Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa.
The scale-up of antiretroviral therapy (ART) has been one of the success stories of sub-Saharan Africa, where coverage has increased from about 2% in 2003 to more than 40% 5 years later. However, tempering this success is a growing concern about patient retention (the proportion of patients who are alive and remaining on ART in the health system). Based on the personal experience of the authors, 10 key interventions are presented and discussed that might help to improve patient retention. These are (1) the need for simple and standardized monitoring systems to track what is happening, (2) reliable ascertainment of true outcomes of patients lost to follow-up, (3) implementation of measures to reduce early mortality in patients both before and during ART, (4) ensuring uninterrupted drug supplies, (5) consideration of simple, non-toxic ART regimens, (6) decentralization of ART care to health centres and the community, (7) a reduction in indirect costs for patients particularly in relation to transport to and from clinics, (8) strengthening links within and between health services and the community, (9) the use of ART clinics to deliver other beneficial patient or family-orientated packages of care such as insecticide-treated bed nets, and (10) innovative (thinking 'out of the box') interventions. High levels of retention on ART are vital for individual patients, for credibility of programmes and for on-going resource and financial support.


Dinitrogen release from arylpentazole: a picosecond time-resolved infrared, spectroelectrochemical, and DFT computational study.
p-(Dimethylamino)phenyl pentazole, DMAP-N5 (DMAP = Me2N-C6H4), was characterized by picosecond transient infrared spectroscopy and infrared spectroelectrochemistry. Femtosecond laser excitation at 310 or 330 nm produces the DMAP-N5 (S1) excited state, part of which returns to the ground state (τ = 82 ± 4 ps), while DMAP-N and DMAP-N3 (S0) are generated as double and single N2-loss photoproducts with η ≈ 0.14. The lifetime of DMAP-N5 (S1) is temperature and solvent dependent. [DMAP-N3](+) is produced from DMAP-N5 in a quasireversible, one-electron oxidation process (E1/2 = +0.67 V). Control experiments with DMAP-N3 support the findings. DFT B3LYP/6-311G** calculations were used to identify DMAP-N5 (S1), DMAP-N3(+), and DMAP-N in the infrared spectra. Both DMAP-N5 (S1) and [DMAP-N5](+) have a weakened N5 ring structure.


Carbonic anhydrase-mimetic bolaamphiphile self-assembly for CO2 hydration and sequestration.
A biomimetic catalyst was prepared through the self-assembly of a bolaamphiphilic molecule with histidine moieties for the sequestration of carbon dioxide. The histidyl bolaamphiphilic molecule bis(N-α-amidohistidine)-1,7-heptane dicarboxylate has been synthesized and self-assembled to produce analogues of the active sites of carbonic anhydrase (CA) after association with Zn(2+) ions. Spectroscopic analysis demonstrated the coordination of the Zn(2+) ions with histidine imidazole moieties, which is the core conformation of CA active sites. The Zn-associated self-assembly worked as a CA-mimetic catalyst that shows catalytic activity for CO2 hydration. Evaluation of the kinetics of using para-nitrophenylacetate revealed that the kinetic parameters of the CA-mimetic catalyst were maximized at the optimal Zn concentration and that excess Zn ions resulted in deteriorated catalytic activity. The performance of the CA-mimetic catalyst was enhanced by changing the pH value and temperature of the reaction, which implies that the hydrolysis of the substrate is the rate-determining step. The catalyst-assisted sequestration of CO2 was demonstrated by CaCO3 precipitation upon the addition of Ca(2+) ions. This study offers an easy way to prepare enzyme analogues for CO2 sequestration through the self-assembly of bolaamphiphile molecules with designer biochemical moieties.


Directional reversals enable Myxococcus xanthus cells to produce collective one-dimensional streams during fruiting-body formation.
The formation of a collectively moving group benefits individuals within a population in a variety of ways. The surface-dwelling bacterium Myxococcus xanthus forms dynamic collective groups both to feed on prey and to aggregate during times of starvation. The latter behaviour, termed fruiting-body formation, involves a complex, coordinated series of density changes that ultimately lead to three-dimensional aggregates comprising hundreds of thousands of cells and spores. How a loose, two-dimensional sheet of motile cells produces a fixed aggregate has remained a mystery as current models of aggregation are either inconsistent with experimental data or ultimately predict unstable structures that do not remain fixed in space. Here, we use high-resolution microscopy and computer vision software to spatio-temporally track the motion of thousands of individuals during the initial stages of fruiting-body formation. We find that cells undergo a phase transition from exploratory flocking, in which unstable cell groups move rapidly and coherently over long distances, to a reversal-mediated localization into one-dimensional growing streams that are inherently stable in space. These observations identify a new phase of active collective behaviour and answer a long-standing open question in Myxococcus development by describing how motile cell groups can remain statistically fixed in a spatial location.


Outbreaks of syphilis among men who have sex with men attending STI clinics between 2007 and 2015 in the Netherlands: a space-time clustering study.
Infectious syphilis (syphilis) is diagnosed predominantly among men who have sex with men (MSM) in the Netherlands and is a strong indicator for sexual risk behaviour. Therefore, an increase in syphilis can be an early indicator of resurgence of other STIs, including HIV. National and worldwide outbreaks of syphilis, as well as potential changes in sexual networks were reason to explore syphilis trends and clusters in more depth. National STI/HIV surveillance data were used, containing epidemiological, behavioural and clinical data from STI clinics. We examined syphilis positivity rates stratified by HIV status and year. Additionally, we performed space-time cluster analysis on municipality level between 2007 and 2015, using SaTScan to evaluate whether or not there was a higher than expected syphilis incidence in a certain area and time period, using the maximum likelihood ratio test statistic. Among HIV-positive MSM, the syphilis positivity rate decreased between 2007 (12.3%) and 2011 (4.5%), followed by an increasing trend (2015: 8.0%). Among HIV-negative MSM, the positivity rate decreased between 2007 (2.8%) and 2011 also (1.4%) and started to increase from 2013 onwards (2015: 1.8%). In addition, we identified three geospatial clusters. The first cluster consisted of MSM sex workers in the South of the Netherlands (July 2009-September 2010, n=10, p<0.001). The second cluster were mostly HIV-positive MSM (58.5%) (Amsterdam; July 2011-December 2015; n=1123, p<0.001), although the proportion of HIV-negative MSM increased over time. The third cluster was large in space (predominantly the city of Rotterdam; April-September 2015, n=72, p=0.014) and were mostly HIV-negative MSM (62.5%). Using SaTScan analysis, we observed several not yet recognised outbreaks and a rapid resurgence of syphilis among known HIV-positive MSM first, but more recently, also among HIV-negative MSM. The three identified clusters revealed locations, periods and specific characteristics of the involved MSM that could be used when developing targeted interventions.


Artificial intelligence in cardiovascular imaging: state of the art and implications for the imaging cardiologist.
Healthcare, conceivably more than any other area of human endeavour, has the greatest potential to be affected by artificial intelligence (AI). This potential has been shown by several reports that demonstrate equal or superhuman performance in medical tasks that aim to improve efficiency, diagnosis and prognosis. This review focuses on the state of the art of AI applications in cardiovascular imaging. It provides an overview of the current applications and studies performed, including the potential value, implications, limitations and future directions of AI in cardiovascular imaging.It is envisioned that AI will dramatically change the way doctors practise medicine. In the short term, it will assist physicians with easy tasks, such as automating measurements, making predictions based on big data, and putting clinical findings into an evidence-based context. In the long term, AI will not only assist doctors, it has the potential to significantly improve access to health and well-being data for patients and their caretakers. This empowers patients. From a physician's perspective, reliable AI assistance will be available to support clinical decision-making. Although cardiovascular studies implementing AI are increasing in number, the applications have only just started to penetrate contemporary clinical care.


Transbaffle/transconduit puncture using a simple CARTO-guided approach without echocardiography in patients with congenital heart disease.
Catheter ablation (CA) of atrial tachyarrhythmias (ATs) in patients with complex congenital heart disease (CHD) often requires technically challenging transbaffle or transconduit puncture. The aim was to assess the feasibility and safety of transbaffle/transconduit puncture based on computed tomography (CT) three-dimensional (3D) reconstruction merged with electro-anatomical mapping (EAM) without per-procedure echocardiographic guidance. We included 18 consecutive CHD patients in two centers who had atrial-switch or Fontan surgery and underwent CA of AT by an antegrade approach requiring intracardiac puncture. Twelve patients with atrial-switch surgery and six patients with extracardiac Fontan surgery were referred for CA of AT. Cardiac CT with 3D reconstruction was performed before the procedure. The 3D volume of the systemic venous atrium or extracardiac conduit acquired by EAM was merged with the corresponding CT 3D reconstruction. The ablation catheter was positioned at the optimal puncture site. Under fluoroscopic guidance, the needle was positioned next to the ablation and the puncture was performed. Balloon expansion of the puncture site was performed in every case of transconduit puncture and in two (17%) cases of transbaffle puncture. Overall, 17 intra-atrial reentrant tachycarrythmias and 9 focal ATs were successfully ablated, with no acute complications. The median time to access the pulmonary atrium was 78.5 minutes (range, 55-185) and total median fluoroscopy time was 23 minutes (range, 7-53). Transbaffle and transconduit punctures can be performed safely in CHD patients by using a simple technique relying on CT 3D reconstruction and EAM.


Two-center validation of Pilot Tone Based Cardiac Triggering of a Comprehensive Cardiovascular Magnetic Resonance Examination.
The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. To evaluate the performance of PTC triggering in a comprehensive CMR exam. Fifteen volunteers and twenty patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.


