miR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome.

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-ß2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.

Assessment of a conduction-repolarisation metric to predict Arrhythmogenesis in right ventricular disorders.

BACKGROUND: The re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry. This study aimed to test feasibility of an RVI-based algorithm to predict the earliest endocardial activation site of ventricular tachycardia (VT) during electrophysiological studies and occurrence of haemodynamically significant ventricular arrhythmias in follow-up. METHODS: Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n = 11), Brugada Syndrome (BrS) (n = 13) and focal RV outflow tract VT (n = 9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array in the RV. RESULTS: Lowest values of RVI co-localised with VT earliest activation site in ARVC/BrS but not in focal VT. The distance between region of lowest RVI and site of VT earliest site (Dmin) was lower in ARVC/BrS than in focal VT (6.8 ±â€¯6.7 mm vs 26.9 ±â€¯13.3 mm, p = 0.005). ARVC/BrS patients with inducible VT had lower Global-RVI (RVIG) than those who were non-inducible (-54.9 ±â€¯13.0 ms vs -35.9 ±â€¯8.6 ms, p = 0.005) or those with focal VT (-30.6 ±â€¯11.5 ms, p = 0.001). Patients were followed up for 112 ±â€¯19 months. Those with clinical VT events had lower Global-RVI than both ARVC and BrS patients without VT (-54.5 ±â€¯13.5 ms vs -36.2 ±â€¯8.8 ms, p = 0.007) and focal VT patients (-30.6 ±â€¯11.5 ms, p = 0.002). CONCLUSIONS: RVI reliably identifies the earliest RV endocardial activation site of VT in BrS and ARVC but not focal ventricular arrhythmias and predicts the incidence of haemodynamically significant arrhythmias. Therefore, RVI may be of value in predicting VT exit sites and hence targeting of re-entrant arrhythmias.

Contribution of CT scan and CT-guided aspiration in the management of retropharyngeal abscess in children based on a series of 18 cases.

OBJECTIVE: This study was designed to analyse the contribution of CT scan to the management of retropharyngeal abscess in children and the place of CT-guided percutaneous aspiration as an alternative to surgical drainage. MATERIALS AND METHODS: Retrospective study including 18 children with a mean age of 38 months [range: 5-67 months] presenting with retropharyngeal infection between 2006 and 2011. All cases were initially assessed by contrast-enhanced CT scan of the neck. Clinical, radiological treatment and bacteriological data were collected. Radiological results were correlated with surgical and percutaneous aspiration findings (presence or absence of an abscess). RESULTS: The initial CT scan detected 14 abscesses, 3 cases of non-suppurative lymphadenitis and one case of retropharyngeal oedema. One case of non-suppurative lymphadenitis progressed to abscess after failure of antibiotic therapy and was treated surgically. Surgical drainage revealed a purulent collection in 11 cases and no collection in 3 cases. Four CT-guided percutaneous aspirations were successfully performed. Three cases were treated by antibiotics alone (2 cases of lymphadenitis and 1 case of retropharyngeal oedema). Bacteriological examinations revealed the presence of Streptococcus pyogenes in 78.5% of cases. The positive predictive value of the initial CT scan was 78.8% in our series. CONCLUSION: Contrast-enhanced neck CT scan confirmed the diagnosis of retropharyngeal abscess and the indication for surgical drainage. It must be performed urgently, on admission. When it is decided to treat the patient with antibiotics alone, follow-up imaging should be performed in the absence of improvement 24 to 48 hours after starting antibiotics. CT-guided percutaneous aspiration is both a diagnostic modality confirming abscess formation of an inflammatory lesion of the retropharyngeal space as well as a therapeutic tool, sometimes avoiding the need for surgical drainage.

The morning blood pressure surge is related to serum cholesterol.

A morning blood pressure surge (MBPS) may be either a mechanism for, or a marker of, increased cardiovascular events. This study has examined factors which may influence the morning surge: age, gender, metabolic factors, sympathetic function, blood pressure and arterial stiffness. Four measures of the MBPS were examined--sleep-trough surge, pre-awake surge, rate of blood pressure rise and a Power function. Subjects underwent ambulatory blood pressure monitoring, glucose tolerance test, central pulse wave velocity, sympathetic autonomic function tests (mental stress and sustained handgrip). MBPS was associated with age, hypertension, blood pressure variability and serum lipids. After adjustment for age and waist circumference, all four measures of MBPS remained positively associated with low-density lipoprotein (LDL) cholesterol. The novel finding of a significant relationship between measures of MBPS and LDL-cholesterol is an intriguing link between two major cardiovascular risk factors.

