, the size of soil seed bank was semi-sunny slope > sunny slope > semi-shady slope > shady slope. The number of mature, immature and nibbled seeds and seed vigor of soil seed bank showed a decreasing trend with time, while the number of moldy seeds increased. The seeds in soil seed bank mainly existed in the litter layer, followed by the 0-2 cm soil layer, with few seeds in the 2-5 cm soil layer. The seedling density of Q. aliena var. acureserrata was significantly different among the four slopes. The semi-sunny slope, with the highest seedling density, was more suitable for seed germination and seedling growth of Q. aliena var. acureserrata than other slopes.


Highly Sensitive Detection of Microstructure Variation Using a Thickness Resonant Transducer and Pulse-Echo Third Harmonic Generation.
In nonlinear ultrasound testing, the relative nonlinear parameter is conveniently measured as a sensitive means of detecting and imaging overall variation of microstructures and damages. Compared to the quadratic nonlinear parameter (β'), the cubic nonlinear parameter (γ'), calculated as the third harmonic amplitude divided by the cube of the fundamental amplitude, has generally a higher value, providing better sensitivity in nonlinear parameter mapping. Since the third harmonic amplitude is about two orders of magnitude lower than the fundamental amplitude, efficient excitation and highly sensitive reception of third harmonic is very important. In this paper, we explore an odd harmonic thickness resonant transducer that meets the requirements for pulse-echo third harmonic generation (THG) measurements. We also address the problem of source nonlinearity that may be present in the measured amplitude of the third harmonic and propose a method to properly correct it. First, we measure γ' for a series of aluminum specimens using the through-transmission method to observe the behavior of γ' as a function of specimen thickness and input voltage, and examine the effects of various corrections such as attenuation, diffraction and source nonlinearity. Next, we apply the odd harmonic resonant transducer to pulse-echo THG measurements of precipitation heat-treated specimens. It is shown that such transducer is very effective in generation and detection of fundamental and third harmonics under finite amplitude toneburst excitation. The highly sensitive detectability of γ' are presented as a function of aging time, and the sensitivity of γ' is compared with that of β' and β'2.


Measurement of head-turn in ocular torticollis.
There is a need for a simple and accurate method to measure head-turn in patients who suffer from torticollis secondary to ocular disease. In the technique described here, a fixation object is moved from a point in front of the patient to a point at which the patient's face is straight. The distance that the object is moved is proportional to the amount of head-turn the patient has. With a simple mathematical calculation, the angle of head-turn can be determined, even during a routine clinical evaluation.


[Traumatic asphyxia and continuous venovenous hemofiltration. Report of a case].
A 32-year-old man was admitted with traumatic asphyxia, with aspiration to the bronchi after being buried under sand. The condition progressed to respiratory distress syndrome and systemic inflammatory response. Because ventilatory and hemodynamic deterioration was rapid and severe, in spite of mechanical ventilation and vasoactive drugs, we instated early continuous arteriovenous hemofiltration, which also allowed us to meet the patient's full nutritional needs. We believe that the patient's very satisfactory progress can be attributed to the early use of this procedure, along with appropriate specific treatment.


Landau-Zener Transition in a Continuously Measured Single-Molecule Spin Transistor.
We monitor the Landau-Zener dynamics of a single-ion magnet inserted into a spin-transistor geometry. For increasing field-sweep rates, the spin reversal probability shows increasing deviations from that of a closed system. In the low-conductance limit, such deviations are shown to result from a dephasing process. In particular, the observed behaviors are successfully simulated by means of an adiabatic master equation, with time averaged dephasing (Lindblad) operators. The time average is tentatively interpreted in terms of the finite time resolution of the continuous measurement.


The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury.
The first reported reference to delayed onset muscle soreness (DOMS) was that by Theodore Hough in 1902. Hough stated that when an untrained skeletal muscle performed exercise, it often resulted in discomfort that did not manifest until 8-10 h post-exercise, and concluded that this could not be solely attributed to fatigue. Since Hough's initial observation there has been a proliferation in research into DOMS, and despite this, the exact aetiology remains unclear. This review explores the concept of DOMS in relation to the likely causative factors and also discusses possible reasons for the equivocal findings in the literature. Free radicals are unquestionably produced during and following various forms of contractile activity and are known to result in skeletal muscle damage. Given the link between DOMS and contraction-induced muscle damage, post-exercise free radical production has been associated with DOMS; however, the precise nature of this relationship remains unsubstantiated. This review will address free radical production during and following exercise, discuss methods of assessing their generation, and critically evaluate their relationship with DOMS. There is increasing literature to suggest that free radicals act as signalling molecules, specifically activating redox sensitive transcription factors, which are necessary for muscle regeneration and adaptation following damage. Consequently free radicals may play a key physiological role in the aetiology of DOMS as opposed to a pathological role. Evidence for and against free radicals causing DOMS will be presented, and finally a suggested role of free radicals in DOMS will be proposed.


Model peptide studies of Ag+ binding sites from the silver resistance protein SilE.
Using model peptides, each of the nine MX2H or HXnM (n = 1, 2) motifs of the silver resistance protein SilE has been shown to coordinate to one Ag+ ion by its histidine and methionine residues with Kd in the μM range. This suggests an Ag+ buffering role for SilE in the case of high Ag+ overload.


Radiotherapy in the management of pancreatic islet cell tumors.
Malignant islet cell tumors are commonly treated with surgical resection. Chemotherapy is reserved for residual, unresectable, or metastatic disease. The role for radiotherapy has not been clearly defined. This article describes three cases of advanced islet cell tumors treated effectively with radiotherapy. This experience, in addition to that from other published reports, suggests that radiotherapy is a useful mode for treating advanced islet cell carcinoma.


17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.
Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH.


Meta-analysis of randomized trials on the efficacy of vascular closure devices after diagnostic angiography and angioplasty.
The aim of this meta-analysis was to evaluate the safety and efficacy of vascular closure devices (VCDs). This meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews. The literature search yielded 31 prospective, randomized studies including 7,528 patients who were randomized to VCDs or manual/mechanical compression after diagnostic angiography and/or endovascular procedures. Most of these studies have excluded patients at high risk of puncture site complications. Meta-analysis showed similar results in the study groups in terms of groin hematoma, bleeding, pseudoaneurysm, and blood transfusion. Lower limb ischemia and other arterial ischemic complications (0.3% vs 0%, P = .07) as well as need of surgery for vascular complications (0.7% vs 0.4%, P = .10) were somewhat more frequent with arterial puncture closure devices. The incidence of groin infection was significantly more frequent with VCDs (0.6% vs 0.2%, P = .02). The use of VCD was uniformly associated with a significantly shorter time to hemostasis. Such differences where more evident in patients undergoing percutaneous coronary intervention, whereas these methods were associated with similar rates of adverse events among patients undergoing diagnostic coronary angiography. The use of VCDs is associated with a significantly shorter time to hemostasis and thus may shorten recovery. However, the use of VCDs is associated with a somewhat increased risk of infection, lower limb ischemia/arterial stenosis/device entrapment in the artery, and need of vascular surgery for arterial complications. Further studies are needed to get more conclusive results, particularly in patients at high risk of femoral puncture-related complications.


A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.
Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.


High-frequency fluctuation measurements by far-infrared laser Faraday-effect polarimetry-interferometry and forward scattering system on MST.
Magnetic fluctuation-induced transport driven by global tearing modes has been measured by Faraday-effect polarimetry and interferometry (phase measurements) in the MST reversed field pinch. However, the role of small-scale broadband magnetic and density turbulence in transport remains unknown. In order to investigate broadband magnetic turbulence, we plan to upgrade the existing detector system by using planar-diode fundamental waveguide mixers optimized for high sensitivity. Initial tests indicate these mixers have ×10 sensitivity improvement compared to currently employed corner-cube Schottky-diode mixers and ×5 lower noise. Compact mixer design will allow us to resolve the wavenumbers up to k ∼ 1-2 cm(-1) for beam width w = 1.5 cm and 15 cm(-1) for beam width w = 2 mm. The system can also be used to measure the scattered signal (amplitude measurement) induced by both plasma density and magnetic fluctuations.