Gas chromatography-mass spectrometry screening for phytochemical 4-desmethylsterols accumulated during development of Tunisian peanut kernels (Arachis hypogaea L.).
4-Desmethylsterols, the main component of the phytosterol fraction, have been analyzed during the development of Tunisian peanut kernels ( Arachis hypogaea L.), Trabelsia (AraT) and Chounfakhi (AraC), which are monocultivar species, and Arbi (AraA), which is a wild species, by gas chromatography-mass spectrometry. Immature wild peanut (AraA) showed the highest contents of beta-sitosterol (554.8 mg/100 g of oil), campesterol (228.6 mg/100 g of oil), and Delta(5)-avenasterol (39.0 mg/100 g of oil) followed by peanut cultivar AraC with beta-sitosterol, campesterol, and Delta(5)-avenasterol averages of 267.7, 92.1, and 28.6 mg/100 g of oil, respectively, and similarly for AraT 309.1, 108.4, and 27.4 mg/100 g of oil, respectively, were found. These results suggest that, in immature stages, phytosterol contents can be important regulator factors for the functional quality of peanut oil for the agro-industry chain from plant to nutraceuticals.


PET Quantification of the Norepinephrine Transporter in Human Brain with (S,S)-18F-FMeNER-D2.
Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, (S,S)-11C-MRB and (S,S)-18F-FMeNER-D2, have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with (S,S)-11C-MRB and defluorination with (S,S)-18F-FMeNER-D2, which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using (S,S)-18F-FMeNER-D2 PET. Methods: We analyzed our previous (S,S)-18F-FMeNER-D2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of (S,S)-18F-FMeNER-D2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established methods of quantification of NET densities in the brain including the cerebral cortex unaffected by defluorination using (S,S)-18F-FMeNER-D2 These results suggest that we can accurately quantify NET density with a 90-min (S,S)-18F-FMeNER-D2 scan in broad brain areas.


Effects of neck exercises on swallowing function of patients with stroke.
[Purpose] This study examined the effects of neck exercises using PNF on the swallowing function of stroke patients with dysphasia. [Subjects and Methods] A total of 26 study subjects were selected and randomly divided into an experimental group of 13 subjects, who received the PNF-based short neck flexion exercises, and a control group of 13 subjects, who received the Shaker exercise. [Results] The experimental group showed statistically significant improvements in premature bolus loss, residue in the valleculae, laryngeal elevation, epiglottic closure, residue in the pyriform sinuses, and coating of the pharyngeal wall after swallowing, and improvements in pharyngeal transit time, and aspiration on both the new VFSS scale and the ASHA NOMS scale. [Conclusion] PNF-based short neck flexion exercises appear to be effective at improving swallowing function of stroke patients with dysphagia.


Identification of arthritis-related gene clusters by microarray analysis of two independent mouse models for rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population worldwide. Previously, we showed that human T-cell leukemia virus type I-transgenic mice and interleukin-1 receptor antagonist-knockout mice develop autoimmunity and joint-specific inflammation that resembles human RA. To identify genes involved in the pathogenesis of arthritis, we analyzed the gene expression profiles of these animal models by using high-density oligonucleotide arrays. We found 1,467 genes that were differentially expressed from the normal control mice by greater than threefold in one of these animal models. The gene expression profiles of the two models correlated well. We extracted 554 genes whose expression significantly changed in both models, assuming that pathogenically important genes at the effector phase would change in both models. Then, each of these commonly changed genes was mapped into the whole genome in a scale of the 1-megabase pairs. We found that the transcriptome map of these genes did not distribute evenly on the chromosome but formed clusters. These identified gene clusters include the major histocompatibility complex class I and class II genes, complement genes, and chemokine genes, which are well known to be involved in the pathogenesis of RA at the effector phase. The activation of these gene clusters suggests that antigen presentation and lymphocyte chemotaxis are important for the development of arthritis. Moreover, by searching for such clusters, we could detect genes with marginal expression changes. These gene clusters include schlafen and membrane-spanning four-domains subfamily A genes whose function in arthritis has not yet been determined. Thus, by combining two etiologically different RA models, we succeeded in efficiently extracting genes functioning in the development of arthritis at the effector phase. Furthermore, we demonstrated that identification of gene clusters by transcriptome mapping is a useful way to find potentially pathogenic genes among genes whose expression change is only marginal.


The structure of Rv3717 reveals a novel amidase from Mycobacterium tuberculosis.
Bacterial N-acetylmuramoyl-L-alanine amidases are cell-wall hydrolases that hydrolyze the bond between N-acetylmuramic acid and L-alanine in cell-wall glycopeptides. Rv3717 of Mycobacterium tuberculosis has been identified as a unique autolysin that lacks a cell-wall-binding domain (CBD) and its structure has been determined to 1.7 Å resolution by the Pt-SAD phasing method. Rv3717 possesses an α/β-fold and is a zinc-dependent hydrolase. The structure reveals a short flexible hairpin turn that partially occludes the active site and may be involved in autoregulation. This type of autoregulation of activity of PG hydrolases has been observed in Bartonella henselae amidase (AmiB) and may be a general mechanism used by some of the redundant amidases to regulate cell-wall hydrolase activity in bacteria. Rv3717 utilizes its net positive charge for substrate binding and exhibits activity towards a broad spectrum of substrate cell walls. The enzymatic activity of Rv3717 was confirmed by isolation and identification of its enzymatic products by LC/MS. These studies indicate that Rv3717, an N-acetylmuramoyl-L-alanine amidase from M. tuberculosis, represents a new family of lytic amidases that do not have a separate CBD and are regulated conformationally.


Low-temperature magnetic resonance imaging with 2.8 μm isotropic resolution.
We demonstrate the feasibility of high-resolution 1H magnetic resonance imaging (MRI) at low temperatures by obtaining an MRI image of 20 μm diameter glass beads in glycerol/water at 28 K with 2.8 μm isotropic resolution. The experiments use a recently-described MRI apparatus (Moore and Tycko, 2015) with minor modifications. The sample is contained within a radio-frequency microcoil with 150 μm inner diameter. Sensitivity is additionally enhanced by paramagnetic doping, optimization of the sample temperature, three-dimensional phase-encoding of k-space data, pulsed spin-lock detection of 1H nuclear magnetic resonance signals, and spherical sampling of k-space. We verify that the actual image resolution is 2.7 ± 0.3 μm by quantitative comparisons of experimental and calculated images. Our imaging approach is compatible with dynamic nuclear polarization, providing a path to significantly higher resolution in future experiments.


Comment on "Designing river flows to improve food security futures in the Lower Mekong Basin".
The designer flow regime proposed by Sabo et al (Research Articles, 8 December 2017, p. 1270) to support fisheries in the Lower Mekong Basin fails to account for important ecological, political, and economic dimensions. In doing so, they indicate that dam impacts can be easily mitigated. Such an action would serve to increase risks to food and livelihood futures in the basin.


Isolation of Su(var)3-7 mutations by homologous recombination in Drosophila melanogaster.
The Su(var)3-7 gene, a haplo-suppressor and triplo-enhancer of position-effect variegation (PEV), encodes a zinc finger heterochromatin-associated protein. To understand the role of this protein in heterochromatin and genomic silencing, mutations were generated by homologous recombination. The donor fragment contained a yellow(+) gene and 7.6 kb of the Su(var)3-7 gene inserted between two FRTs. The Su(var)3-7 sequence contained three stop codons flanking an I-SceI cut site located in the 5' half of the gene. Using two different screening approaches, we obtained an allelic series composed of three mutant alleles. The three mutations are dominant suppressors of PEV. One behaves as a null mutation and results in a maternal-effect recessive lethal phenotype that can be rescued by a zygotic paternal wild-type gene. A P transposon zygotically expressing a Su(var)3-7 full-length cDNA also rescues the mutant phenotype. One hypomorphic allele is viable and the pleiotropic phenotype showed by adult flies indicates that rapidly and late dividing cells seem the most affected by reduced amounts of Su(var)3-7 protein. All three mutants were characterized at the molecular level. Each expresses a portion of the Su(var)3-7 protein that is unable to enter the nucleus and bind chromatin.


Estivation-responsive microRNAs in a hypometabolic terrestrial snail.
When faced with extreme environmental conditions, the milk snail (Otala lactea) enters a state of dormancy known as estivation. This is characterized by a strong reduction in metabolic rate to <30% of normal resting rate that is facilitated by various behavioural, physiological, and molecular mechanisms. Herein, we investigated the regulation of microRNA in the induction of estivation. Changes in the expression levels of 75 highly conserved microRNAs were analysed in snail foot muscle, of which 26 were significantly upregulated during estivation compared with controls. These estivation-responsive microRNAs were linked to cell functions that are crucial for long-term survival in a hypometabolic state including anti-apoptosis, cell-cycle arrest, and maintenance of muscle functionality. Several of the microRNA responses by snail foot muscle also characterize hypometabolism in other species and support the existence of a conserved suite of miRNA responses that regulate environmental stress responsive metabolic rate depression across phylogeny.


Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.
Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1-/- mast cells or selective mast cell deletion of Tph1 enhances uncoupling protein 1 (Ucp1) expression in white adipose tissue and protects mice from developing obesity and insulin resistance. These data suggest that therapies aimed at inhibiting mast cell Tph1 may represent a therapeutic approach for the treatment of obesity and type 2 diabetes.