Modulation of mammary gland development in pre-pubertal mice as affected by soya and milk protein supplements.

The objective of the present study was to determine the effects of soya and whey milk protein, α-lactalbumin (α-LA), on mammary gland morphology and the structural support of the gland, in pre-pubertal mice after 7 d of treatment. In Expt 1, weaned (day 21) CD1 mice were given one of the four treatments, three included dietary supplements: (1) control diet, casein, (2) soya, (3) α-LA and (4) subcutaneous injection of 2·5 µg oestradiol benzoate in 20 µl maize oil and fed the control diet. All diets were isoenergetic with equal protein concentrations. All groups that were not treated with oestradiol received the vehicle. Whole-mount analyses were performed to determine longitudinal ductal growth and terminal end bud development. DNA was extracted from the gland and assessed by spectrophotometry (260/280 nm). Tissue extracts for extracellular matrix (ECM) proteins, matrix metalloproteinase-2 (MMP(2)), tissue inhibitor of MMP(2) (TIMP(2)), and serum oestradiol and mammary tissue epidermal growth factors (EGF) were measured by immunoassays. Expt 2 utilised the Her2/neu transgenic strain, with the same protocols. Statistical significance was determined by one-way ANOVA. From Expt 1 and 2, soya and α-LA significantly increased ductal elongation when compared with the oestrogen and control groups. These results were corroborated by data on total DNA and the ratio of MMP(2):TIMP(2). The ratio of MMP(2):TIMP(2) was affected by α-LA. Serum oestradiol was decreased only in the oestradiol-treated groups in both experiments. Soya is known to be oestrogenic and can act on epithelia directly. The mechanism by which α-LA affects glandular development is by modulating the ECM or by promoting the synthesis/activity of EGF.

Transition voltage spectroscopy and the nature of vacuum tunneling.

Transition voltage spectroscopy (TVS) has been proposed as a tool to analyze charge transport through molecular junctions. We extend TVS to Au-vacuum-Au junctions and study the distance dependence of the transition voltage V(t)(d) for clean electrodes in cryogenic vacuum. On the one hand, this allows us to provide an important reference for V(t)(d) measurements on molecular junctions. On the other hand, we show that TVS forms a simple and powerful test for vacuum tunneling models.

Regional variations in action potential alternans in isolated murine Scn5a (+/-) hearts during dynamic pacing.

AIM: clinical observations suggest that alternans in action potential (AP) characteristics presages breakdown of normal ordered cardiac electrical activity culminating in ventricular arrhythmogenesis. We compared such temporal nonuniformities in monophasic action potential (MAP) waveforms in left (LV) and right ventricular (RV) epicardia and endocardia of Langendorff-perfused murine wild-type (WT), and Scn5a(+/-) hearts modelling Brugada syndrome (BrS) for the first time. METHODS: a dynamic pacing protocol imposed successively incremented steady pacing rates between 5.5 and 33 Hz. A signal analysis algorithm detected sequences of >10 beats showing alternans. Results were compared before and following the introduction of flecainide (10 microm) and quinidine (5 microm) known to exert pro- and anti-arrhythmic effects in BrS. RESULTS: sustained and transient amplitude and duration alternans were both frequently followed by ventricular ectopic beats and ventricular tachycardia or fibrillation. Diastolic intervals (DIs) that coincided with onsets of transient (tr) or sustained (ss) alternans in MAP duration (DI*) and amplitude (DI') were determined. Kruskal-Wallis tests followed by Bonferroni-corrected Mann-Whitney U-tests were applied to these DI results sorted by recording site, pharmacological conditions or experimental populations. WT hearts showed no significant heterogeneities in any DI. Untreated Scn5a (+/-) hearts showed earlier onsets of transient but not sustained duration alternans in LV endocardium compared with RV endocardium or LV epicardium. Flecainide administration caused earlier onsets of both transient and sustained duration alternans selectively in the RV epicardium in the Scn5a (+/-) hearts. CONCLUSION: these findings in a genetic model thus implicate RV epicardial changes in the arrhythmogenicity produced by flecainide challenge in previously asymptomatic clinical BrS.

Therapeutic frontiers: preventing and treating infectious diseases by inhibiting bacterial quorum sensing.

