Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks.
To elucidate the relationship between intragenic DNA methylation and chromatin marks, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and in the colorectal cancer cell line HCT116 as well as its counterpart with double knockout of DNMT1 and DNMT3B (HCT116-DKO). Analysis of H3K36me3 profiles indicated that this intragenic mark of active genes is associated with two categories of genes: (i) genes with low CpG density and H3K9me3 in the gene body or (ii) genes with high CpG density and DNA methylation in the gene body. We observed that a combination of low CpG density in gene bodies together with H3K9me3 and H3K36me3 occupancy is a specific epigenetic feature of zinc finger (ZNF) genes, which comprise 90% of all genes carrying both histone marks on chromosome 19. For genes with high intragenic CpG density, transcription and H3K36me3 occupancy were not changed in conditions of partial or intensive loss of DNA methylation in gene bodies. siRNA knockdown of SETD2, the major histone methyltransferase responsible for production of H3K36me3, did not reduce DNA methylation in gene bodies. Our study suggests that the H3K36me3 and DNA methylation marks in gene bodies are established largely independently of each other and points to similar functional roles of intragenic DNA methylation and intragenic H3K9me3 for CpG-rich and CpG-poor genes, respectively.


The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs.
Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease.


[Clinical findings in four cattle with abscesses in the cervical vertebrae].
The purpose of this paper was to describe the clinical findings in four cattle with abscesses in the cervical vertebrae. In all of the animals there was generalized ataxia and normal behaviour, mentation and cranial nerve function. All animals had marked difficulty rising and had generalized ataxia. The most important haematological and biochemical findings were a mildly increased concentration of plasma protein in all animals and a markedly increased fibrinogen concentration in two animals. A sample of cerebrospinal fluid (CSF) was collected from three animals. The protein content was mildly increased in the CSF samples of two animals. Based on the clinical findings, a tentative diagnosis of central nervous system disease with localisation in the neck region was made in all of the animals. Due to a poor prognosis, all of the animals were slaughtered. Postmortem examination revealed abscesses in the region of C3 to C6, which had resulted in extramedullary compression of the spinal cord. The abscesses varied in diameter from 2 to 8 cm.


Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer.
Lower limb lymphedema (LLL) is the most disabling adverse effect of surgical treatment of vulvar cancer. This study describes the use of microsurgical lymphatic venous anastomosis (LVA) to prevent LLL in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND). The study included 8 patients with invasive carcinoma of the vulva who underwent unilateral or bilateral ILND. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). An historical control group of 7 patients, which underwent ILND without LVA, was used as comparison. After 1 month from the surgery, all patients underwent a lymphoscintigraphy. In the study group, 4 patients underwent bilateral ILND, and 4 patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean (SD) time required to perform a monolateral LVA was 23.1 (3.6) minutes (range, 17-32 minutes). The mean (SD) follow-up was 16.7 (6.2) months; there was only 1 case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed a total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (P = 0.092). This study shows for the first time the feasibility of LVA in patients with vulvar cancer undergoing ILND. Future studies including larger series of patients should clarify whether this microsurgical technique reduces the incidence of LLL after ILND.


Types and Frequencies of Pre-Analytical Errors in the Clinical Laboratory at the University Hospital of Korea.
The results of laboratory tests play a critical role in patient management, so the clinical laboratory is obligated to report accurate results. However, the pre-analytical phase, in which human factors are mainly involved, is clearly a vulnerable part of the laboratory process. This study was conducted to investigate and analyze pre-analytical errors. The author intended to reduce these errors by some measures in order to enhance the credibility of the laboratory. A retrospective study was conducted to identify the rates and the types and frequencies of pre-analytical errors in the laboratory and analyze them according to the departments of patients, the sections of the laboratory, and the wards of the hospital. The reasons for these errors were persistently identified and analyzed in order to make efforts to reduce the errors. The activities for quality improvement including education and training programs on the phlebotomy teams were also accomplished to reduce these errors. The overall rate of pre-analytical errors was 0.40%. The rate of these errors significantly decreased from 0.44% in 2017 to 0.36% in 2018. In particular, the proportion of improper volume decreased from 46.1% in 2017 to 36.4% in 2018. The most common pre-analytical error was 'improper volume' (41.5%), followed by 'undue clotting' (32.8%). These errors were overwhelmingly more common in inpatients than in outpatients. The rate of these errors was the highest in stat section (1.95%). Clinical laboratory should make efforts to reduce pre-analytical errors in order to report accurate and expeditious results. Reduction of these errors can be achieved through analyzing and correcting the reasons for them and education and training on the phlebotomy teams and, as a result, the credibility of the laboratory may also be enhanced.


Platelet biology and function: plaque erosion vs. rupture.
The leading cause of heart disease in developed countries is coronary atherosclerosis, which is not simply a result of ageing but a chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. The composition and location of atherosclerotic plaques determine the phenotype of the lesion and whether it is more likely to rupture or to erode. Although plaque rupture and erosion both initiate platelet activation on the exposed vascular surface, the contribution of platelets to thrombus formation differs between the two phenotypes. In this review, plaque phenotype is discussed in relation to thrombus composition, and an overview of important mediators (haemodynamics, matrix components, and soluble factors) in plaque-induced platelet activation is given. As thrombus formation on disrupted plaques does not necessarily result in complete vessel occlusion, plaque healing can occur. Therefore, the latest findings on plaque healing and the potential role of platelets in this process are summarized. Finally, the clinical need for more effective antithrombotic agents is highlighted.


The future of biodiversity.
Recent extinction rates are 100 to 1000 times their pre-human levels in well-known, but taxonomically diverse groups from widely different environments. If all species currently deemed "threatened" become extinct in the next century, then future extinction rates will be 10 times recent rates. Some threatened species will survive the century, but many species not now threatened will succumb. Regions rich in species found only within them (endemics) dominate the global patterns of extinction. Although new technology provides details of habitat losses, estimates of future extinctions are hampered by our limited knowledge of which areas are rich in endemics.


Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness.
Recessive mutations of SLC26A4 (PDS) are a common cause of Pendred syndrome and non-syndromic deafness in western populations. Although south and east Asia contain nearly one half of the global population, the origins and frequencies of SLC26A4 mutations in these regions are unknown. We PCR amplified and sequenced seven exons of SLC26A4 to detect selected mutations in 274 deaf probands from Korea, China, and Mongolia. A total of nine different mutations of SLC26A4 were detected among 15 (5.5%) of the 274 probands. Five mutations were novel and the other four had seldom, if ever, been identified outside east Asia. To identify mutations in south Asians, 212 Pakistani and 106 Indian families with three or more affected offspring of consanguineous matings were analysed for cosegregation of recessive deafness with short tandem repeat markers linked to SLC26A4. All 21 SLC26A4 exons were PCR amplified and sequenced in families segregating SLC26A4 linked deafness. Eleven mutant alleles of SLC26A4 were identified among 17 (5.4%) of the 318 families, and all 11 alleles were novel. SLC26A4 linked haplotypes on chromosomes with recurrent mutations were consistent with founder effects. Our observation of a diverse allelic series unique to each ethnic group indicates that mutational events at SLC26A4 are common and account for approximately 5% of recessive deafness in south Asians and other populations.


Structure/function analysis of peptoid/lipitoid:DNA complexes.
Previous transfection studies of cationic peptoid polymers (N-substituted polyglycines) and cationic lipitoid polymers (peptoid-phospholipid conjugates) have shown that only the polymers which possessed a repeating (cationic, hydrophobic, hydrophobic) substituent sequence are efficient in gene transfer in vitro. To determine if there is a physical attribute of peptoid and lipitoid complexes that correlates with efficient gene transfection, biophysical, and transfection measurements were performed with polymer:DNA complexes containing each of seven structurally diverse peptoid polymers and two lipitoids that possess different hydrophobic substituents. These measurements revealed that the biophysical properties of these complexes (size, zeta-potential, ethidium bromide exclusion) varied with polymer structure and complex (+/-) charge ratio but were not directly predictive of transfection efficiency. Unique alterations in the circular dichroism spectra of DNA were observed in complexes containing several of the peptoids and both lipitoids, although FTIR spectroscopy demonstrated that the DNA remained in the B-form. The lack of correlations between the physical properties and the transfection activities of these polyplexes suggests that a further subpopulation examination of these complexes by these methods may reveal hidden structure-activity relationships.


Self-stabilization of an optical frequency comb using a short-path-length interferometer.
We stabilized the repetition rate of an optical frequency comb using a self-referenced phase-locked loop. The phase-locked loop generated its error signal with a fiber-optic delay-line interferometer that had a path-length difference of 8 m. We used the stabilized repetition rate to generate a 10 GHz signal with a single-sideband phase noise that was limited by environmental noise to -120 dBc/Hz at an offset frequency of 1 kHz. Modeling results indicate that thermoconductive noise sets a fundamental phase noise limit for an 8 m interferometer of -152 dBc/Hz at a 1 kHz offset frequency. The short length of the interferometer indicates that it could be realized as a photonic integrated circuit, which may lead to a chip-scale stabilized optical frequency comb with an ultralow-phase-noise repetition rate.