Adipocytes spectrum - From homeostasia to obesity and its associated pathology.
Firstly identified by anatomists, the fat tissue is nowadays an area of intense research due to increased global prevalence of obesity and its associated diseases. Histologically, there are four types of fat tissue cells which are currently recognized (white, brown, beige, and perivascular adipocytes). Therefore, in this study we are reviewing the most recent data regarding the origin, structure, and molecular mechanisms involved in the development of adipocytes. White adipocytes can store triglycerides as a consequence of lipogenesis, under the regulation of growth hormone or leptin and adiponectin, and release fatty acids resulted from lipolysis, under the regulation of the sympathetic nervous system, glucocorticoids, TNF-α, insulin, and natriuretic peptides. Brown adipocytes possess a mitochondrial transmembrane protein thermogenin or UCP1 which allows heat generation. Recently, thermogenic, UCP positive adipocytes have been identified in the subcutaneous white adipose tissue and have been named beige adipocytes. The nature of these cells is still controversial, as current theories are suggesting their origin either by transdifferentiation of white adipocytes, or by differentiation from an own precursor cell. Perivascular adipocytes surround most of the arteries, exhibiting a supportive role and being involved in the maintenance of intravascular temperature. Thoracic perivascular adipocytes resemble brown adipocytes, while abdominal ones are more similar to white adipocytes and, consequently, are involved in obesity-induced inflammatory reactions. The factors involved in the regulation of adipose stem cells differentiation may represent potential pathways to inhibit or to divert adipogenesis. Several molecules, such as pro-adipogenic factors (FGF21, BMP7, BMP8b, and Cox-2), cell surface proteins or receptors (Asc-1, PAT2, P2RX5), and hypothalamic receptors (MC4R) have been identified as the most promising targets for the development of future therapies. Further investigations are necessary to complete the knowledge about adipose tissue and the development of a new generation of therapeutic tools based on molecular targets.


Surgical management of urachal tumors: Can the umbilicus be sparred in localized disease?
Urachal adenocarcinoma represents the third most common histological type of non-urotelial bladder cancer. A very low incidence of this disease and the lack of prospective studies have led to a rich and heterogeneous treatment history. Currently, the standard of care for these patients is represented by partial cystectomy en bloc with resection of the urachal ligament and total omphalectomy. The aim of this article is to present our experience and results in the management of patients with urachal adenocarcinoma. Between 2005 and 2015, 16 patients have undergone surgical treatment for urachal adenocarcinoma in "Fundeni" Clinical Institute and Madrid University Hospital "Infanta Sofia." Partial cystectomy was performed in 11 (68.76%) patients, while radical cystectomy en bloc with omphalectomy was performed in 5 (31.25%) patients, which were not amendable to a limited resection. The Sheldon classification was used, as it provides appropriate disease staging and is the most commonly utilized. Postoperative pathological results showed that 7 (43.75%) patients had localized tumors, and more than one-third (37.5%) of the patients had locally advanced Sheldon III disease, while 3 patients had distant metastasis at the time of surgery. Lymph node involvement was present in 3 patients (18.75%). Mean follow-up time was 2.5 years, ranging from 4 months to 7.6 years. Three patients (18.75%) were lost to follow-up, without any documented signs of local or systemic recurrence and were cancer free at the time of the last evaluation. In cases with lymph node involvement, local recurrence or distant metastasis, patients underwent cisplatin- or 5-fluorouracil-based salvage chemotherapy. Surgical treatment represents the gold standard, while adjuvant chemotherapy has a limited impact on overall survival. The utility of navel resection is questionable due to the rarity of direct invasion or local recurrence.


Asthma, corticosteroid use and schizophrenia: A nationwide population-based study in Taiwan.
Asthma and corticosteroid use have been implicated as possible risk factors for schizophrenia. The retrospective cohort study herein aimed to investigate the association between asthma, corticosteroid use, and schizophrenia. Longitudinal data (2000 to 2007) from adults with asthma (n = 50,046) and without asthma (n = 50,046) were compared on measures of schizophrenia incidence using Taiwan's National Health Insurance Research Database (NHIRD). Incidence of schizophrenia diagnosis (ICD-9 codes 295.XX) between 2000 and 2007 were compared between groups. Competing risk-adjusted Cox regression analyses were conducted, adjusting for sex, age, residence, socioeconomic status, corticosteroid use, outpatient and emergency room visit frequency, Charlson comorbidity index, and total length of hospital stays days for any disorder. Of the 75,069 subjects, 238 received a diagnosis of schizophrenia. The mean (SD) follow-up interval for all subjects was 5.8 (2.3) years. After adjusting for potential confounding factors, asthma was associated with significantly greater hazard ratio for incident schizophrenia 1.40 (95% CI = 1.05, 1.87). Additional factors associated with greater incidence of schizophrenia were rural residence, lower economic status, and poor general health. Older age (i.e. ≥65 years) was negatively associated with schizophrenia incidence. Corticosteroid use was not associated with increased risk for schizophrenia. Asthma was associated with increased risk for schizophrenia. The results herein suggest that a convergent disturbance in the immune-inflammatory system may contribute to the pathoetiology of asthma and schizophrenia.


Low-level microwave irradiation attenuates naloxone-induced withdrawal syndrome in morphine-dependent rats.
The effect of microwave irradiation on naloxone-induced withdrawal syndrome was studied in rats made morphine dependent by subcutaneous implantation of morphine pellets. Morphine-dependent rats were either exposed to pulsed low-level microwaves (2450 MHz, 1 mW/cm2, 500 pps, 2 musec pulses) or sham-irradiated for 45 min before the naloxone injection. We found that microwave-exposed rats showed significantly less weg-dog-shakes and had higher body temperature than the sham-exposed animals during withdrawal. There was no significant difference in the incident of diarrhea between the two groups of animals. These data further support the results of our previous research suggesting that pulsed low-level microwave irradiation activates endogenous opioids in the rat.


'Around the edges': using behaviour change techniques to characterise a multilevel implementation strategy for a fall prevention programme.
Implementation strategies are needed to ensure that evidence-based healthcare interventions are adopted successfully. However, strategies are generally poorly described and those used in everyday practice are seldom reported formally or fully understood. Characterising the active ingredients of existing strategies is necessary to test and refine implementation. We examined whether an implementation strategy, delivered across multiple settings targeting different stakeholders to support a fall prevention programme, could be characterised using the Behaviour Change Technique (BCT) Taxonomy. Data sources included project plans, promotional material, interviews with a purposive sample of stakeholders involved in the strategy's design and delivery and observations of staff training and information meetings. Data were analysed using TIDieR to describe the strategy and determine the levels at which it operated (organisational, professional, patient). The BCT Taxonomy identified BCTs which were mapped to intervention functions. Data were coded by three researchers and finalised through consensus. We analysed 22 documents, 6 interviews and 4 observation sessions. Overall, 21 out a possible 93 BCTs were identified across the three levels. At an organisational level, identifiable techniques tended to be broadly defined; the most common BCT was restructuring the social environment. While some activities were intended to encourage implementation, they did not have an immediate behavioural target and could not be coded using BCTs. The largest number and variety of BCTs were used at the professional level to target the multidisciplinary teams delivering the programme and professionals referring to the programme. The main BCTs targeting the multidisciplinary team were instruction on how to perform the (assessment) behaviour and demonstration of (assessment) behaviour; the main BCT targeting referrers was adding objects to the environment. At the patient level, few BCTs were used to target attendance. In this study, several behaviour change techniques were evident at the individual professional level; however, fewer techniques were identifiable at an organisational level. The BCT Taxonomy was useful for describing components of a multilevel implementation strategy that specifically target behaviour change. To fully and completely describe an implementation strategy, including components that involve organisational or systems level change, other frameworks may be needed.


Smelling right: the scent of male lemurs advertises genetic quality and relatedness.
Sexual selection theory predicts that competitors or potential mates signal their quality or relatedness to conspecifics. Researchers have focused on visual or auditory modes of signal transmission; however, the importance of olfactory indicators is gaining recognition. Using a primate model and a new integrative analytical approach, we provide the first evidence relating male olfactory cues to individual genome-wide heterozygosity and to the genetic distance between individuals. The relationships between male semiochemical profiles and genetic characteristics are apparent only during the highly competitive and stressful breeding season. As heterozygosity accurately predicts health and survivorship in this population, we identify scrotal olfactory cues as honest indicators of male quality, with relevance possibly to both sexes. Beyond showing that semiochemicals could underlie kin recognition and nepotism, we provide a putative olfactory mechanism to guide male-male competition and female mate choice.


A trait-based test for habitat filtering: convex hull volume.
Community assembly theory suggests that two processes affect the distribution of trait values within communities: competition and habitat filtering. Within a local community, competition leads to ecological differentiation of coexisting species, while habitat filtering reduces the spread of trait values, reflecting shared ecological tolerances. Many statistical tests for the effects of competition exist in the literature, but measures of habitat filtering are less well-developed. Here, we present convex hull volume, a construct from computational geometry, which provides an n-dimensional measure of the volume of trait space occupied by species in a community. Combined with ecological null models, this measure offers a useful test for habitat filtering. We use convex hull volume and a null model to analyze California woody-plant trait and community data. Our results show that observed plant communities occupy less trait space than expected from random assembly, a result consistent with habitat filtering.


