[Choosing of disaggregants for the treatment of patients with instable angina without lifting the ST segment].
The cases study dealt with choosing an individual antiaggregant therapy for patients with instable angina (IA) without lifting the ST segment. Seventy-eight patients with IA, who were treated, apart from routine therapy, by different disaggregants, were examined. The aggregation of platelets was tested on the laser LA 230 "Biola" analyzer, Russia. Aspirin effectively suppressed the adrenalin-induced aggregation of platelets in 20 of 26 patients; cardiomagnil effectively suppressed it in all 17 patients; and plavix reliably reduced the ADP-induced aggregation of platelets. Both types of platelets aggregation were reliably reduced in combined therapy (plavix plus cardiomagnil). Thus, the combined therapy by drugs with different action mechanisms was proven to most effective in patients with IA.


Practice Patterns of Fenestrated Aortic Aneurysm Repair: Nationwide Comparison of Z-Fen Adoption at Academic and Community Centers Since Commercial Availability.
Over the past decade, a number of endovascular approaches have evolved to treat aortic aneurysms with anatomy that is not amenable to traditional endovascular repair, although the optimal practice and referral patterns remain in question. The Zenith fenestrated (Z-Fen) endograft (Cook Medical) represents the first commercially available fenestrated graft product in the United States. We aim to quantify practice patterns in Z-Fen use during the first 5 years of commercial availability, and we identify predictors of high and low uptake. This is a retrospective review of complete order records for Z-Fen endografts since June 2012. We performed univariate and multivariate regressions of predictors that surgeons and centers would be in the top and bottom quartiles of annual Z-Fen use. Since June 15, 2012, 744 surgeons have been trained to use Z-Fen, and 4133 cases have been performed at 409 trained centers. The average annual number of cases per trained surgeon was 4.46 [95% confidence interval (CI), 3.58-5.70]; however, many surgeons performed few or no cases following training, and there was a skew toward users with low average annual volumes (25th percentile 1.23, 50th percentile 2.35, 75th percentile 4.93, and 99th percentile 33.29). Predictors of high annual use in the years following training included academic center (aOR 5.87, P = .001) and training within the first 2 years of availability (aOR 46.23, P < .001). While there is literature supporting the safety and efficacy of Z-Fen, adoption has been relatively slow in an era when the vast majority of vascular surgeons have advanced endovascular skills. Given the training and resources required to use fenestrated or branched aortic endovascular devices, referral patterns should be determined and training should be focused on centers with high expected volumes.


Identification of Genome-Wide Variants and Discovery of Variants Associated with Brassica rapa Clubroot Resistance Gene Rcr1 through Bulked Segregant RNA Sequencing.
Clubroot, caused by Plasmodiophora brassicae, is an important disease on Brassica species worldwide. A clubroot resistance gene, Rcr1, with efficacy against pathotype 3 of P. brassicae, was previously mapped to chromosome A03 of B. rapa in pak choy cultivar "Flower Nabana". In the current study, resistance to pathotypes 2, 5 and 6 was shown to be associated with Rcr1 region on chromosome A03. Bulked segregant RNA sequencing was performed and short read sequences were assembled into 10 chromosomes of the B. rapa reference genome v1.5. For the resistant (R) bulks, a total of 351.8 million (M) sequences, 30,836.5 million bases (Mb) in length, produced 120-fold coverage of the reference genome. For the susceptible (S) bulks, 322.9 M sequences, 28,216.6 Mb in length, produced 109-fold coverage. In total, 776.2 K single nucleotide polymorphisms (SNPs) and 122.2 K insertion / deletion (InDels) in R bulks and 762.8 K SNPs and 118.7 K InDels in S bulks were identified; each chromosome had about 87% SNPs and 13% InDels, with 78% monomorphic and 22% polymorphic variants between the R and S bulks. Polymorphic variants on each chromosome were usually below 23%, but made up 34% of the variants on chromosome A03. There were 35 genes annotated in the Rcr1 target region and variants were identified in 21 genes. The numbers of poly variants differed significantly among the genes. Four out of them encode Toll-Interleukin-1 receptor / nucleotide-binding site / leucine-rich-repeat proteins; Bra019409 and Bra019410 harbored the higher numbers of polymorphic variants, which indicates that they are more likely candidates of Rcr1. Fourteen SNP markers in the target region were genotyped using the Kompetitive Allele Specific PCR method and were confirmed to associate with Rcr1. Selected SNP markers were analyzed with 26 recombinants obtained from a segregating population consisting of 1587 plants, indicating that they were completely linked to Rcr1. Nine SNP markers were used for marker-assisted introgression of Rcr1 into B. napus canola from B. rapa, with 100% accuracy in this study.


Isolation and identification of antimicrobial compound from Mentha longifolia L. leaves grown wild in Iraq.
Mentha longifolia L. (Lamiaceae) leaves have been traditionally implemented in the treatment of minor sore throat and minor mouth or throat irritation by the indigenous people of Iraq, although the compounds responsible for the medicinal properties have not been identified. In the present study, an antimicrobial compound was isolated and characterized, and its biological activity was assessed. The compound was isolated and characterized from the extracted essential oil using different spectral techniques: TLC, FTIR spectra and HPLC. Antimicrobial activity of the compound was assessed using both disc diffusion and microdilution method in 96 multi-well microtiter plates. A known compound was isolated from the essential oil of the plant and was identified as (-) menthol. The isolated compound was investigated for its antimicrobial activity against seven selected pathogenic and non-pathogenic microorganisms: Staphylococcus aureus, Streptococcus mutans, Streptococcus faecalis, Streptococcus pyogenis, Lactobacillus acidophilus, Pseudomonas aeruginosa and the yeast Candida albicans. Menthol at different concentrations (1:1, 1:5, 1:10, 1:20) was active against all tested bacteria except for P. aeruginosa, and the highest inhibitory effect was observed against S. mutans (zone of inhibition: 25.3 mm) using the disc diffusion method. Minimal inhibitory concentration MIC values ranged from 15.6-125.0 microg/ml, and the most promising results were observed against S. aureus and S. mutans (MIC 15.6 microg/ml) while, S. faecalis, S. pyogenis and L. acidophilus ranked next (MIC 31.2 microg/ml). Furthermore, menthol achieved considerable antifungal activity against the yeast C. albicans (zone of inhibition range: 7.1-18.5 mm; MIC: 125.0). The isolation of an antimicrobial compound from M. longifolia leaves validates the use of this plant in the treatment of minor sore throat and minor mouth or throat irritation.


Ergotism and the Salem witch panic: a critical analysis and an alternative conceptualization.
The controversial hypothesis that the Salem witchcraft panic of 1692 resulted from ergot poisoning was recently defended by Mary Matossian. She argued that (a) weather conditions in Salem were conducive to the growth of ergot, (b) new evidence concerning the age distribution of ergot sufferers is consistent with the ages of those who exhibited symptoms at Salem, and (c) the symptoms displayed and reported at Salem were those of convulsive ergotism. Each of these propositions is critically examined and rejected, and the events purportedly explained by the ergot hypothesis are accounted for within a social psychological framework. This perspective views the Salem crisis as a sociopolitical drama played out in terms of the worldview shared by seventeenth-century Puritans. The symptoms of demonic affliction are conceptualized as role enactments learned in and legitimated by the community, rather than as the results of disease.


Health-related research at the American Petroleum Institute.
On behalf of its oil-company members, API has studied the effects of the materials to which people may be exposed and aspects of the effects of the total work environment on employees' health. This chapter sets out the mechanisms by which the research is conducted, illustrates the type of research performed, and describes the availability of the results to those interested in the scientific community.


Getting high for likes: Exploring cannabis-related content on TikTok.
With over 1 billion monthly users globally, a third of whom are under 14 years, TikTok's popularity is indisputable. Publicly available cannabis-related content on this platform may influence perceptions of cannabis use. We aimed to examine how cannabis-related videos are portrayed on TikTok. Data were collected from TikTok using hashtag-based keywords on cannabis-related videos (n = 1377). Seven researchers documented video metrics (i.e. views, likes, comments) and independently coded videos for sentiment and theme. After removing duplicates and non-related content, the final sample contained 881 videos. These videos had a median view count of 518 700 (SD = ±1 082 905), median likes count of 99 900 (SD = ±206 647) and median comment count of 931 (SD = ±2977). Many videos portrayed cannabis use positively (54.14%; collectively viewed 417 million times), with 15.84% of this subset actively depicting cannabis or administration products. The thematic analysis identified seven non-mutually exclusive themes. Content portraying cannabis use as entertaining or humorous accounted for 71.74% of videos, with a further 42.90% discussing personal cannabis use experiences and 24.63% promoting the social and cultural acceptability of cannabis use. Our sample revealed over half of videos portrayed cannabis use positively and none were age restricted. All were publicly accessible through standard web and smartphone applications. With previous research demonstrating that exposure to cannabis-related content can influence adolescents' attitudes and problematic cannabis use, it is important more effective age restrictions and regulations are introduced to social media platforms.


High efficiency radio frequency antennas for amplifier free quantum sensing applications.
Radio frequency (RF) signals are frequently used in emerging quantum applications due to their spin state manipulation capability. Efficient coupling of RF signals into a particular quantum system requires the utilization of carefully designed and fabricated antennas. Nitrogen vacancy (NV) defects in diamond are commonly utilized platforms in quantum sensing experiments with the optically detected magnetic resonance (ODMR) method, where an RF antenna is an essential element. We report on the design and fabrication of high efficiency coplanar RF antennas for quantum sensing applications. Single and double ring coplanar RF antennas were designed with -37 dB experimental return loss at 2.87 GHz, the zero-field splitting frequency of the negatively charged NV defect in diamond. The efficiency of both antennas was demonstrated in magnetic field sensing experiments with NV color centers in diamond. An RF amplifier was not needed, and the 0 dB output of a standard RF signal generator was adequate to run the ODMR experiments due to the high efficiency of the RF antennas.