Stratifying nutritional restriction in cancer therapy: Next stop, personalized medicine.
Dietary interventions combined with cancer drugs represent a clinically valid polytherapy. In particular nutrient restriction (NR) in the form of varied fasting or caloric restriction regimens holds great clinical promise, conceptually due to the voracious anabolic appetite of cancer cells. This metabolic dependency is driven by a strong selective pressure to increasingly acquire biomass of a proliferating tumor and can be therapeutically exploited as vulnerability. A host of preclinical data suggest that NR can potentiate the efficacy of, or alleviate resistance to, cancer drugs. However, complicating clinical implementation are the many variables involved, such as host biology, cancer stage and type, oncogenic mutation landscape, tumor heterogeneity, variations in treatment modalities, and patient compliance to NR protocols. This calls for systematic preclinical screens and co-clinical studies to predict effective combinations of NR with cancer drugs and to allow for patient stratification regarding responsiveness to polytherapy. Such screen-and-stratify pipelines should consider tumor heterogeneity as well as the role of immune effectors in the tumor microenvironment and may lead to biomarker discovery advancing the oncology field toward personalized options with improved translatability to clinical settings. This opinion-based review provides a critical overview of recent literature investigating NR for cancer treatment, pinpoints limitations of current studies, and suggests standardizations and refinements for future studies and trials. The proposed measures aim to increase the translational value of preclinical data and effectively harness the vast potential of NR as adjuvant for cancer therapy.


Expression of the surface antigen 4F2hc affects system-L-like neutral-amino-acid-transport activity in mammalian cells.
Mammalian cells possess a variety of amino acid-transport systems with overlapping substrate specificity. System L is one of the major amino acid-transport systems of non-epithelial cells. By expression cloning we have recently demonstrated that the surface antigen 4F2hc (CD98) is a necessary component for expression of system-L-like amino acid-transport activity in C6-BU-1 rat glioma cells [Bröer, Bröer and Hamprecht (1995) Biochem. J. 312, 863-870]. 4F2hc mRNA was detected in CHO cells, COS cells, activated lymphocytes isolated from mouse spleen and primary cultures of astrocytes. In all these cell types, Na+-independent isoleucine transport was mediated by system L. No contribution of system y+L to isoleucine or arginine transport was detected in C6-BU-1 cells. In lymphocytes, both system-L-like amino acid-transport activity and 4F2hc mRNA levels increased after treatment with phorbol ester plus ionomycin. Antisense oligonucleotides caused modest inhibition of Na+-independent isoleucine transport in C6-BU-1 cells and primary cultures of astroglial cells, whereas arginine transport was unaffected. Overexpression of 4F2hc cDNA in CHO cells resulted in an increase in Na+-independent isoleucine transport.


Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal delivery.
The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity. C-terminal-amidated (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were analyzed by liquid chromatography-mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol. Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration-time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased the stability or possibly reduced the instability of AT1002, which resulted in an increased permeation-enhancing effect of AT1002. These results suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal drug delivery, which may lead to the development of a practical drug delivery technology for drugs with low bioavailability.


Heparin-binding apoproteins. Effects on lipoprotein lipase and hepatic uptake of remnants.
Apoprotein-free heparin-binding and non-binding chylomicrons were used as substrates to test the effects on lipoprotein lipase activity of (a) chylomicron protein I; (b) the mixture of proteins I, II and apoprotein E and (c) human beta 2-glycoprotein I. No activation of the enzyme was observed with any of those apoproteins. When rats were injected simultaneously with [3H]cholesterol-labelled heparin-binding chylomicrons (containing proteins I and II) and [14C]cholesterol-labelled non-binding chylomicrons, no differences were detected between the rates of removal from circulation of those two types of particles. Clearance of chylomicrons from circulation was accompanied by the incorporation of 3H and 14C labels into the livers at similar rates. It is concluded that proteins I, II and apoprotein E have no effect on the degradation of chylomicrons by lipoprotein lipase and that the hepatic recognition of remnants does not appear to be affected by proteins I and II.


Microbiological evaluation of a newly constructed animal facility.
Newly constructed animal facilities require microbiological evaluation prior to occupation to ensure that all facets of the design not only function accordingly and that the building is ready for introduction of new, healthy animal species and personnel. Our objective was to perform microbiological monitoring to ensure the integrity of systems implemented within our facility, both new and those transferred from existing facilities. This monitoring included environmental sampling of the autoclaves, cage washers, tunnel washers, and water system to ensure operant conditions. A sentinel surveillance program also was conducted using Crl:CD1(ICR) mice, C57BL/6J mice, and Crl:CD(SD) rats to make certain the facility had not been contaminated by any infectious agents that could affect animal health prior to their introduction into the facility. On the basis of these results, we introduced new animals, transferred existing animals, relocated personnel, and implemented new measures for sanitation that previously had not been used in any of our other facilities.


Toxicity Evaluation of the Subacute Diazinon in Aged Male Rats: Hematological Aspects.
Age-dependent Organophosphates (OPs) toxicity is a controversial topic. The present study was designed to investigate the effect of the sub-acute exposure to diazinon (DZN), one of the main OPs insecticides, on the hematological alterations in adult and aged male rats. For the aim of this approach, the adult and aged rats were administered with DZN (15 mg/kg, orally) for 4 weeks. Then, the blood samples were collected from the retro-orbital sinus for measuring red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), platelets (PLT), MCV (mean corpuscular volume), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin (MCHC). The obtained results indicated that DZN significantly decreased RBCs (4.93 ± 0.41), Htc (28.12 ± 1.21), Hb (10.31 ± 0.36), MCHC (30.51 ± 2.04), MCV (62.86 ± 2.58), and PLT (265.6 ± 34.81) values in the adult and aged rats versus the age-matched control rats. Moreover, RBC, Hb, and Htc levels decreased significantly in the aged rats versus adult rats. However, no significant differences were observed between MCHC, MCV, and PLT levels in adult and aged rats. Moreover, the MCH concentration did not change in any group. Additionally, DZN did not deteriorate the hematological alterations in the aged rats versus adult rats. the present study showed that the toxicity of DZN is not associated with age. However, more studies should be conducted to confirm this finding.


Paraparesis caused by transarterial chemoembolization: A case report.
Transarterial chemoembolization (TACE) is an effective modality for the treatment of Hepatocellular Carcinoma. It is used to treat small tumors and to downstage large tumors to meet liver transplant criteria. TACE can be associated with multiple side effects, including fever, right upper quadrant pain, nausea, vomiting, hepatic failure, hepatic encephalopathy, cholecystitis and pancreatitis. Neurological complications after TACE are rare, usually caused by cerebral embolism, and confirmed by means of imaging studies. Spinal cord ischemia secondary to TACE is extremely rare and can lead to significant morbidity. We report a case of paraparesis caused by TACE with normal imaging and nerve conduction studies, suggestive of localized vasculitis.


Polyamines directly induce release of cytochrome c from heart mitochondria.
Cytochrome c release from mitochondria to the cytosol represents a critical step in apoptosis, correlated to the activation of the caspase cascade. In this report, we show that addition of micromolar concentrations of polyamines to isolated rat heart mitochondria induces the release of cytochrome c. Spermine, which is effective at concentrations of 10-100 microM, is more potent than spermidine, whereas putrescine has no effect up to 1 mM. The release of cytochrome c caused by spermine is a rapid, saturable and selective process that is independent of mitochondria damage. Spermine, unlike polylysine, is able to release a discrete amount of cytochrome c from intact, functional mitochondria. The cytochrome c-releasing power of spermine is not affected by cyclosporin A, differently from the effect of permeability transition inducers. In a cardiac cell-free model of apoptosis, the latent caspase activity of cytosolic extracts from cardiomyocytes could be activated by cytochrome c released from spermine-treated heart mitochondria. These data indicate a novel mechanism of cytochrome c release from the mitochondrion, and suggest that prolonged and sustained elevation of polyamines, characteristic of some pathologies such as heart hypertrophy, could be involved in the development of apoptosis.


Improving Characterization of Understudied Human Microbiomes Using Targeted Phylogenetics.
Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was overselected for sequencing, prioritized bacteria from underrepresented body sites (such as skin and respiratory and urinary tracts), and sequenced and assembled genomes for 665 new bacterial strains. Here, we show that addition of these genomes improved read mapping rates of Human Microbiome Project (HMP) metagenomic samples by nearly 30% for the previously underrepresented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and a clinical perspective.IMPORTANCE The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily feces), while other sites such as the skin, respiratory tract, and urinary tract are underrepresented, resulting in as little as 13% of bacterium-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select underrepresented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.


[Absorption of testosterone-7alpha-3H by reproductive tract tissues of male-embryo rats in vitro].
The dynamics of testosterone-7alpha-3H consumption by the reproductive tract rudiments (tubules, urogenital sinus and genital tubercle) and the muscles has been studied in the in vitro experiments immediately after the isolation of embryos (16-21 days of development), as well as after the preliminary two days cultivation in the diffusion chambers (13-20 days of development). In the first series of experiments, the selective, specific consumption of the labelled androgen was observed at all stages under study, whereas in the second series of experiments the specific and selective consumption in the organs-targets was noted from the 15th day of development (in the genital tubercle and urogenital sinus). No selective consumption in the tubules was noted.


