TELOMERE AND TELOMERASE MODULATION BY BERGAMOT POLYPHENOLIC FRACTION IN EXPERIMENTAL PHOTOAGEING IN HUMAN KERATINOCYTES.

Photoageing represents the addition of extrinsic chronic ultraviolet radiation-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. In this study, we evaluated the effect of 38% BPF, a highly concentrated extract of the bergamot fruit (Citrus bergamia) on UVB-induced photoageing by examining inflammatory cytokine expression, telomere length/telomerase alterations and cellular viability in human immortalized HaCaT keratinocytes. Our results suggest that 38% BPF protects HaCaT cells against UVB-induced oxidative stress and markers of photoageing in a dose-dependent manner and could be a useful supplement in skin care products. Together with antioxidant properties, BPF, a highly concentrated extract of the bergamot fruit, appears to modulate basic cellular signal transduction pathways leading to anti-proliferative, anti-aging and immune modulating responses.

From Birth Control to Sex Control: Unruly Young Women and the Origins of the National Abstinence-Only Mandate.

In the early 1980s, conservative politicians in the United States argued that the federal government was promoting promiscuity by providing teens with confidential access to government-funded family planning services. Claiming the problem was not that young women were getting pregnant but that they were having sex, they promised a new national policy-one that would stress self-discipline and family values over sexual indulgence. As argued in this paper, the resulting abstinence-only federal mandate both draws upon and reinforces traditional sexual scripts, which hold young women responsible for keeping male passion in check, thus selectively burdening them with the work of "doing abstinence."

Short communication: Projecting milk yield using best prediction and the MilkBot lactation model.

The accuracy and precision of 3 lactation models was estimated by summarizing means and variability in projection error for next-test milk and actual 305-d milk yield (M305) for 50-d intervals in a large Dairy Herd Improvement Association data set. Lactations were grouped by breed (Holstein, Jersey, and crossbred) and parity (first vs. later). A smaller, single-herd data set with both Dairy Herd Improvement Association data and daily milk weights was used to compare M305 calculated from test-day data with M305 computed by summing daily milk weights. The lactation models tested were best prediction (BP), the nonlinear MilkBot (MB) model, and a null model (NM) based on a stepwise function. The accuracy of the models was ranked (best to worst) MB, BP, and NM for later-parity cows and MB, NM, and BP for first-parity cows, with MB achieving accuracy in projecting daily milk of 0.5 kg or better in most groups. The models generally showed better accuracy after 50 d in milk. Best prediction and NM had low accuracy for crossbred cows and first-parity Holstein and Jersey cows. The MB model appears to be more precise than BP, and NM had low precision, especially for M305. Regression of model-generated M305 on summed M305 showed BP and MB to be equally efficient in ranking lactations, but MB was better at quantifying differences.

On-farm evaluation of the effect of metabolic diseases on the shape of the lactation curve in dairy cows through the MilkBot lactation model.

The effects of metabolic diseases (MD) occurring during the transition period on milk production of dairy cows have been evaluated in many different ways, often with conflicting conclusions. The present study used a fitted lactation model to analyze specific aspects of lactation curve shape and magnitude in cows that avoided culling or death in the first 120 d in milk (DIM). Production and health records of 1,946 lactations in a 1-yr follow-up study design were collected from a transition management facility in Germany to evaluate both short- and long-term effects of MD on milk production. Milk production data were fitted with the nonlinear MilkBot lactation model, and health records were used to classify cows as healthy (H), affected by one MD (MD), or by multiple MD (MD+). The final data set contained 1,071 H, 348 MD, and 136 MD+ cows, with distinct incidences of 3.7% twinning, 4.8% milk fever, 3.6% retained placenta, 15.4% metritis, 8.3% ketosis, 2.0% displaced abomasum, and 3.7% mastitis in the first 30 DIM. The model containing all healthy and diseased cows showed that lactations classified as H had milk production that increased faster (lower ramp) and also declined faster (lower persistence) compared with cows that encountered one or more metabolic problems. The level of production (scale) was only lowered in MD+ cows compared with H and MD cows. Although the shape of the lactation curve changed when cows encounter uncomplicated (single) MD or complicated MD (more than one MD), the slower increase to a lower peak seemed to be compensated for by greater persistency, resulting in the overall 305-d milk production only being lowered in MD+ cows. In the individual disease models, specific changes in the shape of the lactation curve were found for all MD except twinning. Milk fever, retained placenta, ketosis, and mastitis mainly affected the lactation curve when accompanied by another MD, whereas metritis and displaced abomasum affected the lactation curve equally with or without another MD. Overall, 305-d milk production was decreased in complicated metritis (10,603 ± 50 kg vs. 10,114 ± 172 kg). Although care should be taken in generalizing conclusions from a highly specialized transition management facility, the current study demonstrated that lactation curve analysis may contribute substantially to the evaluation of both short- and long-term effects of metabolic diseases on milk production by detecting changes in the distribution of production that are not apparent when only totals are analyzed.

