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Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.

SummaryDiabetic heart disease is highly prevalent and characterized by diastolic dysfunction. The mechanisms of diabetic heart disease are poorly understood and no targeted therapies are available. Here we show that the diabetic myocardium (type 1 and type 2) is characterized by marked glycogen elevation and ectopic cellular localization - a paradoxical metabolic pathology given suppressed cardiomyocyte glucose uptake in diabetes. We demonstrate involvement of a glycogen-selective autophagy pathway (‘glycophagy’) defect in mediating this pathology. Genetically manipulated deficiency of Gabarapl1, an Atg8 autophagy homologue, induces cardiac glycogen accumulation and diastolic dysfunction. Stbd1, the Gabarapl1 cognate autophagosome partner is identified as a unique component of the early glycoproteome response to hyperglycemia in cardiac, but not skeletal muscle. Cardiac-targeted in vivo Gabarapl1 gene delivery normalizes glycogen levels, diastolic function and cardiomyocyte mechanics. These findings reveal that cardiac glycophagy is a key metabolic homeostatic process perturbed in diabetes that can be remediated by Gabarapl1 intervention.

Diabetic heart disease typically features a restrictive/ hypertrophic cardiac phenotype characterised by diastolic dysfunction with preserved systolic performance. Little is known about the early adaptational mechanisms that underpin maintenance of systolic performance in diabetic diastolic dysfunction and how this may contribute to disease progression. This study aimed to evaluate cardiomyocyte contractility in a high-fat diet (HFD) mouse model of diastolic dysfunction. Echocardiography (GE Vivid 9) was performed in 33 wk old male C57Bl/6 mice fed a high-fat diet (HFD, 43% kcal fat, 24 wks duration). Isolated cardiomyocytes (paced 2Hz, 2.0mM Ca 2+ , 37C) were subjected to progressive axial stretch. Sarcomere length/ shortening, tension and intracellular calcium transients (Fura-2AM, 5μM) were simultaneously measured (Myostretcher, Ionoptix). HFD hearts displayed in vivo (22.2±1.4 vs 16.7±1.0 E/E’; pin vitro diastolic dysfunction (0.244±0.039 vs 0.075±0.017 nN/pl/ %cell stretch; p2+ transient amplitude but was correlated with length dependence of Ca 2+ sensitivity (n=17 cells, R 2 =0.4039 p2 =0.8442, p

Control of cardiomyocyte cytosolic Ca(2+) levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca(2+), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca(2+) channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca(2+) levels promote the binding of a Ca(2+)/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post-translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post-translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post-translational modification has a role in determining target selectivity of downstream Ca(2+) transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co-localizes with CaMKIIδB in the nuclear/myofilament fraction, contrasting with a co-enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδC . It has also been possible to conclude that a hyper-phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper-activation of the CaMKIIδB , which exerts anti-arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca(2+) uptake and maintain cytosolic Ca(2+) levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.

Systematic experimental results describing the dynamic wetting properties of bamboo fibres were analysed by applying the molecular-kinetic theory of wetting. Results suggest that the bamboo fibre surface represents a well-defined system for wetting analysis. The surface free energy components were calculated according to the acid–base theory. These values were then used to calculate the theoretical work of adhesion, spreading coefficient, wetting tension, and interfacial energy. The wetting behaviour of various thermoplastic matrices (polypropylene, maleic anhydride-grafted polypropylene,polyvinylidene-fluoride, and polyethylene-terephthalate) was characterized. Surface chemical components were identified using XPS. Additionally,transverse 3-point bending tests and single fibre pull-out tests were performed. This integrated physical–chemical–mechanical approach was used to study the effect of adhesion on the mechanical strength of thermoplastic composites reinforced with bamboo,showing that increase in physical adhesion can explain the improved interfacial and longitudinal strength in bamboo polyvinylidene-fluoride (PVDF) composites compared to the other thermoplastic matrices used in this study. Surface energy components of bamboo fibres and PVDF were matched, resulting in an improvement of the physical adhesion.

