First Report of Heterodera ripae on Common Nettle in Spain.
Soil and root samples were collected from May to October 2010 from cultivated and wild plants during a survey for hop cyst nematodes. Cyst nematodes were detected in roots of common nettle (Urtica dioica L.) with severe plant yellowing in four natural areas of León and Burgos provinces, Spain, where common nettle is grown in organic farming systems as a substrate for pharmaceutical products. Cysts were isolated by flotation and sieving methods. Cysts and juveniles were analyzed by morphological and molecular methods. The cyst nematodes obtained from soil and plant samples from all four locations had uniform morphological and molecular characteristics that differed from those of Heterodera humuli. Cysts (n = 25) had the following characteristics: lemon shaped, yellow to pale brown; cyst wall with ridges forming an irregular zigzag pattern; young cysts covered by subcrystalline layer; vulval cone bifenestrate with circular or subcircular fenestrae; bullae absent; underbridge weak; body length (not including the neck) ranging from 295 to 489 μm (mean of 418 μm); body width ranging from 208 to 375 μm (mean of 310 μm); fenestrate length of 39 to 58 μm (mean of 46.5 μm) and width of 25.2 to 30.9 μm (mean of 25.1 μm); underbridge length from 51 to 90 μm (mean of 69.2 μm); and vulval slit length from 26 to 40 μm (mean of 33 μm). J2 (n = 20) had the following characteristics: body length ranging from 338 to 380 μm (mean of 359.3 μm); stylet length from 21 to 24 μm (mean of 22.1 μm) with knobs rather wide and slightly projecting anteriorly; tail conical with a length of 41 to 52.5 μm (mean of 45.6 μm) and hyaline part of tail ranging from 18 to 25 μm (mean of 23.3 μm); lateral field with four lines. All morphological data and characters were consistent with those of H. ripae (1). DNA from single cysts was extracted to amplify the internal transcribed spacer (ITS) region of rDNA by PCR with forward primer TW81 (5'-GTTTCCGTAGGTGAACCTGC-3') and reverse primer AB28 (5'-ATATGCTTAAGTTCAGCGGGT-3') (2). The PCR product was digested by restriction enzymes (AluI, CfoI, HaeI, HinfI, PstI, RsaI, TaqI, and Tru9I) to obtain restriction fragment length polymorphism profiles (2). ITS products cloned and assayed using the ABI PRISM 3100 Genetic Analyzer (Applied Biosystems, Salamanca, Spain) were subjected to a database search using BLAST (National Centre for Biotechnology Information) to confirm the identification. These sequences exhibited 99.0% similarity with that of a H. ripae isolate from Germany (GenBank Accession No. AF274407.1). In glasshouse proofs of pathogenicity with these populations of H. ripae, 25 full cysts placed in nylon net bags were inoculated in 9-cm-diameter pots with 10 replicates per plant. After 12 weeks, soil from each pot was dried and cysts extracted. Cysts did not develop on roots of common hop (Humulus lupulus L.) and hemp (Cannabis sativa L.), but in common nettle there was an increase in nematode populations, with all plants severely stunted and yellowing, which confirmed the nematodes' pathogenicity. H. ripae has been previously reported in Russia, Estonia, Latvia, Armenia, Moldova, Ukraine, Bulgaria, Slovakia, Germany, and Belgium (1). To our knowledge, this is the first report of H. ripae in Spain. The identification of H. ripae in nettle fields is important in this region where it could cause large yield reductions if not properly managed. References: (1) S. A. Subbotin et al. Russ. J. Nematol. 5:143, 1997. (2) S. A. Subbotin et al. Nematology 5:515, 2003.


Enterococcus devriesei sp. nov., associated with animal sources.
The taxonomic position of two bovine strains, LMG 13603 and LMG 14595, assigned to the species Enterococcus raffinosus on the basis of biochemical features, was reinvestigated. Both reference strains and two other isolates, 6/1 (=LMG 22829) originating from a charcoal-broiled river lamprey and IE38.4 (=LMG 22830) from the air of a poultry slaughter by-product processing plant, occupied a clearly separate position, on the basis of sequence analysis of the housekeeping gene pheS (encoding the phenylalanyl-tRNA synthase alpha-subunit), relative to the type strain of E. raffinosus and all other enterococcal species with validly published names. 16S rRNA gene sequencing of strains LMG 13603, LMG 14595, 6/1 and IE38.4 confirmed their phylogenetic position in the Enterococcus avium species group, there being more than 99 % 16S rRNA gene sequence similarity to most members of the group, including E. raffinosus, and revealed Enterococcus pseudoavium as the closest phylogenetic relative (99.8-99.9 %). Further phenotypic and genotypic analyses using whole-cell-protein electrophoresis, (GTG)(5)-PCR fingerprinting, ribotyping and DNA-DNA hybridization experiments demonstrated that all four strains represent a novel enterococcal species, for which the name Enterococcus devriesei sp. nov. is proposed. The type strain is LMG 14595T (=CCM 7299T).