Density-dependent cell-cell communication, or quorum sensing (QS), has been demonstrated in numerous species of bacteria. The basic function of QS is likely to confer a nutritional advantage, particularly in a highly populated, mixed-species environment. QS also has ramifications on the production of colonization and virulence factors. Pheromone-like substances secreted into the extracellular milieu appear to govern many of the transcription products in these bacteria. At a high cell density, the QS systems are triggered, and the transcription of the colonization factors are suppressed and replaced by the expression of virulence factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems. Several QS-modulating therapies, such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have been investigated and may prove to be helpful in diminishing the translation of QS-directed toxins or by prematurely activating the QS response to alert the immune system to bacteria hiding in a low cell density. QS represents a recently discovered method of bacterial communication and population control, which may prove to be a unique mechanism to prevent, suppress, and/or treat infectious diseases.

Kiss and tell: what do we know about pre- and early adolescent females who report dating? A pilot study.

STUDY OBJECTIVE: To evaluate the implications of dating in pre- and early adolescent females. DESIGN: Cross-sectional survey. SETTING: Child psychiatry clinic; pediatric clinic; family clinic. PARTICIPANTS: Pre- and early adolescent females (n = 80) aged 11-14 and their parents. INTERVENTION: Pre- and early adolescent females aged 11-14 and a parent were recruited during a regular clinic visit. Pre- and early adolescent females completed a survey that included measures of dating; sensation seeking; lifetime individual and peer drug use; Attention Deficit Hyperactive Disorder, Oppositional Defiant Disorder and Conduct Disorder symptoms; and onset of menses. Parents were asked similar questions about their child's dating behaviors and peer relationships. MAIN OUTCOME MEASURE: Association of early dating with individual and peer drug use, sensation seeking, aggressive behavior, and onset of menses. RESULTS: In pre- and early adolescent females, dating regularly is associated with nicotine and alcohol use, sensation seeking, and aggressive behavior. Dating regularly is also associated with onset of menses and a younger age of onset of menses in those who had started menstruating. Parents under-report their child's dating practices and associated high-risk behaviors. CONCLUSION: Early dating is associated with nicotine and alcohol use, sensation seeking, aggressive behavior, and early onset of menses in adolescent females. Questions about early dating are a simple and efficient way to open inquiry of both parents and children about high-risk behaviors in the clinic setting.

Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort.

In dominant spinocerebellar ataxias (SCAs), the issue of whether non-CAG dependent factors contribute to onset age remains unsettled. Data on SCA genotype, onset age, normal/expanded CAG repeat length, sex of the patient and transmitting parent, and family details were available from 802 patients. Based on the model [log(10) (age at onset) = k - b CAG(exp) + epsilon], we examined changes in adjusted R(2) and residual standard error following incorporation of the other factors in this model. The expanded repeat explained 44.3 to 74.9% of onset age variance, although this was less than 50% in SCA3 and SCA6, implicating a large effect of non-CAG factors. The relation between onset age and CAG repeat was similar for SCA1, 3, 6, and 7, but different for SCA2, pointing to different polyglutamine effects in SCA2. For SCA2 and SCA3, 17.1 and 45.5% of onset age variance, respectively, were explained by currently (unidentified) familial factors. We found a significant contribution of the nonexpanded allele in SCA1 and SCA6. Besides polyglutamine motif (determined by the expanded CAG repeat length), we identified the following age at onset modifiers: protein context in SCA2; familial factors in SCA2 and SCA3; and the nonexpanded CAG repeat in SCA1 and SCA6.

Papillary adenocarcinoma of the extrahepatic bile duct in a Holstein cow.

A 15-year-old female Holstein cow was presented with a history of anorexia and weight loss. Abnormal physical examination findings included poor body condition, dehydration, icterus, and photodermatitis on nonpigmented areas of the skin of the dorsum. At necropsy, the common bile duct was greatly enlarged, with thickened walls, and tightly adhered to the hepatic capsular surface and serosa of adjacent loops of the small intestine. Two sessile, yellowish, friable, well-circumscribed, cauliflower-like, bulging masses (14 and 8 cm in diameter) were attached to the inner surface of the common bile duct blocking its lumen. Microscopically, the tumor was composed of well-differentiated, columnar epithelial cells with oval or round, vesicular, basal nuclei arranged in papillary projections. Periodic acid-Schiff-positive material accumulated in the apical cytoplasm of the neoplastic cells. Immunostaining of the tumor cells was positive for cytokeratin (CK) of wide-spectrum screening and for CK 7. The diagnosis of papillary adenocarcinoma of the extrahepatic bile duct was based on the morphologic features of the neoplasm and evidence of local invasion. To the best of our knowledge, extrahepatic bile duct carcinomas have not been described in cattle.