Integration of TB into child health policies in Africa's high-burden countries: a normative analysis.

Integration of paediatric TB care into decentralised child health services has the potential to reduce the large proportion of childhood TB that remains undiagnosed. We performed a review of national guidelines and policies for TB and child health to evaluate the normative integration of paediatric TB into existing child health programmes in 15 high TB burden countries in Africa. While integration is addressed in 80% of the national strategic plans for TB, the child health strategies insufficiently address TB in their plans to reduce child mortality. Emphasis needs to be put on multi-sectoral collaboration among national health programmes.

Intégrer la prise en charge antituberculeuse de l'enfant aux services de soins pédiatriques décentralisés pourrait permettre de réduire la proportion élevée de cas de TB pédiatriques qui restent non diagnostiqués. Nous avons examiné les politiques et recommandations nationales en matière de TB et de soins pédiatriques afin d'évaluer l'intégration normative de la TB pédiatrique aux programmes de prise en charge pédiatrique existant dans 15 pays africains à forte prévalence de TB. Cette intégration est abordée dans 80% des plans stratégiques nationaux pour la TB, mais les stratégies relatives aux soins pédiatriques ne tiennent pas suffisamment compte de la TB dans leurs plans visant à réduire la mortalité infantile. Il convient de mettre l'accent sur la collaboration multisectorielle entre les programmes de santé nationaux.

Adults with type 1 diabetes eat a high-fat atherogenic diet that is associated with coronary artery calcium.

AIMS/HYPOTHESIS: Coronary heart disease is the leading cause of mortality among people with type 1 diabetes. Diet is an important lifestyle factor that relates to risk of CHD. The aim of this study was to examine how diet and adherence to dietary guidelines differ between adults with and without type 1 diabetes, and their correlation with CHD risk factors and coronary artery calcium (CAC). METHODS: The study involved 571 people with type 1 diabetes and 696 controls, aged 19 to 56 years, who were asymptomatic for CHD. CAC was measured by electron-beam computed tomography. RESULTS: Compared with the controls, adults with type 1 diabetes reported a diet higher in fat, saturated fat and protein but lower in carbohydrates. Fewer than half of those with type 1 diabetes met dietary guidelines for fat and carbohydrate intake, and only 16% restricted saturated fat to less than 10% of daily energy intake. Adults with type 1 diabetes were significantly less likely to meet dietary guidelines than controls. Fat and saturated fat intakes were positively correlated, but carbohydrate intake was negatively correlated with CHD risk factors and HbA(1c). A high-fat diet and higher intake of protein were associated with greater odds of CAC, while higher carbohydrate intake was associated with reduced odds of CAC. CONCLUSIONS/INTERPRETATION: Adults with type 1 diabetes reported consuming higher than recommended levels of fat and saturated fat. High fat intake was associated with increased CHD risk factors, worse glycaemic control and CAC. An atherogenic diet may contribute to the risk of CHD in adults with type 1 diabetes.

Design of organic molecules with large two-photon absorption cross sections.

A strategy for the design of molecules with large two-photon absorption cross sections, delta, was developed, on the basis of the concept that symmetric charge transfer, from the ends of a conjugated system to the middle, or vice versa, upon excitation is correlated to enhanced values of delta. Synthesized bis(styryl)benzene derivatives with donor-pi-donor, donor-acceptor-donor, and acceptor-donor-acceptor structural motifs exhibit exceptionally large values of delta, up to about 400 times that of trans-stilbene. Quantum chemical calculations performed on these molecules indicate that substantial symmetric charge redistribution occurs upon excitation and provide delta values in good agreement with experimental values. The combination of large delta and high fluorescence quantum yield or triplet yield exhibited by molecules developed here offers potential for unprecedented brightness in two-photon fluorescent imaging or enhanced photosensitivity in two-photon sensitization, respectively.

Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing.

ABX464 is a first-in-class, clinical-stage, small molecule for oral administration that has shown strong anti-inflammatory effects in the DSS-model for inflammatory bowel disease (IBD) and also prevents replication of the HIV virus. ABX464 which binds to cap binding complex (CBC) has demonstrated safety and efficacy in a phase 2a proof-of-concept clinical trial in patients with Ulcerative colitis. Previously, with limited technologies, it was not possible to quantify the effect of ABX464 on viral and cellular RNA biogenesis. Here, using RNA CaptureSeq and deep sequencing, we report that ABX464 enhances the splicing of HIV RNA in infected PBMCs from six healthy individuals and also the expression and splicing of a single long noncoding RNA to generate the anti-inflammatory miR-124 both ex vivo and in HIV patients. While ABX464 has no effect on pre-mRNA splicing of cellular genes, depletion of CBC complex by RNAi leads to accumulation of intron retention transcripts. These results imply that ABX464 did not inhibit the function of CBC in splicing but rather strengthens it under pathological condition like inflammation and HIV infection. The specific dual ability of ABX464 to generate both anti-inflammatory miR-124 and spliced viral RNA may have applicability for the treatment of both inflammatory diseases and HIV infection.

LAVIA--an evaluation of the potential safety benefits of the French intelligent speed adaptation project.

This paper presents the potential safety benefits of the experimental French LAVIA Intelligent Speed Adaptation system, according to road network and system mode, based on observed driving speeds, distributions of crash severity and crash injury risk. Results are given for car frontal and side impacts that together, represent 80% of all serious and fatal injuries in France. Of the three system modes tested (advisory, driver select, mandatory), our results suggest that driver select would most significantly reduce serious injuries and death. We estimate this 100% utilization of cars equipped with this type of speed adaptation system would decrease injury rates by 6% to 16% over existing conditions depending on the type of crash (frontal or side) and road environment considered. Some limitations associated with the analysis are also identified. LAVIA is the acronym for Limiteur s'Adaptant à la VItesse Autorisée, a French Intelligent Speed Adaptation (ISA) project that was set up towards the end of 1999. At the time, 1998 French national road safety statistics recorded 8437 road related deaths, a figure which had shown virtually no positive evolution since 1994. Detailed analysis of the contributory factors involved in fatal road crashes highlighted the time-honoured crash and injury causation mechanisms - alcohol, speed and seatbelts. Of the three, excessive speed (over and above the posted speed limit) was a contributory factor in half of all fatal crashes Inappropriate behaviour such as excessive speeding can be dealt with either by legislative or driver-incentive programmes. The first of these two solutions involves the introduction of new legislation and/or the enforcement of existing laws. This is the domain of Public Authorities and will not be discussed in detail here. Alternatively, incentive schemes can involve the implementation of speed related driver assistance systems, categorised according to their voluntary or mandatory character and the degree of autonomy proposed to or imposed on the driver. The LAVIA project set out to address several possible combinations of these two factors. The generic term Intelligent Speed Adaptation (ISA) encompasses a wide range of different technologies aimed at improving road safety by reducing traffic speed and homogenising traffic flow, within the limit of posted speed limits. "Fixed speed limit" systems inform the vehicle of the posted speed limit whereas "variable speed limit" systems take into account certain locations on the road network where a speed below the posted limit is desirable, such as sharp curves, pedestrian crossings or crash black spots. Taken one step further, speed limit systems may also take into account weather and traffic flow conditions. These systems are known as "dynamic speed limit" systems and benefit from real time updates for a specific location. The different ISA systems are generally characterised by the degree of freedom of choice given to the driver in moderating his or her speed. Speed limit technologies may be advisory (informing drivers of the current speed limit and speed limit changes), voluntary (allowing the driver to decide whether or not to implement speed limitation) or mandatory (imposing the current speed limit). The information supplied may be provided by way of the road infrastructure (and associated equipment), may be acquired autonomously by the vehicle or may be based on an interaction between the infrastructure and the vehicle. Even the most basic of these systems should be considered as a very useful driver aid, helping the driver to stay within the posted speed limit, avoiding "unnecessary" speeding fines through inattention, modelling driver behaviour through the long term reduction of speeds and reducing driver workload by limiting visual speedometer controls. Vehicle-based ISA systems should not be confused with internal systems. These latter systems rely upon the driver entering the desired travel speed, which is then maintained by cruise control or set as a maximum value by automatic speed regulators. Although these systems will not be discussed in detail here, it should be noted that the engine management technologies that they employ are a vital component of ISA systems.