Cutaneous changes: an initial manifestation of pulmonary Wegener's granulomatosis.
Cutaneous vasculitis can occur as an isolated dermatologic disorder or as manifestation of a potentially life-threatening systemic vasculitis such as Wegener's granulomatosis (WG). The aim of the study was to characterize cutaneous lesions in 66 WG patients (30 female, 36 male) and to assess the viability of skin biopsy the diagnosis of WG. Skin involvement was observed in 21 (32%) WG patients; in 14 (21%) patients as an initial manifestation and in other seven during the diagnosis establishment. Cutaneous lesions included palpable purpura(n=10), subcutaneous nodules(=4), hemorrhagic bullae (n=3), ulcers (n=2), pustules (n=1), pyoderma gangrenosum (n =1). The patient with pulmonary WG can present initially with cutaneous symptoms and positive PR3-ANCA serologic test results. Leukocytoclastic vasculitis (LCV) was the predominant histopathologic pattern.


Induction of interferon gamma in human gingival fibroblasts challenged with phytohaemagglutinin.
Interferon gamma (IFN-gamma) is a potential immunoregulatory cytokine, which is secreted mainly by cells of immune origin. In this study, we examined the capacity of human gingival fibroblasts as non-professional immune cells to express IFN-gamma messenger RNA (mRNA) and to produce the protein. Cultures of fibroblast cells were established from gingival biopsies from three children. The expression of mRNA for IFN-gamma was studied by in situ hybridization, and the level of IFN-gamma was determined by cell-released capturing ELISA. Treatment of the cells with phytohaemagglutinin (PHA) (2.5, 5.0, and 10 microg/ml) increased the number of IFN-gamma mRNA expressing cells and the protein production at 1, 6, and 24 h. Non-stimulated cells did not reveal measurable levels of IFN-gamma mRNA or the protein. The inflammatory cytokines interleukin 1beta (IL-1beta) (100 microg/ml) and tumour necrosis factor alpha (TNFalpha) (10 ng/ml) did not affect IFN-gamma mRNA expression or protein production. Treatment of the cells with 1 microM phorbol 12-myristate-13-acetate (PMA) stimulated IFN-gamma mRNA expression but had no effect on IFN-gamma protein production. We conclude that human gingival fibroblasts not only transcribe IFN-gamma mRNA but also produce the IFN-gamma protein in response to PHA. The finding that human gingival fibroblasts, produce the cytokine IFN-gamma, further support the concept that these cells take an active part in the modulation of the inflammatory and immune response in the periodontal tissue.


[Hernia inguinalis uteri in the male].
Persistent Müllerian duct syndrome (also known as uterine inguinal hernia) is described and two cases are reported. In this rare type of male pseudohermaphroditism there is no disturbance of either primary or secondary external masculinization. Consequently, this anomaly is always diagnosed incidentally, generally at operation for cryptorchidism or inguinal hernia. In addition to bilateral normal testes, these patients possess a uterus with two uterine tubes. The persistence of the internal female genitalia is caused by the insufficiency of the MIF hormone (Müllerian Inhibiting Factor). Early orchiopexy is recommended. Removal of the female internal genitalia is seldom required.


Oxygen in stem cell biology: a critical component of the stem cell niche.
The defining hallmark of stem cells is their ability to self-renew and maintain multipotency. This capacity depends on the balance of complex signals in their microenvironment. Low oxygen tensions (hypoxia) maintain undifferentiated states of embryonic, hematopoietic, mesenchymal, and neural stem cell phenotypes and also influence proliferation and cell-fate commitment. Recent evidence has identified a broader spectrum of stem cells influenced by hypoxia that includes cancer stem cells and induced pluripotent stem cells. These findings have important implications on our understanding of development, disease, and tissue-engineering practices and furthermore elucidate an added dimension of stem cell control within the niche.


[Comparative characteristics of vanadium-containing compounds, possessing insulin-like effects].
The serum glucose concentration, HbAc1, fructoseamine, the activity of AST, ALT, amylase, glycogen content and glucokinase activity in rat hepatocytes were examined in streptozotocin-diabetic rats during long-term orthovanadate and vanadyl sulphate treatment. The improvement of this parameters were demonstrated after oral orthovanadate and vanadyl sulphate administration. However, insulin-mimetic properties of vanadyl sulphate were more marked in comparison with orthovanadate. LD-50 and cytotoxicity analysis in isolated hepatocytes showed that vanadyl sulphate was less toxic than orthovanadate.


Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes.
To determine the effect of 400 IU/day of the antioxidant vitamin E on the susceptibility of plasma LDL and lymphocyte DNA to oxidative damage in type 1 diabetes. We studied 42 patients with type 1 diabetes and 31 age- and sex-matched control subjects in a randomized prospective double-blind placebo-controlled trial by using 400 IU/day of oral vitamin E for 8 weeks. Measurements were made of single-strand breaks in lymphocyte DNA at baseline and after hydrogen peroxide-induced stress (comet assay) and of copper-induced LDL oxidization and plasma antioxidant profiles. Plasma LDL and lymphocyte DNA were more resistant to induced oxidative change in the type 1 diabetes group than in control subjects. Vitamin E supplementation reduced LDL oxidizability in the control subjects but not in the type 1 diabetes group and had no effect on oxidative DNA damage in either group. The type 1 diabetes group had a significantly poorer plasma antioxidant profile with lower mean serum concentrations of alpha-tocopherol and most carotenoids than control subjects. Plasma LDL and lymphocyte DNA appear to be more resistant to oxidative change in type 1 diabetic subjects than in control subjects, and there was no evidence of oxidatively induced DNA or LDL change in type 1 diabetes. This study does not support the hypothesis of oxidative damage in these patients, and a dose of vitamin E (400 IU/day) that reduced LDL oxidative susceptibility in control subjects did not do so in patients with type 1 diabetes.


A national survey of family medicine residency education in geriatric medicine: comparing findings in 2004 to 2001.
We compared findings from this 2004 survey with our 2001 survey to determine progress in family medicine residency programs' efforts to better train residents to care for America's aging population. A survey was mailed and made available on-line to all 470 family medicine residency directors in the United States. The response rate was 71%. Ninety-six percent of family medicine residencies have a required geriatrics curriculum, compared to 92% in 2001. There was a significant increase in the number of required lecture hours in geriatrics in 2004 as compared to 2001. Since 2001, the median number of MD geriatrics faculty per program has nearly doubled from .5 full-time equivalent (FTE) to .9 FTE. Conflicting time demands with other curricula was ranked as the most significant barrier to geriatrics education in both 2004 and 2001. However, in 2001, the attitude of residents was listed as a significant barrier by 32.1% of the program directors as compared to just 3.6% in 2004. Family medicine educators are continuing to improve the training of residents to provide state-of-the-art care for the aging population. Faculty must take advantage of this period of experimentation in residency education to identify best practices for geriatrics education.


Identification and characterization of Escherichia coli DNA helicase II mutants that exhibit increased unwinding efficiency.
Using a combination of both ethyl methanesulfonate and site-directed mutagenesis, we have identified a region in DNA helicase II (UvrD) from Escherichia coli that is required for biological function but lies outside of any of the seven conserved motifs (T. C. Hodgman, Nature 333:22-23, 1988) associated with the superfamily of proteins of which it is a member. Located between amino acids 403 and 409, alterations in the amino acid sequence DDAAFER lead to both temperature-sensitive and dominant uvrD mutations. The uvrD300 (A406T) and uvrD301 (A406V) alleles produce UV sensitivity at 44 degrees C but do not affect sensitivity to methyl methanesulfonate (MMS). In contrast, the uvrD303 mutation (D403AD404A) causes increased sensitivity to both UV and MMS and is dominant to uvrD+ when present at six to eight copies per cell. Several of the alleles demonstrated a strong antimutator phenotype. In addition, conjugal recombination is reduced 10-fold in uvrD303 strains. Of all of the amino acid substitutions tested, only an alanine-to-serine change at position 406 (uvrD302) was neutral. To determine the biochemical basis for the observed phenotypes, we overexpressed and purified the UvrD303 protein from a uvrD delta294 deletion background and characterized its enzymatic activities. The highly unusual UvrD303 protein exhibits a higher specific activity for ATP hydrolysis than the wild-type control, while its Km for ATP binding remains unchanged. More importantly, the UvrD303 protein unwinds partial duplex DNA up to 10 times more efficiently than wild-type UvrD. The DNA binding affinities of the two proteins appear comparable. Based on these results, we propose that the region located between amino acids 403 and 409 serves to regulate the unwinding activity of DNA helicase II to provide the proper balance between speed and overall effectiveness in the various DNA repair systems in which the protein participates.


Effect of bile on Vibrio parahaemolyticus.
Many enteric pathogens are thought to enter a viable but nonculturable state when deprived of nutrients. Virulent strains of the enteric pathogen Vibrio parahaemolyticus are rarely isolated from their low-nutrient aquatic environments, possibly due to their nonculturability. Host factors such as bile may trigger release from dormancy and increase virulence in these strains. In this study, the addition of bile or the bile acid deoxycholic acid to estuarine water-cultured bacteria led to an increase in the direct viable count and colony counts among the virulent strains. This effect was not demonstrated in the nonvirulent strains, and it was reversed by extraction of bile acids with cholestyramine. Bile-treated V. parahaemolyticus had lower levels of intracellular calcium than untreated cells, and this effect coincided with an increase in the number of metabolically active cells. Chelation of intracellular calcium with BAPTA/AM (R. Y. Tsien, Biochemistry 19:2396-2402, 1980) produced similar results. Addition of bile to V. parahaemolyticus cultures in laboratory medium enhanced factors associated with virulence such as Congo red binding, bacterial capsule size, and adherence to epithelial cells. These results suggest that a bile acid-containing environment such as that found in the human host favors growth of virulent strains of V. parahaemolyticus and that bile acids enhance the expression of virulence factors. These effects seem to be mediated by a decrease in intracellular calcium.


Nordic walking improves mobility in Parkinson's disease.
Nordic walking may improve mobility in Parkinson's disease (PD). Here, we examined whether the beneficial effects persist after the training period. We included 19 PD patients [14 men; mean age 67.0 years (range 58-76); Hoehn and Yahr stage range 1-3] who received a 6-week Nordic walking exercise program. Outcome was assessed prior to training (T1), immediately after the training period (T2) and-in a subgroup of 9 patients--5 months after training (T3). At T2, we observed a significant improvement in timed 10-m walking, the timed get-up-and-go-test (TUG), the 6-min walking test and quality of life (PDQ-39). All treatment effects persisted at T3. Compliance was excellent, and there were no adverse effects. These preliminary findings suggest that Nordic walking could provide a safe, effective, and enjoyable way to reduce physical inactivity in PD and to improve the quality of life. A large randomized clinical trial now appears justified.