Micellar anisometry in lyotropic uniaxial nematic phases studied by transversal NMR relaxation dispersion.

A new method, based on the measurement of the (23 )( )Na nuclei spin-spin NMR relaxation times ( T2 ), is proposed to investigate the shape of micelles in lyotropic nematic phases. We investigate the ternary lyotropic mixture of sodium dodecyl sulfate, 1-decanol, and water by using the NMR technique, measuring T2 in the two lyotropic uniaxial nematic phases. The characteristic relaxation time curves of each particular phase are analyzed by considering that they are constituted by a superposition of exponential decays with typical characteristic times: in a sense, a T2 spectroscopy. The analysis of the T2 dispersion profiles in both the uniaxial nematic calamitic and discotic phases indicates that our results can be interpreted in terms of the model of intrinsically biaxial micelles in all the nematic phases.

Reactor scale-up in AOPs: from laboratory to commercial scale.

A procedure to scale-up photoreactors employed in AOPs using laboratory information has been developed. Operating with a model compound the proposed procedure was applied to the decomposition of formic acid in water solution using hydrogen peroxide and UV radiation. With laboratory experiments the parameters of the kinetic equation were obtained in a small batch reactor operated within a recycling apparatus. The whole system was modeled employing radiation and mass balances. These balances were used together with a non-linear parameter estimator to derive the model kinetic constants. Then, these results were used in the modeling of the large-scale reactor to predict exit conversions in an isothermal, continuous, tubular flow reactor that is 2 m long and has a volume of 12 I. Once more, radiation and mass balances were used to predict formic acid output concentrations. Experimental data in the large-scale apparatus are in good agreement with theoretical predictions.

Mixed lipid aggregates containing gangliosides impose different 2H-NMR dynamical parameters on water environment depending on their lipid composition.

Water dynamics in samples of ceramide tetrasaccharide (Gg4Cer) vesicles and GM1 ganglioside micelles at 300:1 water/lipid mole ratio were studied by using deuterium nuclear magnetic resonance (2H-NMR). GM1 imposes a different restriction on water dynamics that is insensitive to temperatures either above or below its phase transition temperature or below the freezing point of water. The calculated correlation times are in the range of 10(-10) s, typical of water molecules near to the polar groups. Pure GM1 micelles have two distinct water microenvironments dynamically characterized. Their dynamic parameters remain constant with temperature ranging from -18 to 32 degrees C, but the amount of strongly associated water is modified. By contrast, a mixture of single soluble carbohydrates corresponding to GM1 polar head group does not preserve the dynamic parameters of water hydration when the temperature is varied. Incorporation of cholesterol or lysophosphatidylcholine into GM1 micelles substantially increases the mobility of water molecules compared with that found in pure GM1 micelles. The overall results indicate that both the supramolecular organization and the local surface quality (lipid-lipid interaction) strongly influence the interfacial water mobility and the extent of hydration layers in glycosphingolipid aggregates.

Water decolorization using UV radiation and hydrogen peroxide: a kinetic study.

Sometimes, provision of water for domiciliary consumption faces the problem of natural contamination originated by the presence of organic substances such as humic or fulvic acids. Very often, after conventional sanitary treatments this water exhibits a persistent yellowish coloration that affects its use. Moreover, these substances may act as precursors of tri-halomethanes formation during pre-disinfection with chlorine. This paper presents, with a simplified mechanistic approach, the intrinsic reaction kinetics of natural water decolorization employing UV radiation and hydrogen peroxide. The main variables for the model are: contaminant concentration expressed as TOC, hydrogen peroxide concentration and the photon absorption rate.

The effect of hot beverages, cold beverages, and chewing gum on oral temperature.

BACKGROUND: A prospective blood donor's oral temperature is affected by external stimuli such as drinking a hot or cold beverage or chewing gum. These stimuli can cause a deferral or an inappropriate acceptance for a certain unknown time. STUDY DESIGN AND METHODS: Ten volunteer subjects were exposed to each of the three stimuli in separate studies. Oral and tympanic membrane temperatures were taken before exposure, immediately after exposure, and at various times until the subject's temperature returned to baseline. RESULTS: The drinking of a hot beverage caused an immediate mean temperature elevation of 2.6 degrees F which would lead to deferral for 7 of 10 subjects. All subjects were acceptable for blood donation (temperature <99.6 degrees F) by 5 minutes. A cold beverage lowered the temperature; the temperature in 6 subjects returned to baseline by 10 minutes and that in 4 did so by 30 minutes. Gum chewing caused minimal temperature elevations; only 1 donor's temperature reached 99.6 degrees F, and it was at acceptable levels for blood donation by 5 minutes. CONCLUSION: Drinking a hot beverage and, to a much lesser degree, gum chewing can lead to a deferral for elevated temperature, but subjects were acceptable by 5 minutes. Cold beverages are of more concern, because they suppress the temperature for a short time and could theoretically lead to acceptance of a febrile, possibly infectious donor.