Brain-derived neurotrophic factor val66met polymorphism affects prefrontal energy metabolism in bipolar disorder.
Brain-derived neurotrophic factor val66met polymorphism has been implicated in the pathophysiology of bipolar disorder. We investigated the neurochemistry of the left dorsolateral prefrontal cortex of bipolar disorder and healthy participants in relation to the brain-derived neurotrophic factor val66met polymorphism using H-magnetic resonance spectroscopy. Absolute N-acetyl-aspartate, phosphocreatine+creatine (PCr+Cr), choline-containing compounds, myo-inositol, and glutamate levels were measured. Bipolar disorder met-carriers had lower PCr+Cr levels than bipolar disorder val/val patients, and bipolar disorder val/val patients had higher PCr+Cr levels than val/val healthy controls. These results indicate that bipolar disorder met-carriers have abnormal energy metabolism in the left dorsolateral prefrontal cortex.


The epistemic innocence of psychedelic states.
One recent development in epistemology, the philosophical study of knowledge, is the notion of 'epistemic innocence' introduced by Bortolotti and colleagues. This concept expresses the idea that certain suboptimal cognitive processes may nonetheless have epistemic (knowledge-related) benefits. The idea that delusion or confabulation may have psychological benefits is familiar enough. What is novel and interesting is the idea that such conditions may also yield significant and otherwise unavailable epistemic benefits. I apply the notion of epistemic innocence to research on the transformative potential of psychedelic drugs. The popular epithet 'hallucinogen' exemplifies a view of these substances as fundamentally epistemically detrimental. I argue that the picture is more complicated and that some psychedelic states can be epistemically innocent. This conclusion is highly relevant to policy debates about psychedelic therapy. Moreover, analysing the case of psychedelics can shed further light on the concept of epistemic innocence itself.


Assisted reproductive technologies: Conundrums and challenges.
A few weeks ago, a leading multi-city IVF clinic published an advertisement in a leading news daily. The advertisement sounded ominous, "The longer you wait, the lower your chances" - it referred to one's chances of getting pregnant. The subtext was far too easy to decipher: the content was thoroughly gendered and directed solely at women, particularly at career-oriented women who delay their marriages and childbearing plans far too long, supposedly lowering their fertility in the process. It also sounded benevolent in its attempt to warn these "erring" women. It is socially accepted that women are responsible for increasing the infertility rates in the country by their "poor, untimely, and problematic prioritisation of life choices". While men produce sperm that are regenerative, a woman's reproductive potential is perpetually on a decline; born with a fixed number of egg cells, she never produces any more in her lifetime. However, male infertility is an interesting area to delve into; 40-50% of total infertility is male factor infertility (MFI) (1).


Black chokeberry juice (Aronia melanocarpa) reduces incidences of urinary tract infection among nursing home residents in the long term--a pilot study.
Urinary tract infection (UTI) is a major problem in nursing homes, and the mainstay of treatment is antibiotics. The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in specific nutrients, for example, cranberries, to prevent recurring UTI. Black chokeberry (Aronia melanocarpa [Michx] Elliott) is a rich source of phenolics, and thus, dietary intake of black chokeberry juice may reduce the incidences of UTI requiring medical treatment. In this pilot study, we examined the frequency of medically treated UTI among residents in 6 nursing homes who were offered black chokeberry juice or a placebo during a 6-month crossover intervention. The residents were offered a placebo drink for a 3-month period followed by chokeberry juice for the next 3 months (group A) or vice versa (group B). The juice was characterized by a high content of total phenolics (715 mg gallic acid equivalent, 100 mL(-1)), including B-type procyanidins, anthocyanins, and chlorogenic acids. Daily intake of chokeberry juice was 156 mL per resident in group A (n = 110) and 89 mL per resident in group B (n = 126). Urinary tract infection comprised 55% of all medically treated infections during the study period. The results revealed no immediate reduction in the frequency of UTI or the total use of antibiotics; however, during the subsequent 3-month period of juice administration, a reduction in antibiotics toward UTI was observed in both groups. The incidence of UTI was reduced by 55% in group A and 38% in group B. No changes in other infections or in use of prophylactics were observed.