Beyond antibiotics for pulmonary nontuberculous mycobacterial disease.
Pulmonary nontuberculous mycobacterial disease (NTM) remains a significant clinical challenge with suboptimal therapy. This review focuses on recent understandings around the pathogenesis of NTM disease and nonantibiotic therapeutic approaches that are being pursued. The absence of animal models that truly replicate human disease remains a major problem for NTM research with most findings coming from tuberculosis or tuberculosis-like studies. Recent research reiterates the known key roles of interferon gamma (IFNγ), tumor necrosis factor, interleukin-12 and granulocyte-macrophage colony stimulation factor (GM-CSF) in immunity to NTM. Autoantibodies to some of these factors may be important. Recent nonantibiotic research has focused on either boosting the immune response to NTM (e.g. with IFNγ or GM-CSF) or using other compounds to kill these pathogens (e.g. inhaled NO, gallium, etc.). Our poor understanding of the immune deficit leading to NTM disease continues to hinder the development of highly effective therapies. New approaches are promising but need significant validation before being considered viable therapeutic options.


Anti-proliferative activity and chemoprotective effects towards DNA oxidative damage of fresh and cooked Brassicaceae.
Epidemiological evidence shows that regular consumption of Brassicaceae is associated with a reduced risk of cancer and heart disease. Cruciferous species are usually processed before eating and the real impact of cooking practices on their bioactive properties is not fully understood. We have evaluated the effect of common cooking practices (boiling, microwaving, and steaming) on the biological activities of broccoli, cauliflower and Brussels sprouts. Anti-proliferative and chemoprotective effects towards DNA oxidative damage of fresh and cooked vegetable extracts were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and Comet assays on HT-29 human colon carcinoma cells. The fresh vegetable extracts showed the highest anti-proliferative and antioxidant activities on HT-29 cells (broccoli>cauliflower = Brussels sprouts). No genotoxic activity was detected in any of the samples tested. The cooking methods that were applied influenced the anti-proliferative activity of Brassica extracts but did not alter considerably the antioxidant activity presented by the raw vegetables. Raw, microwaved, boiled (except broccoli) and steamed vegetable extracts, at different concentrations, presented a protective antioxidative action comparable with vitamin C (1 mm). These data provide new insight into the influence of domestic treatment on the quality of food, which could support the recent epidemiological studies suggesting that consumption of cruciferous vegetables, mainly cooked, may be related to a reduced risk of developing cancer.


Evaluation of the lymph flow with lymphoscintigraphy after rotationplasty for the treatment of bone tumors.
We studied the cases of eleven patients in whom a rotationplasty had been done after wide resection of the distal part of the femur. All patients had had a malignant tumor of bone, but none had the complication of edema or leakage of lymph after the rotationplasty. We made lymphoscintiscans soon after the operation in four patients and weeks or months later in all eleven patients. There was a delay in the flow of lymph in three of the four patients who were examined lymphoscintigraphically soon after the operation and there was obstruction of flow in the fourth patient, but there was evidence of a decreased rate of flow in only two of the eleven patients at the time of the later examination.


Genetic differential susceptibility on trial: meta-analytic support from randomized controlled experiments.
The most stringent test of differential susceptibility theory is provided by randomized control trials examining the moderating role of genetic markers of differential susceptibility in experimental manipulations of the environment (Gene × Experimental Environment interactions), being at least 10 times more powerful than correlational Gene × Environment interaction studies. We identified 22 experiments involving 3,257 participants with various developmental outcomes (e.g., externalizing problems, internalizing behaviors, and cognitive development). Effect sizes contrasting experimental versus control group were computed both for subjects with the polymorphism considered indicative of heightened susceptibility (e.g., the dopamine receptor D4 gene seven-repeat allele and the serotonin transporter polymorphic region short allele) and others expected to be low in susceptibility (e.g., the dopamine receptor D4 gene four-repeat allele and the serotonin transporter polymorphic region short allele). Clear-cut experimental support for genetic differential susceptibility emerged: the combined effect size of the interventions for the susceptible genotypes amounted to r = .33 (95% confidence interval = 0.23, 0.42; p < .01) versus a nonsignificant r = .08 (95% confidence interval = -0.02, 0.17; p = .12) for the hypothesized nonsusceptible genotypes. Macrotrials showed more evidence of genetic differential susceptibility than microtrials, and differential susceptibility was more clearly observed in trials with externalizing and cognitive outcomes than with internalizing problems. This meta-analysis shows proof of principle for genetic differential susceptibility and indicates that it is time to explore its mechanisms and limits. The concept of differential susceptibility alters the idea of constitutional "risk" factors (reactive temperament and risk genotypes), and points to intervention efficacy hidden in Gene × Environment interactions.


Synthesis, biological activity, and three-dimensional quantitative structure-activity relationship model for a series of benzo[c]quinolizin-3-ones, nonsteroidal inhibitors of human steroid 5alpha-reductase 1.
New 5alpha-reductase 1 (5alphaR-1) inhibitors were designed to complete a consistent set of analogues suitable for a 3D QSAR study. These compounds were synthesized by a modification of the aza-Robinson annulation, further functionalized by Pd-catalyzed cross-coupling processes, and were tested with human 5alphaR-1 expressed in Chinese hamster ovary 1827 cells. It turned out that the potency of the resulting inhibitors was strongly dependent on the type of substitution at the 8 position, with the IC(50) values ranging from 8.1 to 1050 nM. The construction of this homogeneous set of molecules allowed a 3D QSAR study. In particular, comparative molecular field analysis (CoMFA) was used to correlate the potency of the inhibitors with their physicochemical features. Highly accurate evaluations of the atomic point charges were carried out by means of quantum chemical calculations at the DFT/B3LYP level of theory followed by the RESP fitting procedure. It turned out that increasing the reliability of electrostatic parameters greatly affected the statistical results of the QSAR analysis. The 3D QSAR model proposed could be very useful in the further development of 5alphaR-1 inhibitors, which are suitable candidates to be evaluated as drugs in the treatment of 5alphaR-1 related diseases such as acne and alopecia in men and hirsutism in women.


CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and Neurons.
The cyclic AMP response element binding protein (CREB) is a primary hub of activity-driven genetic programs in neurons controlling plasticity, neurogenesis and survival. By contrast, the gene networks coordinated by CREB in astrocytes are unknown despite the fact that the astrocytic CREB is also activity-driven and neuroprotective. Herein we identified the transcriptional programs regulated by CREB in astrocytes as compared to neurons using, as study materials, transcriptome databases of astrocyte exposed to well-known activators of CREB-dependent transcription as well as publicly available transcriptomes of neuronal cultures. Functional CREB signatures were extracted from the transcriptomes using Gene Ontology, adult-brain gene lists generated by Translating Ribosome Affinity Purification (TRAP) and CREB-target gene repositories. We found minimal overlap between CREB signatures in astrocytes and neurons. In astrocytes, the top triad of functions regulated by CREB consists of 'Gene expression', 'Mitochondria', and 'Signalling', while in neurons it is 'Neurotransmission', 'Signalling' and 'Gene expression', the latter two being represented by different genes from those in astrocytes. The newly generated databases will provide a tool to explore novel means whereby CREB impinges on brain functions requiring adaptive, long-lasting changes by coordinating transcriptional cascades in astrocytes.


Renal cell carcinoma (RCC): fatter is better? A review on the role of obesity in RCC.
Obesity represents a well-known risk factor for renal cell carcinoma development. Several studies evaluated the relationship between obesity and outcome in patients with non-metastatic and metastatic renal cell carcinoma using different parameters such as BMI, visceral fat area and s.c. fat area. These studies suggest that obesity is associated with a better prognosis in renal cell carcinoma patients. This phenomenon is called obesity paradox and it was found in other diseases in which obesity represents an established risk factor such as heart failure, diabetes, atrial fibrillation, hypertension and coronary heart disease. The purpose of this review is to analyze the mechanisms by which obesity increases the risk of renal cell carcinoma development, to describe the evidence available to date about the link obesity-outcome and to evaluate the mechanisms to explain this apparently paradoxical relationship.


Steered molecular dynamics simulations for studying protein-ligand interaction in cyclin-dependent kinase 5.
In this study, we applied steered molecular dynamics (SMD) simulations to investigate the unbinding mechanism of nine inhibitors of the enzyme cyclin-dependent kinase 5 (CDK5). The study had two major objectives: (i) to create a correlation between the unbinding force profiles and the inhibition activities of these compounds expressed as IC50 values; (ii) to investigate the unbinding mechanism and to reveal atomistic insights, which could help identify accessory binding sites and transient interactions. Overall, we carried out 1.35 μs of cumulative SMD simulations. We showed that SMD could qualitatively discriminate binders from nonbinders, while it failed to properly rank series of inhibitors, particularly when IC50 values were too similar. From a mechanistic standpoint, SMD provided useful insights related to transient and dynamical interactions, which could complement static description obtained by X-ray crystallography experiments. In conclusion, the present study represents a further step toward a systematic exploitation of SMD and other dynamical approaches in structure-based drug design and computational medicinal chemistry.


The red rubber sump.
This is a simple technique for sump drainage of a solitary hepatic abscess which will remain patent as the abscess heals. Because of its simplicity, this technique is applicable for many surgical problems requiring sump drainage.


