Assessment of residual viability by enoximone echocardiography in patients with previous myocardial infarction correlation with positron emission tomographic studies and functional follow-up.
The aim of this study was to evaluate enoximone echocardiography (EE) for the identification of residual myocardial viability in postinfarction patients. Findings obtained during EE were compared with those acquired by myocardial uptake of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and functional follow-up results. Twenty-five patients underwent EE and PET (18)F-FDG studies. An asynergic segment was considered as having contractile enhancement when the wall motion score decreased by > or = 1 grade during EE and was defined as viable if (18)F-FDG uptake score was > or = 2 grade on PET. Of 293 dysfunctional segments at baseline, 139 (47%) were viable by PET criteria; 117 (40%) had contractile enhancement induced by enoximone (P = 0.07). Agreement between EE and PET was found in 75% of involved segments (K = 0.46, P < 0.001). The majority of discrepancies (65%, P < 0.01) were mainly due to discordant segments in which PET revealed evidence of (18)F-FDG uptake but EE showed no change in wall motion. In 179 revascularized segments, negative predictive value for functional recovery of both tests reached the same value (89% for both), whereas positive predictive value was 82% for EE and 68% for PET, respectively (P < 0.05). Sensitivity was 85% for EE and 88% for PET (P = ns); specificity was 87% and 70%, respectively (P < 0.01). EE yields a fair concordance with PET study. Compared with PET, despite a similar negative accuracy, EE shows a greater specificity for prediction of function recovery after revascularization. (Echocardiography 2010;27:544-551).


Inequalities in health at older ages: a longitudinal investigation of the onset of illness and survival effects in England.
previous studies have suggested a decline in the relationship between socioeconomic circumstances and health or functioning in later life, but this may be due to survival effects. to examine whether wealth gradients in the incidence of illness decline with age, and, if so, whether this decline is explained by differential mortality. the study included participants in the first two waves of the English Longitudinal Study of Ageing (ELSA), a large national longitudinal study of the population aged 50+ in England, who reported good health, no functional impairment, or no heart disease at baseline. Wealth inequalities in onset of illness over 2 years were examined across age groups, with and without the inclusion of mortality. Outcome measures were functional impairment, heart disease, self-reported health, and all-cause mortality (in conjunction with self-reported health and disability) or circulatory-related mortality (in relation to heart disease). wealth predicted onset of functional impairment equally across age groups. For self-reported health and heart disease, wealth gradients in the onset of illness declined with age. Selective mortality contributed to this decline in the oldest age groups. socioeconomic inequality in developing new health problems persist into old age for certain illnesses, particularly functional impairment, but not for heart disease. Selective mortality explains only some of the decline in health inequalities with age.


cAMP-dependent protein kinase from Dictyostelium discoideum.
The cAMP-dependent protein kinase (cAK) from Dictyostelium discoideum is an enzyme composed of one catalytic and one regulatory subunit. Upon binding of cAMP, the holoenzyme dissociates to liberate free active catalytic subunits. The cAK is developmentally regulated, ranging from very little activity in vegetative cells to maximal expression in postaggregative cells. Although there is no immunological cross-reaction between the subunits of cAKs from Dictyostelium and from other organisms, they share several biochemical properties. A complete cDNA for the regulatory subunit has been cloned and sequenced. Only one copy of the gene for the regulatory subunit is present per haploid genome. On the basis of the comparison of the structure of the cAK from Dictyostelium with its counterparts in yeast and higher eukaryotes, we propose a model for the evolution of cyclic-nucleotide-binding proteins.


Use of Doppler ultrasound in assessing leg ulcers.
This article outlines the use of a hand-held Doppler ultrasound device as an aid in the assessment of patients with active and healed leg ulcers. It describes the benefits and limitations of Doppler assessment, the steps of the procedure, how to calculate the ankle-brachial pressure index accurately and how to recognise the significance of the findings.


Equilibrium of nucleotides in the dogfish brain.
In the past, the results of experiments on the time course of concentration changes of adenylates, phosphocreatine, and free creatine in muscle appeared compatible with an equilibrium hypothesis involving only the Lohmann and the myokinase reactions. Other reports, however, denied the applicability of the equilibrium hypothesis to the same tissue. The controversy may have been due to the high probability of experimental errors since time sampling was performed at second intervals. We presently test the hypothesis in the living brain of the small-spotted dogfish shark (Scyliorhinus canicula), an animal-model allowing for timing of sampling at hourly intervals. According to our earlier work, the dogfish shark can easily be resuscitated 8.2 h on average after being brought into the state of "suspended animation" at 0 degree C body temperature and exposed, out of water, to an atmosphere of nitrogen gas. To obtain a complete mathematical description of the time course of concentration changes of brain adenylates and phosphocreatine, we devised a kinetic model based on principles of classical multicompartmental analysis and biochemical kinetics. Model testing of the equilibrium hypothesis resulted in very good agreement between the hypothesis and our experimental data. Time-course modeling, achieved by simultaneously fitting the time series of our data by the set of four equations constituting our model resulted in an excellent agreement between data points and the computed curves. Finally, modeling of the depletion profiles of brain energy status concerning three of its descriptors (energy charge, total adenylate, and primary energy stores expressed in high-energy phosphate equivalents) allowed for a correlation to be established between energy status and the "revival time," a valuable physiological descriptor of tolerance.


Studies on reconstituted partially purified glycerophosphate acyltransferase from Escherichia coli.
Solubilized glycerophosphate acyltransferase from Escherichia coli was reconstituted in small unilamellar vesicles consisting of phosphatidylcholine/phosphatidylglycerol in a molar ratio of 4:1. Glycerol 3-phosphate, trapped inside these vesicles, cannot be acylated by the enzyme upon addition of extra-vesicular palmitoyl-CoA. Thus, substrate-binding sites and active sites are asymmetrically oriented in the model membrane. When up to 10 mol/100 mol lysophosphatidic acid was incorporated in the vesicles a decrease in glycerophosphate acyltransferase activity is observed at amounts exceeding 1 mol% lysophosphatidate. Similar experiments, using lysophosphatidylcholine and phosphatidic acid, suggest the decrease to result from an increase in negative surface charge. Reconstituted glycerophosphate acyltransferase exhibits a preference for palmitoyl-CoA over oleoyl-CoA. This preference increases considerably at elevated temperatures. The glycerophosphate acyltransferase could, therefore, participate in the temperature-dependent changes in the fatty acid composition of the phospholipids in E. coli.


EGR3-HDAC6-IL-27 Axis Mediates Allergic Inflammation and Is Necessary for Tumorigenic Potential of Cancer Cells Enhanced by Allergic Inflammation-Promoted Cellular Interactions.
The objective of this study was to investigate mechanisms of allergic inflammation both in vitro and in vivo in details. For this, RNA sequencing was performed. Early growth response 3 gene (Egr3) was one of the most highly upregulated genes in rat basophilic leukemia (RBL2H3) cells stimulated by antigen. The role of Egr3 in allergic inflammation has not been studied extensively. Egr3 was necessary for passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA). Egr3 promoter sequences contained potential binding site for NF-κB p65. NF-κB p65 directly regulated Egr3 expression and mediated allergic inflammation in vitro. Histone deacetylases (HDACs) is known to be involved in allergic airway inflammation. HDAC6 promoter sequences contained potential binding site for EGR3. EGR3 showed binding to promoter sequences of HDAC6. EGR3 was necessary for increased expression of histone deacetylase 6 (HDAC6) in antigen-stimulated RBL2H3 cells. HDAC6 mediated allergic inflammation in vitro and PSA. TargetScan analysis predicted that miR-182-5p was a negative regulator of EGR3. Luciferase activity assay confirmed that miR-182-5p was a direct regulator of EGR3. MiR-182-5p mimic inhibited allergic inflammation both in vitro and in vivo. Cytokine array showed that HDAC6 was necessary for increased interleukin-27 (IL-27) expression in BALB/C mouse model of PSA. Antigen stimulation did not affect expression of EBI3, another subunit of IL-27 in RBL2H3 cells or BALB/C mouse model of PCA or PSA. IL-27 receptor alpha was shown to be able to bind to HDAC6. IL-27 p28 mediated allergic inflammation in vitro, PCA, and PSA. Mouse recombinant IL-27 protein promoted features of allergic inflammation in an antigen-independent manner. HDAC6 was necessary for tumorigenic and metastatic potential enhanced by PSA. PSA enhanced the metastatic potential of mouse melanoma B16F1 cells in an IL-27-dependent manner. Experiments employing culture medium and mouse recombinant IL-27 protein showed that IL-27 mediated and promoted cellular interactions involving B16F1 cells, lung macrophages, and mast cells during allergic inflammation. IL-27 was present in exosomes of antigen-stimulated RBL2H3 cells. Exosomes from antigen-stimulated RBL2H3 cells enhanced invasion of B16F1 melanoma cells in an IL-27-dependemt manner. These results present evidence that EGR3-HDAC6-IL-27 axis can regulate allergic inflammation by mediating cellular interactions.


In situ quantification of β-carotene partitioning in oil-in-water emulsions by confocal Raman microscopy.
Confocal Raman microscopy (CRM) was able to quantify the β-carotene concentration in oil droplets and determine the partitioning characteristics of β-carotene within the emulsion system in situ. The results were validated by a conventional method involving solvent extraction of β-carotene separately from the total emulsion as well as the aqueous phase separated by centrifugation, and quantification by absorption spectrophotometry. CRM also enabled the localization of β-carotene in an emulsion. From the Raman image, the β-carotene partitioning between the aqueous and oil phases of palm olein-in-water emulsions stabilized by whey protein isolate (WPI) was observed. Increasing the concentration of β-carotene in an emulsion (from 0.1 to 0.3g/kg emulsion) with a fixed gross composition (10% palm olein:2% WPI) decreased the concentration of β-carotene in the oil droplet. CRM is a powerful tool for in situ analyses of components in heterogeneous systems such as emulsions.