Disenrollment from Medicare HMOs.
Since the program's inception, there has been great interest in determining whether beneficiaries who enter and subsequently leave Medicare health maintenance organizations (HMOs) are more or less costly than those remaining in fee-for-service (FFS) Medicare. To examine whether relatively high-cost beneficiaries disenroll from Medicare HMOs (disenrollment bias) and whether disenrollment bias varies by Medicare HMO market characteristics. In addition, we compare rates of surgical procedures and hospitalizations for ambulatory care-sensitive conditions for disenrollees and continuing FFS beneficiaries. Cross-sectional analysis of 1994 Medicare data. Medicare beneficiaries were first sampled from the 124 counties with at least 1000 Medicare HMO enrollees. From this pool, HMO disenrollees and a sample of continuing FFS beneficiaries were drawn. The FFS beneficiaries were assigned dates of "pseudodisenrollment." Expenditures and inpatient service use were compared for 6 months after disenrollment or pseudodisenrollment. The HMO disenrollees were no more likely than the continuing FFS beneficiaries to have positive total expenditures (Part A plus Part B) or Part B expenditures in the first 6 months after disenrollment. However, disenrollees were more likely to have Part A expenditures. Among beneficiaries with spending, disenrollees had higher total and Part B expenditures than continuing FFS beneficiaries. Moreover, the disparity in total and Part B spending between disenrollees and continuing FFS beneficiaries increased with HMO market penetration. Although Part A spending was higher for disenrollees with spending, it was not sensitive to changes in market share. The HMO disenrollees received more surgical procedures and were hospitalized for more of the ambulatory care-sensitive conditions than the FFS beneficiaries. On several measures, Medicare HMOs experienced favorable disenrollment relative to continuing FFS beneficiaries as recently as 1994, which increased as HMO market share increased.


Birefringence and optical power confinement in horizontal multi-slot waveguides made of Si and SiO2.
Through simulations and measurements, we show that in multi-slot thin film waveguides, the TM polarized modes can be confined mostly in the low refractive index layers of the waveguide. The structure consisted of alternating layers of a-Si and SiO(2), in the thickness range between 3 and 40 nm, for which the slots were the SiO(2) layers. Simulations were performed using the transfer matrix method and experiments using the m-line technique at 1.55 mum. The dependence of the birefringence and of the power confinement in the slots was studied as a function of the waveguide thickness, the Si and SiO(2) layer thicknesses, and the SiO(2) / Si layer thickness ratio. We find a large birefringence-a refractive index difference between TE and TM modes-as large as 0.8. For TM polarized modes, up to ~ 85% of the total power in the fundamental mode can be confined in the slots.


What Are the Key Gut Microbiota Involved in Neurological Diseases? A Systematic Review.
There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.


Breast cancer screening by mammography in Norway. Is it cost-effective?
Mammography screening is a promising method for improving prognosis in breast cancer. In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50-69 years had been invited to a two-yearly mammographic screening programme 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years. The cost per woman screened was calculated 75.4 Pounds, the cost per cancer detected 10.365 Pounds and the cost per life year (LY) saved 8.561 Pounds. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death. Mammography screening in Norway looks cost-effective. Time has come to encourage national screening programmes.


Dissociation between serum neutralizing and glycoprotein antibody responses of infants and children who received inactivated respiratory syncytial virus vaccine.
The serum antibody response of infants and children immunized with Formalin-inactivated respiratory syncytial virus (RSV) vaccine 20 years ago was determined by using an enzyme-linked immunosorbent assay specific for the RSV fusion (F) and large (G) glycoproteins and a neutralization assay. Twenty-one young infants (2 to 6 months of age) developed a high titer of antibodies to the F glycoprotein but had a poor response to the G glycoprotein. Fifteen older individuals (7 to 40 months of age) developed titers of F and G antibodies comparable to those in children who were infected with RSV. However, both immunized infants and children developed a lower level of neutralizing antibodies than did individuals of comparable age with natural RSV infections. Thus, the treatment of RSV with Formalin appears to have altered the epitopes of the F or G glycoproteins or both that stimulate neutralizing antibodies, with the result that the immune response consisted largely of "nonfunctional" (i.e., nonneutralizing) antibodies. Subsequent natural infection of the vaccinees with wild-type RSV resulted in enhanced pulmonary disease. Despite this potentiation of illness, the infected vaccinees developed relatively poor G, F, and neutralizing antibody responses. Any or all of three factors may have contributed to the enhancement of disease in the RSV-infected vaccinees. First, nonfunctional antibodies induced by the inactivated RSV vaccine may have participated in a pulmonary Arthus reaction during RSV infection. Second, the poor antibody response of infants to the G glycoprotein present in the Formalin-inactivated vaccine may have been inadequate to provide effective resistance to subsequent wild-type virus infection. Third, the relatively reduced neutralizing antibody response of the infant vaccinees to wild-type RSV infection may have contributed to their enhanced disease by delaying the clearance of virus from their lungs.