The LUBAC participates in lysophosphatidic acid-induced NF-κB activation.
The natural bioactive glycerophospholipid lysophosphatidic acid (LPA) binds to its cognate G protein-coupled receptors (GPCRs) on the cell surface to promote the activation of several transcription factors, including NF-κB. LPA-mediated activation of NF-κB relies on the formation of a signalosome that contains the scaffold CARMA3, the adaptor BCL10 and the paracaspase MALT1 (CBM complex). The CBM complex has been extensively studied in lymphocytes, where it links antigen receptors to NF-κB activation via the recruitment of the linear ubiquitin assembly complex (LUBAC), a tripartite complex of HOIP, HOIL1 and SHARPIN. Moreover, MALT1 cleaves the LUBAC subunit HOIL1 to further enhance NF-κB activation. However, the contribution of the LUBAC downstream of GPCRs has not been investigated. By using murine embryonic fibroblasts from mice deficient for HOIP, HOIL1 and SHARPIN, we report that the LUBAC is crucial for the activation of NF-κB in response to LPA. Further echoing the situation in lymphocytes, LPA unbridles the protease activity of MALT1, which cleaves HOIL1 at the Arginine 165. The expression of a MALT1-insensitive version of HOIL1 reveals that this processing is involved in the optimal production of the NF-κB target cytokine interleukin-6. Lastly, we provide evidence that the guanine exchange factor GEF-H1 favors MALT1-mediated cleavage of HOIL1 and NF-κB signaling in this context. Together, our results unveil a critical role for the LUBAC as a positive regulator of NF-κB signaling downstream of LPA receptors.


The potential role of green tea catechins in the prevention of the metabolic syndrome - a review.
The metabolic syndrome (MetS) represents an emerging health burden for governments and health care providers. Particularly relevant for prevention and early management of MetS are lifestyle conditions including physical activity and the diet. It has been shown that green tea, when consumed on a daily basis, supports health. Many of the beneficial effects of green tea are related to its catechin, particularly (-)-epigallocatechin-3-gallate (EGCG), content. There is conclusive evidence from in vitro and animal studies which provide the concepts for underlying functional mechanisms of green tea catechins and their biological actions. An increasing number of human studies have explored the effects of green tea catechins on the major MetS conditions such as obesity, type-2 diabetes and cardiovascular risk factors. This article provides a comprehensive overview of the human studies addressing the potential benefits of green tea catechins on the MetS. The number of human studies in this field is still limited. However, the majority of human epidemiological and intervention studies demonstrate beneficial effects of green tea or green tea extracts, rich in EGCG on weight management, glucose control and cardiovascular risk factors. The optimal dose has not yet been established. The current body of evidence in humans warrants further attention. In particular, well-controlled long-term human studies would help to fully understand the protective effects of green tea catechins on parameters related to the MetS.


Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus.
1. An increase in capillary blood flow and pressure has been implicated in the pathogenesis of diabetic microangiopathy. Abnormal vascular reactivity of the resistance vasculature may play a contributory role by permitting alterations in regional haemodynamics. 2. We have studied the contractile behavior of isolated resistance arteries from normotensive patients with insulin-dependent diabetes mellitus and non-diabetic matched control subjects. Contractile responses to potassium (123 mmol/l), noradrenaline (10(-8) to 3 x 10(-5) mol/l) and angiotensin II (10(-11) to 3 x 10(-8) mol/l) were recorded. Relaxation studies were performed in maximally contracted vessels using acetylcholine (10(-8) to 10(-5) mol/l) and bradykinin (10(-9) to 10(-6) mol/l) (endothelium-dependent) and sodium nitroprusside (10(-9) to 10(-5) mol/l) (endothelium-independent). 3. The maximal contractile responses to potassium (P < 0.05), noradrenaline (P < 0.01) and angiotensin II (P < 0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P < 0.05), but was normal with bradykinin and sodium nitroprusside. 4. These results suggest that there may be a defect in the endothelial cell acetylcholine receptor excitation-coupling in diabetes mellitus rather than a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxation of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tissue blood flow, a rise in capillary pressure and, as a result, an increase in vascular permeability.


From efficacy to equity: Literature review of decision criteria for resource allocation and healthcare decisionmaking.
Resource allocation is a challenging issue faced by health policy decisionmakers requiring careful consideration of many factors. Objectives of this study were to identify decision criteria and their frequency reported in the literature on healthcare decisionmaking. An extensive literature search was performed in Medline and EMBASE to identify articles reporting healthcare decision criteria. Studies conducted with decisionmakers (e.g., focus groups, surveys, interviews), conceptual and review articles and articles describing multicriteria tools were included. Criteria were extracted, organized using a classification system derived from the EVIDEM framework and applying multicriteria decision analysis (MCDA) principles, and the frequency of their occurrence was measured. Out of 3146 records identified, 2790 were excluded. Out of 356 articles assessed for eligibility, 40 studies included. Criteria were identified from studies performed in several regions of the world involving decisionmakers at micro, meso and macro levels of decision and from studies reporting on multicriteria tools. Large variations in terminology used to define criteria were observed and 360 different terms were identified. These were assigned to 58 criteria which were classified in 9 different categories including: health outcomes; types of benefit; disease impact; therapeutic context; economic impact; quality of evidence; implementation complexity; priority, fairness and ethics; and overall context. The most frequently mentioned criteria were: equity/fairness (32 times), efficacy/effectiveness (29), stakeholder interests and pressures (28), cost-effectiveness (23), strength of evidence (20), safety (19), mission and mandate of health system (19), organizational requirements and capacity (17), patient-reported outcomes (17) and need (16). This study highlights the importance of considering both normative and feasibility criteria for fair allocation of resources and optimized decisionmaking for coverage and use of healthcare interventions. This analysis provides a foundation to develop a questionnaire for an international survey of decisionmakers on criteria and their relative importance. The ultimate objective is to develop sound multicriteria approaches to enlighten healthcare decisionmaking and priority-setting.


[Management of Primary Hyperoxaluria Type 1 in Italy].
Primary hyperoxaluria type 1 is a rare genetic disease; the onset of symptoms ranges from childhood to the sixth decade of life and the disease may go unrecognized for several years. There is an urgent need for drugs able to inhibit the liver production of oxalate and to prevent the disease progression; lumasiran, an innovative molecule based on RNAi interference, is one of the most promising drugs. A group of leading Italian experts on this disease met to respond to some unmet medical needs (early diagnosis, availability of genetic tests and dosage of plasma oxalate, timing of liver transplantation, need for etiologic treatment), based on the analysis of the main scientific evidence and their personal experience. Children showing the characteristic symptoms of the disease usually undergo a metabolic screening and obtain an early diagnosis, while the experience is very limited in adults and the diagnosis difficult. It is therefore essential to increase the knowledge around this disease and the importance of metabolic and genetic screening to define a checklist of shared clinical and laboratory criteria and to establish a multidisciplinary management of potential patients. Oxalate is the cause of the disease: it is crucial to reduce both oxaluria and oxalemia through appropriate therapeutic strategies, able to prevent and/or reduce renal and systemic complications of primary type 1 hyperoxaluria. Lumasiran allows to significantly reduce the levels of oxalate both in blood and in urine, halting the course of the disease and preventing serious renal and systemic complications, if the therapy is started at an early stage of the disease.


Special features of the priming process for a secretory IgA response. B cell priming with cholera toxin.
Administration of cholera toxin/toxoid by either intraduodenal or parenteral routes increases the frequency of antigen-sensitive B cells in Peyer's patches (PP) and in distant lymphoid tissues greater than 50-fold. The special feature of mucosal priming with toxin is its unique effectiveness at generating secondary B cells, whose progeny express IgA exclusively, and such cells appear in highest frequency in PP and in appreciable numbers in spleen. Thus, this deliberate intraduodenal immunization seems to mimic the natural priming process induced by enteric bacterial colonization, which we have postulated to account for the high frequencies of IgA-committed cells specific for bacterial determinants in the PP of conventionally reared mice. furthermore, as a result of intraduodenal immunization, antigen-specific memory B cells are disseminated to sites distant form that of antigen application, including the lymphoid follicles associated with the respiratory mucosa. Direct antigenic stimulation of cells in the PP therefore results in effective cross-priming among mucosal and systemic sites through division, differentiation, and disemination of antigen-sensitive secondary B cells.


A rapid bootstrap algorithm for the RAxML Web servers.
Despite recent advances achieved by application of high-performance computing methods and novel algorithmic techniques to maximum likelihood (ML)-based inference programs, the major computational bottleneck still consists in the computation of bootstrap support values. Conducting a probably insufficient number of 100 bootstrap (BS) analyses with current ML programs on large datasets-either with respect to the number of taxa or base pairs-can easily require a month of run time. Therefore, we have developed, implemented, and thoroughly tested rapid bootstrap heuristics in RAxML (Randomized Axelerated Maximum Likelihood) that are more than an order of magnitude faster than current algorithms. These new heuristics can contribute to resolving the computational bottleneck and improve current methodology in phylogenetic analyses. Computational experiments to assess the performance and relative accuracy of these heuristics were conducted on 22 diverse DNA and AA (amino acid), single gene as well as multigene, real-world alignments containing 125 up to 7764 sequences. The standard BS (SBS) and rapid BS (RBS) values drawn on the best-scoring ML tree are highly correlated and show almost identical average support values. The weighted RF (Robinson-Foulds) distance between SBS- and RBS-based consensus trees was smaller than 6% in all cases (average 4%). More importantly, RBS inferences are between 8 and 20 times faster (average 14.73) than SBS analyses with RAxML and between 18 and 495 times faster than BS analyses with competing programs, such as PHYML or GARLI. Moreover, this performance improvement increases with alignment size. Finally, we have set up two freely accessible Web servers for this significantly improved version of RAxML that provide access to the 200-CPU cluster of the Vital-IT unit at the Swiss Institute of Bioinformatics and the 128-CPU cluster of the CIPRES project at the San Diego Supercomputer Center. These Web servers offer the possibility to conduct large-scale phylogenetic inferences to a large part of the community that does not have access to, or the expertise to use, high-performance computing resources.