Directed evolution of Zymomonas mobilis sugar facilitator Glf to overcome glucose inhibition.
Cellular import of D-xylose, the second most abundant sugar in typical lignocellulosic biomass, has been evidenced to be an energy-depriving process in bacterial biocatalysts. The sugar facilitator of Zymomonas mobilis, Glf, is capable of importing xylose at high rates without extra energy input, but is inhibited by D-glucose (the primary biomass sugar), potentially limiting the utility of this transporter for fermentation of sugar mixtures derived from lignocellulose. In this work we developed an Escherichia coli platform strain deficient in glucose and xylose transport to facilitate directed evolution of Glf to overcome glucose inhibition. Using this platform, we isolated nine Glf variants created by both random and site-saturation mutagenesis with increased xylose utilization rates ranging from 4.8-fold to 13-fold relative to wild-type Glf when fermenting 100 g l-1 glucose-xylose mixtures. Diverse point mutations such as A165M and L445I were discovered leading to released glucose inhibition. Most of these mutations likely alter sugar coordinating pocket for the 6-hydroxymethyl group of D-glucose. These discovered glucose-resistant Glf variants can be potentially used as energy-conservative alternatives to the native sugar transport systems of bacterial biocatalysts for fermentation of lignocellulose-derived sugars.


Decision analysis to support wastewater management in coral reef priority area.
A cocktail of land-based sources of pollution threatens coral reef ecosystems, and addressing these has become a key management and policy challenge in the State of Hawai'i, other US territories, and globally. In West Maui, Hawai'i, nearly one quarter of all living corals were lost between 1995 and 2008. Onsite disposal systems (OSDS) for sewage leak contaminants into drinking water sources and nearshore waters. In recognition of this risk, the Hawai'i State Department of Health (DOH) is prioritizing areas for cesspool upgrades. Independently, we applied a decision analysis process to identify priority areas to address sewage pollution from OSDS in West Maui, with the objective of reducing nearshore coral reef exposure to pollution. The decision science approach is relevant to a broader context of coastal areas both statewide and worldwide which are struggling with identifying pollution mitigation actions on limited budgets.


Discrimination-related stress, blood pressure and epstein-barr virus antibodies among latin american immigrants in Oregon, us.
Perceived discrimination has been linked to poor health outcomes among ethnic and racial minorities in the United States, though the relationship of discrimination-related stress to immigrant health is not well understood. This article reports findings from a preliminary study that examined blood pressure and Epstein-Barr virus antibody levels in relation to self-reported indicators of stress, acculturation and social support among 79 adult immigrant Latino farm workers in Oregon, US. Findings show that increases in discrimination-related stress predicted elevated systolic blood pressure (SBP) and Epstein-Barr virus antibody levels among male participants. Though female participants reported similar levels of discrimination stress, this perceived stress was not reflected in biological measures. Among women, greater English language engagement was linked to higher SBP, and more years in the US was associated with higher diastolic blood pressure. Study results suggest that male and female immigrants' physiological responses to stress may be influenced in distinctive ways by processes of adjustment to life in the US. If replicated, the finding that discrimination stress predicts elevated SBP may have clinical and public health implications given that elevated SBP is an established risk factor for cardiovascular disease.


An evolutionary model for protein-coding regions with conserved RNA structure.
Here we present a model of nucleotide substitution in protein-coding regions that also encode the formation of conserved RNA structures. In such regions, apparent evolutionary context dependencies exist, both between nucleotides occupying the same codon and between nucleotides forming a base pair in the RNA structure. The overlap of these fundamental dependencies is sufficient to cause "contagious" context dependencies which cascade across many nucleotide sites. Such large-scale dependencies challenge the use of traditional phylogenetic models in evolutionary inference because they explicitly assume evolutionary independence between short nucleotide tuples. In our model we address this by replacing context dependencies within codons by annotation-specific heterogeneity in the substitution process. Through a general procedure, we fragment the alignment into sets of short nucleotide tuples based on both the protein coding and the structural annotation. These individual tuples are assumed to evolve independently, and the different tuple sets are assigned different annotation-specific substitution models shared between their members. This allows us to build a composite model of the substitution process from components of traditional phylogenetic models. We applied this to a data set of full-genome sequences from the hepatitis C virus where five RNA structures are mapped within the coding region. This allowed us to partition the effects of selection on different structural elements and to test various hypotheses concerning the relation of these effects. Of particular interest, we found evidence of a functional role of loop and bulge regions, as these were shown to evolve according to a different and more constrained selective regime than the nonpairing regions outside the RNA structures. Other potential applications of the model include comparative RNA structure prediction in coding regions and RNA virus phylogenetics.


AIDS-related discrimination in Asia.
The Asia Pacific Network of People Living with HIV/AIDS (APN+) conducted the first regional documentation of AIDS-related discrimination in Asia. This project was an action-based, peer-implemented study that aimed to develop an understanding of the nature, pattern and extent of AIDS-related discrimination in several Asian countries. Trained HIV-positive people interviewed 764 positive people in four countries (India 302; Indonesia 42; Thailand 338; the Philippines 82) using a structured questionnaire. Findings indicate that the major area of discrimination in each country is within the health sector, where over half of those surveyed experienced some form of discrimination. In all countries, the majority of people did not receive pre-test counselling before being tested for HIV. People who reported coerced testing were significantly more likely than other respondents to face subsequent AIDS-related discrimination. A considerable number of respondents were refused treatment after being diagnosed with HIV and many experienced delayed provision of treatment or health services. Breaches of confidentiality by health workers were common. Within the family and the community, women were significantly more likely to experience discrimination than men, including ridicule and harassment, physical assault and being forced to change their place of residence because of their HIV status. These findings have serious implications, particularly in light of the increasing trend in many countries to test all pregnant women in order to prevent transmission of HIV to their unborn children.


The value of (18)F-FDG PET/CT in the assessment of active idiopathic retroperitoneal fibrosis.
The different stages in idiopathic retroperitoneal fibrosis (IRF) are generally assessed by assay of inflammatory markers and analysis of contrast-enhanced CT images of the retroperitoneal mass. We investigated the potential role of (18)F-FDG PET/CT in this clinical setting. (18)F-FDG uptake was assessed visually and semiquantitatively (using maximum standardized uptake values, SUVmax) in images of the abdominal mass in 22 patients prospectively enrolled from June 2008 to December 2010 who underwent a total of 33 PET/CT studies. The accuracy in discriminating active from inactive disease was calculated assuming as reference a biochemical instrumental evaluation of patients with IRF mostly based on the level of inflammatory indices and contrast enhancement (CE) of the mass at the time of each PET study. In particular, the relationship between SUVmax and CE, the latter calculated from the change in radiodensity (Hounsfield units) between the basal and postcontrast venous portal phases, was evaluated on a three-point scale (0 <20 HU, 1 20-30 HU, 2 ≥ 30 HU). SUVmax and CE scores were correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. The value of PET/CT in assessing the variation of disease activity over time was also investigated by analysing the changes in metabolic volume (MV) of the retroperitoneal lesion between repeat patient studies. PET/CT accurately discriminated (93.9 %) active from inactive disease. Significant agreement (p < 0.01) was observed between visual and semiquantitative analysis of (18)F-FDG uptake, and CE score. A significant correlation (p < 0.01) was found among SUVmax, CRP levels (rho = 0.54) and ESR (rho = 0.55). Corresponding variations in MV and CE score were observed in patients with multiple studies (p < 0.01; rho = 0.68). (18)F-FDG PET/CT may be considered an alternative imaging method for the assessment of different stages of IRF.


Risk of Ischemic Stroke in Patients With Non-Valvular Atrial Fibrillation Not Receiving Oral Anticoagulants - Korean Nationwide Population-Based Study.
Atrial fibrillation, the most common cardiac arrhythmia, is associated with an elevated thromboembolic risk, including ischemic stroke. Guidelines recommend the stratification of individual stroke risk and tailored antithrombotic therapy. This study investigated the demographics, comorbidities, and prognosis of non-valvular AF (NVAF) in Korean patients.Methods and Results:We extracted data on 10,846 patients with newly diagnosed NVAF who were naïve to oral anticoagulants from the National Health Insurance Service-National Sample Cohort. CHADS2and CHA2DS2-VASc scores were calculated for each subject using claims data. The study endpoints were ischemic stroke, thromboembolism, and mortality. Mean age was 63.7 years, and 46.8% of the patients were women. Women were older and had higher CHADS2and CHA2DS2-VASc scores. During 30,138 person-years of follow-up, ischemic stroke occurred at a rate of 2.95/100 person-years. CHADS2and CHA2DS2-VASc scores showed good performance in risk prediction. CHA2DS2-VASc score performed better at discriminating stroke risk in patients with low-risk profiles. The presence of female sex and vascular disease added little improvement in risk prediction. Korean NVAF patients had high risk of stroke and mortality, and had multiple comorbidities. While both CHADS2and CHA2DS2-VASc schema had good performance in risk prediction, CHA2DS2-VASc score was superior in identifying truly low-risk patients. Given that Asian ethnicity is associated with bleeding events, individualized accurate risk prediction is necessary to improve patient outcomes.