Remote Treatment Monitoring on Hospitalization and Technique Failure Rates in Peritoneal Dialysis Patients.
An integrated kidney disease healthcare company implemented a peritoneal dialysis (PD) remote treatment monitoring (RTM) application in 2016. We assessed if RTM utilization associates with hospitalization and technique failure rates. We used data from adult (age ≥18 years) patients on PD treated from October 2016 through May 2019 who registered online for the RTM. Patients were classified by RTM use during a 30-day baseline after registration. Groups were: nonusers (never entered data), moderate users (entered one to 15 treatments), and frequent users (entered >15 treatments). We compared hospital admission/day and sustained technique failure (required >6 consecutive weeks of hemodialysis) rates over 3, 6, 9, and 12 months of follow-up using Poisson and Cox models adjusted for patient/clinical characteristics. Among 6343 patients, 65% were nonusers, 11% were moderate users, and 25% were frequent users. Incidence rate of hospital admission was 22% (incidence rate ratio [IRR]=0.78; P=0.002), 24% (IRR=0.76; P<0.001), 23% (IRR=0.77; P≤0.001), and 26% (IRR=0.74; P≤0.001) lower in frequent users after 3, 6, 9, and 12 months, respectively, versus nonusers. Incidence rate of hospital days was 38% (IRR=0.62; P=0.013), 35% (IRR=0.65; P=0.001), 34% (IRR=0.66; P≤0.001), and 32% (IRR=0.68; P<0.001) lower in frequent users after 3, 6, 9, and 12 months, respectively, versus nonusers. Sustained technique failure risk at 3, 6, 9, and 12 months was 33% (hazard ratio [HR]=0.67; P=0.020), 31% (HR=0.69; P=0.003), 31% (HR=0.69; P=0.001), and 27% (HR=0.73; P=0.001) lower, respectively, in frequent users versus nonusers. Among a subgroup of survivors of the 12-month follow-up, sustained technique failure risk was 26% (HR=0.74; P=0.023) and 21% (HR=0.79; P=0.054) lower after 9 and 12 months, respectively, in frequent users versus nonusers. Our findings suggest frequent use of an RTM application associates with less hospital admissions, shorter hospital length of stay, and lower technique failure rates. Adoption of RTM applications may have the potential to improve timely identification/intervention of complications.


No Pain and No Gain: Kommerell's Diverticulum with a Right-Sided Aortic Arch, and an Aberrant Left Subclavian Artery Presenting in a Body Builder with Muscle Bulk Imbalance.
A 22-year-old right-handed male presented to the Sports Medicine clinic with concerns of upper extremity muscle asymmetry. Physical examination showed gross muscular asymmetry when comparing the left upper extremity to the right. Radial pulses were 2 + on the right and 1 + on the left. Due to concern for vascular anomaly, computed tomography angiography was performed which revealed a right-sided aortic arch with Kommerell's diverticulum and aberrant left subclavian artery. The patient underwent a left carotid subclavian bypass successfully, but his recovery was complicated by an upper extremity deep venous thrombosis. He is currently on novel anticoagulant but has been released to normal activities and doing well. Kommerell's Diverticulum (KD) is a rare congenital anomaly caused by a persistent remnant of the fourth primitive dorsal arch during embryological development. Although the prevalence of KD is rare, it is important to identify and diagnose this condition to provide definitive care.


Low but not high frequency of intermittent hypoxia suppresses endothelium-dependent, oxidative stress-mediated contractions in carotid arteries of obese mice.
Obstructive sleep apnea is characterized by intermittent hypoxia (IH) during sleep and predisposes to endothelial dysfunction. Obesity is a major risk factor for the occurrence of sleep apnea. The present study compared the functional impact of low- (IH10; 10 hypoxic events/h) and high-frequency (IH60; 60 hypoxic events/h) IH for 4 wk on endothelial function in male C57BL/6 mice with or without high-fat (HF) diet-induced obesity. Mean arterial blood pressure (tail cuff method) was increased in obese mice after IH60 exposure, i.e., HF + IH60 group. The serum levels of the oxidative stress marker malondialdehyde were augmented in lean IH60 and HF groups, with a further increase in HF + IH60 but a reduction in HF + IH10 mice compared with the HF group. Vascular responsiveness was assessed as changes in isometric tension in isolated arteries. Relaxations to the endothelium-dependent vasodilator acetylcholine were impaired in HF + IH60 aortae. Endothelium-dependent contractions (EDC; response to acetylcholine in the presence of the nitric oxide synthase inhibitor l-NAME) in carotid arteries were augmented in the HF group, but this HF-induced augmentation was suppressed by low-frequency IH exposure. The addition of apocynin (antioxidant) reduced EDC in HF and HF + IH60 groups but not in HF + IH10 group. In conclusion, these findings suggest that exposure of obese mice to mild IH exerts preconditioning-like suppression of endothelium-dependent and oxidative stress-mediated contractions. When IH severity increases, this suppression diminishes and endothelial dysfunction accelerates. NEW & NOTEWORTHY The present study demonstrates, for the first time, that low-frequency intermittent hypoxia may exert a preconditioning-like suppression of oxidative stress-induced endothelium-dependent contractions in mice with diet-induced obesity. This relative suppression was diminished as intermittent hypoxia became more severe, and a deleterious effect on endothelial function emerged.


Asymptotic theory for gene mapping.
In genetic linkage mapping, the precision of the location estimate depends on both the number of individuals and the number of markers. Convergence rates and limit laws are established for several situations in which the number of markers depends on the sample size. Practical implications of the results are discussed.


Predicting risk of 2-year incident dementia using the CAMCOG total and subscale scores.
being able to identify individuals at high risk of dementia is important for diagnostics and intervention. Currently, there is no standard approach to assessing cognitive function in older aged individuals to best predict incident dementia. to identify cognitive changes associated with an increased risk of 2-year incident dementia using the Cambridge Cognitive Examination (CAMCOG). longitudinal population representative sample aged 65+ years. individuals were from the Medical Research Council Cognitive Function and Ageing Study. Classification and Regression Tree analysis was used to detect the optimal cut-off value for the CAMCOG total, subscales and composite memory and non-memory scores, for predicting dementia. Sensitivity and specificity of each cut-off score were assessed. from the 2,053 individuals without dementia at the first assessment, 137 developed dementia at the 2-year follow-up. The results indicate similar discriminative accuracy for incident dementia based on the CAMCOG total, memory subscale and composite scores. However, sensitivity and specificity of cut-off values were generally moderate. Scores on the non-memory subscales generally had high sensitivity but low specificity. Compared with the CAMCOG total score they had significantly lower discriminative accuracy. in a population setting, cut-off scores from the CAMCOG memory subscales predicted dementia with reasonable accuracy. Scores on the non-memory scales have lower accuracy and are not recommend for predicting high-risk cases unless all non-memory subdomain scores are combined. The added value of cognition when assessed using the CAMCOG to other risk factors (e.g. health and genetics) should be tested within a risk prediction framework.


148-W single-frequency Nd:YAG Innoslab μs-amplifier at 1064 nm with high efficiency.
In this paper, a single-frequency quasi-continuous-wave partially pumped slab (Innoslab) amplifier at 1064 nm is reported. The 4.4-W single-frequency seed laser was amplified to 148.1 W with optical-optical efficiency of 30.4%. The output pulse duration was 141.4 μs at the repetition of 500 Hz. The beam quality factors of M2 were 1.41 and 1.37 in the horizontal and vertical direction respectively. The experimental results match well with the numerical simulation. To the best of our knowledge, this is the first report on single-frequency Nd:YAG Innoslab amplifier with such a high output power and efficiency.


The Xanthomonas campestris gumD gene required for synthesis of xanthan gum is involved in normal pigmentation and virulence in causing black rot.
A cloned 4.1-kb EcoRI fragment from Xanthomonas campestris pv. campestris was previously shown to complement the non-mucoid mutant P22 and increase xanthan gum production after being transformed into the wild-type strain Xc17. The gene responsible for these effects was identified, sequenced, and shown to be the gumD gene which has previously been proposed to encode glucose transferase activity, an enzyme required for adding the first glucose residue to the isoprenoid glycosyl carrier lipid during xanthan synthesis. A gumD mutant, isolated from Xc17 by gene replacement, was shown to possess altered pigment xanthomonadin profiles and exhibit reduced virulence in causing black rot in broccoli. This study appears to be the first to demonstrate that interruption of a gene required for xanthan synthesis can lead to reduced virulence of X. campestris.


Knockdown of deoxythymidylate kinase suppresses progression and epithelial-mesenchymal-transition of lung adenocarcinoma via STAT3 signaling.
Current research has shown that inhibiting deoxythymidylate kinase (DTYMK) can significantly reduce development of lung cancer without liver kinase B1. However, its underlying regulatory mechanism is still unclear. We therefore aimed to investigate whether DTYMK inhibitors could suppress lung adenocarcinoma (LUAD) progression. In this study, human tissues, A549 cells, and xenograft tumors were used to explore the regulation and mechanism of DTYMK on LUAD cell proliferation and migration. Meanwhile, YMU1 (a DTYMK inhibitor) was applied to A549 cells and xenograft tumors to investigate its potential as a drug for LUAD. DTYMK was overexpressed in LUAD tissues and correlated with tumor stage. Knockdown of DTYMK suppressed cell viability, migration, and invasion. In addition, the activation of signal transducers and activators of transcription 3 (STAT3) was repressed upon DTYMK inhibition. YMU1 showed the same effect as DTYMK knockdown in vivo and in vitro. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may have the potential to inhibit the development of LUAD.NEW & NOTEWORTHY DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may serve as a novel drug to suppress the development of LUAD.


Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5.
The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.


Recent advances in imaging Alzheimer's disease.
Advances in brain imaging technology in the past five years have contributed greatly to the understanding of Alzheimer's disease (AD). Here, we review recent research related to amyloid imaging, new methods for magnetic resonance imaging analyses, and statistical methods. We also review research that evaluates AD risk factors and brain imaging, in the context of AD prediction and progression. We selected a variety of illustrative studies, describing how they advanced the field and are leading AD research in promising new directions.


Guilty pleasures II: restrained eaters' implicit preferences for high, moderate and low-caloric food.
In a previous study, restrained eaters showed stronger implicit preferences for high-caloric food compared to unrestrained eaters. Caloric density and palatability are however almost always intertwined, and it was never tested whether this high-calorie food preference of restrained eaters follows from the energy density or the palatability of high-calorie foods. Here, it was examined whether restrained eaters may hold stronger implicit preferences than unrestrained eaters for palatable food in general, irrespective of caloric density. Participants were randomly assigned to one of three conditions: Using two unipolar SCIATs positive and negative implicit associations were measured with palatable food of either high, moderate, or low caloric density. Results showed a strong effect of dietary restraint on implicit food preferences independently of caloric density, indicating stronger implicit preferences for all types of palatable food with increased dietary restraint. With respect to negative implicit associations, participants showed stronger negative implicit associations with high-calorie food than with moderate-calorie or low-calorie food, regardless of dietary restraint. Thus, restrained eaters show enhanced implicit preferences, not only for high caloric food, but for palatable food in general compared to unrestrained eaters.


[Perception independent of interest: a contribution to the relationship between people and animals].
In occidental cultures the relation of humans to animals is determined by the human perception of the outer world. Using motives from evolutionary epistemology it is argued that the evolutionary pressure to adapt increasingly obscures perception, where perception means relating to the outer world in a way that is independent of interests. Therefore, the pressure to adapt and to realise the interest to adapt obscures perception. This results in a reduced self-perception. Two phenomena exemplify this: persons ignoring their own bodies and a reductive perception relating to animals, such as reducing the value of animals to mere human resources. This reductive perception explains the very limited success of the animal rights-debate.


Differentiating Carotid Free-Floating Thrombus From Atheromatous Plaque Using Intraluminal Filling Defect Length on CTA: A Validation Study.
To validate a previously proposed filling defect length threshold of >3.8 mm on CT angiography (CTA) to discriminate between free-floating thrombus (FFT) and plaque of atheroma. This was a prospective multicenter observational study of 100 participants presenting with TIA/stroke symptoms and a carotid intraluminal filling defect on initial CTA. Follow-up CTA was obtained within 1 week and at weeks 2 and 4 if the intraluminal filling defect was unchanged in length. Resolution or decreased length was diagnostic of FFT, whereas its static appearance after 4 weeks was indicative of plaque. Diagnostic accuracy of FFT length was assessed by receiver operating characteristic analysis. Ninety-five participants (mean [SD] age 68 [13] years, 61 men, 83 participants with FFT, 12 participants with a plaque) were evaluated. The >3.8-mm threshold had a sensitivity of 88% (73 of 83) (95% confidence interval [CI] 78%-94%) and specificity of 83% (10 of 12) (95% CI 51%-97%) (area under the curve 0.91, p < 0.001) for the diagnosis of FFT. The optimal length threshold was >3.64 mm with a sensitivity of 89% (74 of 83) (95% CI 80%-95%) and specificity of 83% (10 of 12) (95% CI 51%-97%). Adjusted logistic regression showed that every 1-mm increase in intraluminal filling defect length is associated with an increase in odds of FFT of 4.6 (95% CI 1.9-11.1, p = 0.01). CTA enables accurate differentiation of FFT vs plaque using craniocaudal length thresholds. ClinicalTrials.gov Identifier: NCT02405845. This study provides Class I evidence that in patients with TIA/stroke symptoms, the presence of CTA-identified filling defects of lengths >3.8 mm accurately discriminates FFT from atheromatous plaque.


Roles of target cell membrane carbohydrate and lipid in Entamoeba histolytica interaction with mammalian cells.
Latex beads and liposomes carrying glycoproteins with carbohydrate sequences recognized by an Entamoeba histolytica galactose-specific binding protein were assessed for their ability to adhere to trophozoites and to stimulate amoeba actin polymerization. Glycoprotein-conjugated beads bound significantly to amoebae but did not stimulate actin polymerization. Glycoprotein-bearing liposomes bound to amoebae and did enhance actin polymerization, as do recognized glycosphingolipid-bearing liposomes (G. B. Bailey, E. D. Nudelman, D. B. Day, C. F. Harper, and J. R. Gilmour, Infect. Immun. 58:43-47, 1990). Liposome-stimulated actin polymerization occurred only if the vesicle contained negatively charged phospholipid. It was concluded that both glycoprotein and glycosphingolipid glycans on the target cell surface are involved in attachment to E. histolytica but do not themselves induce the transmembrane signals that lead to cytoskeleton activation and target destruction. This requires interaction with lipids of the target membrane bilayer.


Overcrowding and intensive exposure as determinants of measles mortality.
Data from a 1979 measles epidemic in an urban district of Guinea- Bissau indicate that state of nutrition is not a major determinant of outcome of infection. However, overcrowding increases the risk of early infection and the severity of disease. In instances in which several children have measles simultaneously, the case fatality rate is significantly higher than for isolated cases. This tendency is apparently a result of intensity of exposure; within the same house, secondary cases have a much higher age-specific case fatality rate than index cases. It is suggested that the association between intensive exposure and severity of infection may be due to increase rates of intercurrent infection and/or a greater dose of infection. Since it is not only the malnourished children who die of measles, vaccination may have a greater importance for survival patterns than has previously been assumed.


[Iodine uptake and the effect of radioiodine treatment--status after the addition of iodine to salt].
Iodine uptake and the effect of radioiodine treatment of nontoxic goiter were investigated after the introduction of iodine to salt. A retrospective study was done of 61 patients (48 women and 13 men with a median age of 56 (range 28-78)) with nontoxic goiter, examined by 24-hour radioiodine uptake. 42 of the patients were treated with radioiodine (median 600 MBq, range 200-600 MBq). The results were compared with those from a study done 10 years ago in the same area. Iodine uptake decreased significantly, from 40% (range 16-67%) in 1981-1993 to 25% (range 13-62%) in 2001-2003. 38 of the 42 patients were examined, and of these 34 (90%) had benefited from the treatment (53% of the 38 patients showed a complete effect) as estimated by the patient and the physician, based on the patient's original symptoms and the physician's clinical judgement. Four patients developed hypothyroidism, one radiation-induced thyroiditis and three Graves" disease. Iodine uptake is significantly lowered after the addition of iodine to salt. Radioiodine therapy of nontoxic goiter will continue to be effective.


Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis.
Irradiation of rat testes leads to the failure to support differentiation of the surviving spermatogonia due to damage of the somatic environment. To determine the involvement of Sertoli cells in this somatic damage, we transplanted seminiferous tubule cells from normal immature GFP-transgenic rats into the testes of irradiated rats. The donor Sertoli cells colonized and developed in the host testes. In many seminiferous tubules, the donor Sertoli cells formed abnormal spherical structures in the lumen, but in some tubules they formed a normal-appearing epithelium, but with only isolated spermatogonia, on the basement membrane. When the donor cells were injected into the interstitial region of the testis, they formed tubule-like structures containing Sertoli cells and occasional isolated spermatogonia, both of donor origin. Surprisingly, in host tubules adjacent to these newly formed donor-cell tubules or adjacent to the endogenous tubules with abnormal donor Sertoli-cell structures, endogenous spermatogonia differentiated to the spermatocyte or even to spermatid stages. Around these newly donor cell-formed tubules and the host tubules with abnormal donor Sertoli-cell structures, many cells including macrophages, which perhaps represented chronic inflammation, accumulated in the interstitium. We conclude that the donor Sertoli cells that colonized the seminiferous tubules did not directly support recovery of spermatogenesis. Instead, the colonizing Sertoli cells acted indirectly on the interstitium to stimulate localized differentiation of endogenous spermatogonia.


The impact of truncation and missing family links in population-based registers on familial risk estimates.
Family history information is often incomplete in population-based disease registers because of truncation and/or missing family links. In this study, the authors simulated complete populations of related individuals with realistic age, family structure, and incidence rates. After mimicking the realities of register-based data, such as left truncation of family history and missing family links due to death, the authors explored recovery of familial association parameters from standard epidemiologic models. Truncation of family history produced almost no bias for a familial risk of 2 and 50 years of follow-up, but it had a dramatic impact when the familial risk was 10. The age distribution of disease and the magnitude of background incidence rates also affected family history loss and thus the magnitude of bias. One can safeguard against bias by starting follow-up later, with the number of registration years to be ignored in the analysis depending on the value of familial risk. The missing familial links due to death had no effect, except when there was differential mortality for cases with and without a family history of disease. In summary, truncation, and to a lesser extent missing family links, induces bias in familial risk estimates from population-based registers.


Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095.
Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies. Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with 131I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5-5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years. The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy. The first dose of RLT with 131I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia.