Compromised respiratory function in lethal influenza infection is characterized by the depletion of type I alveolar epithelial cells beyond threshold levels.
During influenza virus infection, it is unclear how much alveolar cell loss can be tolerated before the host succumbs to the disease. We sought to define relevant correlates of disease severity in the mouse influenza model, hypothesizing that a susceptibility threshold exists for alveolar epithelial cell loss. We compared lung pathology, virus spread, alveolar epithelial cell depletion, arterial blood oxygenation, physiological responses measured by unrestrained plethysmography, and oxygen consumption and carbon dioxide production by gas analysis in mice at intervals after infection with virus strains and doses that cause mild (x31) or severe (PR/8) influenza. Both mild and severe infections showed similar degrees of lung damage and virus dissemination until day 6 after inoculation but diverged in survival outcomes from day 9. Day 6 PR/8-infected mice had normal respiratory and gas exchange functions with 10% type I cell loss. However, day 10 PR/8-infected mice had 40% type I cell loss with a concomitant drastic decreases in tidal and minute volumes, Vo(2), Vco(2), and arterial blood oxygenation, compared with a maximum 3% type I cell loss for x31 on day 10 when they recovered body weight and respiratory functions. Alterations in breaths per minute, expiratory time, and metabolic rate were observed in both infections. A threshold for maintenance of proper respiratory function appears to be crossed once 10% of alveolar type I cells are lost. These data indicate that lethality in influenza virus infection is a matter of degree rather than quality.


Efficacy of pre-operative computed tomography evaluation of the tympanic cavity for hearing improvement after stapes surgery for tympanosclerosis with stapes fixation.
Our aim was to determine if stapes surgery is useful for treating inflammatory ear diseases. Thirteen patients underwent single-stage or staged surgery for stapes fixation due to tympanosclerosis alone or with cholesteatoma. Operative criteria were: no tympanic membrane retraction, perforation or adhesion; middle-ear cavity with aeration >1 year; a fixed stapes. Computed tomography was used to analyse the relation between operative success and pre-operative pneumatisation. Success rate at six months was 75 per cent. Hearing results were stable with little deterioration and no complications. Patients with poor pneumatisation had good results (with improved air-bone gap) only after staged surgery. Well-aerated ears heard better even with single-stage surgery. Pre-operative computed tomography and intra-operative findings are necessary to determine the pneumatisation status of tympanic mastoid cavities. If criteria approved, poorly pneumatised patients underwent staged surgery. Stapedectomy achieved good hearing results for inflammatory middle-ear disease with stapes fixation.


Maximizing chromatographic information from environmental extracts by GCxGC-ToF-MS.
Comprehensive two-dimensional gas chromatography (GCxGC) coupled with a time-of-flight (ToF) detector allows the separation of many constituents of previously unresolved complex mixtures (UCM) of contaminants in sediment samples. In addition to the powerful chromatographic resolution, automated mass spectral deconvolution and identification system software enables a spectral deconvolution of closely eluting peaks. An extract of highly polluted sediment from the river Elbe (Czech Republic) was submitted to noninvasive extraction and fractionation, and analyzed by GCxGC-ToF-MS. More than 400 compounds were tentatively identified from three fractions. Some of the identified analytes, although not belonging to the group of priority pollutants, are known to have a toxic potential. Examples are chlorinated polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, quinones, aminoquinones, dinaphthofurans, and thiaarenes. Due to the lack of a more thorough cleanup, the life-span of the GC-column is substantially reduced, whereas the ion source of the MS needs more frequent maintenance. The procedure described is, however, not meant for routine purposes. This procedure delivers, in one run, a wealth of information that may be useful for further elucidation of toxicological properties of sediment samples by a tentative identification of previously unknown compounds.


Genetic structure and gene flow among Brazilian populations of Heliothis virescens (Lepidoptera: Noctuidae).
Population genetic studies are essential to the better application of pest management strategies, including the monitoring of the evolution of resistance to insecticides and genetically modified plants. Bacillus thuringiensis Berliner (Bt) crops have been instrumental in controlling tobacco budworm, Heliothis virescens (F.) (Lepidoptera: Noctuidae), a pest that has developed resistance to many common insecticides once used for its management. In our study, microsatellite markers were applied to investigate the genetic structure and patterns of gene flow among Brazilian populations of H. virescens from cotton, Gossypium hirsutum L., and soybean, Glycine max (L.) Merr., fields, aiming to propose means to improve its management in the field. In total, 127 alleles were found across nine microsatellites loci for 205 individuals from 12 localities. Low levels of gene flow and moderate to great genetic structure were found for these populations. Host plant association, crop growing season, and geographic origin were not responsible for the genetic structuring among Brazilian populations of H. virescens. Other factors, such as demographic history and seasonal variability of intrapopulation genetic variation, were suggested to be molding the current pattern of genetic variability distribution.


Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization.
Diguanylate cyclases (DGCs) are key enzymes of second messenger signaling in bacteria. Their activity is responsible for the condensation of two GTP molecules into the signaling compound cyclic di-GMP. Despite their importance and abundance in bacteria, catalytic and regulatory mechanisms of this class of enzymes are poorly understood. In particular, it is not clear if oligomerization is required for catalysis and if it represents a level for activity control. To address this question we perform in vitro and in vivo analysis of the Caulobacter crescentus diguanylate cyclase PleD. PleD is a member of the response regulator family with two N-terminal receiver domains and a C-terminal diguanylate cyclase output domain. PleD is activated by phosphorylation but the structural changes inflicted upon activation of PleD are unknown. We show that PleD can be specifically activated by beryllium fluoride in vitro, resulting in dimerization and c-di-GMP synthesis. Cross-linking and fractionation experiments demonstrated that the DGC activity of PleD is contained entirely within the dimer fraction, confirming that the dimer represents the enzymatically active state of PleD. In contrast to the catalytic activity, allosteric feedback regulation of PleD is not affected by the activation status of the protein, indicating that activation by dimerization and product inhibition represent independent layers of DGC control. Finally, we present evidence that dimerization also serves to sequester activated PleD to the differentiating Caulobacter cell pole, implicating protein oligomerization in spatial control and providing a molecular explanation for the coupling of PleD activation and subcellular localization.


Physiological correlates of perceptual learning in monkey V1 and V2.
Performance in visual discrimination tasks improves with practice. Although the psychophysical parameters of these improvements have suggested the involvement of early areas in visual cortex, there has been little direct study of the physiological correlates of such perceptual learning at the level of individual neurons. To examine how neuronal response properties in the early visual system may change with practice, we trained monkeys for more than 6 mo in an orientation discrimination task in which behaviorally relevant stimuli were restricted to a particular retinal location and oriented around a specific orientation. During training the monkeys' discrimination thresholds gradually improved to much better than those of naive monkeys or humans. Although this improvement was specific to the trained orientation, it showed little retinotopic specificity. The receptive field properties of single neurons from regions representing the trained location and a location in the opposite visual hemifield were measured in V1 and V2. In most respects the receptive field properties in the representations of the trained and untrained regions were indistinguishable. However, in the regions of V1 and V2 representing the trained location, there were slightly fewer neurons whose optimal orientation was near the trained orientation. This resulted in a small but significant decrease in the V1 population response to the trained orientation at the trained location. Consequently, the observed neuronal populations did not exhibit any orientation-specific biases sufficient to explain the orientation specificity of the behavioral improvement. Pooling models suggest that the behavioral improvement was accomplished with a task-dependent and orientation-selective pooling of unaltered signals from early visual neurons. These data suggest that, even for training with stimuli suited to the selectivities found in early areas of visual cortex, behavioral improvements can occur in the absence of pronounced changes in the physiology of those areas.


Long-Term Impact of War, Civil War, and Persecution in Civilian Populations-Conflict and Post-Traumatic Stress in African Communities.
This chapter describes how chronic conflict, warfare, and persecution, as lived experiences, have created significant mental distress in communities on the African continent. There is a growing body of research that highlights increasing mental distress in Africa e.g., about sexuality, health, disease, modernity, climate, politics, culture, religion, ethnicities, race, economies etc. Many of these stresses and uncertainties are driven by political persecution, war, and conflict. This has shaped many African people's attitudes and government policies and an increasing scholarly interest in exploring these "uncertainties and mental distresses in Africa." The chapter will show how trauma, as seen in conflict/post-conflict settings in Africa, causes significant mental stress and associated social problems as well as medically-defined PTSD syndromes, anxiety, and depression which cause much morbidity and retard development in many African communities. Taking a classical look at post-traumatic stress disorder, PTSD, the chapter explores the presentation of the various physical and mental clinical syndromes related to war-trauma on the African continent and the consequent health-seeking behaviors of the African peoples in this regard. The term "culture-bound PTSD syndromes" will be introduced and discussed in the broader context of treatment, rehabilitation, and prevention on the continent and worldwide. It will also discuss the dilemma of the vicious cycles of trauma driven by appetitive aggression in today's Africa which portends to further retard socio-economic development and drives the trans-generational perpetuation of ethnic-based conflicts including genocides. Despite this mass traumatization, the chapter points to the virtual absence of post-conflict mental health policies in almost all African countries, hence leading to discussions of "best-practices" recommendations.


Oral administration of blueberry inhibits angiogenic tumor growth and enhances survival of mice with endothelial cell neoplasm.
Endothelial cell neoplasms are the most common soft tissue tumor in infants. Subcutaneous injection of spontaneously transformed murine endothelial (EOMA) cells results in development of hemangioendothelioma (HE). We have previously shown that blueberry extract (BBE) treatment of EOMA cells in vitro prior to injection in vivo can significantly inhibit the incidence and size of developing HE. In this study, we sought to determine whether oral BBE could be effective in managing HE and to investigate the mechanisms through which BBE exerts its effects on endothelial cells. A dose-dependent decrease in HE tumor size was observed in mice receiving daily oral gavage feeds of BBE. Kaplan-Meier survival curve showed significantly enhanced survival for mice with HE tumors given BBE, compared to control. BBE treatment of EOMA cells inhibited both c-Jun N-terminal kinase (JNK) and NF-kappaB signaling pathways that culminate in monocyte chemoattractant protein-1 (MCP-1) expression required for HE development. Antiangiogenic effects of BBE on EOMA cells included decreased proliferation by BrdU assay, decreased sprouting on Matrigel, and decreased transwell migration. Thus, this work provides first evidence demonstrating that BBE can limit tumor formation through antiangiogenic effects and inhibition of JNK and NF-kappaB signaling pathways. Oral administration of BBE represents a potential therapeutic antiangiogenic strategy for treating endothelial cell neoplasms in children.