The association of testosterone with nicotine use in young adult females.

This pilot laboratory study examined the relationship of testosterone levels, carbon monoxide (CO) levels, current and adolescent nicotine use, and histories of pubertal onset in 30 young adult female smokers. These females had completed questionnaires regarding nicotine use in the 7th through 10th grades, and again at age 21 as part of a cohort study of drug use. In addition, history of pubertal onset was obtained at age 21, as were testosterone and CO levels. Testosterone levels were positively correlated with cigarette use in the last 30 days (P< or =.01), CO levels (P< or =.05), cigarette use reported in the 7th and 10th grades (P< or =.05), and negatively correlated with age of pubertal onset (P< or =.001). The relationship of testosterone to nicotine will be discussed.

Cytokeratin immunoreactivity in mouse tissues: study of different antibodies with a new detection system.

The cross-reactivity of a group of monoclonal antibodies (MABs) generated against human cytokeratins (CKs) was investigated in mouse tissues. Formalin-fixed and paraffin-embedded sections of lung, stomach, small and large intestine, liver, and kidney were immunostained with MABs after epitope retrieval with enzyme digestion. AE1/AE3, a "cocktail" of two MABs that recognizes basic and acidic CKs, 5D3 MAB to low molecular weight CKs (8, 18, and 19), and monospecific MABs to CK 7 and 20 were tested. Additionally, CK 17 and 34betaE12 MABs to high molecular weight CKs were evaluated in the same organs and in sections from skin and preputial glands. We employed the new universal animal system (ARK) as the detection system. The results showed intense reactivity for the first group of antibodies used, with topographic distribution similar to that in human tissues, with the exception of CK 7 in lung parenchyma, which displayed reactivity only in type II pneumocytes, with negativity of adjacent bronchial epithelium. Also of note was the lack of reaction of liver hepatocytes and renal tubular cells to AE1/AE3 and 5D3 MABs. Regarding the second group of antibodies, no reaction was obtained for CK 17 in the tissues tested. On the contrary, 34betaE12 MAB yielded intense reactivity in cells of epidermis and hair follicles. Compared to other detection systems used previously in this animal, ARK produced a well-defined reactivity at the cellular level without any background. We conclude that a useful panel of anti-CK antibodies commonly used in human pathology can be applied successfully to mouse tissues after enzyme digestion, leading to a more accurate definition of cellular populations in this laboratory animal.

Production of intoxication states by actors--acoustic and temporal characteristics.

This paper is the second of a series; the first has been published (J Forensic Sci, 1998;43:1153-62). The goal in the initial pair of experiments was to determine if speakers (actors) could effectively mimic the speech of intoxicated individuals and also volitionally reduce the degradation to their speech that resulted from severe inebriation. To this end, two highly controlled experiments involving 12 actor-speakers were carried out. It was found that, even when sober, nearly all of them were judged drunker (when pretending) than when they actually were severely intoxicated. In the second experiment, they tried to sound sober when highly intoxicated; here most were judged less inebriated than they were. The goal of this second paper is to identify some of the speech characteristics that allowed the subjects to achieve the cited illusions. The focus here is on four paralinguistic factors: fundamental frequency (F0), speaking rate, vocal intensity, and nonfluency level. For the simulation of intoxication study, it was found that F0 was raised along with increased intoxication but raised even more when this state was feigned. A slowing of speaking rate was associated with increasing intoxication, but this shift also was greater when the speaker simulated intoxication. The most striking contrast was found for the nonfluencies; they were doubled for actual intoxication, but quadrupled when intoxication was simulated. On the other hand, the shifts exhibited by the subjects when they attempted to sound sober were not as clear cut. Indeed, no systematic relationships were found here for either F0 or vocal intensity. Both speaking rate and the number of nonfluencies shifted appropriately, but these changes were not statistically significant. In sum, discernable suprasegmental relationships occurred for both studies (but especially the first); further, it is predicted that useful cues also will be found embedded in the segmentals (the sounds of speech).