Comparison of outcomes in patients with active infective endocarditis and a paravalvular abscess on a prosthetic valve versus a native valve.
We investigated in-hospital and long-term mortality in 16 patients with infective endocarditis and paravalvular abscess on a prosthetic valve (6 of whom underwent surgery) and in 12 patients with infective endocarditis and paravalvular abscess on a native valve (8 of whom underwent surgery). The only significant risk factor for in-hospital mortality in patients with prosthetic or native value paravalvular abscess was age (P < 0.001). In-hospital mortality was 33% in patients with prosthetic valve paravalvular abscess undergoing surgery and 33% in patients treated medically (P = not significant). In-hospital mortality was 25% in patients with native valve paravalvular abscess undergoing surgery and 25% in patients treated medically (P = not significant). At 4.8-year follow up, survival of patients with prosthetic valve paravalvular abscess was 67% for patients treated surgically versus 40% for patients treated medically (P = not significant). At 4.8-year follow up, survival of patients with native valve paravalvular abscess was 75% for patients treated surgically versus 50% for patients treated medically (P = not significant).


Acute Psychotic Episode Precipitated by Opioid Withdrawal in a Case of Bipolar I Disorder.
Psychosis is a state of mind where an individual loses touch with reality and cannot differentiate between their perceptions and the real world. They experience one or more of the following: delusions, hallucinations, disorganized speech or catatonic behavior. While it can have a sporadic onset, drug-induced psychosis is also very common. When a person consuming large quantities of a particular drug, such as opioids, stops consuming the drug and enters the rehabilitation stage, this is a vulnerable time due to abrupt chemical changes. It can predispose the individual to psychosis due to withdrawal from the drug. Here, we present a 30-year-old Caucasian female who underwent rehabilitation and was treated successfully with buprenorphine/naloxone (Suboxone) for eight months. However, due to a comorbid psychiatric condition, mania, she was not able to adhere to her medication regimen, which led to an abrupt discontinuation of her maintenance medication, and this led to psychotic symptoms, including agitation, hallucinations, delusions, and bizarre behavior surrounding her family and individual health. Later, she restarted on buprenorphine/naloxone, which led to a gradual recovery and disappearance of her psychotic symptoms.


Porous Al2O3-CNT Nanocomposite Membrane Produced by Spark Plasma Sintering with Tailored Microstructure and Properties for Water Treatment.
Ceramic-based nanocomposite membranes are gaining great attention in various applications, such as water treatment; gas separation; oil and gas, amid their superior fouling resistance and remarkable chemical/thermal stability. Here, we report for the first time the use of spark plasma sintering (SPS) process to fabricate a porous alumina-carbon nanotubes (Al2O3-CNT) nanocomposite membrane for water treatment. The challenge is this work is to achieve a balance between the amount of porosity, desired for a high water flux, and the membrane strength level, required to resist the applied pressure during a water flow experiment. The effect of SPS process parameters (pressure, temperature, heating rate, and holding time) on the microstructure and properties of the developed membrane was investigated and correlated. A powder mixture composed of Al2O3 and 5 wt % CNT was prepared with the addition of starch as a pore former and gum Arabic and sodium dodecyl sulfate as dispersants. The powder mixture was then sintered using SPS to produce a solid but porous nanocomposite membrane. The structure and microstructure of the developed membrane were characterized using X-ray diffraction and field emission scanning electron microscopy. The performance of the membrane was assessed in terms of porosity, permeability, and mechanical properties. Moreover, the adsorption capability of the membrane was performed by evaluating its removal efficacy for cadmium (II) from water. The microstructural analysis revealed that CNT were distributed within the alumina matrix and located mainly along the grain boundaries. The permeability and strength were highly influenced by the sintering pressure and temperature, respectively. The results indicated that the membrane sintered at a pressure of 10 MPa, temperature of 1100 °C, holding time of 5 min, and heating rate of 200 °C/min exhibited the best combination of permeability and strength. This developed membrane showed a significant removal efficiency of 97% for cadmium (II) in an aqueous solution.


Alcohol and aggression in men: a comparison of brewed and distilled beverages.
The effects of distilled and brewed alcoholic beverages on aggressive behavior were compared in a 2 x 2 factorial design with 16 subjects per cell (N = 64 men social drinkers). One-half of the sample population was told that they would be consuming an alcohol (distilled spirits) beverage and the other half that they would be consuming beer. Within each of these conditions, one-half of the subjects received the expected drug (alcohol) and one-half was given a corresponding placebo beverage. Aggression was measured using a modified version of the Buss aggression machine. Subjects who consumed beer or believed that they were consuming beer were significantly less aggressive than subjects who consumed distilled spirits or believed that they were consuming distilled spirits. Differences between subjects receiving the drug (alcohol) and the placebo were not significant.


The use of stem cells in ischemic heart disease treatment.
Ischemic heart disease is a major cause of death and disabilities worldwide. Unfortunately, not all patients are suitable for direct revascularization. Cell-based therapies may be alternative options because of their potential to promote neovascularisation and endothelial repair, improving myocardial perfusion. The success of cell-based therapies depends on the type of implanted stem cells, delivery method and underlying disease. Several different cell populations including bone marrow-derived mononuclear cells (MNCs), mesenchymal stromal cells (MSCs), CD34+, CD133+, endothelial progenitor cells, adipose-derived mesenchymal stromal cells (ASCs) and stem cells from placenta and umbilical cord have been investigated. Presently, no consensus exists about the best cell type for clinical regenerative therapy. Because the system of coronary arteries in the ischemic area is poor and most of the coronary artery is significantly narrowed or closed, direct implantation of stem cells in the ischemic area of the heart muscle appears an attractive method.


3: Community-acquired pneumonia.
Community-acquired pneumonia is caused by a range of organisms, most commonly Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae and respiratory viruses. Chest x-ray is required for diagnosis. A risk score based on patient age, coexisting illness, physical signs and results of investigations can aid management decisions. Patients at low risk can usually be managed with oral antibiotics at home, while those at higher risk should be further assessed, and may need admission to hospital and intravenous therapy. For S. pneumoniae infection, amoxycillin is the recommended oral drug, while benzylpenicillin is recommended for intravenous use; all patients should also receive a tetracycline (eg, doxycycline) or macrolide (eg, roxithromycin) as part of initial therapy. Flucloxacillin or dicloxacillin should be added if staphylococcal pneumonia is suspected, and gentamicin or other specific therapy if gram-negative pneumonia is suspected; a third-generation cephalosporin plus intravenous erythromycin is recommended as initial therapy for severe cases. Infections that require special therapy should be considered (eg, tuberculosis, melioidosis, Legionella, Acinetobacter baumanii and Pneumocystis carinii infection).


A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects.
A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.


Phenotypic plasticity as a cause and consequence of population dynamics.
Predicting complex species-environment interactions is crucial for guiding conservation and mitigation strategies in a dynamically changing world. Phenotypic plasticity is a mechanism of trait variation that determines how individuals and populations adapt to changing and novel environments. For individuals, the effects of phenotypic plasticity can be quantified by measuring environment-trait relationships, but it is often difficult to predict how phenotypic plasticity affects populations. The assumption that environment-trait relationships validated for individuals indicate how populations respond to environmental change is commonly made without sufficient justification. Here we derive a novel general mathematical framework linking trait variation due to phenotypic plasticity to population dynamics. Applying the framework to the classical example of Nicholson's blowflies, we show how seemingly sensible predictions made from environment-trait relationships do not generalise to population responses. As a consequence, trait-based analyses that do not incorporate population feedbacks risk mischaracterising the effect of environmental change on populations.


Plasma S100beta and NSE levels and progression in multiple sclerosis.
Plasma levels of the glial cell marker S100beta and the neuronal marker neuron-specific enolase (NSE) are elevated in various conditions of central nervous system damage. In this study we investigated whether plasma levels of S100beta and NSE are related to disease progression in multiple sclerosis (MS). Plasma levels of S100beta and NSE were measured in 25 patients with relapsing remitting MS (RRMS), 23 with secondary progressive MS (SPMS) and 16 with primary progressive MS (PPMS). All MS patients were in a clinically stable phase. Progression and disability were evaluated during a follow-up period of five years. We found that plasma NSE levels were lower in patients with clinically relevant worsening on the Expanded Disability Status Scale (EDSS), defined as 1 point increase from EDSS <6.0 or 0.5 point increase from EDSS> or =6 after five years (p=0.042), and in patients with a progressive disease course (p=0.01). There was a significant negative correlation between plasma NSE levels and both EDSS and Multiple Sclerosis Severity Status (MSSS) scores at baseline and after five years of follow-up (r=-0.33 and -0.38, p=0.027 and 0.003). There were no significant differences between patient groups in plasma S100beta levels. Plasma NSE levels appear inversely related to disease progression in MS.


Nanotechnological approaches for the development of herbal drugs in treatment of diabetes mellitus - a critical review.
Diabetes mellitus (DM) is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. The number of people with diabetes is increasing due to population growth, ageing, urbanisation and increasing prevalence of obesity and physical inactivity. Apart from currently available therapeutic options, many herbal medicines have been recommended for the treatment of diabetes. Herbal drugs are prescribed widely because of their effectiveness, less side effects and relatively low cost. Several pharmacopoeias have provided parameters to maintain quality and standardise procedures in identification/authentication of herbal inputs and their products. Available literature related to folklore medicine used in the treatment of diabetes extended to nanoformulation of herbal drugs up to date was cited. The use of bioactive compounds leads to new hope to improve the life expectancy and health status of the population for the formulation of novel drugs. Recently, many studies have shown that nanotechnology has the potential to be used in different biological and medical applications, mainly as targeted drug delivery systems to minimise and delay the chronic effects of diabetes. Herein, the authors presented a thorough review of the available herbal medicines and the possibilities of developing their nanoformulations in the treatment of DM.