Accumulation of partly folded states in the equilibrium unfolding of the pneumococcal choline-binding module C-LytA.
Choline-binding modules are present in some virulence factors and many other proteins of Streptococcus pneumoniae (Pneumococcus). The most extensively studied choline-binding module is C-LytA, the C-terminal moiety of the pneumococcal cell-wall amidase LytA. The three-dimensional structure of C-LytA is built up from six loop-hairpin structures forming a left-handed beta-solenoid with four choline-binding sites. The affinity of C-LytA for choline and other structural analogues allows its use as an efficient fusion tag for single-step purification of hybrid proteins. In the present study, we characterize the folding and stability of C-LytA by chemical and thermal equilibrium denaturation experiments. Unfolding experiments using guanidinium chloride at pH 7.0 and 20 degrees C suggest the existence of two partly folded states (I1 and I2) in the following model: N (native)-->I1<=>I2. The N-->I1 transition is non-co-operative and irreversible, and is significant even in the absence of a denaturant. In contrast, the I1<=>I2 transition is co-operative and reversible, with an associated freeenergy change (DeltaG(0)) of 30.9+/-0.8 kJ x mol(-1). The residual structure in the I2 state is unusually stable even in 7.4 M guanidinium chloride. Binding of choline stabilizes the structure of the native state, induces its dimerization and prevents the accumulation of the I1 species ([N]2<=>[I2]2, DeltaG(0)=50.1+/-0.8 kJ x mol(-1)). Fluorescence and CD measurements, gel-filtration chromatography and limited proteolysis suggest that I1 differs from N in the local unfolding of the N-terminal beta-hairpins, and that I2 has a residual structure in the C-terminal region. Thermal denaturation of C-LytA suggests the accumulation of at least the I1 species. These results might pave the way for an effective improvement of its biotechnological applications by protein engineering.


Adrenomedullin inhibits adipogenesis under transcriptional control of insulin.
We generated preadipocyte cell lines impaired in adrenomedullin production through integration of an adrenomedullin small interfering RNA expression vector. The reduction of adrenomedullin synthesis strongly accelerated adipose differentiation. These results were bolstered when overexpression of active adrenomedullin peptide led to delayed differentiation. Therefore, we propose that adrenomedullin is an antiadipogenic factor. Moreover, we checked whether insulin, a proadipogenic factor, regulates expression of adrenomedullin. We observed that insulin had an inhibitory effect on adrenomedullin expression in isolated human adipocyte cells. This response was dose dependent and was reversed by resistin, a new anti-insulin agent. We quantified circulating adrenomedullin in healthy obese patients and observed a threefold increase of adrenomedullin compared with lean patients. Furthermore, adrenomedullin plasma levels are negatively correlated to plasma insulin levels in these obese patients. The insulin inhibitory response was also observed in vivo in Sprague-Dawley rats but not in the insulin-resistant Zucker rat, suggesting that adrenomedullin expression is upregulated in insulin-resistant adipose cells. Using adrenomedullin promoter-luciferase reporter gene constructs, we have shown that the adrenomedullin response to insulin is mediated by insulin-responsive elements. These findings provide new insight into fat mass development and the relationship between obesity and elevated circulating adrenomedullin levels in diabetic patients.


[Academician Aleksandr Mikhaĭlovich Ugolev. The development of his scientific ideas].
The science suffered a severe loss with the sudden death in November 2, 1991, of and outstanding physiologist Academician Alexander Mikhaĭlovich Ugolev at the age of 66. All life of this man was devoted to the development of the national science. It was the aim and meaning of his life, he has contributed to scientific progress in every possible way. The major scientific interests of A. M. Ugolev were focused on the basic and applied areas of food assimilation, including the physiology of nutrition and digestion. The works of the scientist in this field of knowledge were world-wide recognized. During his scientific activity Dr. Ugolev conducted a number of brilliant studies which remained unforgettable trace in physiology and for ever will be a part of golden fund of science. This was promoted by a unique combination of his illustrious abilities of physiologist and general biologist as well as evolutionist with the gift of experimenter and excellent surgeon. His experimental skill can serve and example of an elegant combination of bold intentions and their masterly realizations. But the most remarkable and world-wide recognized discovery of the scientist was that of membrane digestion--previously unknown mechanism of food assimilation. Just this basic discovery is emphasized in the review devoted to the memory of unforgettable master. The fragmentariness of material depends on a desire to present concisely the major characteristics of membrane digestion.


A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell function and therapy of murine leukemia.
Acute myeloid leukemia (AML), the most common adult acute leukemia in the United States, has the poorest survival rate, with 26% of patients surviving 5 years. Adoptive immunotherapy with T cells genetically modified to recognize tumors is a promising and evolving treatment option. However, antitumor activity, particularly in the context of progressive leukemia, can be dampened both by limited costimulation and triggering of immunoregulatory checkpoints that attenuate T-cell responses. Expression of CD200 (OX2), a negative regulator of T-cell function that binds CD200 receptor (CD200R), is commonly increased in leukemia and other malignancies and is associated with poor prognosis in leukemia patients. To appropriate and redirect the inhibitory effects of CD200R signaling on transferred CD8+ T cells, we engineered CD200R immunomodulatory fusion proteins (IFPs) with the cytoplasmic tail replaced by the signaling domain of the costimulatory receptor, CD28. An analysis of a panel of CD200R-CD28 IFP constructs revealed that the most effective costimulation was achieved in IFPs containing a dimerizing motif and a predicted tumor-T-cell distance that facilitates localization to the immunological synapse. T cells transduced with the optimized CD200R-CD28 IFPs exhibited enhanced proliferation and effector function in response to CD200+ leukemic cells in vitro. In adoptive therapy of disseminated leukemia, CD200R-CD28-transduced leukemia-specific CD8 T cells eradicated otherwise lethal disease more efficiently than wild-type cells and bypassed the requirement for interleukin-2 administration to sustain in vivo activity. The transduction of human primary T cells with the equivalent human IFPs increased proliferation and cytokine production in response to CD200+ leukemia cells, supporting clinical translation. This trial was registered at www.clinicaltrials.gov as #NCT01640301.


Republication of "A Biomechanical Comparison of Limited Open Versus Krackow Repair for Achilles Tendon Rupture".
Soft tissue complications after Achilles tendon repair has led to increased interest in less invasive techniques. Various limited open techniques have gained popularity as an alternative to open operative repair. The purpose of this study was to biomechanically compare an open Krackow and limited open repair for Achilles tendon rupture. We hypothesized that there would be no statistical difference in load to failure, work to failure, and initial linear stiffness. A simulated Achilles tendon rupture was created 4 cm proximal to its insertion in 18 fresh-frozen cadaveric below-knee lower limbs. Specimens were randomized to open or limited open PARS Achilles Jig System repair. Repairs were loaded to failure at a rate of 25.4 mm/s to reflect loading during normal ankle range of motion. Load to failure, work to failure, and initial linear stiffness were compared between the 2 repair types. The average load to failure (353.8 ± 88.8 N vs 313.3 ± 99.9 N; P = .38) and work to failure (6.4 ± 2.3 J vs 6.3 ± 3.5 J; P = .904) were not statistically different for Krackow and PARS repair, respectively. Mean initial linear stiffness of the Krackow repair (17.8 ± 5.4 N/mm) was significantly greater than PARS repair (11.8 ± 2.5 N/mm) (P = .011). No significant difference in repair strength was seen, but higher initial linear stiffness for Krackow repair suggests superior resistance to gap formation, which may occur during postoperative rehabilitation. With equal repair strength, but less soft tissue devitalization, the PARS may be a favorable option for patients with risk factors for soft tissue complications.


The effect of duration of intravenous infusion on maximum and threshold blood concentration for drugs exhibiting biexponential elimination kinetics.
The relationships among peak blood concentration (Cmax), the time (tD) during which blood concentrations are maintained above the minimum effective concentration (Cmin), and the duration of a constant-rate intravenous infusion (T) of a drug exhibiting biexponential pharmacokinetics were simulated by digital computer using Newton iterative procedures. These simulations showed that, in contrast with our previous findings for drugs with monoexponential pharmacokinetics, the relationships are more complex due to the larger number of variables. Therefore, investigation of these relationships for biexponential drugs should be done on a drug by drug basis. Accordingly, meperidine and sulfamethoxazole were chosen as examples of drugs which exhibit biexponential kinetics and were used to determine what errors were involved in using the simpler guidelines for drugs which exhibit monoexponential kinetics as an approximation. These simulations showed the following . (a) The effect of T on Cmax may be adequately estimated by using the guidelines for monoexponential kinetics with the elimination half-life (t1/2) taken as t1/2 lambda1, provided that lambda1 is 20 to 30 times lambda2 and that the AUC of the distribution phase (i.e., C1/lambda1) comprises greater than about 20% of the total AUC. (b) As with monoexponential drugs, it is possible to obtain a larger tD by infusing the dose compared to that obtained with a bolus, if the value of C(0)/Cmin less than 2.5. (c) Using th approximation of monoexponential pharmacokinetics to estimate the effect of T on tD will underestimate both tD and the maximum infusion time, which will just attain the Cmin unless the AUC of the distribution phase comprises only a very small proportion of the total AUC. (d) The simulations with meperidine also showed that the nature of the relationship between tD and T varies depending on whether Cmin is maintained in the distribution phase or in both the distribution and elimination phases.