Barriers and alternatives to pediatric rheumatology referrals: survey of general pediatricians in the United States.
Access to pediatric rheumatology (PR) care is limited, however the impact that limited access to PR has on pediatricians has not been examined. The goal of this study was to investigate barriers to PR referrals and resulting alternative referral patterns among primary pediatricians. A web-based survey was emailed to primary pediatricians practicing in Minnesota, North Dakota, and South Dakota in order to investigate access to PR care issues. Basic descriptive analysis was performed. The response rate was 15 % (93/609). Twenty-nine percent (27/92) of respondents' clinics were at least two hours by car from a pediatric rheumatologist, and 9 % (8/92) were more than six hours away. Ninety-two percent (85/92) had referred a patient to PR at least once, but 89 % (83/93) had experienced a situation in which they considered a referral to PR but ultimately did not. Many had referred to other subspecialists instead: 29 % (24/83) to pediatric infectious disease, 20 % to adult rheumatology, and 12 % to pediatric orthopedics, while 34 % managed the patient themselves. Thirty-five percent (32/60) had referred to an adult rheumatologist, commonly due to decreased travel (44 %), while physician preference was never selected as a reason. Pediatricians often refer children with possible rheumatic disease to specialists other than PR mainly due to long travel distances. Referral to adult rheumatologists occurs, but not based on pediatrician preference. These findings suggest that the PR workforce is inadequate to meet demand, at least in the Upper Midwest. Interventions are needed to improve access to PR care.


Identification and characterization of a cDNA derived from multiple splicing that encodes envelope glycoprotein gp105 of human herpesvirus 6.
The glycoprotein complex gp82-gp105 is a major virion envelope glycoprotein complex of human herpesvirus 6 variant A (HHV-6A) and consists of a number of related polypeptides. Monoclonal antibodies (MAbs) 2D4, 2D6, and 13D6 against this glycoprotein complex neutralized HHV-6A infectivity. We have previously reported the isolation, mapping, and characterization of a portion of the viral genomic DNA fragment encoding the gp82-gp105 complex and the identification of the neutralizing epitope (B. Pfeiffer, Z. N. Berneman, F. Neipel, C. K. Chang, S. Tirwatnapong, and B. Chandran, J. Virol. 67:4611-4620, 1993). This gene was further characterized by the identification of a 2.3-kb genomic fragment and by the identification of a 2.5-kb cDNA clone. The genomic sequence contains a short open reading frame (ORF) encoding the epitope recognized by the MAbs. The identified cDNA showed specificity for HHV-6 in Southern blot analysis with viral DNA. In Northern (RNA) blot analysis with total RNA from HHV-6A(GS)-infected cells, the cDNA insert specifically hybridized with several RNA species. Restriction mapping analysis localized this cDNA to the HHV-6A(U1102) genomic BamHI G fragment, at the right end of the unique long segment of the genome and to the SalI L and SalI O fragments within the left and right terminal direct repeat regions, respectively. In vitro transcription and translation of the cDNA revealed a polypeptide of about 88.5 kDa which was glycosylated in the presence of microsomal membranes to a polypeptide of approximately 104.2 kDa. Both polypeptides were immunoprecipiated by MAb 2D6, verifying the identity of the cDNA as encoding the gp105 in the gp82-gp105 complex. Sequence analysis of the cDNA revealed a large ORF potentially encoding a 650-amino-acid protein with 11 potential N-linked glycosylation sites and 18 cysteine residues. A potential membrane-spanning domain is located only near the amino terminus of the putative protein, indicating that gp105 may be a class 2 glycoprotein. Comparison of the cDNA nucleotide sequence with sequences from HHV-6A(U1102) genomic BamHI G and SalI L fragments revealed that the gene encoding gp105 contains 12 exons, spanning over 20 kb of the viral genome, with intron 1 spanning about 8 kb of genomic DNA. The first exon of the cDNA mapped to the right and left terminal direct repeats, while the other exons mapped within the unique long segment of the genome.(ABSTRACT TRUNCATED AT 400 WORDS)


Plasmon resonances and near-field optical microscopy: a self-consistent theoretical model.
Electromagnetic optical interactions between a small metal sphere and a metallic surface are studied by using a self-consistent approach in the presence of an external field. The intensity scattered by the metal particle is given for different polarizations of the incident field. This quantity, determined from a local treatment of the response function of the two interacting systems, exhibits a spatial dependence with respect to the approach distance close to that obtained from recent experimental studies. Moreover, at large separation, retardation effects included from a dipolar propagator give rise to pseudoperiodic oscillations such as the ones observed in reflection near-field optical microscopy. In the near-field range, plasmon modes of the whole system probe surface introduce narrow resonances in the scattered intensity versus the probe-sample separation.


High-intensity endurance training in 20- to 30- and 60- to 70-yr-old healthy men.
Factors contributing to maximal incremental and short-term exercise capacity were measured before and after 12 wk of high-intensity endurance training in 12 old (60-70 yr) and 10 young (20-30 yr) sedentary healthy males. Peak O2 uptake in incremental cycle ergometer exercise increased from 1.60 +/- 0.073 to 2.21 +/- 0.073 (SE) l/min (38% increase) in the old subjects and from 2.54 +/- 0.141 to 3.26 +/- 0.181 l/min (29%) in the young subjects. Peak cardiac output, estimated by extrapolation from a series of submaximal measurements by the CO2 rebreathing method, increased by 30% (from 12.7 to 16.5 l/min) in the old subjects, associated with a 6% increase (from 126 to 135 ml/l) in arteriovenous O2 difference; in the young subjects there were equal 14% increases in both variables (18.0 to 20.5 l/min and 140 to 159 ml/l, respectively). Submaximal mean arterial pressure and cardiac output were lower posttraining in the old subjects; total vascular conductance and cardiac stroke volume increased. Although peak power at the start of a short-term maximal isokinetic test did not change, total work accomplished in 30 s at a pedaling frequency of 110 revolutions/min increased in both groups, from 11.2 to 12.6 kJ and from 15.7 to 16.9 kJ in the old and young, respectively; fatigue during the 30-s test was less, and postexercise plasma lactate concentrations were lower. In older subjects, increases in aerobic power after high-intensity endurance training are at least as large as in younger subjects and are associated with increases in vascular conductance, maximal cardiac output, and stroke volume.


Aging and the anticoagulant response to warfarin therapy.
To assess the effect of aging on the anticoagulant response to warfarin. Retrospective cohort study. A university hospital outpatient anticoagulation clinic. All patients (n = 530) monitored in the anticoagulation clinic over a 10-year period (1980 to 1990). The 530 study patients had a mean age of 61.5 (+/- 14.7) years (age range, 12 to 90 years). The patients were stratified into four age groups: younger than 50 years (n = 97); 50 to 59 years (n = 107); 60 to 69 years (n = 149); and 70 years or older (n = 177). For each patient, a dose-adjusted mean prothrombin time ratio was calculated by dividing the mean prothrombin time ratio by the mean daily warfarin dose. Older patients were more likely to be female (P less than 0.001), to have more medical problems (P less than 0.001), to be taking more medications (P less than 0.001), and to weigh less than younger patients (P less than 0.001). Across age groups, there were no significant differences in the use of medications that potentiated or inhibited the anticoagulant effects of warfarin. The prothrombin time ratio, when adjusted for dose, was significantly increased in older patients (P less than 0.001). The increased anticoagulant response to warfarin seen with increasing patient age persisted even after simultaneously controlling for relevant demographic and clinical variables in a multivariate model. Other factors significantly associated with an increased sensitivity to warfarin included use of a medication with a potentiating interactive effect with warfarin, female gender, and overall medication use. Increased body weight and duration of warfarin use exceeding 6 months were found to be inversely related to anticoagulant response. The anticoagulant response to warfarin is exaggerated with advancing age. This finding emphasizes the need for close monitoring of older patients treated with warfarin therapy.


Effects of leptin on cat intestinal motility.
In a previous study, we established that leptin controls food intake and immune responses by acting on intestinal vagal chemosensitive mechanoreceptors via a functional link with interleukin-1 beta (Il-1 beta). Since the control of intestinal motility is one of the main roles of the vagal afferent fibres, we investigated the effects of leptin on intestinal electromyographic (EMG) activity which reflects intestinal motility. For this purpose, the effects of locally injected leptin on small intestine spontaneous EMG activity were studied in 23 anaesthetised cats. The EMG activity was recorded using bipolar electrodes implanted in the proximal small intestine. Leptin and Il-1 beta (0.1, 1 and 10 microg), administered through the artery irrigating the upper part of the intestine 20 min after cholecystokinin (CCK, 10 microg, I.A.), had significant (P < 0.001) excitatory effects on intestinal EMG activity. The effects of both substances were blocked by the endogenous interleukin-1 beta receptor antagonist (Il-1ra, 250 microg, I.A.), by atropine (250 microg, I.A.) and by vagotomy. In the absence of CCK, leptin and Il-1 beta had no effect on intestinal electrical activity. It can therefore be concluded that: (1) leptin is effective only after the previous intervention of CCK, (2) the enhancement of the electrical activity induced by leptin involves Il-1 beta receptors and the cholinergic excitatory pathway, (3) the modes whereby the leptin-induced enhancement of EMG activity occurs strongly suggest that these effects are due to a long-loop reflex involving intestinal vagal afferent fibres and the parasympathetic nervous system.