The mystery of the fourth clone: comparative genomic analysis of four non-typeable Streptococcus pneumoniae strains with different susceptibilities to optochin.
Optochin-resistant pneumococci can be rarely caught in clinical microbiology laboratories because of the routine identification of all such strains as viridans group non-pneumococci. We were lucky to find four non-typeable Streptococcus pneumoniae clones demonstrating the different susceptibilities to optochin: one of them (Spn_13856) was resistant to optochin, while the other three (Spn_1719, Spn_27, and Spn_2298) were susceptible. Whole genome nucleotide sequences of these strains were compared to reveal the differences between the optochin-resistant and optochin-susceptible strains. Two adjacent genes coding maltose O-acetyltransferase and uridine phosphorylase which were presented in the genomes of all optochin-susceptible strains and missed in the optochin-resistant strain were revealed. Non-synonymous substitutions in 14 protein-coding genes were discovered, including the Ala49Ser mutation in the C-subunit of the F0 part of the ATP synthase rotor usually associated with pneumococcal optochin resistance. Modeling of a process of optochin interaction with the F0 part of the ATP synthase rotor indicates that the complex of optochin with "domain C" composed by wild-type C-subunits is more stable than the same complex composed of Ala49Ser mutant C-subunits.


Serum bilirubin levels in breast- and formula-fed infants in the first 5 days of life.
A prospective study was conducted in a level II maternity unit to investigate the incidence of hyperbilirubinemia in healthy, term, breast-fed and formula-fed infants. Serum bilirubin levels were determined for 176 breast-red and 164 formula-fed infants in cord blood and on days 1, 2, 3 and 5 after birth. The mean total bilirubin levels were significantly higher on each postnatal day in the breast-fed infants, as was the proportion of infants with peak levels above 12 mg/dl (205 mumol/l; 28% v. 6%). The breast-fed infants also had significantly higher proportional weight losses on each postnatal day than the formula-fed infants. However, there was no correlation between the cumulative weight loss on day 3 and bilirubin levels on the same day with either feeding regimen. None of the infants required an exchange transfusion or prolonged care in hospital for hyperbilirubinemia.


MicroRNAs induced in melanoma treated with combination targeted therapy of Temsirolimus and Bevacizumab.
Targeted therapies directed at commonly overexpressed pathways in melanoma have clinical activity in numerous trials. Little is known about how these therapies influence microRNA (miRNA) expression, particularly with combination regimens. Knowledge of miRNAs altered with treatment may contribute to understanding mechanisms of therapeutic effects, as well as mechanisms of tumor escape from therapy. We analyzed miRNA expression in metastatic melanoma tissue samples treated with a novel combination regimen of Temsirolimus and Bevacizumab. Given the preliminary clinical activity observed with this combination regimen, we hypothesized that we would see significant changes in miRNA expression with combination treatment. Using microarray analysis we analyzed miRNA expression levels in melanoma samples from a Cancer Therapy Evaluation Program-sponsored phase II trial of combination Temsirolimus and Bevacizumab in advanced melanoma, which elicited clinical benefit in a subset of patients. Pre-treatment and post-treatment miRNA levels were compared using paired t-tests between sample groups (patients), using a p-value < 0.01 for significance. microRNA expression remained unchanged with Temsirolimus alone; however, expression of 15 microRNAs was significantly upregulated (1.4 to 2.5-fold) with combination treatment, compared to pre-treatment levels. Interestingly, twelve of these fifteen miRNAs possess tumor suppressor capabilities. We identified 15 putative oncogenes as potential targets of the 12 tumor suppressor miRNAs, based on published experimental evidence. For 15 of 25 miRNA-target mRNA pairings, changes in gene expression from pre-treatment to post-combination treatment samples were inversely correlated with changes in miRNA expression, supporting a functional effect of those miRNA changes. Clustering analyses based on selected miRNAs suggest preliminary signatures characteristic of clinical response to combination treatment and of tumor BRAF mutational status. To our knowledge, this is the first study analyzing miRNA expression in pre-treatment and post-treatment human metastatic melanoma tissue samples. This preliminary investigation suggests miRNAs that may be involved in the mechanism of action of combination Temsirolimus and Bevacizumab in metastatic melanoma, possibly through inhibition of oncogenic pathways, and provides the preliminary basis for further functional studies of these miRNAs.