A comparison of crushed ice and continuous flow cold therapy.
Crushed ice was compared to continuous flow cold therapy for control of postoperative pain after arthroscopic patellar tendon autograft anterior cruciate ligament (ACL) reconstruction. With all other variables held constant, cold was administered by either continuous flow (group 1) or crushed ice (group 2). The cold therapy was constant for 3 days, then as needed in days 4 through 7. Data were collected by investigator evaluations and patient diaries. Pain was assessed by visual analog scale (VAS) and categorical pain scale (Likert). Eighty-seven patients were included (52 continuous flow and 35 crushed ice). Continuous passive motion averaged 54 hours for group 1 and 43 hours for group 2 (P<.05). Knee motion at one week averaged more (5 degrees/88 degrees) for group 1 (flexion range: 48 degrees-155 degrees) than for group 2 (6 degrees/77 degrees) (flexion range: 25 degrees-125 degrees) (P=.03). Likert pain scores for group 2 patients were always statistically greater than group 1 patients from the first hour through postoperative day 6 (P<.01). The average VAS pain was always greater for group 2 and statistically greater for postoperative day 1 (P<.01). Hydrocodone bitartrate with acetaminophen use in group 2 was greater than in group 1 for postoperative days 1 (P<.001) and 2 (P=.035). The respective cold modality VAS measured performance was 9.1 for group 1 and 7.8 for group 2 (P<.01). During postoperative days 4 through 6, group 1 patients applied their cold modality for 47.9 hours but group 2 patients applied their cold modality for 29.5 hours (P<.01). Compared to crushed ice, continuous flow cold therapy lowered VAS and Likert pain scores more, reduced hydrocodone bitartrate with acetaminophen use, was used more often, increased continuous passive motion, increased 1-week knee flexion, and was given significantly higher performance ratings by patients. Continuous flow cold is superior to crushed ice for outpatient ACL reconstruction pain and should not be considered an equivalent modality.


902 MHz mobile phone does not affect short term memory in humans.
We studied the effects of an electromagnetic field (EMF) as emitted by a 902 MHz mobile phone on human short term memory. This study was a replication with methodological improvements to our previous study. The improvements included multi-centre testing and a double blind design. A total of 64 subjects (32 men) in two independent laboratories performed a short term memory task (n-back) which poses a varying memory load (0-3 items) on the subjects' memory. They performed the task twice, once each under EMF and sham exposure. Reaction times (RTs) and accuracy of the responses were recorded. The order of exposure and memory load conditions were counterbalanced across subjects and gender. There were no statistically significant differences in performance between the two laboratories. We could not replicate our previous results: the EMF had no effect on RTs or on the accuracy of the subjects' answers. The inability to replicate previous findings could have been caused by lack of actual EMF effects or the magnitude of effects being at the sensitivity threshold of the test used.


Development and validation of electronic surveillance tool for acute kidney injury: A retrospective analysis.
Timely detection of acute kidney injury (AKI) facilitates prevention of its progress and potentially therapeutic interventions. The study objective is to develop and validate an electronic surveillance tool (AKI sniffer) to detect AKI in 2 independent retrospective cohorts of intensive care unit (ICU) patients. The primary aim is to compare the sensitivity, specificity, and positive and negative predictive values of AKI sniffer performance against a reference standard. This study is conducted in the ICUs of a tertiary care center. The derivation cohort study subjects were Olmsted County, MN, residents admitted to all Mayo Clinic ICUs from July 1, 2010, through December 31, 2010, and the validation cohort study subjects were all patients admitted to a Mayo Clinic, Rochester, campus medical/surgical ICU on January 12, 2010, through March 23, 2010. All included records were reviewed by 2 independent investigators who adjudicated AKI using the Acute Kidney Injury Network criteria; disagreements were resolved by a third reviewer. This constituted the reference standard. An electronic algorithm was developed; its precision and reliability were assessed in comparison with the reference standard in 2 separate cohorts, derivation and validation. Of 1466 screened patients, a total of 944 patients were included in the study: 482 for derivation and 462 for validation. Compared with the reference standard in the validation cohort, the sensitivity and specificity of the AKI sniffer were 88% and 96%, respectively. The Cohen κ (95% confidence interval) agreement between the electronic and the reference standard was 0.84 (0.78-0.89) and 0.85 (0.80-0.90) in the derivation and validation cohorts. Acute kidney injury can reliably and accurately be detected electronically in ICU patients. The presented method is applicable for both clinical (decision support) and research (enrollment for clinical trials) settings. Prospective validation is required.


Effect of allopurinol in decreasing proteinuria in type 2 diabetic patients.
Diabetic nephropathy is the most prevalent cause of end-stage renal disease. Besides factors such as angiotensin II, cytokines, and vascular endothelial growth factor, uric acid may play a role as the underlying cause of diabetic nephropathy. We evaluated allopurinol effects on proteinuria in diabetic patients with nephropathy. In a double-blinded randomized controlled trial on 40 patients with type 2 diabetes mellitus and diabetic nephropathy (proteinuria, at least 500 mg/24 h and a serum creatinine level less than 3 mg/dL), allopurinol (100 mg/d) was compared with placebo. Administration of antihypertensive and renoprotective drugs (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers continued for both groups, without changes in dosage. Proteinuria was compared at baseline and 2 and 4 months between the two groups. Each group consisted of 9 men and 11 women. There were no difference between two groups regarding age, body mass index, duration of diabetes mellitus, systolic and diastolic blood pressure, fasting blood glucose, blood urea nitrogen, serum creatinine, serum potassium, and urine volume. Serum levels of uric acid (P = .02) and 24-hour urine protein (P = .049) were significantly lower in the patients on allopurinol, after 4 months of receiving allopurinol, compared with the control group. Low-dose allopurinol can reduce severity of proteinuria after 4 months of drug administration, which is probably due to decreasing the serum level of uric acid. Thus, allopurinol can be administered as an adjuvant cost-effective therapy for patients with diabetic nephropathy.


Measurement of Aerobic Capacity Using Mouthpiece vs. Mask for Data Collection.
Measurement of aerobic capacity is an important task that must be done accurately in order for data to be worthwhile. Measurement is traditionally obtained through the use of a nose-clip, mouthpiece, and headgear apparatus. This method of collecting gas has proven to be difficult due to the high incidence of losing the nose clip during exercise, the awkwardness and discomfort of the apparatus, and the loss of oral communication. This study compares this method with using a gas collection mask for physiological measurement. Masks have been avoided due to leakage that causes errors in data. Maximal and submaximal values for Ve, VO2, HR, and RER were compared for both methods of collection. Results show that the mask produced values equal to those of the mouthpiece, nose clip, and headgear. Significantly more discomfort, as well as influence on running economy, was reported with the headgear. The data show that leakage is not a significant problem. Based on preliminary studies and data from this study, using the mask is recommended. Data suggests that further studies look at facial shape, as well as masks of different size and material, with regards to eliminating any data errors occurring in the mask.


What determines Alnus-associated ectomycorrhizal community diversity and specificity? A comparison of host and habitat effects at a regional scale.
· Global-scale analyses of ectomycorrhizal (ECM) fungi communities emphasize host plant families as the main drivers of diversity. This study aims to test, on Alnus-ECM communities, which fungi are said to be 'host-specific', to what extent host species, habitat and distance explain their alpha and beta diversity variations, and their specificity. · In France, ECM communities associated with two subgenera and five species of Alnus, were sampled on 165 trees from 39 lowland to subalpine sites. In all, 1178 internal transcribed spacer (ITS) sequences of ECM fungi clustered in 86 molecular operational taxonomic units (MOTUs). · The species richness was low but still variable, and the evenness of communities was lower on organic soils and in Corsica. Similarity between communities was influenced both by host, soil parameters, altitude and longitude, but not by climate and distance. A large majority of 'specific' fungi were shared between host species within a subgenus, and showed habitat preferences within the subgenus distribution range. · Our study confirms that Alnus ECM communities are low in diversity, highly conserved at a regional scale, and partly shared between congeneric host species. A large part of alpha and beta diversity variations remained unexplained, and other processes may shape these communities.


Stress differentially affects fear conditioning in men and women.
Stress and fear conditioning processes are both important vulnerability factors in the development of psychiatric disorders. In behavioral studies considerable sex differences in fear learning have been observed after increases of the stress hormone cortisol. But neuroimaging experiments, which give insights into the neurobiological correlates of stress × sex interactions in fear conditioning, are lacking so far. In the current functional magnetic resonance imaging (fMRI) study, we tested whether a psychosocial stressor (Trier Social Stress Test) compared to a control condition influenced subsequent fear conditioning in 48 men and 48 women taking oral contraceptives (OCs). One of two pictures of a geometrical figure was always paired (conditioned stimulus, CS+) or never paired (CS-) with an electrical stimulation (unconditioned stimulus). BOLD responses as well as skin conductance responses were assessed. Sex-independently, stress enhanced the CS+/CS- differentiation in the hippocampus in early acquisition but attenuated conditioned responses in the medial frontal cortex in late acquisition. In early acquisition, stress reduced the CS+/CS- differentiation in the nucleus accumbens in men, but enhanced it in OC women. In late acquisition, the same pattern (reduction in men, enhancement in OC women) was found in the amygdala as well as in the anterior cingulate. Thus, psychosocial stress impaired the neuronal correlates of fear learning and expression in men, but facilitated them in OC women. A sex-specific modulation of fear conditioning after stress might contribute to the divergent prevalence of men and women in developing psychiatric disorders.


'Some men just don't want to get hurt': perspectives of U.S. Virgin Islands men toward partner violence and HIV risks.
Objectives: Global evidence suggests that individuals who experience intimate partner violence (IPV) can have accelerated risk for HIV transmission. The U.S. Virgin Islands (USVI) has high per capita rates of HIV and IPV that can have devastating effects on women's health. Catalysts for these health disparities may be shaped by cultural and social definitions of conventional masculinity. Thus, understanding USVI men's perceptions about HIV risks and IPV are a necessary component of developing strategies to improve women's health. This study aimed to describe perceptions of HIV risks and IPV among USVI men.Design: We conducted two focus groups with 14 men living on St. Thomas and St. Croix, USVI. The focus group interview guide was culturally relevant and developed using findings from research conducted about these issues on USVI. Thematic analysis was used to analyze focus group data. Transcripts were coded and categorized by four research team members and discrepancies were reconciled. Themes were developed based on the emerging data.Results: Focus group participants were all US citizens born on the USVI, had a median age range of 20-25, 86% (12) were of African descent and 14% (2) were Hispanic. Themes emerging from the data were: (1) validating status, (2) deflecting responsibility, and (3) evoking fear and distrust. These ideas underscored the ways that attitudes and beliefs informed by gender and social norms influence IPV and sexual behavior between intimate partners.Conclusion: USVI society could benefit from interventions that aim to transform norms, promote healthy relationships, and encourage health-seeking behavior to improve the health of women partners.