[Difficult AV optimization in a patient with a biventricular implantable cardioverter defibrillator]. / 13. Folge: Schwierigkeiten bei der AV-Zeit-Optimierung einer Patientin mit biventrikulärem implantierbaren Kardioverter/Defibrillator.

This quiz presents the case of a patient who deteriorated clinically after AV delay optimization of a biventricular implantable cardioverter defibrillator. It illustrates that these complex devices require profound knowledge of their function.

[Implantable loop recorders in the diagnosis of syncope]. / Implantierbare Loop-Rekorder in der Synkopendiagnostik.

In syncope patients, it is essential to make the right diagnosis with respect to underlying etiology. Cardiac (arrhythmic and structural) syncopal episodes carry untoward prognostic implication compared with reflex syncope. While rhythm-symptom correlation of a spontaneous syncopal episode is key to making the correct diagnosis, in case of unclear syncope the early implantation of a loop recorder leads to faster, more efficacious, and more cost-effective diagnosis. This review article summarizes the current data regarding diagnostic accuracy and clinical role of implantable loop recorders. It outlines the superiority of loop recorders in the management of unclear syncope according to present knowledge.

Prevalence, characteristics and clinical implications of regular atrial tachyarrhythmias in patients with atrial fibrillation: insights from a study using a new implantable device.

OBJECTIVES: This study prospectively analyzed atrial tachyarrhythmia (AT) organization and antitachycardia pacing (ATP) success in patients with an implanted device for AT therapy. BACKGROUND: In patients with atrial fibrillation (AF), the incidence of regular, slow ATs amendable by ATP is unknown. METHODS: Forty patients with previously documented AT (70% with AF) received a new pacemaker with atrial electrogram (AEG) storage and atrial ATP capabilities for standard pacing indications. The AEGs acquired during the first month (study phase 1) were classified into high (type I), intermediate (type II) and low (type III) degrees of organization. Atrial ATP was then activated, and treated AT episodes were retrieved three and six months after implantation (study phase 2). RESULTS: Of 824 AEGs retrieved before ATP activation (study phase 1), 351 (43%) were classified as type 1, 47% as type II and 10% as type III. Episodes of AT starting as type I (35%) and type II or III (65%) maintained their type over 1 min in 73%. All patients with an exclusive history of AF also showed type I AEGs. In 361 subsequently treated AT episodes (study phase 2), ATP was successful in 62% of type I and 34% of type II episodes, but not in type III (p < 0.0001). CONCLUSIONS: The majority of patients with a history of AF show not only disorganized but also highly organized AT episodes, which can be successfully terminated by ATP.

Synteny conservation and chromosome rearrangements during mammalian evolution.

An important problem in comparative genome analysis has been defining reliable measures of synteny conservation. The published analytical measures of synteny conservation have limitations. Nonindependence of comparisons, conserved and disrupted syntenies that are as yet unidentified, and redundant rearrangements lead to systematic errors that tend to overestimate the degree of conservation. We recently derived methods to estimate the total number of conserved syntenies within the genome, counting both those that have already been described and those that remain to be discovered. With this method, we show that approximately 65% of the conserved syntenies have already been identified for humans and mice, that rates of synteny disruption vary approximately 25-fold among mammalian lineages, and that despite strong selection against reciprocal translocations, inter-chromosome rearrangements occurred approximately fourfold more often than inversions and other intra-chromosome rearrangements, at least for lineages leading to humans and mice.

Identification of iron ligands in tyrosine hydroxylase by mutagenesis of conserved histidinyl residues.