An Investigation of the Characteristics of Edentulous Patients Who Choose or Refuse Implant Treatment.
To investigate whether pretreatment patient satisfaction, oral health-related quality of life, or diagnostic complexity are predictive of a decision to choose implant treatment. Edentulous patients requesting dentures were enrolled in a prospective observational study. All subjects were provided with conventional dentures and then given the option to proceed with the placement of two mandibular implants and to have their prosthesis modified into an implant overdenture. Subjects were classified according to the Prosthodontic Diagnostic Index (PDI-CE) and asked to complete a Denture Satisfaction Questionnaire and the Oral Health Impact Profile for edentulous patients (OHIP-EDENT) at pretreatment, following the provision of new dentures, and following modification to overdentures. Of the 125 subjects who had conventional dentures, 15 proceeded with implant treatment. The subjects who decided to have implants were not significantly different in terms of diagnostic complexity or level of satisfaction. Those who chose implants were significantly younger, had newer dentures, and had higher OHIP-EDENT scores at baseline. The most common reason for not being satisfied with dentures but avoiding implants was fear of surgery. The majority of subjects in this study were satisfied with conventional denture treatment, despite registering its limitations. Subjects who were more anatomically compromised were not more likely to choose implant treatment. It remains to be shown whether fear of surgery can be overcome in order to increase the uptake of implant treatment and improve patient outcomes.


Synaptic responses of guinea pig cingulate cortical neurons in vitro.
1. Intracellular recordings were made from layer V/VI neurons of the guinea pig anterior cingulate cortex to investigate postsynaptic potentials (PSPs) evoked by electrical stimulation of the subcortical white matter (forceps minor). 2. Four distinct types of PSPs were recorded (at the resting potential) under normal physiological conditions; 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials (EPSPs) were followed by bicuculline- or picrotoxin-sensitive depolarizing or hyperpolarizing inhibitory postsynaptic potentials (IPSPs), which were further followed by phaclofen-sensitive, long-lasting hyperpolarizing postsynaptic potentials (LPSPs). The average times-to-peak for the EPSP, depolarizing and hyperpolarizing IPSPs, and LPSP were 10, 22, 28, and 146 ms, respectively. 3. In the presence of CNQX and bicuculline, high-intensity electrical stimulation elicited a longer lasting EPSP with a time-to-peak of 21 ms. The amplitude and duration of the EPSP decreased with membrane hyperpolarization and increased with membrane depolarization. The EPSP was reversibly abolished by D,L-2-amino-5-phosphonovaleric acid (D,L-APV). 4. The bicuculline- or picrotoxin-sensitive depolarizing and hyperpolarizing IPSPs and the phaclofen-sensitive LPSP were markedly suppressed by CNQX, suggesting that glutamate (Glu) and/or aspartate nerve terminals project to GABAergic interneurons, and that the GABAergic interneurons are activated mainly by non-N-methyl-D-aspartate (non-NMDA) receptors. 5. In the presence of picrotoxin, the average reversal potential for the compound EPSP was 0 mV, which was similar to that (-6 mV) for the Glu-induced depolarization. In a solution containing D,L-APV at low concentrations, the average reversal potentials for the depolarizing and hyperpolarizing IPSPs and for the early and late components of the gamma-aminobutyric acid (GABA)-induced responses were -62, -72, -70, and -61 mV, respectively. Thus the value for the depolarizing IPSP was similar to that for the late response to GABA, whereas the value for the hyperpolarizing IPSP was almost the same as that for the early response to GABA. The average reversal potential of -90 mV for the LPSP was similar to -93 mV for the baclofen-induced hyperpolarization and to -94 mV for the spike afterhyperpolarization. 6. Application of phaclofen decreased the interspike interval of the spontaneous firing and reversed the increase in the interspike interval after subcortical stimulation. This result indicates that, even in a slice preparation, the anterior cingulate neurons are under tonic inhibitory control exerted by spontaneously active GABAergic interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)


Sleep and immune function: glial contributions and consequences of aging.
The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5'-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging.


Cortical neuronal apoptosis in CADASIL.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the NOTCH3 gene and is a model of pure vascular dementia. Cortical atrophy has been reported to be associated with cognitive decline in the disease, although the underlying mechanism is unknown. We postulated that apoptosis may be involved in this process. We report the clinical history, magnetic resonance imaging findings, and pathologic examinations of 4 patients (2 of whom were demented) who died from complications of the disease. Apoptosis was evaluated in brain tissue using antibodies against activated caspase3 and in situ end labeling assays for DNA fragmentation. Widespread neuronal apoptosis in the cerebral cortex (predominantly in layers 3 and 5) was observed in all patients. This was not seen in 3 non-CADASIL controls. Semiquantitative analysis suggested that apoptosis was more extensive in the presence of larger load of subcortical ischemic lesions and smaller brain volumes. Neuronal apoptosis may be involved in cortical atrophy in CADASIL and appears related to the burden of subcortical ischemic lesions. These findings may have important implications in other small vessel diseases and may provide a potential target for future therapeutic interventions.


Phage & phosphatase: a novel phage-based probe for rapid, multi-platform detection of bacteria.
Genetic engineering of bacteriophages allows for the development of rapid, highly specific, and easily manufactured probes for the detection of bacterial pathogens. A challenge for novel probes is the ease of their adoption in real world laboratories. We have engineered the bacteriophage T7, which targets Escherichia coli, to carry the alkaline phosphatase gene, phoA. This inclusion results in phoA overexpression following phage infection of E. coli. Alkaline phosphatase is commonly used in a wide range of diagnostics, and thus a signal produced by our phage-based probe could be detected using common laboratory equipment. Our work demonstrates the successful: (i) modification of T7 phage to carry phoA; (ii) overexpression of alkaline phosphatase in E. coli; and (iii) detection of this T7-induced alkaline phosphatase activity using commercially available colorimetric and chemilumiscent methods. Furthermore, we demonstrate the application of our phage-based probe to rapidly detect low levels of bacteria and discern the antibiotic resistance of E. coli isolates. Using our bioengineered phage-based probe we were able to detect 10(3) CFU per mL of E. coli in 6 hours using a chemiluminescent substrate and 10(4) CFU per mL within 7.5 hours using a colorimetric substrate. We also show the application of this phage-based probe for antibiotic resistance testing. We were able to determine whether an E. coli isolate was resistant to ampicillin within 4.5 hours using chemiluminescent substrate and within 6 hours using a colorimetric substrate. This phage-based scheme could be readily adopted in labs without significant capital investments and can be translated to other phage-bacteria pairs for further detection.


Donor cycle and donor segmentation: new tools for improving blood donor management.
An adequate donor population is of key importance for the entire blood transfusion chain. For good donor management, a detailed overview of the donor database is therefore imperative. This study offers a new description of the donor cycle related to the donor management process. It also presents the outcomes of a European Project, Donor Management IN Europe (DOMAINE), regarding the segmentation of the donor population into donor types. Blood establishments (BEs) from 18 European countries, the Thalassaemia International Federation and a representative from the South-Eastern Europe Health Network joined forces in DOMAINE. A questionnaire assessed blood donor management practices and the composition of the donor population using the newly proposed DOMAINE donor segmentation. 48 BEs in 34 European countries were invited to participate. The response rate was high (88%). However, only 14 BEs could deliver data on the composition of their donor population. The data showed large variations and major imbalances in the donor population. In 79% of the countries, inactive donors formed the dominant donor type. Only in 21%, regular donors were the largest subgroup, and in 29%, the proportion of first-time donors was higher than the proportion of regular donors. Good donor management depends on a thorough insight into the flow of donors through their donor career. Segmentation of the donor database is an essential tool to understand the influx and efflux of donors. The DOMAINE donor segmentation helps BEs in understanding their donor database and to adapt their donor recruitment and retention practices accordingly. Ways to use this new tool are proposed.