Quality of life in subgroups of individuals with whiplash-associated disorders.
The term whiplash associated disorders (WAD) includes a wide range of complaints, with neck pain as predominating symptom. Living with long term pain influences quality of life. In previous studies of other chronic pain patients, subgrouping has been made according to thermal pain thresholds measured in quantitative sensory testing (QST). The aims of the present study are threefold, (1) to evaluate thermal pain thresholds and health related quality of life in WAD patients compared to healthy pain-free individuals, (2) to explore whether subgrouping of the WAD patients is possible according to thermal pain thresholds over trapezius, and if so (3) to explore differences between the subgroups. Twenty-six patients with WAD and 18 healthy pain-free controls took part in the study. Thermal pain thresholds were measured in two sites (over the thenar and the trapezius muscle) using quantitative sensory testing (QST). Health related quality of life (HRQoL) was assessed using the SF-36. The visual analogue scale was used to rate pain intensity and unpleasantness related to the experimental situation. WAD patients are more sensitive to thermal pain, and scored lower on the SF-36 in all scales when compared with healthy pain-free individuals. After analyzing clusters (K-means algorithm) two subgroups of WAD emerge, pain insensitive and pain sensitive. The pain insensitive group differed significantly from the pain sensitive group in the Role Emotional subscale of SF-36 (p=0.025). Thermal pain hyperalgesia, especially for cold, seems to be a determinant for subgrouping WAD patients. These results support that such a classification of a heterogenous group could be of importance in tailoring treatment and early interventions.


Non-homogeneous models of sequence evolution in the Bio++ suite of libraries and programs.
Accurately modeling the sequence substitution process is required for the correct estimation of evolutionary parameters, be they phylogenetic relationships, substitution rates or ancestral states; it is also crucial to simulate realistic data sets. Such simulation procedures are needed to estimate the null-distribution of complex statistics, an approach referred to as parametric bootstrapping, and are also used to test the quality of phylogenetic reconstruction programs. It has often been observed that homologous sequences can vary widely in their nucleotide or amino-acid compositions, revealing that sequence evolution has changed importantly among lineages, and may therefore be most appropriately approached through non-homogeneous models. Several programs implementing such models have been developed, but they are limited in their possibilities: only a few particular models are available for likelihood optimization, and data sets cannot be easily generated using the resulting estimated parameters. We hereby present a general implementation of non-homogeneous models of substitutions. It is available as dedicated classes in the Bio++ libraries and can hence be used in any C++ program. Two programs that use these classes are also presented. The first one, Bio++ Maximum Likelihood (BppML), estimates parameters of any non-homogeneous model and the second one, Bio++ Sequence Generator (BppSeqGen), simulates the evolution of sequences from these models. These programs allow the user to describe non-homogeneous models through a property file with a simple yet powerful syntax, without any programming required. We show that the general implementation introduced here can accommodate virtually any type of non-homogeneous models of sequence evolution, including heterotachous ones, while being computer efficient. We furthermore illustrate the use of such general models for parametric bootstrapping, using tests of non-homogeneity applied to an already published ribosomal RNA data set.


Costs for integrating wind into the future ERCOT system with related costs for savings in CO2 emissions.
Wind power can make an important contribution to the goal of reducing emissions of CO2. The major problem relates to the intrinsic variability of the source and the difficulty of reconciling the supply of electricity with demand particularly at high levels of wind penetration. This challenge is explored for the case of the ERCOT system in Texas. Demand for electricity in Texas is projected to increase by approximately 60% by 2030. Considering hourly load data reported for 2006, assuming that the pattern of demand in 2030 should be similar to 2006, and adopting as a business as usual (BAU) reference an assumption that the anticipated additional electricity should be supplied by a combination of coal and gas with prices, discounted to 2007 dollars of $2 and $6 per MMBTU respectively, we conclude that the bus-bar price for electricity would increase by about 1.1 ¢/kWh at a wind penetration level of 30%, by about 3.4 ¢/kWh at a penetration level of 80%. Corresponding costs for reductions in CO2 range from $20/ton to $60/ton. A number of possibilities are discussed that could contribute to a reduction in these costs including the impact of an expanded future fleet of electrically driven vehicles.


Specific interactions study in complexes of poly(mono-n-alkyl itaconates) with tertiary polyamides.
This paper reports an FT-IR study of blends of poly(mono-n-alkyl itaconates) with poly(N,N-dimethylacrylamide) (PDMA) and poly(ethyloxazoline) (PEOX). Strong hydrogen bonding has been found, and both polybases have shown similar acceptor strengths. Derivative techniques show asymmetric profiles for the free carbonyl band of the polybases, resulting in shifted band locations. The extent of the interassociation has been estimated by spectral curve fitting of the polybase carbonyl band. The results show that the interaction degree in blends with PEOX does not depend on the length of the poly(monoalkyl itaconate) side group, while an inter-associating ability loss is observed in blends with PDMA as the side-group size of the polyacid increases. This different behavior is attributed to the greater interspacing between vicinal carbonyl groups in PEOX. This band shows conformational sensitivity and reflects the conformational changes that occur as the steric hindrances present in the medium (due to the bulky side groups of the polyacids) increase.


The small molecule compound C65780 alleviates pain by stabilizing voltage-gated sodium channels in the inactivated and slowly-recovering state.
Noxious pain signals are transduced in the peripheral nervous system as action potentials, which rely on the activities of voltage-gated sodium channels (NaVs). Blocking NaVs is thus a valuable strategy for pain treatment. Here, we report the characterization of a novel NaVs antagonist, 2-(2-(diethylamino)ethyl)indeno[1,2,3-de]phthalazin-3(2H)-one (C65780), and investigation of its action mechanisms. C65780 inhibited the resting NaV1.7, NaV1.8, and NaV1.9 channels with IC50s of 11.3 ± 0.4 μM, 2.7 ± 0.3 μM and 19.2 ± 2.3 μM, respectively. Mechanistic analysis revealed that C65780 quickly bound to its high-affinity receptor site in NaV1.7 as formed by the fast inactivation process and stabilized the channels in a slowly recovering state, for which it facilitated NaV1.7 channels' inactivation by shifting their inactivation-voltage relationship in the hyperpolarizing direction, increasing the plateau proportion of inactivated channels, and blunting their time-dependent recovery. The slow inactivation of NaV1.7, however, is not involved in the action of C65780. In DRG neurons, C65780 also inhibited activity of NaVs, thus dampening neuronal excitability. These effects parlayed into a broad efficacy of orally administrated C65780 in various models of pain, with an efficacy comparable to the antidepressant/neuropathic pain drug Amitriptyline. Excitingly, C65780 demonstrated weaker inactivated state inhibition of related NaV1.4 and NaV1.5 channels compared to amitriptyline, and no toxicity or inhibition of locomotion in a forced-swimming test was observed in mice at pain-relieving doses. These results demonstrate that C65780 acts by trapping NaVs in the inactivated and slowly-recovering state to produce pain relief and may represent an excellent starting compound for developing analgesics.


Determination of plasma cyclic AMP with automated radioimmunoassay system (Gamma-flo).
We have adapted the Gamma-flo automated radioimmunoassay system to analyze for cyclic 3',5'-AMP in plasma. Direct analysis of plasma samples was not possible due to an interfering substance(s) in plasma. Evidence suggested that the interfering substance is human serum albumin. An efficient, relatively simple method was developed by applying the acetylation procedure to ultrafiltrates of plasma samples and utilizing the Gamma-flo system for rapid radioimmunoassay (50 samples per hour) of cyclic AMP content in the filtrates. Coefficient of variation within assays averaged 3% and interassay coefficient of variation was 4.7%. Recovery of cyclic AMP from plasma into the ultrafiltrate ranged from 93 to 100%. Increments of cyclic AMP added to plasma were recovered linearly up to approximately 60 pmol/ml, the highest concentration tested.


Effectiveness of internal Qigong on quality of life, depressive symptoms and self-efficacy among community-dwelling older adults with chronic disease: A systematic review and meta-analysis.
With increasingly aged populations worldwide, the quality of life and psychosocial wellbeing of older adults, especially those with chronic disease, become of increasing importance. There are multiple studies on the use of internal Qigong, a popular mind-body exercise commonly practiced by older adults. However, the effectiveness of internal Qigong on quality of life, depressive symptoms, and self-efficacy on older adults remains unclear. To review updated evidence to determine the effectiveness of internal Qigong interventions on quality of life, depressive symptoms, and self-efficacy among community-dwelling older adults with chronic disease. Six databases (PubMed, CENTRAL, CINAHL, Embase, Scopus, CNKI) were systematically searched for studies from January 2008 to December 2018 in English and Chinese. Relevant randomised controlled trials (RCTs) were screened and assessed for risk of bias by two independent reviewers. A meta-analysis on study outcomes of quality of life, depressive symptoms and self-efficacy using the RevMan 5.3 software was performed. The search retrieved 3439 records. After screening, a total of 13 RCTs with 1340 participants were included in this review. Meta-analysis revealed a significant effect favouring internal Qigong on the quality of life (combined MD = 3.72; 95% CI: 2.27-5.18; p = 0.0001) compared to controls. No significant effects were found for depressive symptoms and self-efficacy. Low heterogeneity among the studies was found for quality of life, whereas high heterogeneity was shown for depressive symptoms and self-efficacy. Internal Qigong appears to have potential benefits on overall quality of life among community-dwelling older adults with chronic disease. The findings of this study suggest potential use of internal Qigong as an adjunct activity for chronic disease management. Future research may enhance the rigour of trials and explore theoretical underpinnings behind Qigong.