Detection of bacterial growth in blood components using oxygen consumption as a surrogate marker in a tertiary oncology setup.
Microbiological contamination of blood and blood products is a well-recognised transfusion risk. This study was performed in the blood bank of our oncology centre, with an objective to detect bacterial contamination in our blood products using oxygen consumption as a surrogate marker [Pall Enhanced Bacterial Detection System (eBDS)]. Results revealed that the percentages of failed units were 1.16% for random donor platelets (RDP), 0.81% for single donor platelets (SDP) and 2.94% for packed red blood cells (PRBCs), of which one RDP and one SDP grew coagulase-negative staphylococcus, while one PRBC culture grew Gram-positive bacilli.


The radiosensitization effect of parthenolide in prostate cancer cells is mediated by nuclear factor-kappaB inhibition and enhanced by the presence of PTEN.
Parthenolide has been shown to have anti-inflammatory and antitumor properties. However, whether and how parthenolide enhances tumor sensitivity to radiation therapy are unknown. In this study, we show that inhibition of the nuclear factor-kappaB (NF-kappaB) pathway is a common mechanism for the radiosensitization effect of parthenolide in prostate cancer cells LNCaP, DU 145, and PC3. Parthenolide inhibits radiation-induced NF-kappaB DNA-binding activity and the expression of its downstream target sod2, the gene coding for an important antiapoptotic and antioxidant enzyme (manganese superoxide dismutase) in the three prostate cancer cells. Different susceptibilities to parthenolide's effect are observed in two radioresistant cancer cells, DU 145 and PC3, with DU 145 cells showing higher sensitivity. This differential susceptibility to parthenolide is due, in part, to the fact that in addition to NF-kappaB inhibition, parthenolide activates the phosphatidylinositol-3-kinase/Akt prosurvival pathway in both cell lines. However, the activated Akt in DU 145 cells is kept at a relatively low level compared with that in PC3 cells due to the presence of functional PTEN. Transfection of wild-type PTEN into PTEN-null cells, PC3, confers the enhanced radiosensitization effect of parthenolide in PTEN-expressing cells. When PTEN expression is knocked down in DU 145 cells, the cells become more resistant to parthenolide's effect. Taken together, these results suggest that parthenolide inhibits the NF-kappaB pathway and activates the phosphatidylinositol-3-kinase/Akt pathway in prostate cancer cells. The radiosensitization effect of parthenolide is due, in part, to the inhibition of the NF-kappaB pathway. The presence of PTEN enhances the radiosensitization effect of parthenolide, in part, by suppressing the absolute amount of activated p-Akt.


ART: a minimal intervention approach to manage dental caries.
The number of studies investigating aspects of the Atraumatic Restorative Treatment (ART) approach has increased in recent years. This tissue preservative treatment approach appears to be less painful and is, therefore, more patient-friendly than conventional caries treatments. The investigations so far have shown that the ART approach is effective for the management of single-surface cavities in both deciduous and permanent dentitions. There appears to be no difference in survival results between single-surface ART restorations and comparable amalgam restorations in the permanent dentition after three years. The surface wear of ART restorations using high-viscosity glass-ionomers after two years is low. ART sealants using high-viscosity glass-ionomers are retained longer than ART sealants using low-viscosity glass-ionomers after three years. It is concluded that the ART approach is beneficial in improving the oral health of many, not only in developing but also in more advanced countries.


Treatment concerns for bullous pemphigoid in the COVID-19 pandemic era.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease with subepidermal involvement, typically affecting the elderly. It has spontaneous remissions and exacerbations with significant morbidity. A novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the new universal coronavirus disease 2019 (COVID-19) pandemic. The pandemic made concerns, especially about immunosuppressive therapy. In this article, we reviewed the management of BP in the COVID-19 pandemic era. The data about the best management of autoimmune bullous diseases like BP, during the outbreak of COVID-19, are evolving and updated every day.


Remarkable improvement of gas-sensing abilities in p-type oxide nanowires by local modification of the hole-accumulation layer.
This paper proposes a method for improving the reducing or oxidizing gas-sensing abilities of p-type oxide nanowires (NWs) by locally modifying the hole-accumulation channel through the attachment of p-type nanoparticles (NPs) with different upper valence band levels. In this study, the sensing behaviors of p-CuO NWs functionalized with either p-NiO or p-Co3O4 NPs were investigated as a model materials system. The attachment of p-NiO NPs greatly improved the reducing gas-sensing performance of p-CuO NWs. In contrast, the p-Co3O4 NPs improved the oxidizing gas-sensing properties of p-CuO NWs. These results are associated with the local suppression/expansion of the hole-accumulation channel of p-CuO NWs along the radial direction due to hole flow between the NWs and NPs. The approach proposed in this study provides a guideline for fabricating sensitive chemical sensors based on p-CuO NWs.


[Protection of edaravone on neurons and its effects on the expression of interleukin-lbeta in juvenile rat hippocampus following status convulsion].
To study the possible protection of edaravone on neurons of the hippocampus after status convulsion (SC) and its effects on the expression of interleukin-1beta (IL-lbeta) in juvenile rats. One hundred and ninety-five juvenile male Sprague-Dawley rats were randomly divided into three groups: SC, edaravone pretreatment and normal saline control (control group). Each group was subdivided into five groups sacrificed at 4, 12, 24, 48 and 72 hrs after SC induction. SC model was prepared using lithium-pilocarpine. The edaravone pretreatment group received edaravone by intraperitoneal injection once daily three days before convulsion induction. Histopathologic changes in the hippocampus were viewed under a light microscope and an electron microscope. Expression of apoptosis cells was observed by TdT-mediated dUTP nick end labeling (TUNEL). Expression of IL-lbeta protein was determined by immunohistochemistry. Under the electron microscrope, a small quantity of neurons showed karyopycnosis and endocytoplasmic reticulum (ER) expanded remarkably 24 hrs after SC induction; at 48 hrs the ER expanding was alleviated somewhat but mitochomdria swelling was more severe. The edaravone pretreatment group showed less severe neuronal changes compared with the SC group under the microscopes. The TUNEL positive cells in the hippocampus of the SC group were significantly more than those of the control group 12 hrs, and peaked at 48 hrs after SC induction. The edaravone pretreatment group showed decreased TUNEL positive cells in the hippocampus compared with the SC group, although the positive cells were more than those in the control group between 12 and 48 hrs after SC induction. The immunohistochemistry assay demonstrated that the expression of IL-lbeta in the hippocampus of the SC group increased significantly compared with that of the control group 12, 24, 48 and 72 hrs after SC induction. Edaravone pretreatment resulted in a significantly decreased IL-lbeta expression in the hippocampus as compared with the SC group. Edaravone pretreatment may decrease the IL-1beta expression and neuronal apoptosis in the hippocampus. This suggests that edaravone may have protective effects against the hippocampal damage caused by SC.


Gastric emptying and small intestinal transit in the piebald mouse model for Hirschsprung's disease.
Gastric emptying and small intestinal transit were investigated in the piebald mouse model for Hirschsprung's disease. These mice exhibited aganglionosis of the terminal segment of the large intestine. This condition was accompanied by fecal stasis and megacolon. Gastric emptying of saline or milk meals was slower in the mice with aganglionic or induced megacolon than in the normal mice, but the rate of emptying was faster than after administration of morphine (10 mg/kg). In the small intestine, the distribution of the radiolabeled marker and the advancing edge of the marker profile were abnormal in the mice with megacolon. There were small differences between the megacolonic and normal mice in the distance traversed by the advancing edge of the intraluminal profile of the marker. These results are evidence for disturbances of gastric and small intestinal motor function that occur in mice secondary to development of megacolon.


Salivary glucose as a metabolic control marker in patients with type 2 diabetes.
A study was made of the correlation between the serum and salivary glucose levels in healthy subjects and in patients with type 2 diabetes, in order to establish the validity of salivary glucose determination in monitoring glycemia. Ninety-seven subjects were included in the study: 47 diabetic patients and 46 controls, aged between 40- and 80-years-of-age. Venous blood and saliva samples were collected in both groups under fasting conditions and after administering a test meal (15% proteins, 55% carbohydrates and 30% lipids). The glucose levels were measured using the glucose oxidase technique. The salivary glucose levels were seen to be greater in the diabetic group vs the controls both under fasting conditions (baseline) and after the meal (postprandial) (p=0.023 and p=0.008, respectively). A significant positive correlation was found between the serum and salivary glucose levels at baseline and under resting conditions, particularly in the diabetic group (r=0.389, p=0.002). The coefficient of determination of the simple linear regression model was R2=0.042, showing salivary glucose to be related to the blood glucose levels. In conclusion, salivary glucose concentration is correlated to serum glucose, particularly in type 2 diabetics.


[Improvements in alarm care speed for the clinical monitor system].
Hypoxia often occurs in the course of emergency treatment the monitoring systems alarm is not heard promptly by the nurses in attendance. In this study, nurses were monitored for the speed of their reactions to such alarms in 326 clinical instances. In 128 instances (39 percent) the nurses reacted immediately (within ten seconds), and in 198 instances (61 percent) the nurses took more than ten seconds to react. In relation to the reactions that took longer than ten seconds, it was discovered that there was: a lack of alertness about dealing with alarms, insufficient knowledge about setting alarms, no coordinated response mechanism, a failure to hear the alarm, limitations affecting the equipment and difficulty detecting the direction of origin of the alarm sound. For these reasons the hospital implemented briefings about alarms during morning meetings, a coordinated response mechanism, improvements in standards concerning the setting and inspection of alarms, the setting of limits on the frequency of patient's visits and the numbers of visitors, and the setting of a standard alarm volume level. As a result, the percentage of nurses responding to alarms within ten seconds increased to eighty percent, raising standards of nursing care, medical treatment and patient safety.