Comparison of Training Intensity Patterns for Cardiorespiratory, Speed, and Strength Exercise Programs.
Vetter, RE, Yu, H, Foose, AK, Adam, PJ, and Dodd, RK. Comparison of training intensity patterns for cardiorespiratory, speed, and strength exercise programs. J Strength Cond Res 31(12): 3372-3395, 2017-Designing effective exercise training programs is important for novice, regular, and elite individuals desiring improvements in physical fitness and performance outcomes without experiencing deleterious physiological or performance effects. The purpose of this research was to understand the impact of training intensity on the effectiveness of training program outcomes. Synthesized analyses of 31 studies provided an overall magnitude for the impact of training program intensity on effect size (ES). Meta-analyses were performed using meta-regression models to assess the impact of training program intensity and the other moderators of training frequency, training weeks, age, ability level, and type of physical exercise training. Inclusion criteria were (a) pretest and posttest outcomes, group size, and mean and SDs were given, (b) only human participants, age 17 or older, and healthy being free of disease, injury, or pregnancy, (c) no supplements or dietary interventions were used, (d) a minimum 4-week training intervention was used, and (e) training protocols included training intensity as its focus. Of the research reviewed, there were 31 studies representing 292 cases used to calculate ES, which met the inclusion criteria. Training frequency, training weeks, age, and ability level did not consistently affect the effectiveness of the different training programs. Intensity level influenced ES across the types of physical training programs: cardiorespiratory, muscular strength, or speed. An aggregated model had a curvilinear effect on training programs with an estimated critical average value of 74%. Muscular strength training using intensities greater than estimated 87.29% resulted in diminishing returns.


Celebrities' impact on health-related knowledge, attitudes, behaviors, and status outcomes: protocol for a systematic review, meta-analysis, and meta-regression analysis.
Celebrities are highly influential people whose actions and decisions are watched and often emulated by wide audiences. Many celebrities have used their prominent social standing to offer medical advice or endorse health products, a trend that is expected to increase. However, the extent of the impact that celebrities have in shaping the public's health-related knowledge, attitudes, behaviors, and status is unclear. This systematic review seeks to answer the following questions: (1) Which health-related outcomes are influenced by celebrities? (2) How large of an impact do celebrities actually have on these health-related outcomes? (3) Under what circumstances do celebrities produce either beneficial or harmful impacts? Ten databases were searched, including MEDLINE, EMBASE, PsycINFO, PubMed, CINAHL, Communication Complete, Sociological Abstracts, Social Sciences Citation Index, Journals @ Scholars Portal, and ProQuest Dissertations & Theses A&I. Two reviewers conducted title and abstract screening and full-text screening to identify primary studies that employed empirical methods (either quantitative or qualitative) to examine celebrities' impact on health-related knowledge, attitudes, behaviors, or status outcomes. The results of this review will contribute to our understanding of celebrity influences and how to design positive evidence-based celebrity health promotion activities. In addition, these findings can help inform the development of media reporting guidelines pertaining to celebrity health news and provide guidance to public health authorities on whether and how to respond to or work with celebrities. PROSPERO CRD42015019268.


Scatter correction for cone-beam computed tomography using moving blocker strips: a preliminary study.
One well-recognized challenge of cone-beam computed tomography (CBCT) is the presence of scatter contamination within the projection images. Scatter degrades the CBCT image quality by decreasing the contrast, introducing shading artifacts, and leading to inaccuracies in the reconstructed CT number. The authors propose a blocker-based approach to simultaneously estimate scatter signal and reconstruct the complete volume within the field of view (FOV) from a single CBCT scan. A physical strip attenuator (i.e., "blocker"), consisting of lead strips, is inserted between the x-ray source and the patient. The blocker moves back and forth along the z-axis during the gantry rotation. With such a design, the data required for the filtering step of the Feldkamp-Davis-Kress (FDK) algorithm are complete in the unblocked region and the entire volume within the FOV has the measurements at different projection views. The two-dimensional scatter fluence is estimated by interpolating the signal from the blocked regions. A modified FDK algorithm and an iterative reconstruction based on the constraint optimization are used to reconstruct CBCT images from unblocked projection data after the scatter signal is subtracted. A simulation study and an experimental study are performed to evaluate the performance of the proposed scatter correction scheme. The scatter-induced shading/cupping artifacts are substantially reduced in CBCT using the proposed strategy. In the simulation study, the mean relative error is reduced from 25% to 3% and 2% in the images reconstructed by the modified FDK and constraint optimization, respectively. In the experimental study using a CatPhan 600 phantom, CT number errors in the selected regions of interest are reduced from 256 to less than 20. An effective scatter correction scheme is proposed for CBCT. A moving blocker consisting of lead strips is inserted between the x-ray source and the patient during CBCT acquisition. The proposed method allows the authors to simultaneously estimate the scatter signal in projection data, reduce the imaging dose, and obtain complete volumetric information within the FOV.


[When does nicotine dependence begin?].
Tobacco use leads in short time to nicotine dependence. Mechanisms of this process remain still not quite understood, of importance is also a question: When does nicotine dependence begin? The present review reports commonly used definition of nicotine dependence (according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and International Statistical Classification of Diseases and Health Related Problems Tenth Revision), as well as its limited value in detecting first symptoms of this process. The review presents also the concept, which links the beginning of dependence with diminished autonomy (i.e., autonomy theory), results of studies supporting this concept, and neurophysiologic model of sensitization-homeostasis for nicotine dependence development. Further, despite phenomenon of sensitization has not been demonstrated in humans, results of animal studies arguing for sensitization-homeostasis theory are presented in the article. Usefulness of the Hooked on Nicotine Checklist in diagnosing first nicotine dependence symptoms in adolescents is also pointed out.


Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study.
This phase 3, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Patients (n = 344) with lymphoma or myeloma received darbepoetin alfa 2.25 microg/kg or placebo s.c., once weekly for 12 weeks. The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group (60%) than in the placebo group (18%) (P < 0.001), regardless of baseline endogenous erythropoietin level. However, increased responsiveness was observed in patients with lower baseline erythropoietin levels. Darbepoetin alfa also resulted in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase (1.80 g/dl vs 0.19 g/dl) and after 12 weeks of treatment (2.66 g/dl vs 0.69 g/dl). A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group (P < 0.001). The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma. Improvements in quality of life were also observed with darbepoetin alfa. The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population. Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy.


Drosophila Nek2 protein kinase knockdown leads to centrosome maturation defects while overexpression causes centrosome fragmentation and cytokinesis failure.
The Nima-related kinase 2 (Nek2) has been implicated in the regulation of centrosome integrity and separation in several species and is a candidate for cell transformation. We now show that reduction of levels of the Drosophila Nek2 by RNAi in cultured cells leads to both dispersal of centrosomal antigens and formation of ectopic bodies of centrosomal antigens. Overexpression of the active DmNek2 kinase resulted in an increase in the number of mitotic cells with fragmented centrosomes. The DmNek2 protein kinase is associated with punctuate bodies within the centrosome consistent with its presence on centrioles. In addition, it is present at lower levels on the midbody during cytokinesis. Midbody association was enhanced following overexpression, whereupon the DmNek2 protein kinase also localised to the cell cortex becoming concentrated in the region of the cleavage furrow in late telophase. Many of such cells showed abnormalities in the organisation of anillin and actin in the cleavage furrow that was associated with formation of ectopic membrane protrusions between each daughter cell. We discuss potential roles for DmNek2 in maintaining centrosome integrity in mitosis, during cytokinesis, and consequently for the fidelity of chromosome segregation.


Side Deposit with Regular Texture Food for Clinical Cases In-Home.
Objective Research has shown effectiveness of nonremoval of the spoon and physical guidance in increasing consumption and decreasing inappropriate mealtime behavior. The side deposit has been used to treat passive refusal in 2 studies (1 in a highly specialized hospital setting) using lower manipulated-texture foods on an infant gum brush. Methods We extended the literature by using regular texture bites of food with a finger prompt and side deposit (placing bites inside the side of the child's mouth via the cheek) in an intensive home-based program setting in Australia, demonstrating that attention and tangible treatments alone were ineffective prior, fading the tangible treatment, showing caregiver training, and following up. 2 male children with autism spectrum disorder (with texture/variety selectivity; one with liquid dependence) participated in their homes. We used a reversal design to replicate effectiveness of the side deposit added to a treatment package. Results For both participants, we observed a >98% decrease in latency to acceptance, a 100% decrease in inappropriate mealtime behavior, and a 100% increase in consumption with the side deposit added. Variety was increased to over 85 regular texture foods. 100% of admission goals were met. Caregivers were trained to high procedural integrity and the protocol was generalized to school and the community. Gains maintained to 3 and 1.5 years. Conclusion This is important work in adding to the literature and support for the side deposit and expanding to regular texture, as well as replicating and extending empirically supported treatments for feeding internationally to the home setting.


Resolving the molecular mechanisms of radiation tumorigenesis: past problems and future prospects.
Major goals in experimental radiobiology continue to be the resolution of the fundamental mechanisms of cellular radiation response and to gain detailed understanding of the contribution made by these responses to the complex in vivo processes of tumor development. The coupling of this framework of fundamental knowledge to epidemiological measures of risk greatly strengthens the biological basis of radiological protection. A selective overview is provided of recent advances in the understanding of the mechanisms and genetics of radiation tumorigenesis and their possible implications. It is suggested that rapid technical and academic advances in biology greatly expand the opportunities to further refine scientific knowledge on tumor risk after radiation.