Criticism of authority in the writings of Moses Maimonides and Fakhr Al-Dīn Al-Rāzī.
Criticism of authority was a prominent feature of medieval philosophical writing. In this study the critiques of two contemporaneous scholars, Moses Maimonides and Fakhr al-Dīn al-Rāzī, are compared. Maimonides criticized Hellenistic authorities, mainly Aritotle. However, the starting point for his critique was Aristotle's admission of the limitations of his own inquiries. Maimonides admired Aristotle's questioning of his own conclusions, indeed, his own thought was characterized by constant selfdoubt. Al-Rāzī criticized an earlier Muslim scholar, Ibn Sinā (Avicenna), an intellectual giant whose imprint was strongly felt in philosophy and medicine. Al Rāzī used his commentaries on a number of Ibn Sīnā's books as a stage for criticizing the master and for arguing for his own, alternative viewpoints.


Gender perspectives of sexual and reproductive practices of people living with HIV/AIDS in Enugu, South East Nigeria.
a major focus of attention in the efforts at controlling the spread of HIV infection has become the role of gender inequality. The objective of the study was to compare the sexual practices of HIV-positive male and female patients who received counselling and treatment at an Anti-retroviral Clinic in Enugu, South-East Nigeria. A comparative cross-sectional descriptive study of patients attending the free anti-retroviral clinic at the University of Nigeria Teaching Hospital Enugu was done. A total of 146 males (30.8%) and 328 females (61.9%) were studied. Although there was no significant difference in the prevalence of sexual activity between the sexes, the reasons for sexual practices differed. Females indulged in risky sexual activity principally in obedience to the demands of their male partners and were more likely to have sexual partners who were unaware of their seropositivity than males. Risky sexual behaviour among women living with HIV/AIDS in Enugu despite exposure to intensive counselling was still mainly driven by the subordinate traditional gender roles of women in this culture.


Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure-activity relationships.
Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the processes of inflammation and carcinogenesis. Flavonoids, which are polyphenolic compounds with a wide distribution throughout the plant kingdom, have potent anti-inflammatory properties. We investigated the effects of flavonols (kaempferol, quercetin, and myricetin) and flavones (flavone, chrysin, apigenin, luteolin, baicalein, and baicalin) on the tumor necrosis factor-alpha (TNF-alpha)-stimulated ICAM-1 expression. Among those flavonoids tested, kaempferol, chrysin, apigenin, and luteolin are active inhibitors of ICAM-1 expression. Additional experiments suggested that apigenin and luteolin were actively inhibiting the IkappaB kinase (IKK) activity, the IkappaBalpha degradation, the nuclear factor-kappaB (NF-kappaB) DNA-protein binding, and the NF-kappaB luciferase activity. TNF-alpha-induced ICAM-1 promoter activity was attenuated using an activator protein-1 (AP-1) site deletion mutant, indicating the involvement of AP-1 in ICAM-1 expression. AP-1-specific DNA-protein binding activity was increased by TNF-alpha, and the supershift assay identified the components of c-fos and c-jun. Extracellular signal-regulated kinase (ERK) and p38 were involved in the c-fos mRNA expression, and c-Jun NH(2)-terminal kinase (JNK) was involved in the c-jun mRNA expression. All three mitogen-activated protein kinase (MAPK) activities were inhibited by apigenin and luteolin. In comparison, kaempferol and chrysin only inhibited the JNK activity. The inhibitory effects of apigenin and luteolin on ICAM-1 expression are mediated by the sequential attenuation of the three MAPKs activities, the c-fos and c-jun mRNA expressions, and the AP-1 transcriptional activity. IKK/NF-kappaB pathway is also involved; however, kaempferol- and chrysin-mediated inhibitions are primarily executed through the attenuation of JNK activity, c-jun mRNA expression, and AP-1 activity. The structure-activity relationships are also explored, and the important role of -OH group at positions 5 and 7 of A ring and at position 4 of B ring is noted. Finally, our results suggested that AP-1 seems to play a more significant role than NF-kappaB in the flavonoid-induced ICAM-1 inhibition.


Ecotoxicity testing and environmental risk assessment of iron nanomaterials for sub-surface remediation - Recommendations from the FP7 project NanoRem.
Nanoremediation with iron (Fe) nanomaterials opens new doors for treating contaminated soil and groundwater, but is also accompanied by new potential risks as large quantities of engineered nanomaterials are introduced into the environment. In this study, we have assessed the ecotoxicity of four engineered Fe nanomaterials, specifically, Nano-Goethite, Trap-Ox Fe-zeolites, Carbo-Iron® and FerMEG12, developed within the European FP7 project NanoRem for sub-surface remediation towards a test battery consisting of eight ecotoxicity tests on bacteria (V. fisheri, E. coli), algae (P. subcapitata, Chlamydomonas sp.), crustaceans (D. magna), worms (E. fetida, L. variegatus) and plants (R. sativus, L. multiflorum). The tested materials are commercially available and include Fe oxide and nanoscale zero valent iron (nZVI), but also hybrid products with Fe loaded into a matrix. All but one material, a ball milled nZVI (FerMEG12), showed no toxicity in the test battery when tested in concentrations up to 100 mg/L, which is the cutoff for hazard labeling in chemicals regulation in Europe. However it should be noted that Fe nanomaterials proved challenging to test adequately due to their turbidity, aggregation and sedimentation behavior in aqueous media. This paper provides a number of recommendations concerning future testing of Fe nanomaterials and discusses environmental risk assessment considerations related to these.


MALDI-2 Mass Spectrometry and Immunohistochemistry Imaging of Gb3Cer, Gb4Cer, and Further Glycosphingolipids in Human Colorectal Cancer Tissue.
The main cellular receptors of Shiga toxins (Stxs), the neutral glycosphingolipids (GSLs), globotriaosylceramide (Gb3Cer/CD77) and globotetraosylceramide (Gb4Cer), are significantly upregulated in about half of the human colorectal carcinomas (CRC) and in other cancers. Therefore, conjugates exploiting the Gb3Cer/Gb4Cer-binding B subunit of Stx (StxB) have attracted great interest for both diagnostic and adjuvant therapeutic interventions. Moreover, fucosylated GSLs were recognized as potential tumor-associated targets. One obstacle to a broader use of these receptor/ligand systems is that the contribution of specific GSLs to tumorigenesis, in particular, in the context of an altered lipid metabolism, is only poorly understood. A second is that also nondiseased organs (e.g., kidney) and blood vessels can express high levels of certain GSLs, not least Gb3Cer/Gb4Cer. Here, we used, in a proof-of-concept study, matrix-assisted laser desorption/ionization mass spectrometry imaging combined with laser-induced postionization (MALDI-2-MSI) to simultaneously visualize the distribution of several Gb3Cer/Gb4Cer lipoforms and those of related GSLs (e.g., Gb3Cer/Gb4Cer precursors and fucosylated GSLs) in tissue biopsies from three CRC patients. Using MALDI-2 and StxB-based immunofluorescence microscopy, Gb3Cer and Gb4Cer were mainly found in dedifferentiated tumor cell areas, tumor stroma, and tumor-infiltrating blood vessels. Notably, fucosylated GSL such as Fuc-(n)Lc4Cer generally showed a highly localized expression in dysplastic glands and indian file-like cells infiltrating adipose tissue. Our "molecular histology" approach could support stratifying patients for intratumoral GSL expression to identify an optimal therapeutic strategy. The improved chemical coverage by MALDI-2 can also help to improve our understanding of the molecular basis of tumor development and GSL metabolism.


DNA-binding mechanism of the Hippo pathway transcription factor TEAD4.
TEA domain (TEAD) family transcription factors are key regulators in development, tissue homeostasis and cancer progression. TEAD4 acts as a critical downstream effector of the evolutionarily conserved Hippo signaling pathway. The well-studied oncogenic protein YAP forms a complex with TEAD4 to regulate gene transcription; so does the tumor suppressor VGLL4. Although it is known that TEAD proteins can bind promoter regions of target genes through the TEA domain, the specific and detailed mechanism of DNA recognition by the TEA domain remains partially understood. Here, we report the crystal structure of TEAD4 TEA domain in complex with a muscle-CAT DNA element. The structure revealed extensive interactions between the TEA domain and the DNA duplex involving both the major and minor grooves of DNA helix. The DNA recognition helix, α3 helix, determines the specificity of the TEA domain binding to DNA sequence. Structure-guided biochemical analysis identified two major binding sites on the interface of the TEA domain-DNA complex. Mutation of TEAD4 at either site substantially decreases its occupancy on the promoter region of target genes, and largely impaired YAP-induced TEAD4 transactivation and target gene transcription, leading to inhibition of growth and colony formation of gastric cancer cell HGC-27. Collectively, our work provides a structural basis for understanding the regulatory mechanism of TEAD-mediated gene transcription.


X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads.
X chromosome dosage compensation is required for male viability in Drosophila. Dosage compensation relative to autosomes is two-fold, but this is likely to be due to a combination of homeostatic gene-by-gene regulation and chromosome-wide regulation. We have baseline values for gene-by-gene dosage compensation on autosomes, but not for the X chromosome. Given the evolutionary history of sex chromosomes, these baseline values could differ. We used a series of deficiencies on the X and autosomes, along with mutations in the sex-determination gene transformer-2, to carefully measure the sex-independent X-chromosome response to gene dosage in adult heads by RNA sequencing. We observed modest and indistinguishable dosage compensation for both X chromosome and autosome genes, suggesting that the X chromosome is neither inherently more robust nor sensitive to dosage change.


The number of neurophysins in the rat. Influence of the concentration of Bromophenol Blue, used as a tracking dye, on the resolution of proteins by polyacrylamide-gel electrophoresis.
1. The concentration of Bromophenol Blue used as tracking dye in polyacrylamide-gel electrophoresis affected the resolution of rat neurophysins. 2. A final dye concentration of 1mug/ml in the tris-glycine running buffer was found to give the best results. 3. The presence of two major and one minor neurophysin(s) in the rat was confirmed. 4. The two major proteins were found to re-run as single discrete bands, which had the same mobilities in the absence of dye and different mobilities in its presence.


Perceived visual speed constrained by image segmentation.
Little is known about how or where the visual system parses the visual scene into objects or surfaces. However, it is generally assumed that the segmentation and grouping of pieces of the image into discrete entities is due to 'later' processing stages, after the 'early' processing of the visual image by local mechanisms selective for attributes such as colour, orientation, depth, and motion. Speed perception is also thought to be mediated by early mechanisms tuned for speed. Here we show that manipulating the way in which an image is parsed changes the way in which local speed information is processed. Manipulations that cause multiple stimuli to appear as parts of a single patch degrade speed discrimination, whereas manipulations that perceptually divide a single large stimulus into parts improve discrimination. These results indicate that processes as early as speed perception may be constrained by the parsing of the visual image into discrete entities.