The ageing society and emergency hospital admissions.
There is strong policy interest, in England as elsewhere, in slowing the growth in emergency hospital admissions, which for older people increased by 3.3% annually between 2001/2 and 2012/3. Resource constrains have increased the importance of understanding rising emergency admissions, which in policy discourse is often explained by population aging. This study examines how far the rise in emergency admissions of people over 65 was due to population ageing, how far to the changing likelihood of entering hospital at each age, and how far to other factors which might be more amenable to policy measures. It shows that: admission rates rose with age from age 40 upward but each successive birth cohort experienced lower emergency admission rates after standardising for age and other effects. This downward cohort effect largely offset the consequences of an older and larger population aged over 65. Other factors which could explain increasing admissions, such as new technologies or rising expectations, appear more important than the changing size and age structure of the population as drivers of rising emergency admissions in old age. These findings suggest that stemming the rate of increase in emergency admissions of older people may be feasible, if challenging, despite population ageing.


Cost-effectiveness of varenicline compared with bupropion, NRT, and nortriptyline for smoking cessation in the Netherlands.
To examine the cost-effectiveness of varenicline, a new pharmacotherapy to support smoking cessation, compared with the currently available pharmacologic alternatives in the Netherlands. The BENESCO-model was used to estimate the long-term health and economic benefits of smoking cessation for a cohort of smokers making a one-time quit attempt. The cohort represented the population of Dutch smokers with respect to gender, age, and prevalence of the smoking-related diseases included in the model: COPD, lung cancer, CHD, stroke, and asthma exacerbations. The model compared the cumulative incidence of smoking-related diseases, (quality-adjusted) life years, intervention costs, and direct medical costs between the cohort treated with varenicline and the same cohort either untreated (unaided cessation) or treated with bupropion, nortriptyline or NRT. The time horizon was lifetime. Future costs were discounted at 4%, health outcomes at 1.5%. The cost of varenicline per additional quitter ranged from 1030 Euro compared with NRT to 4270 Euro compared with nortriptyline. When including the savings due to the reduction in incidence of smoking-related diseases, varenicline generated net savings compared with bupropion and NRT. Compared with nortriptyline and unaided cessation, varenicline was estimated to cost 1650 Euro/QALY and 320 Euro/QALY gained, respectively. At a willingness-to-pay as low as 5000/QALY gained, the probability that varenicline was cost-effective was more than 80% compared to bupropion, NRT, and unaided cessation and about 60% compared to nortriptyline. Treatment with varenicline for smoking cessation is cost-effective compared with nortriptyline and unaided cessation and even cost-saving compared with bupropion and NRT.


Prediction of Balance Compensation After Vestibular Schwannoma Surgery.
Background Balance compensation after vestibular schwannoma (VS) surgery is under the influence of specific preoperative patient and tumor characteristics. Objective To prospectively identify potential prognostic factors for balance recovery, we compared the respective influence of these preoperative characteristics on balance compensation after VS surgery. Methods In 50 patients scheduled for VS surgical ablation, we measured postural control before surgery (BS), 8 (AS8) days after, and 90 (AS90) days after surgery. Based on factors found previously in the literature, we evaluated age, body mass index and preoperative physical activity (PA), tumor grade, vestibular status, and preference for visual cues to control balance as potential prognostic factors using stepwise multiple regression models. Results An asymmetric vestibular function was the sole significant explanatory factor for impaired balance performance BS, whereas the preoperative PA alone significantly contributed to higher performance at AS8. An evaluation of patients' balance recovery over time showed that PA and vestibular status were the 2 significant predictive factors for short-term postural compensation (BS to AS8), whereas none of these preoperative factors was significantly predictive for medium-term postoperative postural recovery (AS8 to AS90). Conclusions We identified specific preoperative patient and vestibular function characteristics that may predict postoperative balance recovery after VS surgery. Better preoperative characterization of these factors in each patient could inform more personalized presurgical and postsurgical management, leading to a better, more rapid balance recovery, earlier return to normal daily activities and work, improved quality of life, and reduced medical and societal costs.


Relationship between numbers and frequencies of stimuli in human muscle fatigue.
The effect of stimulus frequency on the rate of muscle fatigue has been studied on dorsiflexor muscles of the human ankle. It was found that significantly fewer stimuli were required to abolish twitch and tetanic torque when the stimuli were delivered at 15 Hz rather than 30 Hz. At both stimulus frequencies twitch torque disappeared before tetanic torque. The difference in numbers of stimuli required for fatigue was not due to impaired excitation of muscle fibers at either of the two frequencies. At both stimulating frequencies, twitch fatigue appeared to be due to a defect in excitation-contraction coupling and/or the contractile machinery.


Potential Involvement of Obesity-Associated Chronic Inflammation in the Pathogenesis of Idiopathic Spinal Epidural Lipomatosis.
Multicenter case-control study. To characterize the pathogenesis of idiopathic spinal epidural lipomatosis (SEL). SEL is often associated with the history of steroid use or endocrine disorders; however, the pathogenesis of idiopathic SEL remains poorly understood. Sixteen patients who underwent lumbar decompression surgery due to severe idiopathic SEL were included in the study (L group, 15 men and 1 woman; mean age, 71.5 yrs). Fifteen patients without SEL, who underwent decompression surgery for lumbar canal stenosis, were selected as controls (C group, 14 men and 1 woman; mean age, 70.3 yrs). The following parameters were analyzed in these two groups: body mass index (BMI), medical history, histology, the size of adipocytes in the epidural fat (EF) tissues, and the expression level of the transcripts for adiponectin, leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8. The mean BMI of the L group was significantly higher than that of the C group (29.1 vs. 25.2 kg/m, P = 0.006), and there was a significant correlation between BMI and the width of EF in both groups. The average adipocyte size in the EF was significantly larger in the L group than in the C group (2846.8 vs. 1699.0 μm, P = 0.017). Furthermore, the expression levels of the transcripts for TNF-α and IL-1β in the L group were significantly higher than those in the C group [2.59-fold increase (P = 0.023) and 2.60-fold increase (P = 0.015), respectively]. Our data suggest that the pathogenesis of idiopathic SEL is associated with obesity. In addition, the increased expression of two major inflammatory cytokines in the EF in the L group may indicate that SEL is causally related to chronic inflammation. 3.


Evaluating synteny for improved comparative studies.
Comparative genomics aims to understand the structure and function of genomes by translating knowledge gained about some genomes to the object of study. Early approaches used pairwise comparisons, but today researchers are attempting to leverage the larger potential of multi-way comparisons. Comparative genomics relies on the structuring of genomes into syntenic blocks: blocks of sequence that exhibit conserved features across the genomes. Syntenic blocs are required for complex computations to scale to the billions of nucleotides present in many genomes; they enable comparisons across broad ranges of genomes because they filter out much of the individual variability; they highlight candidate regions for in-depth studies; and they facilitate whole-genome comparisons through visualization tools. However, the concept of syntenic block remains loosely defined. Tools for the identification of syntenic blocks yield quite different results, thereby preventing a systematic assessment of the next steps in an analysis. Current tools do not include measurable quality objectives and thus cannot be benchmarked against themselves. Comparisons among tools have also been neglected-what few results are given use superficial measures unrelated to quality or consistency. We present a theoretical model as well as an experimental basis for comparing syntenic blocks and thus also for improving or designing tools for the identification of syntenic blocks. We illustrate the application of the model and the measures by applying them to syntenic blocks produced by three different contemporary tools (DRIMM-Synteny, i-ADHoRe and Cyntenator) on a dataset of eight yeast genomes. Our findings highlight the need for a well founded, systematic approach to the decomposition of genomes into syntenic blocks. Our experiments demonstrate widely divergent results among these tools, throwing into question the robustness of the basic approach in comparative genomics. We have taken the first step towards a formal approach to the construction of syntenic blocks by developing a simple quality criterion based on sound evolutionary principles.


Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study.
Research has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936 (n = 603); and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study (n = 155). Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32-0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease.


Superadded Coinfections and Antibiotic Resistance in the Context of COVID-19: Where do We Stand?
Poor outcomes in the current coronavirus disease 2019 (COVID-19) pandemic have been attributed to superadded bacterial coinfections. The World Health Organization has reported overzealous usage of broad-spectrum antibiotics during this current pandemic raising concerns of increasing antimicrobial resistance? Therefore, the knowledge of coinfection and the common pathogens during these challenging times is essential for antibiotic stewardship practices. The incidence of reported superimposed bacterial and viral coinfections in COVID-19 patients is around 0.04 to 17%. However, more than 70% of patients have received broad-spectrum antibiotics. The presence of a simultaneous coinfection can be suspected in patients with neutrophilic lymphocytosis and elevated procalcitonin in the setting of COVID-19. Multiplex polymerase chain reaction (PCR) panels, with its short turnaround time, aid in the definitive diagnosis of possible coinfection. Acinetobacter baumanii, Mycoplasma pneumonia, influenza virus, Aspergillus, Candida, etc., are commonly implicated pathogens. Rapid characterization of coinfection and avoidance of overzealous use of broad-spectrum antibiotics in COVID-19 patients are the key to prevent antibiotic resistance during this pandemic. Kayarat B, Khanna P, Sarkar S. Superadded Coinfections and Antibiotic Resistance in the Context of COVID-19: Where do We Stand? Indian J Crit Care Med 2021;25(6):699-703.


Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial.
High-dose therapy followed by autologous stem-cell transplantation is standard of care for patients with relapsed or primary refractory Hodgkin's lymphoma. Roughly 50% of patients might be cured after autologous stem-cell transplantation; however, most patients with unfavourable risk factors progress after transplantation. We aimed to assess whether brentuximab vedotin improves progression-free survival when given as early consolidation after autologous stem-cell transplantation. We did this randomised, double-blind, placebo-controlled, phase 3 trial at 78 sites in North America and Europe. Patients with unfavourable-risk relapsed or primary refractory classic Hodgkin's lymphoma who had undergone autologous stem-cell transplantation were randomly assigned, by fixed-block randomisation with a computer-generated random number sequence, to receive 16 cycles of 1·8 mg/kg brentuximab vedotin or placebo intravenously every 3 weeks, starting 30-45 days after transplantation. Randomisation was stratified by best clinical response after completion of salvage chemotherapy (complete response vs partial response vs stable disease) and primary refractory Hodgkin's lymphoma versus relapsed disease less than 12 months after completion of frontline therapy versus relapse 12 months or more after treatment completion. Patients and study investigators were masked to treatment assignment. The primary endpoint was progression-free survival by independent review, defined as the time from randomisation to the first documentation of tumour progression or death. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01100502. Between April 6, 2010, and Sept 21, 2012, we randomly assigned 329 patients to the brentuximab vedotin group (n=165) or the placebo group (n=164). Progression-free survival by independent review was significantly improved in patients in the brentuximab vedotin group compared with those in the placebo group (hazard ratio [HR] 0·57, 95% CI 0·40-0·81; p=0·0013). Median progression-free survival by independent review was 42·9 months (95% CI 30·4-42·9) for patients in the brentuximab vedotin group compared with 24·1 months (11·5-not estimable) for those in the placebo group. We recorded consistent benefit (HR <1) of brentuximab vedotin consolidation across subgroups. The most frequent adverse events in the brentuximab vedotin group were peripheral sensory neuropathy (94 [56%] of 167 patients vs 25 [16%] of 160 patients in the placebo group) and neutropenia (58 [35%] vs 19 [12%] patients). At time of analysis, 28 (17%) of 167 patients had died in the brentuximab vedotin group compared with 25 (16%) of 160 patients in the placebo group. Early consolidation with brentuximab vedotin after autologous stem-cell transplantation improved progression-free survival in patients with Hodgkin's lymphoma with risk factors for relapse or progression after transplantation. This treatment provides an important therapeutic option for patients undergoing autologous stem-cell transplantation. Seattle Genetics and Takeda Pharmaceuticals International.


VME-DWT: An Efficient Algorithm for Detection and Elimination of Eye Blink From Short Segments of Single EEG Channel.
Recent advances in development of low-cost single-channel electroencephalography (EEG) headbands have opened new possibilities for applications in health monitoring and brain-computer interface (BCI) systems. These recorded EEG signals, however, are often contaminated by eye blink artifacts that can yield the fallacious interpretation of the brain activity. This paper proposes an efficient algorithm, VME-DWT, to remove eye blinks in a short segment of the single EEG channel. The proposed algorithm: (a) locates eye blink intervals using Variational Mode Extraction (VME) and (b) filters only contaminated EEG interval using an automatic Discrete Wavelet Transform (DWT) algorithm. The performance of VME-DWT is compared with an automatic Variational Mode Decomposition (AVMD) and a DWT-based algorithms, proposed for suppressing eye blinks in a short segment of the single EEG channel. The VME-DWT detects and filters 95% of the eye blinks from the contaminated EEG signals with SNR ranging from -8 to +3 dB. The VME-DWT shows superiority to the AVMD and DWT with the higher mean value of correlation coefficient (0.92 vs. 0.83, 0.58) and lower mean value of RRMSE (0.42 vs. 0.59, 0.87). The VME-DWT can be a suitable algorithm for removal of eye blinks in low-cost single-channel EEG systems as it is: (a) computationally-efficient, the contaminated EEG signal is filtered in millisecond time resolution, (b) automatic, no human intervention is required, (c) low-invasive, EEG intervals without contamination remained unaltered, and (d) low-complexity, without need to the artifact reference.


Fate of transforming deoxyribonucleate in Bacillus subtilis.
The majority of donor deoxyribonucleate (DNA) at early stages after uptake was found in a complex with a cell component which changes its buoyant behavior on equilibrium density gradients. Analysis of the recipient cell lysates, after treatment to dissociate the complex, showed about two-thirds of the donor molecules in denatured form and the rest associated with recipient DNA. Incubation of cells after DNA uptake leads to the disappearance of denatured donor DNA and to the increase of donor label associated with recipient DNA. Some characteristics of a component from intact cells or spheroplasts with affinity for denatured Bacillus subtilis DNA are described.


Cholera outbreak in southern Tanzania: risk factors and patterns of transmission.
To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rural area (Ifakara) in southern Tanzania, we conducted a prospective hospital-based, matched case- control study, with analysis based on the first 180 cases and 360 matched controls. Bathing in the river, long distance to water source, and eating dried fish were significantly associated with risk for cholera. Toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, was isolated in samples from Ifakara's main water source and patients' stools. DNA molecular analyses showed identical patterns for all isolates.


Age-specific decrease in seroprevalence of schistosomiasis in Puerto Rico.
In our previous work, we reported the first systematic, island-wide, serologic survey for schistosomiasis in Puerto Rico in 40 years. In that study, approximately 3,000 serum samples from the 76 municipalities comprising the island of Puerto Rico were tested for the detection of antibodies to S. mansoni microsomal antigens by the Falcon assay screening test-enzyme-linked immunosorbent assay (FAST-ELISA) and those positive were confirmed by an enzyme-linked immunoelectrotransfer blot (EITB). The highest EITB positivity was found in 17 municipalities, which comprised 48% of all seropositive samples. An additional finding was that 10% of the 215 EITB-positive samples were from individuals 25 years or younger and were for the most part of residents from the high seroprevalence areas. Thus, for this study we focused on 766 individuals 25 years of age or younger (45.5% males and 54.4% females), two-thirds of which were from 10 municipalities with the highest EITB seropositivity, and one-third from the 10 municipalities with the lowest EITB seropositivity found in our previous study. Of all samples, the results showed an overall FAST-ELISA positivity of 11.6%, with males similar to females (12.6 versus 10.7%, respectively). Confirmation by EITB was only 1.8%, with a males three-fold higher than females (3% versus 0.7%). When seropositivity was measured by age in five-year increments, a clear age-specific decrease in seropositivity was observed. Thus, by FAST-ELISA, 16.7% of the 21-25-year-old age group was positive, decreasing to 14.6%, 9.9%, 7.9%, and 9.3% in the 16-20-, 11-15-, 6-10-, and 1-5-year-old age groups, respectively. Confirmatory EITB showed even more impressive results: 4.7%, 2.6%, 1.2%, 0.7%, and 0% in the same age brackets. With regard to the high prevalence municipalities, only four of 10 (11 of 228 = 4.8%) had confirmatory EITB-positive samples and most were from municipalities of the Rio Grande de Loiza River basin and tributaries. The male to female positivity ratio was 4:1. Of the low prevalence municipalities, only single positive cases (by EITB) were found in three disperse municipalities. These results support the concept that there has been little transmission of S. mansoni in Puerto Rico during the first half of the 1990s and confirms anecdotal comments of local physicians who have seen virtually no new infections during the past three years. This makes the documentation of eradication of schistosomiasis from Puerto Rico feasible, a goal that should be set as being before the 100th anniversary of its discovery on the island by Isaac Gonzalez-Martinez in 1904.


Effects of continuous passive motion and elevation on hand edema.
The purpose of this study was to evaluate the efficacy of the use of continuous passive motion (CPM) of the digits in combination with limb elevation to reduce hand edema. The effects of 30 min of CPM of the digits with the limb elevated were compared with the effects of 30 min of limb elevation alone. Each of 16 subjects with hand edema of varied etiology received both treatments, one on each of 2 consecutive days. Measures of hand volume, finger circumference, and finger stiffness were taken before and after each treatment. Analyses comparing mean percentage change scores for both treatments showed large and significant treatment effects for all three dependent measures. The findings indicate that, for this sample, CPM with limb elevation was a more effective treatment for the reduction of hand edema than limb elevation alone. The results of analyses performed on a subgroup of 11 subjects with hemiplegia were similar, thus suggesting that CPM with limb elevation may be an effective method by which to reduce hand edema for this patient population.


Expression and clinical significance of p120 catenin mRNA and protein in pancreatic carcinoma.
The aim of this work was investigate the association of P120 catenin expression with the clinicopathologic features and prognosis of pancreatic carcinoma. RT-PCR was performed to investigate the expression of P120 catenin mRNA and western blotting were performed to investigate the expression of P120 catenin protein in 52 patients with pancreatic carcinoma. The relationships between P120 catenin expression and clinicopathological characteristics and prognosis were analyzed. The mRNA and protein expression of P120 catenin detected by RT-PCR and western blotting in pancreatic carcinoma was significantly lower than that in normal pancreatic tissues (0.227+/-0.067 vs 0.793+/-0.162, t=9.157, P =0.000; 0.665+/-0.192 vs 0.936+/-0.251, t=3.857, P=0.002). Reduced expression of P120 catenin mRNA and protein was significantly correlated with lymph node metastasis (P =0.004, P =0.006), vascular invasion (P =0.022, P =0.039 ), distant metastasis (P =0.037 , P =0.025), differentiated (P =0.033, P =0.013) and pTNM stage (P =0.003, P =0.022) of tumours. Additionally, reduced expression of P120 catenin mRNA and protein in tumour correlated with a worse prognosis and normal expression with a better survival rate (P=0.022, P=0.007). The reduced expression of both P120 catenin mRNA and protein in pancreatic carcinoma suggest that low expressions relate to pancreatic carcinoma development. P120 catenin may be related to pancreatic carcinoma behaviour and be a potential prognostic molecule.