Elderberry (Sambucus nigra L.) Fruit Extract Alleviates Oxidative Stress, Insulin Resistance, and Inflammation in Hypertrophied 3T3-L1 Adipocytes and Activated RAW 264.7 Macrophages.
Oxidative stress and inflammation in hypertrophied adipose tissue with excessive fat accumulation play a crucial role in the development of obesity and accompanying metabolic dysfunctions. This study demonstrated the capacity of elderberry fruit (EDB) extract to decrease the elevated production of reactive oxygen species in hypertrophied 3T3-L1 adipocytes. Treatment with the EDB extract resulted in modulation of mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression of leptin and adiponectin was, respectively, down- and up-regulated. Moreover, glucose uptake stimulation was noticed in mature adipocytes, both sensitive to insulin and insulin resistant. This may suggest a positive effect of EDB extract on insulin resistance status. The extract was also found to alleviate the inflammatory response in activated RAW 264.7 macrophages by down-regulating the expression of proinflammatory genes (TNF-α, IL-6, COX-2, iNOS) and suppressing the enhanced production of inflammatory mediators (TNF-α, IL-6, PGE2, NO). In vitro experiments showed that the EDB extract could inhibit digestive enzymes, including α-amylase, α-glucosidase, and pancreatic lipase, leading to reduced intestinal absorption of dietary lipids and carbohydrates. Further in vivo studies could be postulated to support EDB as a functional food component for the prevention and treatment of obesity and metabolic-immune comorbidities.


Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age.
Background and Purpose: White matter hyperintensities (WMH) are commonly seen on structural MRI of older adults and are a manifestation of underlying and adjacent tissue damage. WMH may contribute to cortical disconnection and cognitive dysfunction, but it is unclear how WMH affect intersecting or nearby white matter tract integrity. This study investigated the effects of WMH on tract microstructure by determining the spatial distribution of water diffusion characteristics in white matter tract areas adjacent to both intersecting and nearby WMH. Methods: We used diffusion and structural MRI data from 52 representative participants from the Lothian Birth Cohort 1936 (72.2 ± 0.7 years) including a range of WMH burden. We segmented WMH, reconstructed 18 main white mater tracts using automated quantitative tractography and identified intersections between tracts and WMH. We measured mean diffusivity (MD) and fractional anisotropy (FA) in tract tissue at 2 mm incremental distances from tract-intersecting and non-intersecting (nearby) WMH. Results: We observed a spatial gradient of FA and MD abnormalities for most white matter tracts which diminished with a similar distance pattern for tract-intersecting and nearby WMH. Overall, FA was higher, while MD was lower around nearby WMH compared with tract-intersecting WMH. However, for some tracts, FA was lower in areas immediately surrounding nearby WMH, although with faster normalization than in FA values surrounding tract-intersecting WMH. Conclusion: WMH have similar effects on tract infrastructure, whether they be intersecting or nearby. However, the observed differences in tract water diffusion properties around WMH suggest that degenerative processes in small vessel disease may propagate further along the tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. Longitudinal studies should address differential effects of intersecting vs. nearby WMH progression and how they contribute to cognitive aging.


In vitro production of beta 2 microglobulin by human myeloma cells.
Serum beta 2 microglobulin (B2M) has recently been shown to be a powerful, although nonspecific, marker of multiple myeloma (MM) disease activity. Since the nature of cells producing high levels of B2M remains obscure in MM, we measured (in vitro) the spontaneous secretion of free B2M in 58 culture samples from 52 patients with MM. In comparison with samples from normal individuals and from individuals with monoclonal gammopathy of unknown significance, an abnormal secretion of B2M was found in 83% of samples containing myeloma cells. Levels of secretion significantly correlated with the percentage of tumor cells, tumor progression, and moreover, with the immunoglobulin type of the tumor. The highest levels of secretion were noted in IgG and IgA MM. Our present results would favor the hypothesis of a direct secretion of B2M by myeloma cells and emphasize the interest of B2M as a marker in a majority of (but not all) patients with MM.


Phase-dependent Andreev molecules and superconducting gap closing in coherently-coupled Josephson junctions.
The Josephson junction (JJ) is an essential element of superconducting (SC) devices for both fundamental and applied physics. The short-range coherent coupling of two adjacent JJs forms Andreev molecule states (AMSs), which provide a new ingredient to engineer exotic SC phenomena such as topological SC states and Andreev qubits. Here we provide tunneling spectroscopy measurements on a device consisting of two electrically controllable planar JJs sharing a single SC electrode. We discover that Andreev spectra in the coupled JJ are highly modulated from those in the single JJs and possess phase-dependent AMS features reproduced in our numerical calculation. Notably, the SC gap closing due to the AMS formation is experimentally observed. Our results help in understanding SC transport derived from the AMS and promoting the use of AMS physics to engineer topological SC states and quantum information devices.


Monoclonal antibodies to TEM-1 plasmid-mediated beta-lactamase.
At least 28 plasmid-mediated beta-lactamases have been described in gram-negative bacteria. To assess the relationship among these enzymes, we produced and characterized 28 murine monoclonal antibodies to the TEM-1 plasmid-mediated beta-lactamase. Radial immunodiffusion identified 3 monoclonal antibodies as immunoglobulin M (IgM), 18 as subclass IgG1, 2 as IgG2a, and 5 as IgG2b. Using a newly described enzyme immunoassay, cross-reactivity of 16 of these monoclonal antibodies was tested against 24 plasmid-determined beta-lactamases. The 16 monoclonal antibodies cross-reacted with TEM-2 and TLE-1 and, to a certain extent, SHV-1. Different levels of cross-reactivity were also observed with OXA-3 (11 of 16), OXA-7 (8 of 16), OXA-1 (2 of 16), OXA-6 (2 of 16), and AER-1 (2 of 16). Six monoclonal antibodies demonstrated partial neutralization of beta-lactamase activity. This study suggests that common epitopes are shared by nine biochemically distinct plasmid-mediated beta-lactamases. On the basis of cross-reactivities with these monoclonal antibodies, we identified four epitopes on TEM-1, TEM-2, TLE-1, and SHV-1 beta-lactamases.


Hymenolepsis diminuta: mucosal mastocytosis and intestinal smooth muscle hypertrophy occur in tapeworm-infected rats.
The mechanisms mediating motility changes during noninvasive tapeworm infection have not been characterized. In contrast, host intestinal motility changes during invasive nematode infection are mediated by mucosal mast cells (MMC). The purpose of this study was to examine and the correlate onset of myoelectric alterations 8 days after initial tapeworm infection with changes in intestinal morphology, MMC numbers, and MMC secretory activity. Segments of the small intestine, the tapeworms normal habitat, along with stomach, colon, and bladder were taken from tapeworm-infected and control rats. Tissues were fixed and stained to identify MMC and for morphologic measurement. Tapeworm-infected and uninfected rats with chronically implanted intestinal electrodes were treated with ketotifen, a mast cell stabilizer, and in vivo myoelectric activity monitored. In tapeworm-infected rats, the muscularis externa, on day 20 postinfection, and crypts of Lieberkuhn, on day 26 postinfection, from the entire small intestine appeared thickened or deeper, respectively. Increased muscularis thickness was due to smooth muscle hypertrophy in both the circular and the longitudinal muscle layers. Mucosal mastocytosis was first observed on day 26 postinfection and occurred only in the ileum of tapeworm-infected rats. Pharmacologic stabilization of mast cells with ketotifen did not prevent onset of enteric myoelectric alterations during tapeworm infection. Stomach, colon, and bladder MMC numbers and tissue dimensions were not different between Hymenolepis diminuta-infected rats and uninfected controls. Initiation of myoelectric alterations 8 days after infection precedes and may be a contributing factor to the onset of both smooth muscle hypertrophy and mucosal mastocytosis. Taken together, our data indicate that mast cells are not an initiating factor nor chronic stimulus maintaining intestinal myoelectric alterations during H. diminuta infection.


The temporal stability of visuomotor adaptation generalization.
Movement adaptation in response to systematic motor perturbations exhibits distinct spatial and temporal properties. These characteristics are typically studied in isolation, leaving the interaction largely unknown. Here we examined how the temporal decay of visuomotor adaptation influences the spatial generalization of the motor recalibration. First, we quantified the extent to which adaptation decayed over time. Subjects reached to a peripheral target, and a rotation was applied to the visual feedback of the unseen motion. The retention of this adaptation over different delays (0-120 s) 1) decreased by 29.0 ± 6.8% at the longest delay and 2) was represented by a simple exponential, with a time constant of 22.5 ± 5.6 s. On the basis of this relationship we simulated how the spatial generalization of adaptation would change with delay. To test this directly, we trained additional subjects with the same perturbation and assessed transfer to 19 different locations (spaced 15° apart, symmetric around the trained location) and examined three delays (~4, 12, and 25 s). Consistent with the simulation, we found that generalization around the trained direction (±15°) significantly decreased with delay and distance, while locations >60° displayed near-constant spatiotemporal transfer. Intermediate distances (30° and 45°) showed a difference in transfer across space, but this amount was approximately constant across time. Interestingly, the decay at the trained direction was faster than that based purely on time, suggesting that the spatial transfer of adaptation is modified by concurrent passive (time dependent) and active (movement dependent) processes.NEW & NOTEWORTHY Short-term motor adaptation exhibits distinct spatial and temporal characteristics. Here we investigated the interaction of these features, utilizing a simple motor adaptation paradigm (recalibration of reaching arm movements in response to rotated visual feedback). We examined the changes in the spatial generalization of motor adaptation for different temporal manipulations and report that the spatiotemporal generalization of motor adaptation is generally local and is influenced by both passive (time dependent) and active (movement dependent) learning processes.