Systematic and functional analysis of non-specific lipid transfer protein family genes in sugarcane under Xanthomonas albilineans infection and salicylic acid treatment.
Plant non-specific lipid transfer proteins (nsLTPs) are small basic proteins that play a significant regulatory role in a wide range of physiological processes. To date, no genome-wide survey and expression analysis of this gene family in sugarcane has been performed. In this study we identified the nsLTP gene family in Saccharum spontaneum and carried out expression profiling of nsLTPs in two sugarcane cultivars (Saccharum spp.) that have different resistance to leaf scald caused by Xanthomonas albilineans (Xa) infection. The effect of stress related to exogenous salicylic acid (SA) treatment was also examined. At a genome-wide level, S. spontaneum AP85-441 had 71 SsnsLTP genes including 66 alleles. Tandem (9 gene pairs) and segmental (36 gene pairs) duplication events contributed to SsnsLTP gene family expansion. Five SsnsLTP proteins were predicted to interact with five other proteins. Expression of ShnsLTPI.8/10/Gb.1 genes was significantly upregulated in LCP85-384 (resistant cultivar), but downregulated in ROC20 (susceptible cultivar), suggesting that these genes play a positive regulatory role in response of sugarcane to Xa infection. Conversely, ShnsLTPGa.4/Ge.3 appears to act as a negative regulator in response Xa infection. The majority (16/17) of tested genes were positively induced in LCP85-384 72 h after SA treatment. In both cultivars, but particularly in LCP85-384, ShnsLTPIV.3/VIII.1 genes were upregulated at all time-points, suggesting that the two genes might act as positive regulators under SA stress. Meanwhile, both cultivars showed downregulated ShnsLTPGb.1 gene expression, indicating its potential negative role in SA treatment responses. Notably, the ShnsLTPGb.1 gene had contrasting effects, with positive regulation of gene expression in response to Xa infection and negative regulation induced by SA stress. Together, our results provide valuable information for elucidating the function of ShnsLTP family members under two stressors and identified novel gene sources for development of sugarcane that are tolerant of environmental stimuli.


Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease.
The abundance of the oligopeptide transporter (Pept-1) in the brush-border membrane of the intestinal epithelium is the central mechanism for regulation of transport of products of protein digestion (dipeptides and tripeptides) and peptidomimetic drugs (for example, beta-lactam antibiotics). Within the past few years, there has been substantial progress in identifying the factors controlling this regulation and the mechanisms of their actions. The purpose of this report is to review this progress. The studies of individual substrates and hormones in a human intestinal cell line (Caco-2) have shown that dipeptides, certain amino acids, insulin, and leptin increase and epidermal growth factor and triiodothyronine decrease the membrane population of Pept-1. In the case of dipeptides, epidermal growth factor, and thyroid hormone, there are parallel changes in the gene expression brought about by alteration of transcription and/or stability of Pept-1 mRNA. In contrast, the treatment with insulin and leptin does not induce any alteration in the Pept-1 gene expression, and the mechanism of increased protein expression appears to be increased trafficking from a preformed cytoplasmic pool to the apical membrane. In vivo studies in rats have shown modulation of protein and gene expressions of the intestinal oligopeptide transporter during the day and during development and in nutritional and metabolic alterations, such as high-protein diet, fasting, and diabetes. Patients with intestinal diseases, such as ulcerative colitis, Crohn's disease, and short-bowel syndrome, may have induction of the Pept-1 expression in their colon. Finally, pharmacological studies have shown that the expression of Pept-1 can be upregulated by agents such as 5 fluorouracil and downregulated by agents such as cyclosporine. In conclusion, the above studies have produced a wealth of new information on regulation of a key transporter in the intestine. This information may have useful applications in nutritional and pharmacological treatments, for example, in diabetic patients needing enteral nutrition or in ulcerative colitis patients needing the suppression of the intestinal inflammation.


Vertical induction of engrailed-2 and other region-specific markers in the early chick embryo.
We investigated the role of vertical signals in the regulation of Engrailed-2, a regionally restricted (mesencephalon/metencephalon) neuroectodermal marker, using epiblast grafted from prospective neuroectoderm or prospective trunk mesoderm at mid-stage 3 in the gastrulating chick embryo. Grafts that were isolated from the rostral (prospective neuroectodermal) epiblast and placed rostral to or at the future mesencephalon/metencephalon level, between the endoderm and epiblast of stage 3d to stage 8 host embryos, expressed Engrailed-2 after 24 hr in culture, whereas these same grafts failed to express this marker when placed at a more caudal level. Grafts from caudal = (prospective trunk mesodermal) epiblast, which would ordinarily not express Engrailed-2, also expressed this marker when placed at the mesencephalon/metencephalon level, and failed to express it when grafted more caudally. The expression of four other markers, L5, Fgf8, Wnt-1, and paraxis, were also evaluated. Collectively, our results show that regionally restricted vertical signals are capable of inducing neuroectoderm from naive tissue, and of patterning epiblast to express some but not all mesencephalon/metencephalon isthmus markers. Experiments using grafts taken from older embryos indicated that the competence of prospective neuroectoderm to become regionally patterned by vertical signals is gradually lost between stage 3c and stage 7. Similarly, prospective mesoderm from the caudal epiblast becomes unable to respond to vertical, neural-inductive signals at these stages. These observations support a role for vertical signals in the induction and patterning of the neuroectoderm at gastrula and early neurula stages.


In brief: genomic imprinting and imprinting diseases.
Genomic imprinting is an epigenetic process by which the male and the female germline confer different DNA methylation marks and histone modifications onto specific gene regions, so that one allele of an imprinted gene is active and the other one is silent. Since the dosage of imprinted genes is important for normal development, growth and behaviour, the loss or duplication of the active allele can cause disease.


Palate morphogenesis. I. Immunological and ultrastructural analyses of mouse palate.
Midpalate was analyzed for the presence of nonmuscle contractile systems. The results indicate that increased amounts of actin and myosin are present in cells of regions 2 and 3. A localization of the contractile proteins in cellular projections (filopodia) and in the peripheral cytoplasm of the cell body was confirmed by indirect immunofluorescence studies, using antibodies directed against smooth muscle myosin and against skeletal muscle actin. Specificity of the immunofluorescence reactions was ascertained by immunoabsorption studies using purified myosin and actin. Electron microscopic observations of the mesenchymal cells in region 2 revealed 70A microfilaments along the cell periphery and packed in fliopodia-like projections which course between the cells. These cells, which surround a small ossification center, show no orientation, but extend up to the cranial base perichondrium and down into the shelf between the tongue side epithelium and the ossification center. The cells and projections are attached to each other by adherens and tight-like junctions, forming a putative cohesive contractile network. Putative contractile cells in region 3 are strikingly aligned perpendicular to the oral epithelium and extend one-third of the distance into the shelf. Projections from region 3 cells are contiguous with basement membrane material of the oral epithelium. Axonal bundles and single axons were commonly observed coursing through regions 2 and 3, often seen in close association with the mesenchymal cells. Both clear and dense-core vesicles were found in the axons and cells of these regions. The possible role of these putative nonmuscle contractile cells in palate morphogenesis is discussed.


Engineering biocompatible benzodithiophene-based polymer dots with tunable absorptions as high-efficiency theranostic agents for multiscale photoacoustic imaging-guided photothermal therapy.
To date, photoacoustic imaging (PAI) and PAI-guided photothermal therapy (PTT) have been performed for noninvasive cancer diagnosis and precise ablation of tumors. To conduct concurrent PAI and PTT, it is essential to develop theranostic agents with strong optical absorption and high photothermal transfer efficiency. In this study, we have engineered theranostic agents with tunable absorptions based on conjugated polymer dots (Pdots) with different structures via the simple precipitation method. The as-synthesized Pdots exhibit strong absorption, high biocompatibility, and superior stability. In addition, the Pdots demonstrate that they can serve as contrast agents for multiscale PAI in vitro and in vivo. More importantly, a high photothermal conversion efficiency up to 40% is reached under irradiation with LED light, resulting in effective cancer treatment with extremely low light dose. Consequently, they show the potential as imaging-guided therapeutic agents for clinical cancer treatment and various biomedical applications.