Silver Diamine Fluoride Treatment Considerations in Children's Caries Management.
By arresting and preventing caries, silver diamine fluoride (SDF) offers an alternate care path for patients for whom traditional restorative treatment is not immediately available. Current data from controlled clinical trials encompassing more than 3,900 children indicate that biannual application of SDF reduces progression of current caries and risk of subsequent caries. The purpose of this paper was to highlight the best evidence from systematic reviews and clinical trials for clinicians to consider the benefits, risks, and limitations as they implement silver diamine fluoride therapy on young children.


Rationing fairly: programmatic considerations.
I conclude with a plea against provincialism. The four problems I illustrated have their analogues in the rationing of goods other than health care. To flesh out a principle that says "people are equal before the law" will involve decisions about how to allocate legal services among all people who can make plausible claims to need them by citing that principle. Similarly, to give content to a principle that assures equal educational opportunity will involve decisions about resource allocation very much like those involved in rationing health care. Being provincial about health care rationing will prevent us from seeing the relationships among these rationing problems. Conversely, a rationing theory will have greater force if it derives from consideration of common types of problems that are independent of the kinds of goods whose distribution is in question. I am suggesting that exploring a theory of rationing in this way is a prolegomenon to serious work in "applied ethics."


Interpopulation and context-related differences in responses of a marine gastropod to predation risk.
We conducted laboratory experiments to investigate interpopulation differences in the behavioural responses of the whelk Buccinum undatum to the predatory lobster Homarus americanus and the asteroid Leptasterias polaris, both in the absence and presence of feeding opportunities. Whelks from three populations in the eastern North Atlantic (1) responded to lobsters by displaying avoidance behaviours (burrowing in the sediments or retreating inside their shell), (2) responded to asteroids by displaying escape responses (rapid crawling, shell rocking behaviour or foot contortions), and (3) more often refrained from feeding in the presence of a lobster than in the presence of an asteroid. Although whelks from the three populations responded similarly to lobsters and asteroids, interpopulation differences were evident. Thus, whelks from populations sympatric with a given predator more frequently displayed 'appropriate' antipredator behaviours (i.e. avoidance in the presence of a lobster, and escape in the presence of an asteroid) than did whelks allopatric with that predator. Also, whelks from a population sympatric with both predators fed less readily in the presence of a given predator than did whelks allopatric with that predator. However, the presence of a lobster or an asteroid had the same impact on the feeding response of whelks from two populations with contrasting predator fields, one sympatric with lobsters, but allopatric with asteroids, and one sympatric with asteroids, but allopatric with lobsters. The results of our study indicate that coexistence (over evolutionary or ecological time) with lobsters and asteroids increases the propensity of the whelk to display avoidance and escape behaviours in the presence of lobsters and asteroids, respectively, but has a less predictable effect on how whelks trade off predation risk and food acquisition. Studies are needed to investigate the roles of inheritance and experience on the development of antipredator behaviours and decision making by prey animals when predation risk conflicts with other fitness-related activities such as the acquisition of food or reproductive opportunities. Copyright 1999 The Association for the Study of Animal Behaviour.


Bb65, a major immunoreactive protein of Bartonella bacilliformis.
A 65 kDa protein (Bb65) has been identified as one of the major specific antigens of Bartonella bacilliformis, the causative agent of bartonellosis which is a bacterial infectious disease of inhabitants of the Andes. The gene encoding this antigen (7B2) was isolated from an expression library made directly from randomly generated fragments of B. bacilliformis genomic DNA using Bartonella antibodies raised in rabbits and sera of bartonellosis patients. The Bartonella 7B2 gene was expressed in Escherichia coli and the recombinant Bb65 protein was purified by column chromatography. Using polyclonal antibodies raised in rabbits, the antigen was shown to be present in all of 13 B. bacilliformis isolates from different Peruvian regions. Immune electron microscopy demonstrated the probable cytoplasmatic localization of Bb65. When applied to enzyme immunoassays, Bb65 sensitively and specifically bound to IgG antibody of sera of bartonellosis patients, convalescents, and immunes from various Peruvian regions. IgM antibody was not recognized by Bb65, neither was IgG antibody circulating during the first 2 weeks of illness. The amino-terminal amino acid sequence of Bb65 was 53% homologous to the 65 kDa heat shock protein of Mycobacterium tuberculosis.


Results of patch testing with a special series of rubber allergens.
The purpose of this study was to examine the results of patch testing with the rubber components on a standard screening tray and compare them with the results of testing with a special series of 27 rubber components (rubber tray). 1670 patients were patch tested with the screening tray and 317 of these were also tested with the rubber tray. 16% of those tested with the rubber tray had a positive response to at least 1 of the rubber allergens on the screening tray and 22% had a positive response to at least 1 of the allergens on the rubber tray. The most common positive response to the rubber tray allergens was to tetramethylthiuram monosulfide. There were no responses to 3 of the components on the rubber tray and there was only 1 positive response to a further 4 components. The diagnostic test characteristics of the rubber components on the screening tray were examined using the rubber tray as the gold standard. The sensitivity of the screening tray was 94%, specificity 51%, positive predictive value 87% and negative predictive value 71%. Of the 317 tested, 11% were found to have a positive to a substance on the rubber tray that was not evident from the results of the screening tray.


Tissue converting enzyme inhibition and cardiovascular effects of converting enzyme inhibitors.
Local renin-angiotensin systems have been described in organ controlling cardiovascular function. Following oral administration of converting enzyme (CE) inhibitors the enzyme was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. Evidence for a contribution of tissue CE inhibition to the cardiovascular actions of CE inhibitors is provided by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after chronic oral CE inhibitor treatment, and by the marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may therefore be an important factor involved in the beneficial effects of CE inhibitors in cardiovascular diseases such as arterial hypertension, congestive heart failure, and cardiac arrhythmias.


Molecular dynamics study of the effects of chain properties on the order formation dynamics of self-assembled monolayers of long-chain molecules.
The order formation dynamics of self-assembled monolayers (SAM) of long-chain molecules were studied using coarse-grained molecular dynamics simulations. The primary kinetic processes of surface order formation from solution are adsorption to the surface and surface diffusion. For long-chain molecules, the degrees of freedom of the chain structure and motion add various complexities to the order formation dynamics. Specifically, the strength of the chain interaction, the chain flexibility and the chain length play a significant role, and this work focused on the effects of these chain properties on the order formation dynamics. The adsorption dynamics of SAM molecules can be explained by the same theoretical framework as the polymer brush. On the other hand, the evolution of highly ordered structure is specific to SAM systems. Simulation results revealed that the development of oriented domains can be grouped into three types, isolated island growth, packing growth, and growth suppression, which depend on temperature and chain flexibility. In packing growth, oriented domains are formed gradually due to the decrease in free volume as the surface density becomes high, while the tilt of the adsorbed chain molecules does not become upright gradually as a whole. Rather, inside the oriented domains, the adsorbed chains adopt "standing" states with tilt angles almost equal to the final values, which contributes to the gradual increase in the total tilt order. The effect of chain length was also studied. In the case of semirigid chain molecules, longer-chain systems showed slightly slower growth in adsorption but faster growth in oriented domains. These simulation results reveal how chain properties influence the dynamics of oriented structure formation on surfaces.


Prospects of HIV-1 entry inhibitors as novel therapeutics.
A great deal of progress has been made in understanding the mechanism of human immunodeficiency virus entry into target cells. Landmark discoveries such as the identification of viral coreceptors and the structure of a portion of the viral envelope protein (Env) bound to its receptor provided important insight into how Env mediates fusion of the viral and cellular membranes. This knowledge has been successfully applied to the development of inhibitors that target discrete steps of the entry process. Some of these compounds efficiently block HIV-1 replication in vitro and are currently being evaluated in clinical trials. In this review, we will introduce the challenges of antiviral therapy and highlight the need for novel therapeutics, such as entry inhibitors, to complement current antiviral regimens. The mechanism by which Env mediates HIV-1 entry and the therapeutic potential of small molecule inhibitors of this dynamic process will be discussed in detail.


Sensing Attribute Weights: A Novel Basic Belief Assignment Method.
Dempster-Shafer evidence theory is widely used in many soft sensors data fusion systems on account of its good performance for handling the uncertainty information of soft sensors. However, how to determine basic belief assignment (BBA) is still an open issue. The existing methods to determine BBA do not consider the reliability of each attribute; at the same time, they cannot effectively determine BBA in the open world. In this paper, based on attribute weights, a novel method to determine BBA is proposed not only in the closed world, but also in the open world. The Gaussian model of each attribute is built using the training samples firstly. Second, the similarity between the test sample and the attribute model is measured based on the Gaussian membership functions. Then, the attribute weights are generated using the overlap degree among the classes. Finally, BBA is determined according to the sensed attribute weights. Several examples with small datasets show the validity of the proposed method.


Epstein-Barr virus: To be a trigger of autoimmune glial fibrillary acidic protein astrocytopathy?
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune disease of central nervous system (CNS). It is unclear whether Epstein-Barr virus (EBV) is related to autoimmune GFAP astrocytopathy. To describe the clinical, laboratory, and imaging characteristics of patients with autoimmune GFAP astrocytopathy. The clinical, laboratory, and imaging findings of patients are presented. The levels of GFAP in CSF were detected by ELISA. T and B cell subsets in CSF were detected by flow cytometry. GFAP-IgG in serum and cerebrospinal fluid (CSF) were tested by cell-based assay (CBA) and tissue-based assay (TBA). All three patients had fever, cognitive dysfunction, limb weakness, and positive GFAP-IgG with EBV infection in CSF. Enteric glia cells may involve in this disease. Typical imaging findings include the gadolinium enhancement of linear perivascular radial perpendicular to the ventricle, meningeal enhancement (especially in midbrain interpeduncal fossa), longitudinally extensive lesions involving spindle cords, and more T2/Flair-hyperintense lesions in the periventricular white matter at late stage. The patients had poor response to antiviral treatment and strong response to steroid pulse therapy. EBV could induce CNS autoimmune response in autoimmune GFAP astrocytopathy. The detection of GFAP-IgG and EBV may facilitate the early diagnosis in these patients.