Long-term prognosis of patients with life-threatening ventricular arrhythmias induced by coronary artery spasm.
Coronary artery spasm (CAS) is associated with ventricular arrhythmias (VA). Much controversy remains regarding the best therapeutic interventions for this specific patient subset. We aimed to evaluate the clinical outcomes of patients with a history of life-threatening VA due to CAS with various medical interventions, as well as the need for ICD placement in the setting of optimal medical therapy. A multicentre European retrospective survey of patients with VA in the setting of CAS was aggregated and relevant clinical and demographic data was analysed. Forty-nine appropriate patients were identified: 43 (87.8%) presented with VF and 6 (12.2%) with rapid VT. ICD implantation was performed in 44 (89.8%). During follow-up [59 (17-117) months], appropriate ICD shocks were documented in 12. In 8/12 (66.6%) no more ICD therapies were recorded after optimizing calcium channel blocker (CCB) therapy. SCD occurred in one patient without ICD. Treatment with beta-blockers was predictive of appropriate device discharge. Conversely, non-dihydropyridine CCB therapy was significantly protective against VAs. Patients with life-threatening VAs secondary to CAS are at particularly high-risk for recurrence, especially when insufficient medical therapy is administered. Non-dihydropyridine CCBs are capable of suppressing episodes, whereas beta-blocker treatment is predictive of VAs. Ultimately, in spite of medical intervention, some patients exhibited arrhythmogenic events in the long-term, suggesting that ICD implantation may still be indicated for all.


Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021.
Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID-19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological-based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non-culture methods employing fungal biomarkers in pre-emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first-line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological-based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.


Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission: Fukuoka BMT Group observations and a literature review.
We retrospectively analyzed the outcomes of 26 patients with acute promyelocytic leukemia (APL) in the first CR (CR1) or second CR (CR2), who underwent autologous PBSCT (auto-PBSCT) between 1992 and 2008. All patients received all-trans retinoic acid-based induction therapy. After two courses of consolidation chemotherapy, upfront auto-PBSCT was performed in 20 patients in the CR1. Five patients had a high WBC count of more than 10 × 10(9)/L (high risk), while 15 patients had a count of less than 10 × 10(9)/L (low risk) at initial presentation. In addition, six patients, who were considered as low-risk patients at presentation, had a relapse after three cycles of consolidation and 2 years of maintenance therapy, but gained the molecular remission after re-induction and consolidation, and underwent auto-PBSCT in the CR2. In 26 recipients, engraftment was rapid and no TRM was documented. All 20 patients autotransplanted in CR1 were still in CR at a median of 133 months (73-193 months), and six patients who underwent auto-PBSCT in CR2 were also still in CR at a median of 41 months (2-187 months) without maintenance therapy. PML/RARα chimeric mRNA was undetectable in PBSC or BM samples examined before auto-PBSCT. Despite a small number of cases studied, our retrospective observations suggest that auto-PBSCT may be an effective treatment option to continue durable CR in the treatment of high-risk APL. We review previous reports and discuss the role of autotransplantation in the treatment of APL patients in CR.


Daily respiratory mortality and PM10 pollution in Mexico City: importance of considering place of death.
Significant associations have been reported between particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10) and ozone ambient concentrations, and daily number of deaths from respiratory causes. The aim of the present study was to assess such associations among elderly (> or =65 yrs) residents of Mexico City. Ambient air pollution data were provided by the Metropolitan Monitoring Network. During the study period, the average daily PM10 ranged 23.4-175.3 microg x m(-3), and ozone 1 h daily maximums ranged 39.4-216.7 ppb. Information was compiled on the primary and underlying causes of death. The analyses were conducted separately according to place of death (within or out of a hospital unit) using time-series methodology. The total number of deaths from all respiratory causes and mortality for chronic obstructive pulmonary diseases (COPD) were significantly related to PM10 over different lags: an increase of 10 microg x m(-3) was related to a 2.9% (95% (CI): 0.9-4.9%) increase and to a 4.1% (95% CI: 1.3%-6.9%) increase with a 3-day lag when death occurred out of medical units, respectively. For deaths occurring in medical units, a longer lag and smaller risk estimate was observed. An interactive effect between PM10 and ozone was detected. This study confirms that there is an important impact of PM10 on respiratory morbidity among elderly subjects. It also indicates that accounting for primary and underlying causes of death, and considering place of death may reduce misclassification and provide more accurate estimates of the adverse impact of PM10 on mortality.


Neuropsychological test performance in illiterate subjects.
The purpose of this study was to further analyze the effects of education across different age ranges on neuropsychological test performance. Two different analyses were performed. The first analysis was conducted in order to pinpoint the impact of school attendance on neuropsychological testing. A group of 64 illiterate normal subjects was selected in the Mexican Republic. Their performance was compared with two barely schooled control groups (1-2 and 3-4 years of schooling). The subjects' ages ranged from 16 to 85 years. In the second analysis, the illiterate subjects were further matched by age and sex with individuals with 1 to 4, 5 to 9, and 10 to 19 years of formal education. The Spanish version of the NEUROPSI neuropsychological test battery (Ostrosky, Ardila, & Rosselli, 1997) was used. Results indicated a significant educational effect on most of the tests. Largest educational effect was noted in constructional abilities (copying of a figure), language (comprehension), phonological verbal fluency, and conceptual functions (similarities, calculation abilities, and sequences). Aging effect was noted in visuoperceptual (visual detection) and memory scores. In the first subject sample, it was evident that, despite using such limited educational range (from 0-4 years of formal education), and such a wide age range (from 16-85 years), schooling represented a stronger variable than age. It is proposed that education effect on neuropsychological test performance represents a negatively accelerated curve, tending to a plateau.


Kinetics of responses to tumor antigens and mouse mammary tumor virus in BALB/cCrgl and BALB/cfC3H mice.
Spleen cells from BALB/cCrgl mice responded to murine mammary tumor virus (MuMTV) in cell-mediated immune assays at higher levels than did the spleen cells from the syngeneic BALB/cfC3H mice. Implantation in BALB/cCrgl with a chemically induced mammary tumor and in BALB/cfCrgl mice with spontaneous mammary tumors (SMT) arising in the same strain resulted in sensitization of these animals to the antigens of their tumors. Reactivities peaked 3 weeks after transplantation, whereas no positive reactions could be detected when tumors reached maximum size. A kinetic study with the use of MuMTV antigen(s) showed that the responses of lymphocytes from BALB/cfC3H with SMT followed the same pattern as that obtained with tumor antigens, which indicated that this might be a de novo sensitization. In sharp contrast, a steady type of response to MuMTV was observed with the spleen cells from BALB/cCrgl mice; i.e., the levels of responsiveness to MuMTV did not significantly vary at any stage of tumor development. In vivo studies explored the possible relevance of the in vitro cell-mediated immunity to the host defenses. MuMTV-expressing mammary tumor cells were implanted in BALB/cCrgl and BALB/cfC3H mice. The total incidence of tumors was significantly reduced and a delay occurred in their time of appearance in BALB/cCrgl mice in relation to BALB/cfC3H animals. Thus the in vitro reactivity to MuMTV antigen(s) in BALB/cCrgl mice was found to be coincidental with a degree of protection against the development of MuMTV-expressing mammary tumors.


Ultrasonic sludge treatment for enhanced anaerobic digestion.
Ultrasound is the term used to describe sound energy at frequencies above 20 kHz. High-powered ultrasound can be applied to a waste stream via purpose-designed tools in order to induce cavitation. This effect results in the rupture of cellular material and reduction of particle size in the waste stream, making the cells more amenable to downstream processing. sonix is a new technology utilising high-powered, concentrated ultrasound for conditioning sludges prior to further treatment. This paper presents recent results from a number of demonstration and full-scale plants treating thickened waste activated sludge (TWAS) prior to anaerobic digestion, therefore enhancing the process. The present studies have proved that the use of ultrasound to enhance anaerobic digestion can be achieved at full scale and effectively result in the TWAS (typically difficult to digest) behaving, after sonication, as if it were a "primary" sludge. The technology presents benefits in terms of increased biogas production, better solids reduction, improved dewatering characteristics of the digested sludge mixture and relatively short payback periods of two years or less subject to the site conditions and practices applicable at that time.


Defining severity of personality disorder using electronic health records: short report.
Severity of personality disorder is an important determinant of future health. However, this key prognostic variable is not captured in routine clinical practice. Using a large clinical data-set, we explored the predictive validity of items from the Health of Nation Outcome Scales (HoNOS) as potential indicators of personality disorder severity. For 6912 patients with a personality disorder diagnosis, we examined associations between HoNOS items relating to core personality disorder symptoms (self-harm, difficulty in interpersonal relationships, performance of occupational and social roles, and agitation and aggression) and future health service use. Compared with those with no self-harm problem, the total healthcare cost was 2.74 times higher (95% CI 1.66-4.52; P < 0.001) for individuals with severe to very severe self-harm problems. Other HoNOS items did not demonstrate clear patterns of association with service costs. Self-harm may be a robust indicator of the severity of personality disorder, but further replication work is required.