Metabolism of alpha- and beta-adrenergic receptors in vitro and in vivo.
Despite considerable evidence that changes in number of adrenergic receptors can occur under various conditions, knowledge of the mechanisms mediating these changes is still rudimentary. As discussed, indirect approaches emphasizing the kinetics of receptor turnover have been the principal means of investigation. These indirect methods, which depend on the ability of a radioligand to detect the receptors, are limited by several factors. Even so, the data obtained using indirect approaches, in particular on various model systems in cell culture, lead to several conclusions: Both alpha 1- and beta-adrenergic receptors are metabolized rather slowly in vitro under basal conditions, in the absence of exposure to agonists. Typical half-lives are greater than 20 hr, a turnover that is slower than that of several other classes of neurotransmitter and hormone receptors (9, 10, 12, 16). Moreover, alpha 1-adrenergic receptors and beta-adrenergic receptors can have substantially different half-lives, even when expressed on the same cell. In view of the relatively slow rate of disappearance of adrenergic receptors under basal conditions, settings in which receptor number increases are almost certainly to result from increases in one or more of the factors that contribute to the rate of receptor appearance on the plasma membrane. Treatment of cells with agonists markedly shortens the half-life of alpha 1- and beta-adrenergic receptors. This shortened half-life results primarily from an enhanced loss of receptors from the plasma membrane, and not from agonist-induced attenuation of receptor appearance. In fact, data acquired from studies of receptor recovery after agonist-induced down-regulation suggest that rates of receptor reappearance are markedly enhanced through either receptor recycling or an increase in receptor synthesis. Limited studies conducted in vivo yield qualitatively similar results to those observed in in vitro studies of the metabolism of adrenergic receptors. In general, adrenergic receptors in the CNS turn over more slowly than those in peripheral tissues. These conclusions help to highlight the many aspects of metabolism of adrenergic receptors that are as yet unknown, including identification and characterization of the cellular machinery responsible for receptor metabolism, elucidation of the molecular events that control metabolism, and assessment of how drugs and other factors influence these events. Future studies are likely to be based on the development of new methodology with antireceptor antibodies, receptor cDNA's, and improved morphological methods (autoradiography, immunohistochemistry, etc).(ABSTRACT TRUNCATED AT 400 WORDS)


Gender Differences in Depressive Symptoms During Adolescence: The Contributions of Weight-Related Concerns and Behaviors.
A theoretical model of gender differences in depressive symptoms during adolescence was evaluated using data from Waves I and II of the National Longitudinal Study of Adolescent Health. The theoretical model under examination was primarily informed by the gender-additive model of gender differences in depressive symptoms during adolescence proposed by Stice and Bearman (2001). In the model, it was posited that BMI would be associated with perceiving oneself as overweight, which would then lead to a higher probability of dieting, which would be associated with greater depressive symptoms. Participants were 10,864 male and female adolescents. Gender did not moderate any of the model pathways, but mediation analysis indicated that gender differences in changes in depressive symptoms were mediated by perceived weight status and dieting. Findings suggest that one explanation for girls' higher depressive symptoms in adolescence relative to boys is girls' greater tendencies to perceive themselves as overweight and to diet.


Budesonide-Loaded Eudragit S 100 Nanocapsules for the Treatment of Acetic Acid-Induced Colitis in Animal Model.
Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues as insufficient drug amount at diseased regions, high adverse effects of released drugs, and unintentionally premature drug release to noninflamed gastrointestinal regions. Herein, the prepared budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules for the treatment of inflammatory bowel disease. Nanocapsules were prepared efficiently by nanoprecipitation technique and composed mainly of the pH-sensitive Eudragit S 100 polymeric coat with a semisynthetic Capryol 90 oily core. Full 31 × 21 factorial design was applied to obtain optimized nanocapsules. Optimal nanocapsules showed mean particle size of 171 nm with lower polydispersity index indicating the production of monodispersed system and negative zeta-potential of - 37.6 mV. Optimized nanocapsules showed high encapsulation efficiency of 83.4% with lower initial rapid release of 10% for first 2 h and higher rapid cumulative release of 72% after 6 h. The therapeutic activity of the prepared budesonide-loaded nanocapsules was evaluated using a rat colitis model. Disease activity score, macroscopical examination, blood glucose level, and histopathological assessment showed marked improvements over that free drug suspension. Obtained results demonstrate that the budesonide-loaded Eudragit S 100 nanocapsules are an effective colon-targeting nanosystem for the treatment of inflammatory bowel disease. Capryol 90 was found to be a successful, and even preferred, alternative to benzyl benzoate, which is commonly employed as the oil core of such nanocapsules.


Impact of the Use of Intravascular Imaging on Patients Who Underwent Orbital Atherectomy.
We assessed the impact of intravascular ultrasound (IVUS)/optical coherence tomography (OCT) on outcomes of patients who underwent orbital atherectomy. Intravascular imaging provides enhanced lesion morphology assessment and optimization of percutaneous coronary intervention (PCI) outcomes. Severe coronary artery calcification increases the complexity of PCI and is associated with worse clinical outcomes. Orbital atherectomy modifies calcified plaque, facilitating stent delivery and optimizing stent expansion. The impact of IVUS/OCT on clinical outcomes after orbital atherectomy is unknown. Of the 458 consecutive real-world patients in our retrospective multicenter registry, a total of 138 patients (30.1%) underwent orbital atherectomy with IVUS/OCT. The primary safety endpoint was the rate of 30-day major adverse cardiac and cerebrovascular events, comprised of death, myocardial infarction (MI), target-vessel revascularization (TVR), and stroke. The IVUS/OCT group and no-imaging group had similar rates of the primary endpoint (1.5% vs 2.5%; P=.48) as well as death (1.5% vs 1.3%; P=.86), MI (1.5% vs 0.9%; P=.63), TVR (0% vs 0%; P=NS), and stroke (0% vs 0.3%; P=.51). The 30-day stent thrombosis rates were low in both groups (0.7% vs 0.9%; P=.82). Emergent coronary artery bypass graft surgery was uncommonly performed in both groups (0.0% vs 0.9%; P=.25). Orbital atherectomy guided by intravascular imaging is feasible and safe. A large prospective randomized trial is needed to determine the clinical benefit of IVUS/OCT during PCI with orbital atherectomy.


Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila.
Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.


Systematic screening for subtelomeric anomalies in a clinical sample of autism.
High-resolution karyotyping detects cytogenetic anomalies in 5-10% of cases of autism. Karyotyping, however, may fail to detect abnormalities of chromosome subtelomeres, which are gene rich regions prone to anomalies. We assessed whether panels of FISH probes targeted for subtelomeres could detect abnormalities beyond those identified by karyotyping in 104 individuals with Pervasive Developmental Disorders (PDDs) drawn from a general clinical population. Four anomalies were detected by karyotyping, while no additional anomalies were detected by subtelomere FISH or by probes targeted for 15q11.2q13 or 22q11.2 in subgroups of our sample. We conclude that while karyotyping may be more broadly indicated for autism than previously supposed, subtelomere FISH appears less likely to be a useful screening tool for unselected PDD populations.


Intimate Partner Violence in Khaliji Women: A Review of the Frequency and Related Factors.
The Gulf Cooperation Council (GCC), locally known as Khaliji, is a group of six Arab nations, including Saudi Arabia, Bahrain, Kuwait, Oman, Qatar, and the United Arab Emirates (UAE). Intimate partner violence (IPV) is a significant public health concern in the aforementioned region, but research that synthesises this trend has remained scarce. The present narrative review examines existing research on the prevalence and frequency of IPV among Khaliji women who inhabit the GCC nations. This review synthesised studies on physical and sexual violence, emotional abuse, and controlling behaviours perpetrated by an intimate partner. The prevalence rates of IPV among Khaliji women were observed to be high: women reported facing different types of abuse from their partners, namely physical (7-71%), sexual (3.7-81%), financial (21.3-26%), and psychological (7.5-89%), which is a culmination of controlling behaviour (36.8%), emotional violence (22-69%), and social violence (34%). Existing studies in the GCC region suggest that the most endorsed IPV was psychological abuse (89%), followed by sexual violence (81%). Qualitative analysis of the content of associated factors resulted in four significant descriptors, such as victim demographics, sociocultural factors, socioeconomic factors, and perpetrator-related issues. Research on IPV is still in its nascent stages, with very few studies emanating from the GCC region. The way forward will require developing culturally appropriate interventions that address the unique risk factors for IPV among the Khaliji population, strengthening institutional responses, and increasing awareness and social support for victims of IPV.


LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers.
Long non-coding RNAs (lncRNAs) are a class of functional RNA molecules that do not encode proteins and are composed of more than 200 nucleotides. LncRNAs play important roles in epigenetic and gene expression regulation. The oncogenic lncRNA GACAT3 was recently discovered to be dysregulated in many tumors. Aberrant expression of GACAT3 contributes to clinical characteristics and regulates multiple oncogenic processes. The association of GACAT3 with a variety of tumors makes it a promising biomarker for diagnosis, prognosis, and targeted therapy. In this review, we integrate the current understanding of the pathological features, biological functions, and molecular mechanisms of GACAT3 in cancer. Additionally, we provide insight into the utility of GACAT3 as an effective diagnostic and prognostic marker for specific tumors, which offers novel opportunities for targeted therapeutic intervention.