Sub-Saharan Africa is facing a crisis in human health resources due to a critical shortage of health workers. The shortage is compounded by a high burden of infectious diseases; emigration of trained professionals; difficult working conditions and low motivation. In particular, the burden of HIV/AIDS has led to the concept of task shifting being increasingly promoted as a way of rapidly expanding human resource capacity. This refers to the delegation of medical and health service responsibilities from higher to lower cadres of health staff, in some cases non-professionals. This paper, drawing on Médecins Sans Frontières' experience of scaling-up antiretroviral treatment in three sub-Saharan African countries (Malawi, South Africa and Lesotho) and supplemented by a review of the literature, highlights the main opportunities and challenges posed by task shifting and proposes specific actions to tackle the challenges. The opportunities include: increasing access to life-saving treatment; improving the workforce skills mix and health-system efficiency; enhancing the role of the community; cost advantages and reducing attrition and international 'brain drain'. The challenges include: maintaining quality and safety; addressing professional and institutional resistance; sustaining motivation and performance and preventing deaths of health workers from HIV/AIDS. Task shifting should not undermine the primary objective of improving patient benefits and public health outcomes.

PROBLEM: A multinational company with operations in several African countries was committed to offer antiretroviral treatment to its employees and their dependants. APPROACH: The Accelerating Access Initiative (AAI), an initiative of six pharmaceutical companies and five United Nations' agencies, offered the possibility of obtaining brand antiretroviral drugs (ARVs) at 10% of the commercial price. PharmAccess, a foundation aimed at removing barriers to AIDS treatment in Africa, helped to establish an HIV policy and treatment guidelines, and a workplace programme was rolled out from September 2001. LOCAL SETTING: Private sector employers in Africa are keen to take more responsibility in HIV prevention and AIDS care. An important hurdle for African employers remains the price and availability of ARVs. RELEVANT CHANGES: The programme encountered various hurdles, among them the need for multiple contracts with multiple companies, complex importation procedures, taxes levied on ARVs, lack of support from pharmaceutical companies in importation and transportation, slow delivery of the drugs, lack of institutional memory in pharmaceutical companies and government policies excluding the company from access to ARVs under the AAI. LESSONS LEARNED: The launch of the AAI enabled this multinational company to offer access to ARVs to its employees and dependants. The private sector should have access to these discounted drugs under the AAI. A network of local AAI offices should be created to assist in logistics of drugs ordering, purchase and clearance. No taxes should be levied on ARVs.

BACKGROUND: The lack of human resources for health is presently recognized as a major factor limiting scale-up of antiretroviral treatment (ART) programs in resourcelimited settings. The mobilization of public and private partners, the decentralization of care, and the training of non-HIV specialist nurses and general practitioners could help increase the number of HIV-infected patients receiving ART. In addition to other forms of training, scheduled teleconferences (TCs) have been organized to support a comprehensive HIV treatment program delivered by a private company's health team. OBJECTIVE: To describe the role of the TC as an additional tool in mentoring a company's health care workers (HCWs). METHOD: For this study, all TC reports were retrospectively reviewed and the questions classified by topic. Participating Heineken physicians evaluated the technical quality and scientific relevance of the TCs through an anonymous survey. RESULTS: From October 2001 to December 2003, 10 HCWs working in 14 operating companies in 5 African countries raised 268 problems during 45 TCs. A total of 79 questions (29%) were asked about antiretroviral (ARV) therapy, 53 (20%) about the diagnosis and treatment of opportunistic infection, 43 (16%) about ARV toxicity, 40 (15%) about care organization and policy, 32 (12%) about laboratory or drug supply, and 21 (8%) about biological parameters. The mean TC attendance rate was 70%. The level of satisfaction among local company physicians was 65% for logistics, 89% for scientific relevance, 84% for applicability of advice, and 85% overall. The most common complaints concerned the poor quality of the telephone connection and language problems for francophone participants. CONCLUSION: Database-supported teleconferencing could be an additional tool to mentor company HCWs in their routine care of HIV-infected workers and family members. The role and costeffectiveness of telemedicine in improving health outcomes should be further studied

The cyclotrimerization of acetylene to benzene on a Pd(111) surface has been studied by scanning tunneling microscopy (STM). The formation of benzene becomes visible upon increasing the acetylene coverage at 140 K. Initially, the acetylene molecules adsorb in a (2 × 2) ordered layer, which is compressed into an ordered (√3 × √3)R30° structure when more acetylene is added. The cyclotrimerization reaction is observed just before saturation of the (√3 × √3)R30° structure and stops when the saturation coverage is reached. Further exposure to acetylene does not result in a reaction, indicating that the cyclotrimerization reaction involves a transient adsorption state, different from that in the (√3 × √3)R30° layer. The (√3 × √3)R30° layer itself is stable up to 230 K, even when a background pressure of acetylene is present. At 230 K, the (√3 × √3)R30° layer decays, a process which is related to the isomerization and further decomposition of acetylene. The results are consistent with the available spectroscopic...