Role of estradiol in the dynamic control of tanycyte plasticity mediated by vascular endothelial cells in the median eminence.
In the ever-changing physiological context of the neuroendocrine brain, the mechanisms by which cellular events involving neurons, astroglia, and vascular cells are coordinated to bring forth the appropriate neuronal signaling is not yet known but is amenable to examination. In the median eminence of the hypothalamus, endothelial cells are key players in the plasticity of tanycytes (specialized astroglia) and neuroendocrine synapse efficacy. Here we report that estradiol acts on both purified endothelial cells and isolated tanycytes to trigger endothelial-to-glial communication that leads to a sudden and massive retraction of tanycyte processes. The blockade of endothelial nitric oxide synthase by in vitro adenoviral-mediated gene transfer of a dominant-negative form of endothelial nitric oxide synthase abrogates the estradiol-induced tanycyte plasticity mediated by endothelial cells. In parallel, increases in prostaglandin-E(2) (PGE(2)) due to changes in cyclooxygenase (COX)-1 and COX-2 expression induced by the exposure of tanycytes to estradiol promote acute tanycyte plasticity. We also demonstrate by electron microscopy that the administration of PGE(2) to median eminence explants induces rapid neuroglial plasticity at the neurovascular junction of neurons that release GnRH (the neuropeptide controlling reproduction). Conversely, preventing local PGE(2) synthesis in the median eminence of adult female rats with the COX inhibitor indomethacin impairs the ovarian cycle, a process that requires a pulsatile, coordinated delivery of GnRH into the hypothalamo-hypophyseal portal system. Taken together, our findings show that estradiol controls the dialog between endothelial cells and astroglia to regulate neuroglial plasticity in the neuroendocrine brain.


The use of transient elastometry for assessing liver fibrosis in patients with HIV and hepatitis C virus coinfection.
Transient elastometry (TE) is accurate for detecting significant liver fibrosis and cirrhosis in hepatitis C virus (HCV)-monoinfected patients. However, this procedure has been insufficiently validated in patients with human immunodeficiency virus (HIV) and HCV coinfection. The purpose of this study was to validate reported cutoff values of TE that discriminate significant liver fibrosis and cirrhosis in HIV-HCV-coinfected subjects. Liver stiffness measurements were obtained for 169 HIV-HCV-coinfected adult patients who had undergone a liver biopsy or who had received a nonhistologic diagnosis of cirrhosis within 12 months before or after a liver stiffness measurement. Patients had received no prior therapy for HCV infection. TE measurements ranged from 3.6 kPa to 75 kPa. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.84-0.93) for significant liver fibrosis and 0.95 (95% confidence interval, 0.92-0.99) for cirrhosis. To diagnose significant liver fibrosis, a cutoff value of 7.2 kPa was associated with a positive predictive value of 88% and a negative predictive value of 75%. Thirty-four patients (20%) were misclassified when this cutoff value was used. Thirteen (24%) of 54 patients with liver stiffness values <7.2 kPa had significant liver fibrosis detected by liver biopsy. To diagnose cirrhosis, a cutoff value of 14.6 kPa was associated with a positive predictive value of 86% and a negative predictive value of 94%. Thus, 13 patients (10%) had disease that was misclassified using this cutoff value. We found that the diagnostic accuracy of TE was high for detecting cirrhosis and good for diagnosis of significant liver fibrosis. However, the performance of TE was low for discriminating mild fibrosis from significant liver fibrosis, which might limit the applicability of this technique in clinical practice.


Female SHR have greater blood pressure sensitivity and renal T cell infiltration following chronic NOS inhibition than males.
Nitric oxide is a critical regulator of blood pressure (BP) and inflammation, and female spontaneously hypertensive rats (SHR) have higher renal nitric oxide bioavailability than males. We hypothesize that female SHR will have a greater rise in BP and renal T cell infiltration in response to nitric oxide synthase (NOS) inhibition than males. Both male and female SHR displayed a dose-dependent increase in BP to the nonspecific NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME: 2, 5, and 7 mg·kg(-1)·day(-1) for 4 days each); however, females exhibited a greater increase in BP than males. Treatment of male and female SHR with 7 mg·kg(-1)·day(-1) L-NAME for 2 wk significantly increased BP in both sexes; however, prior exposure to L-NAME only increased BP sensitivity to chronic NOS inhibition in females. L-NAME-induced hypertension increased renal T cell infiltration and indices of renal injury in both sexes, yet female SHR exhibited greater increases in Th17 cells and greater decreases in regulatory T cells than males. Chronic L-NAME was also associated with larger increases in renal cortical adhesion molecule expression in female SHR. The use of triple therapy to block L-NAME-mediated increases in BP attenuated L-NAME-induced increases in renal T cell counts and normalized adhesion molecule expression in SHR, suggesting that L-NAME-induced increases in renal T cells were dependent on both increases in BP and NOS inhibition. Our data suggest that NOS is critical in the ability of SHR, females in particular, to maintain BP and limit a pro-inflammatory renal T cell profile.