Comparative evaluation of body composition methods and predictions, and calculation of density and hydration fraction of fat-free mass, in obese women.
The objective of this study was to apply a three-component model of body composition to a group of obese women in order to (a) establish the relative value of a number of readily available prediction equations by comparison of the extent of agreement between these predictions and body composition estimated by the model and other reference methods and (b) evaluate density and hydration of fat-free mass. Estimation of body composition was carried out by reference methods and prediction equations and the usefulness of these prediction equations for application specifically to obese women was evaluated. The subjects were 15 obese, otherwise healthy, Caucasian women (body mass index > 30kg/m2 and body fat > 40% of body weight, as originally determined using densitometry). Body composition was estimated using three established reference methods (deuterium dilution which primarily measures total body water, densitometry for body fat and fat-free mass and total body potassium) and the three component model constructed from deuterium dilution and densitometry. Density and hydration fraction of the fat-free mass were calculated from appropriate values obtained as integral parts of the three-component model. In addition, body composition was predicted from various prediction equations incorporating weight and height (some of which include a factor for age), from a number of prediction equations utilizing different terms involving the same whole-body bio-electrical impedance measurement and from measurements of skinfold thickness and near infrared interactance. The extent of agreement between methods was assessed using bias and 95% limits of agreement. Mean density of fat-free mass was found to be 1.104 kg/l (s.d. 0.006kg/l) with a range of 1.093 to 1.117 kg/l, and mean hydration fraction was 0.712 (s.d. 0.016) with a range of hydration from 68.2% to 75.1% (all values were calculated from the three-component model). In general, the reference methods (densitometry, deuterium dilution, the three-component model and total body potassium) demonstrated better agreement with each other than with the prediction methods or equations. In these obese women, skinfold thickness measurements are apparently less reliable (large bias and 95% limits of agreement) than in the lean subjects of a variety of other studies. A majority of interpretations of weight and height measurements and predictions incorporating impedance/resistance measurements are apparently not applicable to this group of obese women, due to large values for both bias and 95% limits of agreement.(ABSTRACT TRUNCATED AT 400 WORDS)


Electronic control of laryngeal spasm. II. Selective blockage of glottic adduction by a closed-loop circuit in the canine.
This work is the continuation of an earlier pilot study in which specially designed electrodes were used to block their own induced action potentials to restrain spasticity. In the current series of experiments, strap muscle and thyroarytenoid contraction (glottic closure) elicited by supramaximal ansa hypoglossi (N = 6) and recurrent laryngeal nerve (N = 4) stimulation (30 to 50 Hz, 0.1 to 6 mA, 0.1 to 1 msec), respectively, allowed afferent information via intramuscular sonomicrometer crystals to trigger a circuit that, in turn, stimulated blocking electrodes passed around the nerves downstream. Simultaneous videorecording of strap and vocal cord motion during direct laryngoscopy with their corresponding excursion tracings demonstrated near-total suppression of contractions within given stimulation "windows." These encouraging results may eventually permit selective restraint of erratic contractions involving laryngeal and other cervical musculatures in the human.


Inhibition of jack bean urease by tetrachloro-o-benzoquinone and tetrachloro-p-benzoquinone.
Tetrachloro-o-benzoquinone (TCoBQ) and tetrachloro-p-benzoquinone (TCpBQ) were studied as inhibitors of jack bean urease in 20 mM phosphate buffer, pH 7.0, 1 mM EDTA, 25 degrees C. The mechanisms of inhibition were evaluated by analysis of the progress curves obtained with two procedures: the reaction initiated by addition of the enzyme and the reaction initiated by addition of the substrate after preincubation of the enzyme with the inhibitor. The obtained results were characteristic of slow-binding inhibition. The effects of different inhibitor concentrations on the initial and steady-state velocities obeyed the relationships of two-step enzyme-inhibitor interaction, qualified as mechanism B. It was found that TCoBQ and TCpBQ are strong urease inhibitors. TCpBQ is more effective than TCoBQ with the overall inhibition constant of K(i)* = 4.5 x 10(-7) mM. The respective inhibition constant of TCoBQ was equal to: K(i)* = 2.4 x 10(-6) mM. The protective experiment proved that the urease active site is involved in the tetrachlorobenzoquinone inhibition process. High effectiveness of thiol protectors against inhibition by TCoBQ and TCpBQ indicates the strategic role of the active site sulfhydryl group in the blocking process. The stability of the complexes: urease-TCoBQ and urease-TCpBQ was tested in two ways: by dilution or addition of dithiothreitol. No recovery of urease activity bound in the urease-inhibitor complexes proves that the complexes are stable and strong.


Statin therapy in the elderly.
The clinical efficacy and safety of statin therapy have been well established from a series of large-scale, randomized controlled trials. These trials, however, have predominantly recruited patients under the age of 70 years. As a consequence, the use of statins in older patients has remained controversial. The results of the first trial to look exclusively at the elderly--the Prospective Study of Pravastatin in the Elderly at Risk--have added enormously to our understanding of the use of statins in the elderly. These findings, together with those from the large elderly cohort within the Heart Protection Study and the smaller elderly subgroups within the other major statin trials, have forced us to re-evaluate any systematic exclusion of elderly patients from statin therapy. The collective evidence now strongly supports the use of statins in the at-risk elderly population.


Effect of white jade snail secretion on antioxidant capacity and intestinal microbial diversity in mouse model of acute gastric ulcer.
In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high-throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. Compared with the control group, the ulcer area in the WJSS low-, medium- and high-concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low-, medium- and high-concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different-concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid-ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti-ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry.


Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.
Cochlear implantation (CI), which directly stimulates the cochlear nerves, is the most effective and widely used medical intervention for patients with severe to profound sensorineural hearing loss. The etiology of the hearing loss is speculated to have a major influence of CI outcomes, particularly in cases resulting from mutations in genes preferentially expressed in the spiral ganglion region. To elucidate precise gene expression levels in each part of the cochlea, we performed laser-capture micro dissection in combination with next-generation sequencing analysis and determined the expression levels of all known deafness-associated genes in the organ of Corti, spiral ganglion, lateral wall, and spiral limbs. The results were generally consistent with previous reports based on immunocytochemistry or in situ hybridization. As a notable result, the genes associated with many kinds of syndromic hearing loss (such as Clpp, Hars2, Hsd17b4, Lars2 for Perrault syndrome, Polr1c and Polr1d for Treacher Collins syndrome, Ndp for Norrie Disease, Kal for Kallmann syndrome, Edn3 and Snai2 for Waardenburg Syndrome, Col4a3 for Alport syndrome, Sema3e for CHARGE syndrome, Col9a1 for Sticker syndrome, Cdh23, Cib2, Clrn1, Pcdh15, Ush1c, Ush2a, Whrn for Usher syndrome and Wfs1 for Wolfram syndrome) showed higher levels of expression in the spiral ganglion than in other parts of the cochlea. This dataset will provide a base for more detailed analysis in order to clarify gene functions in the cochlea as well as predict CI outcomes based on gene expression data.


Practical formal total syntheses of the homocamptothecin derivative and anticancer agent diflomotecan via asymmetric acetate aldol additions to pyridine ketone substrates.
Two practical, efficient, and scalable asymmetric routes to DE ring fragment 7, a key building block in the synthesis of the homocamptothecin derivative diflomotecan 4, are described. The "acetal route" starts from 2-chloro-4-cyanopyridine 8 and represents an enantioselective and optimized modification of the original racemic discovery chemistry synthesis. The inefficient optical resolution procedure was replaced by an efficient asymmetric acetate aldol addition (dr 87:13) to a ketone substrate as the key step generating the (R)-configured quaternary stereocenter with high stereoselectivity. 7 was finally obtained in 8.9% overall yield (er 99.95:0.05) over nine steps, avoiding chromatographic purifications and comparing favorably with the initial procedure. In the related "amide route" starting from 2-chloroisonicotinic acid 41, a secondary amide directing group was used to facilitate the ortho lithiation of the pyridine 3-position. The key step of this protocol again consists of a practical asymmetric acetate aldol addition (dr = 87:13). The DE ring building block 7 was thus obtained in 11.1% overall yield (er > 99.95:0.05) over nine steps requiring only one chromatographic purification.