In 2004, a law was introduced in the Netherlands that gives children conceived by artificial insemination with donor semen (AID), oocytes or embryos the right to learn the identity of the donor when they are 16. The permanently anonymous semen donor will now be replaced by donors that are anonymous at the time of insemination, but traceable later. During the period preceding and immediately following the enactment of the law, the number of semen donors and semen banks dropped drastically and there was a change in the type of donor. The law, furthermore, creates several new moral and psychological dilemmas for both parents and AID-offspring. For parents, for example: should I tell my child that he was conceived by AID, knowing that he may become acquainted with the donor, with all the consequences that may entail? And for AID-offspring, if they have been told that they were conceived by AID: do I really wish to meet the donor? It must still be shown whether AID-offspring will feel a need for contact with the donor, and whether such contact is satisfying.

During routine anatomic dissection of the lower extremities of a 67-year-old male body, a supernumerary ishiocrural muscle was observed. This supernumerary muscle had similarities to a rare variant of the semimembranous muscle. On the left side it arose from the lateral dorsal side of the femur between the short head of the biceps femoris muscle and the origin of the adductor magnus muscle. It inserted on the medial condyle deep to the normal insertion of the semimembranous at the posterior aspect of the articular capsule. This muscle can be regarded either as a short deep semimembranous muscle (M. semimembranosus profondus) or as a short belly of a semitendinous biceps as known in birds. The muscle was situated closely to the vessels and nerves of the popliteal region. On the right side a similar but somewhat fainter muscle was observed whose origin emanated from the fascia of the adductor magnus muscle. The muscle probably has no major clinical importance but might be important to the surgeon who has to intervene in the popliteal region.

We observed a muscle originating from the lateral process of Cl and inserting on the anterior aponeurosis of the rhomboideus major muscle. This accessory muscle was present on the right side only.

A rotational band with seven gamma-ray transitions between states with spin 2 Planck's constant and 16 Planck's constant has been observed in the doubly magic, self-conjugate nucleus (40)(20)Ca(20). The measured transition quadrupole moment of 1.80(+0.39)(-0.29)eb indicates a superdeformed shape with a deformation beta(2) = 0.59(+0.11)(-0.07). The features of this band are explained by cranked relativistic mean field calculations to arise from an 8-particle 8-hole excitation.

The intrinsic quadrupole moment Q(0) of superdeformed rotational bands in A approximately 150 nuclei depends on the associated single-particle configuration. We have derived an empirical formula based on the additivity of effective quadrupole moments of single-particle orbitals that describes existing measurements from (142)Sm to (152)Dy. To further test the formula, the predicted Q(0) moments for two superdeformed bands in (146)Gd of 14.05 eb were confronted with a new measurement yielding 13.9+/-0.4 eb and 13.9+/-0.3 eb, respectively. This excellent agreement provides empirical evidence of extreme single-particle behavior in highly deformed, collective systems.

The ground state band in (46)Cr and the isospin T = 1 band in (46)V have been delineated up to Ipi = 10(+) (tentatively 12(+)). These observations complete the highest spin T = 1 isospin triplet known. Following the isobaric multiplet mass equation, a combination of level energies in (46)Cr, (46)Ti, and (46)V are taken to highlight the angular momentum dependence of the isovector and isotensor parts of the interaction. The results are compared with full- fp-space shell model calculations. The influence of the one-body and two-body contributions to the isovector energy difference are investigated.

The gamma-ray decay of excited states of the two-proton hole nucleus, 206Hg, has been identified using Gammasphere and 208Pb+238U collisions. The yrast states found include a T(1/2) = 92(8) ns 10(+) isomer located above the known 5(-) isomer. The B(E2;10(+)--8(+)) strength is used to derive the quadrupole polarization charge induced by the h(11/2) proton hole. Also, the implied quadrupole moment has been used to provide an absolute scale for the electric field gradient of Hg in Hg metal.

Subpicosecond lifetimes of states in shears band 1 in (197)Pb were measured by means of the recoil distance method employing Gammasphere and the New Yale Plunger Device. The extracted reduced matrix elements, B(M1), show a clear sensitivity to the crossing of different shears configurations reflecting the closing and reopening of the shears blades. The energies and B(M1) values in the band crossing region are successfully described in the framework of the semiclassical model of the shears bands. The relevance of core rotation contributions are shown. The results point to the existence of shears states with an angular momentum coupling angle larger than 90 degrees.