Differential expression of neurotrophins in postnatal C57BL/6 mice striatum.
Neurotrophin expression in early stages of development is crucial for brain assembly and function. In particular, postnatal expression of neurotrophins has not been well documented in the neostriatum and in general neurotrophins or their receptor mRNA's are normally reported, but not protein expression. In the present study, immunocytochemical expression of BDNF, NT-3 and NT-4/5 was characterized in striatal tissue of C57BL/6 mice at postnatal days 10(th )(P10), 21(st) (P21), 42(nd) (P42) and 80(th) (P80). We found that the expression of BDNF diminished along the postnatal time course we evaluated, while staining for NT-4 increased up to age P42 and remained constant, thereafter in the cell's soma. In contrast, NT-3 was first expressed in the neostriatal bundles and later on, in neostriatal cell somas. These results provide information about differences in the spatial and temporal expression of each neurotrophin in the neostriatum during the first 80(th) postnatal days. RT-PCR procedures were also carried out to further determine whether protein levels of neurotrophins observed in the neostriatum were under control of gene expression. All neurotrophin mRNAs were expressed and only mRNA(BDNF) was reduced during the postnatal evaluated days. Differences in temporal expression of neurotrophins may be related to the heterochronic development of neostriatal cell populations, but also with the specificity of each neurotrophin modulating different neuronal targets.


Characteristics, treatment and short-term survival of patients with heart failure in a cardiology private practice in Jamaica.
Randomized clinical trials have demonstrated improvement in mortality with angiotensin converting enzyme inhibitors (ACEIs), beta blockers and aldosterone antagonists. The use of these lifesaving treatments remain inadequate. To determine the clinical features, aetiology, treatment and short-term survival of heart failure in a cardiology private practice in Jamaica. This is a retrospective analysis of the medical records of 1055 consecutive patients presenting to a consultant cardiologist private practice between January 2002 and March 2003. Data were extracted from the records of the first 100 patients with heart failure. Most were over 65 years of age, female, never smoked cigarettes, overweight/obese and hypertensive (82%). The most commonly prescribed medications at one month were ACEIs (91%), beta blockers (88%) and loop diuretics (55%). The main aetiologies were hypertension (54%) and ischaemic heart disease (IHD) (26%). Ninety-one per cent were in sinus rhythm and 6% in atrial fibrillation. Forty-nine per cent had echocardiograms, of these 39% had ejection fractions (EF) > 40% and 27% had EF < or = 20%. The survival at one year was 81%. Hypertension was the major aetiology of heart failure followed by IHD. Medical treatment closely approached the recommended standards of major heart failure guidelines with high ACEI and beta blocker use comparable to recent heart failure trials. Short-term survival was very high.


UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery.
piRNAs silence transposons during germline development. In Drosophila, transcripts from heterochromatic clusters are processed into primary piRNAs in the perinuclear nuage. The nuclear DEAD box protein UAP56 has been previously implicated in mRNA splicing and export, whereas the DEAD box protein Vasa has an established role in piRNA production and localizes to nuage with the piRNA binding PIWI proteins Ago3 and Aub. We show that UAP56 colocalizes with the cluster-associated HP1 variant Rhino, that nuage granules containing Vasa localize directly across the nuclear envelope from cluster foci containing UAP56 and Rhino, and that cluster transcripts immunoprecipitate with both Vasa and UAP56. Significantly, a charge-substitution mutation that alters a conserved surface residue in UAP56 disrupts colocalization with Rhino, germline piRNA production, transposon silencing, and perinuclear localization of Vasa. We therefore propose that UAP56 and Vasa function in a piRNA-processing compartment that spans the nuclear envelope.


Oral contraceptive use and association with glucose, insulin, and diabetes in young adult women: the CARDIA Study. Coronary Artery Risk Development in Young Adults.
We studied the associations between 1) current use of oral contraceptives (OCs) and 2) glucose levels, insulin levels, and diabetes in young women. Subjects were women (n = 1,940) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective observational study of African-Americans and whites aged 18-30 years at enrollment in 1985-1986. We analyzed the cross-sectional associations between 1) current use of OCs and 2) fasting glucose, fasting insulin, and presence of diabetes using generalized estimating equations to adjust for repeated measures. We also examined the effect of current use of OCs on incident diabetes at year 10 of the study. In unadjusted analyses, current use was associated with lower fasting glucose levels [-3.1 mg/dl, 95% CI (-3.7, -2.5)] and reduction in the odds of diabetes [odds ratio 0.56 (0.32, 0.97)], but not lower fasting insulin levels [-0.01 microU/ml (-0.03, 0.02)], compared with nonuse in both African-American and white women. After adjustment for covariates, current use of OCs was still associated with lower fasting glucose levels [-1.8 mg/dl (-2.4, -1.3)] and lower odds of diabetes [odds ratio 0.56 (0.33, 0.95)], although the associations were attenuated. After adjustment, current use of OCs was associated with higher insulin levels [0.12 microU/ml (0.006, 0.23)]. No association existed between pattern of use of OCs and incident diabetes at year 10, although the total number of new persons with diabetes at year 10 was small (n = 17). Current use of OCs is associated with lower glucose levels in young African-American and white women and may be associated with lower odds of diabetes.