Nonsteroidal anti-inflammatory drugs and cardiovascular safety - translating pharmacological data into clinical readouts.
The pharmacological management of pain includes the use of nonsteroidal anti-inflammatory drugs(NSAIDs). They comprise traditional(t) NSAIDs and selective cyclooxygenase(COX)-2 inhibitors (named coxibs). The analgesic and anti-inflammatory effects of NSAIDs are dependent on the extent and duration of COX-2 inhibition in the spinal cord and inflammatory sites. However, the simultaneous inhibition of COX-2 in the vasculature translates into a prothrombotic phenotype and promotes hypertension and heart failure. Areas covered: The results of the clinical pharmacology of coxibs and the most used tNSAIDs provide a mechanistic interpretation of the cardiovascular(CV) outcomes found in randomized clinical trials(RCTs), meta-analyses of RCTs and epidemiological studies. A critical analysis of the design and results of the PRECISION trial, which compared the CV risk of celecoxib, ibuprofen, and naproxen in high-risk CV patients, was performed. Expert opinion: tNSAIDs and coxibs may increase the chance of a heart attack or stroke. The reduction of the dose of NSAIDs may mitigate, but not avoid, the risk of CV adverse effects. The development of novel biomarkers which identify susceptibility phenotypes associated with increased risk of CV complications by COX-2 inhibition is an unmet clinical need that once filled will lead to personalized treatments with NSAIDs.


Global routine vaccination coverage, 2013.
In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization to ensure that all children have access to routinely recommended vaccines. Since then, global coverage with the four core vaccines (Bacille Calmette-Guérin vaccine [for protection against tuberculosis], diphtheria-tetanus-pertussis vaccine [DTP], polio vaccine, and measles vaccine) has increased from <5% to ≥84%, and additional vaccines have been added to the recommended schedule. Coverage with the third dose of DTP vaccine (DTP3) by age 12 months is a key indicator of immunization program performance. Estimated global DTP3 coverage has remained at 83%-84% since 2009, with estimated 2013 coverage at 84%. Global coverage estimates for the second routine dose of measles-containing vaccine (MCV2) are reported for the first time in 2013; global coverage was 35% by the end of the second year of life and 53% when including older age groups. Improvements in equity of access and use of immunization services will help ensure that all children are protected from vaccine-preventable diseases.


Increased brain-derived neurotrophic factor in the serum of persons with nonalcoholic fatty liver disease.
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global health problem. In recent years, the inhibitory effect of brain-derived neurotrophic factor (BDNF) on diabetes mellitus and fatty liver has been clarified. The purpose of this study was to analyze the relationship between serum BDNF and NAFLD which caused by abnormal metabolism of glucose and lipids. This cross-sectional study involved 429 participants (mean age, 63.5 years: men, 38.5%) with low alcohol intake. Of the participants, those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 88), and the others were classified as the normal (n = 341) group. The NAFLD group was further classified into a mild group (n = 60) and a severe group (n = 28) based on the intensity of echogenicity and visualization of the hepatic vessels and diaphragm. Median BDNF levels were higher in the NAFLD group than the normal group (35.5 vs. 42.3 ng/mL, p < 0.01). Furthermore, BDNF levels tended to be associated with the severity of NAFLD (p < 0.01). In addition to the univariate analysis, in the sex- and age-adjusted model, there was a significant association between the BDNF levels and NAFLD severity (p < 0.01). The fully adjusted regression analysis also showed a positive association between the serum BDNF level and NAFLD (p < 0.01). These results suggest that NAFLD patients have a compensatory increase in circulating BDNF levels.


Aphasia Therapy Using the Deblocking Method and Kanji/Kana Issues.
Language facilitation experiments based on deblocking methods were carried out with aphasic patients. Most of the language modality combinations with good facilitations occurred among comprehension modalities, speech modalities, and writing modalities. Prestimulation modalities and facilitated modalities were the same in response for pointing, speech, and writing. If an output route of a particular word had been activated, although the input route was not impaired, a facilitation would be thought to have occurred. The main difference between kanji (morpheme letters) and kana (syllable letters) as stimuli for language therapy was that kanji were more effective in activating the semantic processing capacity, whereas kana were more effective in activating the phonological processing capacity.


[Effect of culture conditions on growth and adhesion of Bacillus licheniformis].
Adhesion to glass of actively growing cells of the thermophilic Bacillus licheniformis, isolated from the Medyaginskaya test borehole (Yaroslavl' oblast), was studied. The reversible adhesion (RA) manifests itself in a decline of cell density (short of cell lysis) in the liquid culture over the first 20-40 min of growth followed by normal exponential growth. The RA is minimal under favorable growth conditions but increases when cells are transferred to a new medium, especially one with a pH, temperature, salinity, or concentration of Ca2+ ions nonoptimal for the given species. Under unfavorable growth conditions, the adhesion becomes irreversible. The obtained data suggest that RA represents an adaptation mechanism important for population survival.


Flanking region variation of ForenSeq™ DNA Signature Prep Kit STR and SNP loci in Yavapai Native Americans.
Massively parallel sequencing (MPS) offers advantages over current capillary electrophoresis-based analysis of short tandem repeat (STR) loci for human identification testing. In particular STR repeat motif sequence information can be obtained, thereby increasing the discrimination power of some loci. While sequence variation within the repeat region is observed relatively frequently in some of the commonly used STRs, there is an additional degree of variation found in the flanking regions adjacent to the repeat motif. Repeat motif and flanking region sequence variation have been described for major population groups, however, not for more isolated populations. Flanking region sequence variation in STR and single nucleotide polymorphism (SNP) loci in the Yavapai population was analyzed using the ForenSeq™ DNA Signature Prep Kit and STRait Razor v2s. Seven and 14 autosomal STRs and identity-informative single nucleotide polymorphisms (iiSNPs), respectively, had some degree of flanking region variation. Three and four of these identity-informative loci, respectively, showed ≥5% increase in expected heterozygosity. The combined length- and sequence-based random match probabilities (RMPs) for 27 autosomal STRs were 6.11×10-26 and 2.79×10-29, respectively. When combined with 94 iiSNPs (a subset of which became microhaplotypes) the combined RMP was 5.49×10-63. Analysis of length-based and sequence-based autosomal STRs in STRUCTURE indicated that the Yavapai are most similar to the Hispanic population. While producing minimal increase in X- and Y-STR discrimination potential, access to flanking region data enabled identification of one novel X-STR and three Y-STR alleles relative to previous reports. Five ancestry-informative SNPs (aiSNPs) and two phenotype-informative SNPs (piSNPs) exhibited notable flanking region variation.


PK-PD Integration Modeling and Cutoff Value of Florfenicol against Streptococcus suis in Pigs.
The aims of the present study were to establish optimal doses and provide an alternate COPD for florfenicol against Streptococcus suis based on pharmacokinetic-pharmacodynamic integration modeling. The recommended dose (30 mg/kg b.w.) were administered in healthy pigs through intramuscular and intravenous routes for pharmacokinetic studies. The main pharmacokinetic parameters of Cmax, AUC0-24h, AUC, Ke, t1/2ke, MRT, Tmax, and Clb, were estimated as 4.44 μg/ml, 88.85 μg⋅h/ml, 158.56 μg⋅h/ml, 0.048 h-1, 14.46 h, 26.11 h, 4 h and 0.185 L/h⋅kg, respectively. The bioavailability of florfenicol was calculated to be 99.14% after I.M administration. A total of 124 Streptococcus suis from most cities of China were isolated to determine the minimum inhibitory concentration (MIC) of florfenicol. The MIC50 and MIC90 were calculated as 1 and 2 μg/ml. A serotype 2 Streptococcus suis (WH-2), with MIC value similar to MIC90, was selected as a representative for an in vitro and ex vivo pharmacodynamics study. The MIC values of WH-2 in TSB and plasma were 2 μg/ml, and the MBC/MIC ratios were 2 in TSB and plasma. The MPC was detected to be 3.2 μg/ml. According to inhibitory sigmoid Emax model, plasma AUC0-24h/MIC values of florfenicol versus Streptococcus suis were 37.89, 44.02, and 46.42 h for the bactericidal, bacteriostatic, and elimination activity, respectively. Monte Carlo simulations the optimal doses for bactericidal, bacteriostatic, and elimination effects were calculated as 16.5, 19.17, and 20.14 mg/kg b.w. for 50% target attainment rates (TAR), and 21.55, 25.02, and 26.85 mg/kg b.w. for 90% TAR, respectively. The PK-PD cutoff value (COPD) analyzed from MCS for florfenicol against Streptococcus suis was 1 μg/ml which could provide a sensitivity cutoff value. These results contributed an optimized alternative to clinical veterinary medicine and showed that the dose of 25.02 mg/kg florfenicol for 24 h could have a bactericidal action against Streptococcus suis after I.M administration. However, it should be validated in clinical practice in the future investigations.