Prompt and delayed gamma-ray cascades in doubly magic 132Sn and its neighbor 131Sn have been studied at Gammasphere using a 248Cm fission source. Isotopic assignments of unknown gamma rays were based on coincidences with known transitions in A = 112-116 Pd fission partners. The yrast level spectra of both tin nuclei are interpreted using empirical nucleon-nucleon interactions from the 132Sn and 208Pb regions. Results include identification of the (nuf(7/2)h(-1)(11/2))9(+) aligned state in 132Sn and of extensive (nuf(7/2)h(-2)(11/2)), (nuf(7/2)d(-1)(3/2)h(-1)(11/2)) and (nuh(-1)(11/2)x3(-)) multiplets in 131Sn. The previously reported beta(-) decay of an unusual 131In high-spin isomer to levels in 131Sn is also elucidated.

Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon.

The ground state rotational bands of the N = Z nuclei (72)Kr, (76)Sr, and (80)Zr have been extended into the angular momentum region where rotation alignment of particles is normally expected. By measuring the moments of inertia of these bands we have observed a consistent increase in the rotational frequency required to start pair breaking, when compared to neighboring nuclei. (72)Kr shows the most marked effect. It has been widely suggested that these "delayed alignments" arise from np-pairing correlations. However, alignment frequencies are very sensitive to shape degrees of freedom and normal pairing, so the new experimental observations are still open to interpretation.

The Saccharomyces cerevisiae gene YPA1 encodes a protein homologous to the phosphotyrosyl phosphatase activator, PTPA, of the mammalian protein phosphatase type 2A (PP2A). In order to examine the biological role of PTPA, we disrupted YPA1 and characterised the phenotype of the ypa1Delta mutant. Comparison of the growth rate of the wild-type strain and the ypa1Delta mutant on glucose-rich medium after nutrient depletion showed that the ypa1Delta mutant traversed the lag period more rapidly. This accelerated progression through "Start" was also observed after release from alpha-factor-induced G1 arrest as evidenced by a higher number of budding cells, a faster increase in CLN2 mRNA expression and a more rapid reactivation of Cdc28 kinase activity. This phenotype was specific for deletion of YPA1 since it was not observed when YPA2, the second PTPA gene in budding yeast was deleted. Reintroduction of YPA1 or the human PTPA cDNA in the ypa1Delta mutant suppressed this phenotype as opposed to overexpression of YPA2. Disruption of both YPA genes is lethal, since sporulation of heterozygous diploids resulted in at most three viable spores, none of them with a ypa1Delta ypa2Delta genotype. This observation indicates that YPA1 and YPA2 share some essential functions. We compared the ypa1Delta mutant phenotype with a PP2A double deletion mutant and a PP2A temperature-sensitive mutant. The PP2A-deficient yeast strain also showed accelerated progression through the G1 phase. In addition, both PP2A and ypa1Delta mutants show similar aberrant bud morphology. This would support the notion that YPA1 may act as a positive regulator of PP2A in vivo.

We report on the simultaneous occurrence in a male cadaver of bilateral clavicular slips to the M. latissimus dorsi, a bilateral variant of M. sterno-cleido-mastoïdeus known as M. cleido-occipitalis (Wood) and an exceptional form of M. levator claviculae posterior on the left side.

Protein contact dermatitis is a dermatosis which usually presents as a chronic eczema with episodic acute exacerbations a few minutes after contact with the offending allergen. Patch tests with the responsible allergen are usually negative, and the diagnosis can only be made by means of scratch or prick tests with the allergen. Sometimes, specific IgE antibodies can be detected in the blood. As there is considerable confusion about this entity, we have reviewed the cases reported in the literature.

Few of the indirect methods for measuring body composition have every been validated against direct human cadaver evidence. Computed tomography (CT), like NMR, has proved to be an important diagnostic tool and they appear to be the techniques of the future for body composition studies. The purpose of the present study (Cadaver Analysis Study III), undertaken at the Vrije Universiteit Brussel in a joint venture with the University of Göteborg, Sweden, was to validate tomographic measurements of volumes and areas from different tissues using data from CT-scanning of unembalmed deep-frozen cadavers and data collected by dissection of the same cadavers. Six Belgian adults were extensively measured and dissected. The body was divided into several slices for comparison of the CT image with photography of the same slice and comparison of tissue-volumes per segment for the whole body. Due to post-mortem changes and the frozen state of the cadavers, the CT measurements were greatly affected by artefacts disturbing adipose tissue (AT) and muscle area determinations. Only the bone area measurements were similar between the two techniques. However, when the volumes (per segment) of the same tissues were considered, no apparent difference was found between CT and dissection data for the muscle volume.