[Clinical basis for a differentiated approach to psychopathic personality adaptation].
In the process of compensation of psychopathy there is a complex reformation of its structure due to the development of secondary compensatory personality changes on the background of primary pathocharacteriological personality traits. However, each form of psychopathy maintains its specific clinical symptoms which should be taken into consideration in a goal-directed formation of conditions, facilitating an adaptation of such patients. Consideration of specific traits in the structure of psychopathy and the reaction of patients to different factors allows one to select conditions where the requirements to the "weak" side of the personality would be reduced, while its relatively "strong" sides were applied productively.


Automated learning of generative models for subcellular location: building blocks for systems biology.
The goal of location proteomics is the systematic and comprehensive study of protein subcellular location. We have previously developed automated, quantitative methods to identify protein subcellular location families, but there have been no effective means of communicating their patterns to integrate them with other information for building cell models. We built generative models of subcellular location that are learned from a collection of images so that they not only represent the pattern, but also capture its variation from cell to cell. Our models contain three components: a nuclear model, a cell shape model and a protein-containing object model. We built models for six patterns that consist primarily of discrete structures. To validate the generated images, we showed that they are recognized with reasonable accuracy by a classifier trained on real images. We also showed that the model parameters themselves can be used as features to discriminate the classes. The models allow the synthesis of images with the expectation that they are drawn from the same underlying statistical distribution as the images used to train them. They can potentially be combined for many proteins to yield a high resolution location map in support of systems biology.


Perceptions of Contraception and Patterns of Switching Contraceptive Methods Among Family-planning Acceptors in West Nusa Tenggara, Indonesia.
The perceptions of family-planning (FP) acceptors regarding contraception influence the reasons for which they choose to switch their method of contraception. The objective of this study was to analyze the perceptions of contraception and rationales for switching contraceptive methods among female FP acceptors in West Nusa Tenggara, Indonesia. This study involved the analysis of secondary data from the Improve Contraceptive Method Mix study, which was conducted in 2013 by the Center for Health Research, University of Indonesia. The design of the study was cross-sectional. We performed 3 stages of sampling using the cluster technique and selected 4819 women who were FP acceptors in West Nusa Tenggara Province, Indonesia as the subjects of this study. The data were analyzed using multiple logistic regression. The predominant pattern of switching contraceptive methods was switching from one non-long-term method of contraception to another. Only 31.0% of the acceptors reported a rational pattern of switching contraceptive methods given their age, number of children, and FP motivations. Perceptions of the side effects of contraceptive methods, the ease of contraceptive use, and the cost of the contraceptives were significantly associated (at the level of α=0.05) with rational patterns of switching contraceptive methods. Perceptions among FP-accepting women were found to play an important role in their patterns of switching contraceptive methods. Hence, fostering a better understanding of contraception through high-quality counseling is needed to improve perceptions and thereby to encourage rational, effective, and efficient contraceptive use.


A brief intervention increases fruit and vegetable intake. A comparison of two intervention sequences.
To evaluate the effectiveness of two subsequent intervention components (motivational and self-regulatory components), placed in different order, to promote fruit and vegetable (FV) intake. After baseline assessment, university students (N=205, aged 18-26 years) were allocated to two groups. One group received a motivational intervention (outcome expectancies, risk perception, and task self-efficacy) followed by a self-regulatory intervention (planning and dietary self-efficacy) after 17 days. The second group received the same intervention conditions in the opposite order. Follow-up assessments were done after another 17 days. Both intervention sequences yielded gains in terms of FV intake and self-efficacy. However, this gain was only due to the self-regulatory component whereas the motivational component did not contribute to the changes. Moreover, changes in intention and self-efficacy mediated between intervention sequence and follow-up behavior, suggesting that improving these proximal predictors of FV intake was responsible for the behavioral gains. Findings highlight the superiority of a self-regulatory intervention over a motivational intervention when it comes to dietary changes in this sample of young adults. Moreover, changes in dietary self-efficacy may drive nutritional changes.


Analysis of intraluminal impedance measurements.
Intraluminal impedance is an emerging technique to monitor the esophagus so that the occurrence of gastroesophageal reflux episodes can be observed. The impedance traces of the esophagus have wide variations which correspond to the occurrence of activities such as swallow or reflux that cause the impedance to change. This paper presents a technique to detect and classify reflux episodes from intraluminal impedance. Evaluation of the technique based on 660 h of combined data from 30 patients showed that the proposed methodology can detect episodes in the esophagus to a sensitivity of 89% with positive predictivity of 83%.


Lipoprotein(a) and inflammation in patients with atrial fibrillation after electrical cardioversion.
Recently few studies tried to confirm the association between AF and lipoprotein(a) (Lp(a)), however the results remained conflicted. In present study we evaluated the possible interaction between Lp(a), inflammatory state and echocardiographic characteristics in patients after successful electrical cardioversion (EC) of persistent AF. We also tried to investigate the role of Lp(a) as a possible prognostic factor for AF recurrence after successful EC. Data of 79 patients admitted due to planned EC was analyzed. After successful procedure patients were monitored for 2 years. For analytical purposes patients were divided in two groups according to AF recurrence. There was no significant difference between Lp(a) levels in both groups. We also didn't find any positive correlation between Lp(a) and CRP levels, as well as between Lp(a) levels and left atrium diameter. For logistic and survival analysis optimal cut-off value of Lp(a)≥0.32 (upper quartile) was used. In logistic regression model with AF recurrence as dependent variable Lp(a) didn't show any statistically significant association with AF recurrence. Survival analysis showed slightly higher AF recurrence rate in group with higher Lp(a) levels but not to the level of statistical significance (log rank test, p=0.62). We weren't able to confirm the association between Lp(a) levels and AF recurrence, inflammation and left atrium diameter in patients after successful EC of persistent AF. Further studies are needed to elucidate the role of Lp(a) in this clinical setting.


Information, motivation, and behavioral skills for early pre-ART engagement in HIV care among patients entering clinical care in KwaZulu-Natal, South Africa.
Little is known regarding factors implicated in early engagement and retention in HIV care among individuals not yet eligible for antiretroviral therapy (pre-ART) in sub-Saharan Africa. Identifying such factors is critical for supporting retention in pre-ART clinical care to ensure timely ART initiation and optimize long-term health outcomes. We assessed patients' pre-ART HIV care-related information, motivation, and behavioral skills among newly diagnosed ART-ineligible patients, initiating care in KwaZulu-Natal, South Africa. The survey was interviewer-administered to eligible patients, who were aged 18 years or older, newly entering care (diagnosed within the last six-months), and ineligible for ART (CD4 count > 200 cells/mm(3)) in one of four primary care clinical sites. Self-reported information, motivation, and behavioral skills specific to retention in pre-ART HIV-care were characterized by categorizing responses into those reflecting potential strengths and those reflective of potential deficits. Information, motivation, and behavioral skills deficits sufficiently prevalent in the overall sample (i.e.,≥30% prevalent) were identified as areas in need of specific attention through intervention efforts adapted to the clinic level. Gender-based differences were also evaluated. A total of 288 patients (75% female) completed structured interviews. Across the sample, eight information, eight motivation, and eight behavioral skills deficit areas were identified as sufficiently prevalent to warrant specific targeted attention. Gender differences did not emerge. The deficits in pre-ART HIV care-related information, motivation, and behavioral skills that were identified suggest that efforts to improve accurate information on immune function and HIV disease are needed, as is accurate information regarding HIV treatment and transmission risk prior to ART initiation. Additional efforts to facilitate the development of social support, including positive interactions with clinic staff and decreasing community-level stigma and to decrease structural and resource-depleting demands of HIV care may be particularly valuable to facilitate retention in pre-ART HIV care.


Sample concentration and purification for point-of-care diagnostics.
The ability to increase the concentration of target analytes in a fixed sample volume can potentially lower the limit of detection for many biosensing techniques, and thus is key in sample preparation for infectious disease diagnosis. Concentration by evaporation is an effective method to achieve target enrichment. However, concentrating human samples, including blood and plasma, by evaporation-based methods is made challenging by high concentrations of proteins and electrolytes. Dehydration of the proteins causes the sample to turn into a gel, hindering further analysis. At the same time, decreasing the volume increases the overall concentration of electrolytes, causing bacterial or viral particle lysis, and making them more difficult to detect in affinity-based biosensors. Thus, we fabricated a microfluidic chip that incorporates both dialysis and concentration in a single design. The chip dialyzes the proteins from the plasma, while maintaining an appropriate concentration of electrolytes and concentrating the sample targets. The process to concentrate plasma or serum samples by a factor of 10 takes less than 30 minutes. As a proof-of-concept, we demonstrated the chip using a defective Human Immunodeficiency Virus (HIV). To distinguish patients on antiretroviral therapy who are failing therapy from those who are not, a diagnostic must be able to detect HIV in plasma down to at least 1000 particles per milliliter. For a number of technical reasons, it is difficult to get on-chip PCR reactions to reach this level of sensitivity, so concentration of HIV from lower viral load samples has the potential to improve the sensitivity of many types of molecular point-of-care viral load tests.