Post-exercise ankle-brachial pressure index demonstrates altered endothelial function in the elderly.
The ankle-brachial pressure index (ABI), the ratio of the systolic blood pressure of the ankle to the systolic brachial pressure, is commonly measured at rest, but ABI values post-exercise enhance the sensitivity of the test and can be used to identify atherosclerotic vascular damage. However, it has not been established whether or not enhanced post-exercise ABI is also associated with endothelial dysfunction. We hypothesized that a decrease in post-exercise ABI is related to impaired endothelial function. To investigate alterations in post-exercise ABI values and endothelial dysfunction in the elderly. The study population comprised 35 men and women aged 51-77 years (mean age: 66 years). Patients with peripheral arterial disease or a history of heart failure were excluded. The ABI was estimated at rest and immediately after exercise. The exercise protocol comprised 2.5 min of active pedal flexion exercises at a speed of 60 times/min. Endothelial function was assessed by measuring flow-mediated vasodilation (FMD) in the brachial artery using ultrasound imaging. No correlation was found between FMD and the ABI at rest. However, a weak correlation was found between FMD and post-exercise ABI (r = 0.46, P = 0.06). A strong correlation was observed between FMD and a decrease in post-exercise ABI compared to baseline readings (r = -0.52, P = 0.01). Multiple linear regression analysis was used to generate a prediction equation for FMD using the percentage decrease in post-exercise ABI. Significant correlations were observed between the ultrasound imaging-measured FMD and the predicted FMD (R(2) = 0.27, P = 0.001). Post-exercise ABI appears to be a simple surrogate marker for endothelial function in the elderly, although larger studies are required for validation.


Assessing the effects of interventions for Aedes aegypti control: systematic review and meta-analysis of cluster randomised controlled trials.
The Aedes aegypti mosquito is the vector for dengue fever, yellow fever, chikungunya, and zika viruses. Inadequate vector control has contributed to persistence and increase of these diseases. This review assesses the evidence of effectiveness of different control measures in reducing Aedes aegypti proliferation, using standard entomological indices. A systematic search of Medline, Ovid, BVS, LILACS, ARTEMISA, IMBIOMED and MEDIGRAPHIC databases identified cluster randomised controlled trials (CRCTs) of interventions to control Aedes aegypti published between January 2003 and October 2016. Eligible studies were CRCTs of chemical or biological control measures, or community mobilization, with entomological indices as an endpoint. A meta-analysis of eligible studies, using a random effects model, assessed the impact on household index (HI), container index (CI), and Breteau index (BI). From 848 papers identified by the search, eighteen met the inclusion criteria: eight for chemical control, one for biological control and nine for community mobilisation. Seven of the nine CRCTs of community mobilisation reported significantly lower entomological indices in intervention than control clusters; findings from the eight CRCTs of chemical control were more mixed. The CRCT of biological control reported a significant impact on the pupae per person index only. Ten papers provided enough detail for meta-analysis. Community mobilisation (four studies) was consistently effective, with an overall intervention effectiveness estimate of -0.10 (95%CI -0.20 - 0.00) for HI, -0.03 (95%CI -0.05 - -0.01) for CI, and -0.13 (95%CI -0.22 - -0.05) for BI. The single CRCT of biological control had effectiveness of -0.02 (95%CI -0.07- 0.03) for HI, -0.02 (95%CI -0.04- -0.01) for CI and -0.08 (95%CI -0.15- -0.01) for BI. The five studies of chemical control did not show a significant impact on indices: the overall effectiveness was -0.01 (95%CI -0.05- 0.03) for HI, 0.01 (95% CI -0.01- 0.02) for CI, and 0.01 (95%CI -0.03 - 0.05) for BI. Governments that rely on chemical control of Aedes aegypti should consider adding community mobilization to their prevention efforts. More well-conducted CRCTs of complex interventions, including those with biological control, are needed to provide evidence of real life impact. Trials of all interventions should measure impact on dengue risk.


Collagen Biocomposites Derived from Fish Waste: Doped and Cross-Linked with Functionalized Fe3O4 Nanoparticles and Their Comparative Studies with a Green Approach.
Collagen-based nanobiocomposites can reabsorb and are biodegradable. These properties are effectively controlled by the number of cross-links. This study demonstrates an effortless and proficient approach for the functionalization of Fe3O4 NPs for cross-linking collagen obtained from biowaste, viz., fish scales of Lates Calcarifer, a marine origin. The size of Fe3O4 NPs (10-40 nm) was confirmed using particle size analysis. The physico-chemical properties of the aminosilane-coated Fe3O4 NPs cross-linked via succinylated collagen (FFCSC) were characterized using different analytical techniques and compared with succinylated collagen doped with Fe3O4 NPs (FDSC). Thermogravimetric analysis indicates cross-linked product FFCSC to be more stable than the FDSC. Also, the antibacterial effect was more pronounced for FFCSC than for FDSC nanobiocomposites. FFCSC exhibited improved mechanical properties which are essential for materials used for wound dressing purposes. Moreover, the cell viability of fibroblasts (3T3-L1) and their morphology studied by SEM and fluorescence microscopy showed biocompatibility of both FDSC and FFCSC. Thus, the current investigation, involves a waste to wealth approach where the collagen-based nanobiocomposites present an easy way to recycle the biowaste to value-added products using simple and clean methods, which are suitable for use in biomedical and environmental applications.


Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.
The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function. MIVAS III is a multicenter cross-sectional study that will take place in the Iberian Peninsula. One thousand subjects aged between 45 and 74 years without cardiovascular disease will be selected. The main variables are demographic information, anthropometric measurements, and habits (tobacco and alcohol). Dietary patterns will be assessed using a frequency consumption questionnaire (FFQ) and the Mediterranean diet adherence questionnaire. Physical activity levels will be evaluated using the International Physical Activity Questionnaire (IPAQ), Marshall Questionnaire, and an Accelerometer (Actigraph). Body composition will be measured using the Inbody 230 impedance meter. Arterial aging will be assessed through various means, including measuring medium intimate carotid thickness using the Sonosite Micromax, conducting analysis with pulse wave velocity (PWA), and measuring pulse wave velocity (cf-PWV) using the Sphygmocor System. Additional cardiovascular indicators such as Cardio Ankle Vascular Index (CAVI), ba-PWV, and ankle-brachial index (Vasera VS-2000®) will also be examined. The study will analyze the intestinal microbiota using the OMNIgene GUT kit (OMR-200) and profile the microbiome through massive sequencing of the 16S rRNA gene. Linear discriminant analysis (LDA), effect size (LEfSe), and compositional analysis, such as ANCOM-BC, will be used to identify differentially abundant taxa between groups. After rarefying the samples, further analyses will be conducted using MicrobiomeAnalyst and R v.4.2.1 software. These analyses will include various aspects, such as assessing α and β diversity, conducting abundance profiling, and performing clustering analysis. Lifestyle acts as a modifier of microbiota composition. However, there are no conclusive results demonstrating the mediating effect of the microbiota in the relationship between lifestyles and cardiovascular diseases. Understanding this relationship may facilitate the implementation of strategies for improving population health by modifying the gut and oral microbiota. clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021.


Characteristics of impaired voluntary cough function in individuals with amyotrophic lateral sclerosis.
Although cough impairment (dystussia) is common in individuals with amyotrophic lateral sclerosis (ALS) and contributes to a reduced physiologic capacity to defend the airway, characteristics of dystussia have not yet been delineated. Therefore, we aimed to compare voluntary cough spirometry airflow patterns between individuals with ALS and healthy age and gender-matched controls. Thirty-two individuals with a diagnosis of probable-definite ALS (El-Escorial Criterion) and 29 healthy age and gender-matched controls underwent voluntary cough spirometry testing. Two blinded raters derived six objective voluntary cough airflow measures including: peak inspiratory phase duration, peak inspiratory flow rate, compression phase duration, peak expiratory rise time, peak expiratory flow rate, and cough volume acceleration. Independent samples t-tests with Cohen's d effect sizes were performed between Healthy versus ALS groups for cough metrics (alpha =0.05). ALS individuals demonstrated prolonged inspiratory phase and expiratory phase rise time durations, reduced inspiratory and expiratory flow rates, and lower cough volume acceleration during voluntary cough production compared with healthy controls (p < 0.05). No differences in compression phase duration were observed (p > 0.05). This study compared characteristics of voluntary cough airflow patterns of individuals with ALS to healthy-matched controls. Findings identified impairments in both inspiratory and expiratory voluntary cough airflow, resulting in slower, weaker, and thus less effectiveness voluntary cough production in ALS individuals. These data afford insight into the impaired physiology underlying inadequate airway clearance and secretion management in individuals with ALS.


Long-term blood pressure changes measured from before to after pregnancy relative to nonparous women.
To prospectively examine whether blood pressure changes persist after pregnancy among women of reproductive age. This was a prospective, population-based, observational cohort of 2,304 (1,167 black, 1,137 white) women (aged 18-30 years) who were free of hypertension at baseline (1985-1986) and reexamined up to six times at 2, 5, 7, 10, or 20 years later (2005-2006). We obtained standardized blood pressure measurements before and after pregnancies and categorized women into time-dependent groups by the cumulative number of births since baseline within each time interval (zero births [referent]; one interim birth and two or more interim births; nonhypertensive pregnancies). The study assessed differences in systolic and diastolic blood pressures among interim birth groups using multivariable, repeated measures linear regression models stratified by baseline parity (nulliparous and parous), adjusted for time, age, race, baseline covariates (blood pressure, body mass index, education, and oral contraceptive use), and follow-up covariates (smoking, antihypertensive medications, oral contraceptive use, and weight gain). Among nulliparas at baseline, mean (95% confidence interval) fully adjusted systolic and diastolic blood pressures (mm Hg), respectively, were lower by -2.06 (-2.72 to -1.41) and -1.50 (-2.08 to -0.92) after one interim birth, and lower by -1.89 (-2.63 to -1.15) and -1.29 (-1.96 to -0.63) after two or more interim births compared with no births (all P<.001). Among women already parous at baseline, adjusted mean blood pressure changes did not differ by number of subsequent births. A first birth is accompanied by persistent lowering of blood pressure from preconception to years after delivery. Although the biologic mechanism is unclear, pregnancy may create enduring alterations in vascular endothelial function. II.