Comparison of anterior and posterior corneal surface irregularity in Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty.
To evaluate the irregularity of the anterior and posterior cornea after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). This clinical study comprised 39 eyes: 13 consecutive eyes after DSAEK, 13 consecutive eyes after PK, and 13 age-matched normal eyes. Corneal elevation data were acquired using a rotating Scheimpflug camera 1 and 3 months after DSAEK and PK. Anterior and posterior corneal elevation data were decomposed into a set of Zernike polynomials up to eighth order. Total higher-order root mean square (RMS) and RMS from third to eighth order were calculated. The astigmatism and irregularity of the anterior and posterior surfaces were compared between DSAEK and PK. The regular astigmatism and tilt components of the anterior surface were significantly lower after DSAEK than after PK at 1 and 3 months (P < 0.001), whereas there was no difference in astigmatism of the posterior surface between the groups (P = 0.07, 0.22). The higher-order RMS and RMSs of third- to eighth-order components of the anterior surface were significantly larger after PK than those after DSAEK at 1 and 3 months (P < 0.01), whereas there were no significant differences between DSAEK and PK in higher-order aberration RMS and RMSs of third- to eighth-order components of the posterior surface. Postoperative corneal irregularity of the anterior surface was greater after PK than after DSAEK, whereas there was no significant difference in posterior surface irregularity. DSAEK is superior to PK in terms of the higher-order irregularity of the anterior surface.


Sounds and scents in (social) action.
Although vision seems to predominate in triggering the simulation of the behaviour and mental states of others, the social perception of actions might rely on auditory and olfactory information not only when vision is lacking (e.g. in congenitally blind individuals), but also in daily life (e.g. hearing footsteps along a dark street prompts an appropriate fight-or-fly reaction and smelling the scent of coffee prompts the act of grasping a mug). Here, we review recent evidence showing that non-visual, telereceptor-mediated motor mapping might occur as an autonomous process, as well as within the context of the multimodal perceptions and representations that characterize real-world experiences. Moreover, we discuss the role of auditory and olfactory resonance in anticipating the actions of others and, therefore, in shaping social interactions.


An investigation of the mechanics of tactile sense using two-dimensional models of the primate fingertip.
Tactile information about an object in contact with the skin surface is contained in the spatio-temporal load distribution on the skin, the corresponding stresses and strains at mechanosensitive receptor locations within the skin, and the associated pattern of electrical impulses produced by the receptor population. At present, although the responses of the receptors to known stimuli can be recorded, no experimental techniques exist to observe either the load distribution on the skin or the corresponding stress-state at the receptor locations. In this paper, the role of mechanics in the neural coding of tactile information is investigated using simple models of the primate fingertip. Four models that range in geometry from a semi-infinite medium to a cylindrical finger with a rigid bone, and composed of linear elastic media, are analyzed under plane strain conditions using the finite element method. The results show that the model geometry has a significant influence on the surface load distribution as well as the subsurface stress and strain fields for a given mechanical stimulus. The elastic medium acts like a spatial low pass filter with the property that deeper the receptor location, the more blurred the tactile information. None of the models predicted the experimentally observed surface deflection profiles under line loads as closely as a simple heterogeneous waterbed model that treated the fingerpad as a membrane enclosing an incompressible fluid (Srinivasan, 1989). This waterbed model, however, predicted a uniform state of stress inside the fingertip and thus failed to explain the spatial variations observed in the neural response. For the cylindrical model indented by rectangular gratings, the maximum compressive strain and strain energy density at typical receptor locations emerged as the two strain measures that were directly related to the electrophysiologically recorded response rate of slowly adapting type I (SAI) mechanoreceptors. Strain energy density is a better candidate to be the relevant stimulus for SAIs, since it is a scalar that is invariant with respect to receptor orientations and is a direct measure of the distortion of the receptor caused by the loads imposed on the skin.


Vascular anomaly, lipoma, and polymicrogyria associated with schizencephaly: developmental and diagnostic insights. Illustrative case.
Schizencephaly is an uncommon central nervous system malformation. Intracranial lipomas are also rare, accounting for approximately 0.1% of brain "tumors." They are believed to be derived from a persistent meninx primitiva, a neural crest-derived mesenchyme that develops into the dura and leptomeninges. The authors present a case of heterotopic adipose tissue and a nonshunting arterial vascular malformation arising within a schizencephalic cleft in a 22-year-old male. Imaging showed right frontal gray matter abnormality and an associated suspected arteriovenous malformation with evidence of hemorrhage. Brain magnetic resonance imaging revealed right frontal polymicrogyria lining an open-lip schizencephaly, periventricular heterotopic gray matter, fat within the schizencephalic cleft, and gradient echo hypointensity concerning for prior hemorrhage. Histological assessment demonstrated mature adipose tissue with large-bore, thick-walled, irregular arteries. Mural calcifications and subendothelial cushions suggesting nonlaminar blood flow were observed. There were no arterialized veins or direct transitions from the arteries to veins. Hemosiderin deposition was scant, and hemorrhage was not present. The final diagnosis was consistent with ectopic mature adipose tissue and arteries with meningocerebral cicatrix. This example of a complex maldevelopment of derivatives of the meninx primitiva in association with cortical maldevelopment highlights the unique challenges from both a radiological and histological perspective during diagnostic workup.