[Solitary hemangioma of the liver manifested by neonatal heart failure].
A new case of solitary angioma of the liver, complicated with heart failure, is reported in a newborn. The rarity of this anatomo-clinical form is emphasized, and the interest of venous catheterization, which permitted an angiogram of good quality, is underlined. Radiotherapy was so rapidly efficient that one is incited to promote this treatment before any other, especially in cases where surgery involves major risks.


Copper-catalyzed reaction of alpha-aryldiazoesters with terminal alkynes: a formal [3 + 2] cycloaddition route leading to indene derivatives.
It was discovered that Cu(IPr)Cl-catalyzed reaction of terminal alkynes with alpha-aryldiazoacetates provides indene derivatives, formal [3 + 2] cycloaddition adducts. Excellent regio- and chemoselectivity were observed to afford either 3H- or 1H-indene esters depending on the reaction conditions employed. The reaction is proposed to proceed via tandem processes: alkyne insertion into copper-carbenoid, intramolecular electrophilic attack on the aromatic ring, and then isomerization.


Human Milk Oligosaccharides Exhibit Antimicrobial and Antibiofilm Properties against Group B Streptococcus.
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillbirth, and neonatal sepsis. Recently, breastfeeding has been thought to represent a potential mode of GBS transmission from mother to newborn, which might increase the risk for late-onset sepsis. Little is known, however, about the molecular components of breast milk that may support or prevent GBS colonization. In this study, we examine how human milk oligosaccharides (HMOs) affect the pathogenesis of GBS. HMOs from discrete donor samples were isolated and profiled by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Growth and biofilm assays show that HMOs from mothers of specific milk groups can modulate the growth and biofilm formation of GBS. High-resolution field-emission gun scanning electron microscopy (SEM) and confocal laser scanning microscopy confirmed the quantitative biofilm assays and demonstrated cell arrangement perturbations in bacterial cultures treated with specific oligosaccharides. These findings demonstrate that HMOs affect the growth and cell biology of GBS. Finally, this study provides the first example of HMOs functioning as antibiofilm agents against GBS.


Characterization of early extracellular matrix secretions in a three-dimensional thixotropic cell culture system.
The extracellular matrix (ECM) provides both molecular and physical cues that affect cell phenotype and function, and hence both normal and abnormal tissue development. The evolution of ECM mechanical properties with time is thus of great importance for cell culture. We have developed a thixotropic polymer-silica nanocomposite gel that may be used to characterize the ECM secretions of cells cultured in a three-dimensional environment. This thixotropic gel can be characterized by its liquefaction stress (τ(y)), defined as the minimum shear stress required to liquefy the gel. When cells were cultivated within these gels, τ(y) was observed to change in a predictable fashion according to the cell type and quantity of ECM secreted. A general trend was observed for different cell lines, where τ(y) increased with increasing ECM concentration when cells were cultivated in gels of lower stiffness, and decreased with increasing ECM concentration when cells were cultivated in gels of higher stiffness. A particular gel stiffness could be identified where increasing the ECM concentration did not change the τ(y) of the gels. We have defined the τ(y) at this point as τ(ECM), which is characteristic for the ECM produced by a specific cell type cultured in the thixotropic gel.


[Impact of the depth of remission by induction chemotherapy on the prognosis of limited stage small cell lung cancer].
Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.


Pleomorphic adenoma of the trachea: report of two cases.
Two unusual cases of pleomorphic adenoma (benign mixed tumor) of the trachea were found in a 56-year-old woman and a 20-year-old man. Both patients had been initially treated for presumed bronchial asthma for 5 years and 4 years, respectively. Pulmonary function tests in each showed typical extrathoracic obstruction. The diagnosis of tracheal lesions in both cases was based principally on the following: 1) dyspnea without complete remission over an extended period of time following initial examination; 2) marked retraction of the supraclavicular and suprasternal notches during inspiration with stridor on physical examination; and 3) a high degree of suspicion. Large tumors were found within the air column of the trachea by soft tissue density X-ray films and electroradiographs of the neck, CT scans of the neck and mediastinum in each patient revealed that the tumor originated from the membranous layers of the trachea in the woman and the posterolateral wall of the trachea in the man. Fiberoptic bronchoscopy confirmed the clinical diagnosis. Both cases were successfully treated by segmental resection of the trachea with end-to-end anastomosis.


REVIEW OF CELIAC DISEASE PRESENTATION IN A PEDIATRIC TERTIARY CENTRE.
Celiac disease is an immune-mediated disorder with a multiform presentation and therefore a challenging diagnosis. Our purpose is to identify the epidemiological, clinical, laboratory and histologic characteristics of children with celiac disease at diagnosis and on follow-up. Children with previously established or newly diagnosed celiac disease, admitted in a tertiary centre in a two-year period (2014-2016) were recruited. Data was collected retrospectively from electronic medical records and clinical notes, and subsequently analysed with SPSS version 20.0. A total of 159 patients, out of 312, were included. Age ranged from 1 to 17 years (mean ± SD: 8.5±4.5 years, 69% girls). Disease presentation was classical in 60%, non-classical in 25%, subclinical in 10% and 5% classified as potential celiac disease. Non-classical and subclinical profiles had a higher mean age at presentation but not statistically significant (P-value 0.24). The most frequent gastrointestinal features at presentation were abdominal pain (58%), diarrhea (43%) and bloating (27%). A positive family history for celiac disease was present in 24% (n=35). We found anaemia in 23%, low ferritin in 63% and a moderate to severe deficiency of 25-hydroxyvitamin D in 62%. celiac disease -specific serologic testing and esophagogastroduodenoscopy were performed in 99%. Histology revealed modified Marsh 2 or 3 enteropathy in 94%, the remaining had normal histology but positive human leukocyte antigen typing. Clinical improvement at 12 months of gluten-free diet was complete in 51% and partial in 49%. IgA tTG normalized after 12-30 months of gluten-free diet in 45%. On growth assessment at diagnosis and after 12-28 months of gluten-free diet, 100% had height increase (mean ±SD: 7.11±4.43 cm) and 96% weight gain (mean ±SD: 5.60±4.91 kg). Our findings outline the diverse clinical presentations of pediatric celiac disease that should be considered irrespective of age. Increased clinician's awareness will enable an early diagnosis and treatment, with subsequent symptom and nutritional status improvement.


Polyp detection in the cecum and ascending colon by dye based chromoendoscopy - Is its routine use justified?
colonoscopy is the best method for detecting polyps, with a reduction in colorectal cancer mortality of 29% and reaching 47% for distal tumors. However, it fails to demonstrate a significant reduction in proximal colon cancer mortality, and is the most common segment with interval neoplasm. The present study aimed to evaluate the impact on detection of polyps of a second sequential evaluation of cecum and ascending colon, with or without the use of indigo carmine chromoendoscopy. prospective, non-randomized clinical trial. Patients were divided into two groups. The first (G1) underwent a routine colonoscopy, followed by a second endoscopy assessment of ascending colon and cecum. The second group (G2) underwent a routine colonoscopy, followed by a second assessment of the ascending colon and cecum with indigo carmine chromoendoscopy. In total, 203 patients were analyzed, 101 in the G1 and 102 in the G2. Newer polyps were identified in both groups after the second assessment with a significantly higher number of polyps detected in the patients in the G2 (p=0.0001). The number of patients who had at least one polyp in the two endoscopic assessments was significantly higher in the G2 (53 or 52% vs 27 or 26.7%, p=0.0002). In the second endoscopic assessment, the number of polyps found was also significantly higher in the G2 (50 or 76.9%) compared to the G1 (15 or 23.1%), p<0.0001. the second assessment with dye-based chromoendoscopy increases the detection of polyps in the ascending colon and cecum.


Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR). The molecular events promoting BDNF-mediated pro-death signalling in hypoxia, however, still remain an enigma. This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia. Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity. Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology. Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure. Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions. Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival. Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.