Familial psychiatric presentation of Huntington's disease.
Symptoms of schizophrenia may be encountered in Huntington's disease (HD) but usually when the full clinical syndrome is apparent; prechoreic psychosis is relatively uncommon. We describe a family where all four members affected with HD presented first with a severe psychiatric syndrome, which in three cases was schizophreniform in nature. Two other living members with no current signs of motor disorder have received psychiatric treatment, one for schizophrenia. Concurrence of psychosis and Huntington's disease in this family is unlikely to have occurred by chance, suggesting that there is some feature in this family which gives rise to the psychotic presentation. Families such as this may contribute to the investigation of genetic factors associated with psychiatric illnesses.


Counterion-mediated hierarchical self-assembly of an ABC miktoarm star terpolymer.
Directed self-assembly processes of polymeric systems represent a powerful approach for the generation of structural hierarchy in analogy to biological systems. Herein, we utilize triiodide as a strongly polarizable counterion to induce hierarchical self-assembly of an ABC miktoarm star terpolymer comprising a polybutadiene (PB), a poly(tert-butyl methacrylate) (PtBMA), and a poly(N-methyl-2-vinylpyridinium) (P2VPq) segment. Hereby, the miktoarm architecture in conjunction with an increasing ratio of triiodide versus iodide counterions allows for a stepwise assembly of spherical micelles as initial building blocks into cylindrical structures and superstructures thereof. Finally, micrometer-sized multicompartment particles with a periodic lamellar fine structure are observed, for which we introduce the term "woodlouse". The counterion-mediated decrease in hydrophilicity of the corona-forming P2VPq block is the underlying trigger to induce this hierarchical structure formation. All individual steps and the corresponding intermediates toward these well-defined superstructures were intensively studied by scattering and electron microscopic techniques, including transmission electron microtomography.


T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro.
Two phenotypes exist in the human population with regard to expression of lactase in adults. Lactase non-persistence (adult-type hypolactasia and lactose intolerance) is characterized by a decline in the expression of lactase-phlorizin hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a high LPH throughout their lifespan. Lactase persistence and non-persistence are associated with a T/C polymorphism at position -13,910 upstream the lactase gene. A nuclear factor binds more strongly to the T-13,910 variant associated with lactase persistence than the C-13,910 variant associated with lactase non-persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified by DNA affinity purification using the sequence of the T-13,910 variant. Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha. Binding sites for other intestinal transcription factors (GATA-6, HNF4alpha, Fox and Cdx-2) were identified in the region of the -13,910 T/C polymorphism. Three of these sites are required for the enhancer activity of the -13,910 region. The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.


The effects of antenatal corticosteroid treatment on IVH-PVh of premature infants.
Intraventricular-periventricular hemorrhage (IVH-PVH) is the most frequent type of intracranial hemorrhage in premature infants and the major cause of neurodevelopmental disabilities in children too. The objective of this work is to evaluate the effects of prenatal corticosteroid treatment on the incidence of IVH-PVH in premature infants. The study enrolled 163 prematures of 26-34 weeks' gestation. They have been divided into two groups: the experimental group (80/163), who have been treated with corticosteroids prenatally and control group (83/163), who have not received such treatment. There is statistically significant difference in IVH-PVH incidence between the experimental group (18/80) and control group (32/83) (chi2 =5,616, p<0,05). There is no statistically significant difference in Apgar score after 5 minutes between the experimental group and control group of IVH-PVH prematures, t= 0,121. There is no statistically significant difference in mean gestation age between the experimental group (30,74 weeks) and control group (29,97 weeks) of IVH-PVH prematures, t= 1,299. There is no statistically significant difference in mean birth weight between the experimental group (1479,44 grams) and control group (1379,37 grams) of IVH-PVH prematures, t= 0,913. Antenatal corticosteroid treatment of premature infants reduced the incidence of IVH-PVH significantly. There is no statistically significant difference in Apgar score after 5 minutes, mean gestation age and mean birth weight between the experimental and control group of IVH PVH prematures.


Comparison of different methods for delayed post-mortem diagnosis of falciparum malaria.
Between 10,000 and 12,000 cases of imported malaria are notified in the European Union each year. Despite an excellent health care system, fatalities do occur. In case of advanced autolysis, the post-mortem diagnostic is impaired. Quicker diagnosis could be achieved by using rapid diagnostic malaria tests. In order to evaluate different methods for the post-mortem diagnosis of Plasmodium falciparum malaria in non-immunes, a study was performed on the basis of forensic autopsies of corpses examined at variable intervals after death in five cases of fatal malaria (with an interval of four hours to five days), and in 20 cases of deaths unrelated to malaria. Detection of parasite DNA by PCR and an immunochromatographic test (ICT) based upon the detection of P. falciparum histidine-rich protein 2 (PfHRP2) were compared with the results of microscopic examination of smears from cadaveric blood, histopathological findings, and autopsy results. In all cases of fatal malaria, post-mortem findings were unsuspicious for the final diagnosis, and autoptic investigations, including histopathology, were only performed because of additional information by police officers and neighbours. Macroscopic findings during autopsy were unspecific. Histopathology confirmed sequestration of erythrocytes and pigment in macrophages in most organs in four patients (not evaluable in one patient due to autolysis). Microscopy of cadaveric blood smears revealed remnants of intraerythrocytic parasites, and was compromised or impossible due to autolysis in two cases. PCR and ICT performed with cadaveric blood were positive in all malaria patients and negative in all controls. In non-immune fatalities with unclear anamnesis, ICT can be recommended as a sensitive and specific tool for post-mortem malaria diagnosis, which is easier and faster than microscopy, and also applicable when microscopic examination is impossible due to autolysis. PCR is more expensive and time-consuming, but may be used as confirmatory test. In highly endemic areas where asymptomatic parasitaemia is common, confirmation of the diagnosis of malaria as the cause of death has to rely on histopathological findings.


Non-cuttable material created through local resonance and strain rate effects.
We have created a new architected material, which is both highly deformable and ultra-resistant to dynamic point loads. The bio-inspired metallic cellular structure (with an internal grid of large ceramic segments) is non-cuttable by an angle grinder and a power drill, and it has only 15% steel density. Our architecture derives its extreme hardness from the local resonance between the embedded ceramics in a flexible cellular matrix and the attacking tool, which produces high-frequency vibrations at the interface. The incomplete consolidation of the ceramic grains during the manufacturing also promoted fragmentation of the ceramic spheres into micron-size particulate matter, which provided an abrasive interface with increasing resistance at higher loading rates. The contrast between the ceramic segments and cellular material was also effective against a waterjet cutter because the convex geometry of the ceramic spheres widened the waterjet and reduced its velocity by two orders of magnitude. Shifting the design paradigm from static resistance to dynamic interactions between the material phases and the applied load could inspire novel, metamorphic materials with pre-programmed mechanisms across different length scales.


MO-D-213CD-04: 4D X-Ray DSA and 4D Fluoroscopy.
During the past decade the use of undersampled acquisition and constrained reconstruction have led to significant increases in data acquisition speed, SNR, spatial resolution and temporal resolution in MR imaging. When a separately acquired constraining image is combined with an angiographic time series the traditional tradeoff between spatial and temporal resolution is greatly reduced. Artifacts and limited resolution that would normally be associated with a rapid highly undersampled temporal image series are mitigated by the constrained reconstruction process which transfers the SNR and spatial resolution of the constraining image to the individual time frames. In rotational C-Arm DSA a 3D image volume is formed from all the projections acquired during the C-Arm rotation. Although the individual projections contain temporal information, the reconstructed 3D image has no temporal information and represents a composite of the vascular filling that has occurred during the iodine injection. However, the 3D cone beam CT reconstruction can be used to constrain the reconstruction of one 3D volume for each of the rotational projections. This extends the traditional DSA time series of 2D images to a series of 3D volumes at rates up to 30 per second. Similar techniques can be used to provide fluoroscopy that can be embedded in the 3D space of the constraining volume and viewed from arbitrary angles without gantry motion. This overcomes the problem of forbidden views and guarantees that an intervention can be done without having to send patients to surgery. Unlike 4D DSA which requires only one source and receptor, 4D Fluoroscopy requires a bi-plane fluoroscopy system. 1. To understand the application of under sampling and constrained reconstruction to 4D DSA and Fluoroscopy.


Gender Differences in Plasma Vitamin C Concentrations and Cognitive Function: A Pilot Cross-Sectional Study in Healthy Adults.
A number of investigations have highlighted the importance of vitamin C in maintaining brain health. Biologically, vitamin C has exhibited roles in neuromodulation, neurodevelopment, vascular support, and neuroprotection. Vitamin C's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed, with little focus on gender variability. The present study explored the interaction between gender and plasma vitamin C on cognitive performance, and the effect of different amounts of plasma vitamin C (adequate/inadequate) on various cognitive tasks by gender. This retrospective analysis was conducted in healthy adults (n = 80, female = 52, male = 28, 24-96 y) with a range of blood plasma vitamin C concentrations. Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and 2 pen-and-paper tests, the Symbol Digits Modalities Test (SDMT) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Food-frequency questionnaires were used to elucidate dietary consumption. After adjusting for a number of potential covariates such as age, number of prescribed medications and dose of vitamin C supplementation, results indicated a significant interaction (P < 0.001) between plasma vitamin C and gender on cognitive function, on both the computerized and pen-and-paper assessments. A novel finding was that the performance of males with inadequate plasma vitamin C was poorer on tasks involving components of memory (short/delayed), inhibition, and visual perception, whereas females presenting with inadequate vitamin C were more compromised on tasks involving psychomotor performance/motor speed. Additionally, females with adequate vitamin C concentrations exhibited higher performance than males on tasks involving recall, recognition, attention, and focus. Further larger-scale investigations are required to establish a cause-and-effect relation and to elucidate whether differences in cognitive function between genders may be attributed to plasma vitamin C status.This trial was registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440&isReview=true as ACTRN12615001140549.