Tyrosine hydroxylase catalyzes the hydroxylation of tyrosine and other aromatic amino acids using a tetrahydropterin as the reducing substrate. The enzyme is a homotetramer; each monomer contains a single nonheme iron atom. Five histidine residues are conserved in all tyrosine hydroxylases that have been sequenced to date and in the related eukaryotic enzymes phenylalanine and tryptophan hydroxylase. Because histidine has been suggested as a ligand to the iron in these enzymes, mutant tyrosine hydroxylase proteins in which each of the conserved histidines had been mutated to glutamine or alanine were expressed in Escherichia coli. The H192Q, H247Q, and H317A mutant proteins contained iron in comparable amounts to the wild-type enzyme, about 0.6 atoms/sub-unit. In contrast, the H331 and H336 mutant proteins contained no iron. The first three mutant enzymes were active, with Vmax values 39, 68, and 7% that of the wild-type enzyme, and slightly altered V/Km values for both tyrosine and 6-methyltetrahydropterin. In contrast, the H331 and H336 mutant enzymes had no detectable activity. The EPR spectra of the H192Q and H247Q enzymes are indistinguishable from that of wild-type tyrosine hydroxylase, whereas that of the H317A enzyme indicated that the ligand field of the iron had been slightly perturbed. These results are consistent with H331 and H336 being ligands to the active site iron atom.

Suicide attempts associated with akathisia.

The authors report two cases of impulsive suicide attempts associated with akathisia. In both cases, suicidal ideation appeared suddenly, concurrent with neuroleptic-induced akathisia, and disappeared when the akathisia was treated.

Residual fluoride concentrations and scanning electron microscopic examination of root surfaces of human teeth after topical application of fluoride in vivo.

Fluoride concentrations in root surfaces of human teeth after a single topical application with a 2% acidulated sodium fluoride solution in vivo were investigated. Increased residual fluoride concentrations in the root surfaces and precipitations on the peritubular dentin, as revealed by SEM micrographs, may be factors in reducing hypersensitivity.

Levans: I. Fractionation, solution viscosity, and chemical analysis of levan produced by Streptococcus salivarius.

Levan produced by Streptococcus salivarius was fractionated into a series of 20 fractions of varying molecular weight. The range of intrinsic viscosities of the fractions was 0.07 to 0.18 dl/gm in water and 0.20 to 0.29 dl/gm in dimethyl sulfoxide. The molecular weight of the unfractionated leval determined by light scattering was 31.5 times 10-6. Small amounts of fatty acids and protein were found associated with levan.

Cognitive factors and stress-induced changes in catecholamine biochemistry.

The purpose of the present research was to determine whether dysfunctional attitudes, a cognitive attribute, predicted changes in catecholamine biochemistry. A cognitive task was used to induce stress in female subjects (n=21), and levels of plasma norepinephrine (NE) and homovanillic acid (HVA) were measured at three time points: at baseline (T1); immediately after stress exposure (T2); and 40 min later (T3). Dysfunctional attitudes were significantly and positively related to levels of plasma NE at T3, controlling for baseline levels. Dysfunctional attitudes were not significantly related to plasma HVA levels at any time point. Our findings provide initial support for the idea that dysfunctional attitudes, an attribute shown to play an important role in some forms of unipolar depression, predict stress-induced alterations in noradrenergic output.

Restoration of periodontal attachment employing enriched collagen solution in the dog.

Three wall intrabony defects were produced in 11 dogs using a round bur followed by curettes and hoes. A copper band was fixed to the tooth with stainless steel ligature wire. Six weeks later, the copper band was removed and the defect was treated with an enriched collagen solution (ECS) prepared from acid-extracted dog skin collagen. Thirty-three defects were treated with ECS and 33 defects were controls. Healing was assessed histologically 4 and 6 weeks after treatment for the presence of new cementum, periodontal ligament and alveolar bone, as well as arrested epithelial downgrowth along the dental root. Unlike the controls, treatment with ECS resulted in restoration of periodontal attachment after 4 weeks. This included formation of new cementum, new alveolar bone and dense connective tissue fiber running between bone and cementum. Control sections showed epithelial migration along the root, separating it from the adjacent connective tissue and thus preventing new attachment.