Corneal pathology and indications for corneal transplant at the Tg. Mures Ophthalmology Clinic.
The purpose of this study was to evaluate the incidence of corneal pathology that presents indication for cornea/transplant, treatment and follow-up of these patients. A retrospective analysis has been undertaken at the Tg. Mures Ophthalmology Hospital. In the study we have included all patients who had corneal pathology with intact deeper ocular structures. We have examined the treatment of these cases and their admittance to corneal transplantation. In 2008 in 99 cases of the 3246 hospitalized patients such a corneal condition has been described that presented indication for corneal transplantation. Most common causes were corneal leucomas, corneal ulcers, bullous keratopathy and corneal dystrophies and degenerations. Fourteen patients tried to benefit from corneal transplant abroad financed by the National Health Insurance Office; others went on their own expense. All together four patients appeared for postoperative control at our Hospital. We have found 99 cases of corneal transplant indication at our Hospital's patients and only a fraction of them have undergone surgery. We can point out a very low level of admittance and a great need for a regional corneal transplantation centers.


Sex differences of urinary and kidney globotriaosylceramide and lyso-globotriaosylceramide in Fabry mice.
The aim of our study was to measure globotriaosylceramide (Gb(3)) and lyso-Gb(3) levels by tandem mass spectrometry in the urine and kidney in Fabry (gla knockout) mice and wild-type controls. We found that urine Gb(3) of male and female Fabry mice was higher than wild-type mice of the same sex but also significantly higher in male mice compared with females of the same genotype. In kidney tissue, sex and genotype-dependent differences in Gb(3) levels paralleled those in the urine. Isoforms C16, C22:1, and C24OHA were particularly higher in males compared with females in both wild-type and Fabry mice. Similarly, kidney lyso-Gb(3) concentrations were significantly higher in 12-month-old male Fabry mice than in their homozygous female counterparts. However, lyso-Gb(3) was undetectable in wild-type mice of both sexes. α-Galactosidase A activity and mRNA levels in kidney were significantly lower in male wild-type mice compared with female mice. This study shows the sex differences in kidney and urine Gb(3) and kidney lyso-Gb(3) levels in both wild-type and Fabry mice, and it suggests that these male-female differences should be taken into consideration when using murine models for Fabry disease.


Contributions of non-occupational activities to total noise exposure of construction workers.
This paper describes how exposures received during routine and episodic non-occupational activities contribute to total noise exposure in a group of occupationally exposed workers. Two-hundred and sixty-six construction apprentices enrolled in a longitudinal hearing loss study and completed questionnaires at 1 yr of follow-up to determine their episodic activities (e.g. concert attendance, power tool use, firearms exposure). Noise exposure levels for these episodic exposures were determined from the published literature. Routine activities were assessed using activity cards filled out over 530 subject-days, along with noise dosimetry measurements made over 124 subject-days of measurement. Equivalent Leq exposure levels were then calculated for specific activities. These activity-specific Leq values were combined into estimated individual annual Leq exposure levels for the 6760 nominal annual non-occupational hours in a year (LAeq6760h), which were then transformed into equivalent levels for a 2000 h exposure period (LA2000hn) for comparison with occupational noise exposure risk criteria. The mean non-occupational LAeq6760h exposure values for the cohort ranged from 56 to 87 dBA (equivalent LA2000hn 62-93 dBA). At the mid range of the routine and episodic activity exposure level distribution, the mean LAeq6760h was 73 dBA (LA2000hn 78 dBA). Nineteen percent of the LA2000hn non-occupational exposures exceeded 85 dBA, the generally recommended occupational limit for a 2000 h workyear, at the mid-range of exposure levels. Due to a lack of available data, firearms use could not be incorporated into the total noise exposure estimates. However, firearms users reported more exposure to other noisy non-occupational activities and had statistically significantly higher estimated exposure levels even without including their firearms exposure than did non-shooters. When compared with the high levels of occupational noise found in construction, non-occupational noise exposures generally present little additional exposure for most workers. However, they may contribute significantly to overall exposure in the subset of workers who frequently participate in selected noisy activities.


Polypill: an affordable strategy for cardiovascular disease prevention in low-medium-income countries.
The simplification of fixed dose medications by using a single 'polypill' is an attractive strategy to improve adherence to medications which has shown benefit to cardiovascular risk factor control and cardiovascular disease prevention or delay in the progression of these diseases. We review the evidence obtained from a series of clinical trials demonstrating an improvement in adherence to the polypill compared to the use of each compound separately, and found similar or better control of the classical cardiovascular risk factors and a similar safety profile. These results suggest that the use of the polypill could have a beneficial impact in cardiovascular morbidity and mortality. Furthermore, the polypill has the potential to improve cost effectiveness and is simple to use. However, before recommending the implementation of the polypill in programs aimed at primary and secondary cardiovascular prevention, we are awaiting the results of several current clinical trials aimed at measuring the impact on the frequency of major cardiovascular outcomes, particularly in low-medium-income countries.


HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT FOR THE ADOPTION OF INNOVATIVE MEDICAL DEVICES WITHIN FRENCH HOSPITALS: OPPORTUNITIES AND CHALLENGES FOR INDUSTRY.
Within French university hospitals, some internal committees are in charge of conducting hospital-based health technology assessment (Hb-HTA) to support managerial decisions regarding the adoption of innovations. For manufacturers, hospitals are usually the entry point for new and innovative medical devices, which cannot be accessed without the Hb-HTA committees' approval. Thus, the main objective of this pilot survey was to explore manufacturers' insights into Hb-HTA processes. A two-step pilot survey was conducted in 2014. First, semi-structured phone interviews were carried out to capture manufacturers' feedback on the Hb-HTA procedure. Second, a prospective and iterative questionnaire designed to explore manufacturers' market access strategies was administered. Eight manufacturers from the medical device industry completed the retrospective phone interviews, and five of them participated in the prospective survey. According to the overall feedback, the Hb-HTA process timeline and transparency are major issues, and the expectations of internal committees, especially in terms of clinical evidence, remain difficult to understand. However, despite this and due to the complexity of reimbursement processes at the national level, manufacturers are increasingly considering hospital adoption through Hb-HTA submission as a viable market access and coverage opportunity. Our study reaffirms the primary role of hospitals in the diffusion of innovative medical devices. However, to ensure efficient and broad access to innovation, cooperation between local and national HTA bodies is critical and should be promoted.


Outcomes of Femtosecond Laser-Assisted Cataract Surgery Compared to Conventional Phacoemulsification in Eyes with Pseudoexfoliation Syndrome.
To compare the outcomes including complications, in a large cohort of eyes with pseudoexfoliation syndrome that underwent Femtosecond Laser-Assisted Cataract Surgery (FLACS) versus conventional phacoemulsification. Retrospective cohort study. A total of 513 eyes from 366 patients with pseudoexfoliation syndrome that underwent cataract surgery between April 1, 2014, and December 31, 2018. Charts were reviewed for preoperative examination findings, intraoperative complications, and post-operative outcomes. Best-corrected visual acuity (BCVA) was measured by logMAR and compared between groups at one month and the final follow-up visit. Of 513 eyes, 71 (13.8%) underwent FLACS, and 442 (86.2%) eyes underwent conventional cataract surgery. Between the two groups, there was no difference in the incidence of vitreous prolapse, capsular tear, pupillary expansion device usage, capsular tension support device usage, or postoperative cystoid macular edema (p > .05 for all). At the final visit, there was no significant difference in BCVA between FLACS and conventional phacoemulsification groups (mean logMAR 0.26 vs. 0.25, p = .87). When comparing FLACS and conventional phacoemulsification in eyes with pseudoexfoliation syndrome, no difference was seen in the incidence of complications. BCVA was comparable between the two groups. Zonular weakness significantly increased the risk of complications in both groups.


Modulation of the transcription factor NF-κB in antigen-presenting cells by bovine respiratory syncytial virus small hydrophobic protein.
Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease in young cattle and is closely related to human RSV (HRSV), which causes severe respiratory disease in infants and the elderly. The RSV genome encodes a small hydrophobic (SH) protein with viroporin activity. Previous studies have shown that recombinant BRSV lacking the SH gene (rBRSVΔSH) is attenuated in the lungs, but not in the upper respiratory tract, of calves and mucosal vaccination with rBRSVΔSH induced long-lasting protective immunity. Attenuation of rBRSVΔSH may be due to the ability of this virus to induce an early innate response as rBRSVΔSH induces higher levels of pro-inflammatory cytokines than wild-type (wt) rBRSV. In this study, we investigated the effects of the BRSV SH protein on NF-κB p65 phosphorylation, a master step in the regulation of pro-inflammatory cytokines. Expression of SH resulted in the inhibition of NF-κB p65 phosphorylation in response to BRSV infection and extracellular lipopolysaccharide, and a reduction in the production of pro-inflammatory cytokines. In contrast, rBRSVΔSH does not inhibit NF-κB p65 phosphorylation in bovine antigen-presenting cells, including monocytes, macrophages and dendritic cells, resulting in increased expression of pro-inflammatory cytokines and increased activation of T cells compared to cells infected with wt BRSV. These findings highlight an important role for the BRSV SH protein in immune modulation.