Influential factors and formation of extrahepatic collateral artery in unresectable hepatocellular carcinoma.
To analyze the influence factors and formation of extrahepatic collateral arteries (ECAs) in unresectable hepatocellular carcinoma (HCC) with or without chemoembolization. Detailed histories of 35 patients with 39 ECAs of HCC and images including computerized tomography scan, digital subtraction angiography were reviewed carefully to identify ECAs of HCC, ECAs arising from, and anatomic location of tumors in liver. Tumor sizes were measured, and relations of ECAs with times of chemoembolization, tumor size, and the anatomic tumor location were analyzed. Complications were observed after chemoembolization through ECAs of HCC with different techniques. Influence factors of formation of ECAs of HCC included the times of repeated chemoembolization, the location of tumors in liver, the tumor size and the types of chemoembolization. ECAs in HCC appeared after 3-4 times of chemoembolization (17.9%), but a higher frequency of ECAs occurred after 5-6 times of chemoembolization (56.4%). ECAs presented easily in peripheral areas (71.8%) of liver abutting to the anterior, posterior abdominal walls, the top right of diaphragm and right kidney. ECAs also occurred easily after complete obstruction of the trunk arteries supplying HCCs or the branches of proper hepatic arteries. Extrahepatic collaterals of HCC originated from right internal thoracic (mammary) artery (RITA, 5.1%), right intercostal artery (RICA, 7.7%), left gastric artery (LGA, 12.8%), right inferior phrenic artery (RIPA, 38.5%), omental artery (OTA, 2.6%), superior mesenteric artery (SMA, 23.1%), and right adrenal and renal capsule artery (RARCA, 10.3%), respectively. The complications after chemoembolization attributed to no super selective catheterization. The formation of ECAs in unresectable HCC is obviously correlated with multiple chemoembolization, tumor size, types of chemoembolization, anatomic location of tumors. Extrahepatic collaterals in HCC are corresponding to the tumor locations in liver.


Isolation and culture of microvascular endothelium from human adipose tissue.
The study of human endothelial cells in tissue culture has been previously limited to umbilical vein, a large vessel source, and microvascular endothelium from human foreskin, spleen, and adrenal. Microvascular endothelium cultured from these sources have required matrix-coated culture flasks, tumor-conditioned medium, or 50% human serum for growth and subcultivation. To obtain cultures of microvascular endothelium with less stringent growth requirements, human adipose tissue was digested with collagenase and endothelial cells were separated from other stromal elements by sequential filtration and layering cells onto 5% albumin. Using standard medium containing 10% fetal calf serum, these cells grew readily to confluence and survived serial passages. When the cultures were subconfluent, cytoplasmic extensions and a capillary-like morphology were observed. Confluent cultures displayed the "cobblestone" appearance characteristic of other endothelial preparations. Electron microscopy demonstrated the presence of characteristic tight junctions and pinocytotic vesicles. Immunofluorescent staining for Factor VIII was positive, and cultures contained angiotensin-converting enzyme activity. Thus, cultures of human microvascular endothelium were readily obtained from adipose tissue and required only standard medium with 10% serum for growth and subcultivation. This system can be used to study human endothelial cell biology and may prove useful in the study of pathologic states such as diabetic microvasculopathy and tumor angiogenesis.


Outbreak of acute hepatitis A in the health area served by the Hospital Universitario Virgen de la Victoria (HUVV): a change in epidemiology.
In 2016, an outbreak of hepatitis A was identified in the Malaga province among patients with specific epidemiological characteristics, which were predominantly males. This is a report of 51 subjects with acute hepatitis A and a mean age of 35.7 years, 90% were male and 55% of cases were men who had had sex with other men within the last two months. Half of them required hospitalization for significant coagulopathy at diagnosis and no cases progressed to fulminant failure or encephalopathy. Four patients had ascites at the time of diagnosis. This outbreak adds to those reported in the United Kingdom and the Netherlands with a similar number of cases and epidemiology. These studies highlight the importance of epidemiological surveillance, the need for vaccination in this particular at risk population and the need for informative campaigns in order to prevent this disease.


Cross-cultural research: trying to do it better. 2. Enhancing data quality.
To describe the dilemmas for cross-cultural research in translating study instruments and implementing quality assurance methods, drawing on strategies utilised in the Mothers in a New Country (MINC) Study. To translation of study instruments in the MINC Study included: forward and back translations, a bilingual group review process, consultation with bilingual content experts, piloting of different versions of translations, a process for exploring unresolved difficulties and caution in interpreting unusual study findings. Interview quality was assessed by: 1. An ongoing review of interviewer-prepared English coding schedules to ensure completeness of data and identify problems with interview administration. 2. Analysis of fully translated transcripts of six randomly selected early interviews to assess the accuracy and consistency with which questions were asked. 3. A comparison of data sources for 45 randomly selected interviews (original language interview schedules, English coding schedules and translated interview transcripts) to determine the rate and nature of discrepancies. Translation strategies that went beyond simple forward and back translations achieved more reliable and appropriate translations. The complexity of language and cultural differences sometimes still meant less than satisfactory results. Interview tapes played an important quality assurance role, enabling feedback to the interviewers and providing a basis of comparison for identification of data discrepancies. Ensuring good data quality in cross-cultural research is both critically important and difficult. Open discussion of the problems and concerted efforts to deal with them would benefit future research.


Large-scale low temperature fabrication of SnO2 hollow/nanoporous nanostructures: the template-engaged replacement reaction mechanism and high-rate lithium storage.
The morphology-controlled synthesis of SnO2 hollow/nanoporous nanostructures (nanotubes, urchin-like morphologies and nanospheres) was achieved via a template-engaged replacement reaction at a mild temperature (lower than 80 °C). The formation mechanism of hollow interior and nanoporous walls for the obtained SnO2 nanostructures (SnO2 nanotubes were used as an example) was investigated based on TEM and HRTEM observations during different reaction stages. It is found that bridge voids firstly form at the MnO2/SnO2 interface, followed by the inward development of voids before the MnO2 core is completely consumed. Two types of short-circuited galvanic cells, MnO2/Mn(2+)∣SnO2/Sn(2+) and concentration cell-SnO2/Sn(2+) (interior)∣SnO2/Sn(2+) (exterior), are probably responsible for the formation of SnO2 nanotubes and outward growth of SnO2 along MnO2. Moreover, the calculation result of the outer diameter of SnO2 nanotubes is in good agreement with the observation results by SEM and TEM. When evaluated as anodes for lithium ion batteries (LIBs), the three SnO2 nanostructures exhibit superior rate capability and cycling performance. Especially, SnO2 nanotubes present the best rate capability: specific capacities of above 800 mA h g(-1) at 200 mA g(-1) and about 500 mA h g(-1) at 4000 mA g(-1) were achieved, respectively. Importantly, the 1D morphology of SnO2 nanotubes can be well preserved after prolonged cycling at a relatively high current density, indicating good structural stability of the resulting nanotubes during the Li(+) insertion/extraction process. These results indicate that the obtained SnO2 hollow/nanoporous nanostructures would be promising anode materials for next-generation LIBs.


Analysis of inflammatory periimplant lesions during a 12-week period of undisturbed plaque accumulation--a comparison between flapless and flap surgery in the mini-pig.
This study's aim was to clarify the influence of soft tissue management on the development of periimplant infection. Four weeks after removal of all maxillary premolars in 12 mini-pigs, four BEGO Semados RI implants were inserted in each maxillary quadrant. Employing a split-mouth design, one quadrant was randomized to flapless insertion while the contralateral side was chosen for flap surgery. Following 1, 2, 4 and 12 weeks of transmucosal implant, healing biopsies were retrieved from the periimplant soft tissue and subjected to further analysis. Histomorphometrically, a significant reduction of transmigration of polymorphonuclear neutrophils (week 1, p = 0.007; week 2, p = 0.021; week 4, p = 0.023; week 12, p = 0.013) as well as the density of the subepithelial inflammatory infiltrates (week 1, p = 0.007; week 2, p = 0.046; week 4, p = 0.003; week 12, p = 0.032) was verified following flapless surgery. Quantification of inducible nitric oxide synthase showed significantly reduced expression in the flapless group 2 (p = 0.027), 4 (p = 0.005) and 12 (p = 0.004) weeks post-insertion. Analysis of CD31 and collagen I immunostained sections revealed more regular capillary distribution as well as higher vessel and collagen density in the flapless group. The data of the present study indicate that flapless placement reduces the incidence of inflammatory periimplant soft tissue lesions during a 12-week period. Considering the beneficial effects of flapless placement on early soft tissue healing and stability, the technique might be preferred in case of an uncomplicated locoregional anatomy with sufficient hard and soft tissue. However, this positive effect might disappear after manipulation of the implant and soft tissue during impression taking or try in of the prosthodontic supraconstruction.


Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.
Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus.


Selective effects of bumetanide on chloride transport in bullfrog cornea.
Frog corneas were mounted in a modified Ussing chamber and short-circuit current (SCC) and unidirectional Cl fluxes were measured. Bumetanide, a loop diuretic, at concentrations as low as 10(-7) M, reduced the SCC 29%. At 10(-5) M, bumetanide reduced the SCC 96% and increased transcorneal electrical resistance 20-51%. The forward Cl flux declined from 0.71 +/- 0.04 to 0.20 +/- 0.03 mueq/h.cm2 (n, 7), while, in separate experiments, the backward Cl flux did not change significantly (from 0.22 +/- 0.03 to 0.23 +/- 0.04; n, 7). When corneas were mounted in Cl-free Ringer and the net Na transport was stimulated with amphotericin B, 10(-5) M bumetanide had no effect on the SCC. In separate experiments the effect of 10(-5) M bumetanide on the O2 consumption was measured in a stirrer bath assembly. Bumetanide decreased the O2 consumption from 352 +/- 14 to 297 +/- 19 microliter/h.cm2 (significantly different from sham-treated controls). This decrease was similar to that obtained with furosemide or when Cl was removed from the bathing medium. We infer from these results that bumetanide is a selective inhibitor of active Cl transport in the bullfrog cornea.