Protective action of Ilex paraguariensis extract against free radical inactivation of paraoxonase-1 in high-density lipoprotein.
Paraoxonase 1 (PON-1), an antioxidant enzyme carried mainly by HDL, has been shown to display cardioprotective effects. In this study, we investigated whether the polyphenol-rich beverage mate, obtained from extract of Ilex paraguariensis (IP), prevented the loss of PON-1 activity from HDL during oxidant stress. The peroxide radical generator 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) induced time- and dose-dependent oxidation of HDL, as measured by lipoperoxide content, which is accompanied by a parallel decrease in the activity of PON-1 (p<0.001). IP extract (2-20 microL/mL) afforded time- and concentration-dependent inhibition of the oxidation, with preservation of apoA-I structure and PON-1 activity. Healthy volunteers drank either 0.5 L of IP extract, 0.5 L of coffee and milk or nothing. PON-1 activity increased an average of 10% above the changes seen when the intake was coffee and milk (p<0.05). In conclusion, we demonstrate that IP extract may, to some extent, prevent the loss of the antiatherogenic function of HDL afforded by PON-1 when the particle is under oxidant stress.


rAAV TGF-β and FGF-2 Overexpression via pNaSS-Grafted PCL Films Stimulates the Reparative Activities of Human ACL Fibroblasts.
Lesions in the human anterior cruciate ligament (ACL) are frequent, unsolved clinical issues due to the limited self-healing ability of the ACL and lack of treatments supporting full, durable ACL repair. Gene therapy guided through the use of biomaterials may steadily activate the processes of repair in sites of ACL injury. The goal of the present study was to test the hypothesis that functionalized poly(sodium styrene sulfonate)-grafted poly(ε-caprolactone) (pNaSS-grafted PCL) films can effectively deliver recombinant adeno-associated virus (rAAV) vectors as a means of overexpressing two reparative factors (transforming growth factor beta-TGF-β and basic fibroblast growth factor-FGF-2) in primary human ACL fibroblasts. Effective, durable rAAV reporter red fluorescent protein and candidate TGF-β and FGF-2 gene overexpression was achieved in the cells for at least 21 days, especially when pNaSS-grafted PCL films were used versus control conditions, such as ungrafted films and systems lacking vectors or films (between 1.8- and 5.2-fold differences), showing interactive regulation of growth factor production. The expression of TGF-β and FGF-2 from rAAV via PCL films safely enhanced extracellular matrix depositions of type-I/-III collagen, proteoglycans/decorin, and tenascin-C (between 1.4- and 4.5-fold differences) in the cells over time with increased levels of expression of the specific transcription factors Mohawk and scleraxis (between 1.7- and 3.7-fold differences) and without the activation of the inflammatory mediators IL-1β and TNF-α, most particularly with pNaSS-grafted PCL films relative to the controls. This work shows the value of combining rAAV gene therapy with functionalized PCL films to enhance ACL repair.


Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice.
There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction.


[Comparison of multislice spiral CT and MRI in diagnosis of occult fracture of knee joint with meniscus and ligament injury].
To investigate the diagnostic value of multislice spiral CT (MSCT) and MRI in occult fracture of knee joint with meniscus and ligament injury. From January 2020 to March 2021, 63 patients with knee occult fracture with meniscus and ligament injury, including 41 males and 22 females, aged from 21 to 67 years old, with an average of (44.35±8.77) years old, the course of disease ranged from 1 to 6 days, with an average of (4.64±1.75) days, the body mass index (BMI) was (19.85±2.78) kg/m2. MSCT and MRI data of 63 patients were collected and statistically analyzed to evaluage their diagnist value. The detection of MRI for occult knee fravtures with meniscus and ligament injury, joint cavity effusion, bone marrow edema, and articular surface injury were 100.00% (63/63), 95.24% (60/63), 42.86% (27/63) and 36.51% (23/63), respectively. The detection rates of MSCT were 49.21% (31/63), 41.27% (26/63), 0.00% (0/63) and 1.59% (1/63), respectively, significantly lwver than that of MRI (P<0.05). The diagnostic sensitivity, specificity and accuracy of MRI were significantly higher than those of MSCT(P<0.05). The sensitivity, specificity and accuracy of magnetic resonance imaging in the diagnosis of occult fracture of knee joint with meniscus and ligament injury are significantly better than that of MSCT. MRI has higher accuracy in the diagnosis of peripheral tissue diseases such as joint cavity, articular surface and bone marrow, and can reduce the risk of clinical misdiagnosis.


Biomarker genes for detecting estrogenic activity of endocrine disruptors via estrogen receptors.
Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D(9k) (CaBP-9k), that may be used to assess estrogenic activity of EDs.


Scleromyxedema: clinical diagnosis and autopsy findings.
Scleromyxedema is a rare chronic cutaneous mucinosis of unknown etiology. It is characterized by papular eruption and scleroderma with microscopic evidence of mucin deposition, fibroblast proliferation, and fibrosis. Most patients with scleromyxedema have monoclonal gammopathy and systemic manifestations resulting in significant morbidity and mortality. Several types of treatment have been reported with partial or inconsistent responses. Despite showing unpredictable evolution, systemic consequences of scleromyxedema and treatment side effects may result in death. We describe a rare case of a patient with scleromyxedema without paraproteinemia with systemic involvement that evolved to death despite treatment with cyclophosphamide.


Measurement of self-esteem in repeat assault victims.
Background characterization of assault-related injuries have demonstrated that lifestyle, substance abuse, education, employment, mental illness, and high-risk behavior contribute to low self-esteem in repeat assault victims. Recurrent-assault patients have never been studied with respect to self-esteem. This study evaluated self-esteem and assault-related injury in 28 consecutive male assault patients (11 first-assault and 17 recurrent-assault patients) and 19 controls with no previous assault history. Study participants were administered the Walmyr Assessment Scales Index of Self-Esteem (WASISE) as part of a three-item survey to determine the relationship between self-esteem and assault-related injury. No demographic differences were found between the groups. The mean (+/- standard error) WASISE score for recurrent-assault patients (34.9 +/- 3.4) was significantly higher than mean scores for no-assault and first-time assault-injured patients (14.7 +/- 1.4 and 15.0 +/- 2.3, respectively). The recurrent-assault patients had a lower mean education level than both no-assault and first-time assault-injured patients (2.1 +/- 0.26 and 1.9 +/- 0.57, respectively). Eighteen (2%) first-time assault-injured and 11 (7%) recurrent-assault patients were employed. These data suggest that self-esteem, education, and employment history need to be considered when evaluating and developing interventions for repeat-assault patients.


Internet and decision-making regarding health among pregnant woman: cross-cultural adaptation of a questionnaire for use in Brazil.
The aim of this study was to translate and cross-culturally adapt the Women's Use of the Internet in Pregnancy Questionnaire (WUIPQ) to Brazilian Portuguese and analyze the psychometric properties of the Preparation for Decision Making Scale (PDMS). This study consisted of the following steps: translation, synthesis, back-translation, evaluation by the author of the original questionnaire, review by the panel of experts, and pretest of the WUIPQ. For such, Brazilian pregnant women and mothers who were members of Facebook groups participated in the study. We measured test-retest reliability as well as internal consistency and performed confirmatory factor analysis (CFA) of the B-PDMS. In the pretest, 88.14% of the participants considered the items of the B-WUIPQ to be clear and pertinent, and 84.09% rated the sequence and organization of the questionnaire as excellent/good. The intraclass correlation coefficient and Cronbach's alpha coefficient for the B-PDMS were 0.850 (95%CI: 0.791-0.899) and 0.91, respectively. CFA revealed factor loadings higher than 0.70 for most items, with a comparative fit index of 0.989, Tucker-Lewis index of 0.984, and root mean square error of approximation of 0.08 (95%CI: 0.06-0.09). The B-WUIPQ presented cross-cultural adapted, and the B-PDMS demonstrated satisfactory psychometric proprieties to Brazilian pregnant women.