Malaria caused by Plasmodium vivax: recurrent, difficult to treat, disabling, and threatening to life--the infectious bite preempts these hazards.
The maxim 'an ounce of prevention is worth a pound of cure' finds few better demonstrations than with malaria caused by Plasmodium vivax. Thoroughly neglected over the past 60 years, the chemotherapy of this complex infection has been dangerous and ineffective until the present. Work is at last being done, but seeing that translate to real improvements at the periphery of care delivery will take years of deliberate effort. In the meantime, patients face substantial risk of debilitating, threatening, and fatal courses of illness associated with a diagnosis of vivax malaria. For some of the most vulnerable to such outcomes--pregnant women and infants--repeated attacks of acute vivax malaria from a single infectious anopheline bite is now not preventable. One of the few measures than can be immediately applied with rigor is vector control, thereby effectively preventing as many of these difficult and dangerous infections as possible. This commentary emphasizes the dire consequences of infection by P. vivax and the real difficulty of dealing with them. That, in turn, emphasizes the many benefits to be derived by preventing them in the first place.


Detection and analysis of statistical differences in anatomical shape.
We present a computational framework for image-based analysis and interpretation of statistical differences in anatomical shape between populations. Applications of such analysis include understanding developmental and anatomical aspects of disorders when comparing patients versus normal controls, studying morphological changes caused by aging, or even differences in normal anatomy, for example, differences between genders. Once a quantitative description of organ shape is extracted from input images, the problem of identifying differences between the two groups can be reduced to one of the classical questions in machine learning of constructing a classifier function for assigning new examples to one of the two groups while making as few misclassifications as possible. The resulting classifier must be interpreted in terms of shape differences between the two groups back in the image domain. We demonstrate a novel approach to such interpretation that allows us to argue about the identified shape differences in anatomically meaningful terms of organ deformation. Given a classifier function in the feature space, we derive a deformation that corresponds to the differences between the two classes while ignoring shape variability within each class. Based on this approach, we present a system for statistical shape analysis using distance transforms for shape representation and the support vector machines learning algorithm for the optimal classifier estimation and demonstrate it on artificially generated data sets, as well as real medical studies.


Short-latency afferent inhibition during selective finger movement.
During individual finger movement, two opposite phenomena occur at the level of the central nervous system that could affect other intrinsic hand muscle representations, unintentional co-activation, and surround inhibition (SI). At rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after electric stimulation of a peripheral nerve [short-latency afferent inhibition (SAI)]. We sought to determine whether SAI changes during selective index finger movement. Effects were measured by the response to transcranial magnetic stimulation in two functionally distinct target muscles of the hand [abductor digiti minimi muscle (ADM), first dorsal interosseus muscle (FDI)]. An increase in SAI in the ADM during index finger movement compared to at rest could help explain the genesis of SI. Electrical stimulation was applied to either the little finger (homotopic for ADM, heterotopic for FDI) or the index finger (heterotopic for ADM, homotopic for FDI). During index finger movement, homotopic SAI was present only in the ADM, and the effect of peripheral stimulation was greater when there was less co-activation. Heterotopic SAI found at rest disappeared with movement. We conclude that during movement, homotopic SAI on the muscle in the surround of the intended movement may contribute to SI.


Gastrointestinal distress is common during a 161-km ultramarathon.
This study examined the incidence, severity, and timing of gastrointestinal (GI) symptoms in finishers and non-finishers of the 161-km Western States Endurance Run. A total of 272 runners (71.0% of starters) completed a post-race questionnaire that assessed the incidence and severity (none = 0, mild = 1, moderate = 2, severe = 3, very severe = 4) of 12 upper (reflux/heartburn, belching, stomach bloating, stomach cramps/pain, nausea, vomiting) and lower (intestinal cramps/pain, flatulence, side ache/stitch, urge to defecate, loose stool/diarrhoea, intestinal bleeding/bloody faeces) GI symptoms experienced during each of four race segments. GI symptoms were experienced by most runners (96.0%). Flatulence (65.9% frequency, mean value 1.0, s = 0.6 severity), belching (61.3% frequency, mean value 1.0, s = 0.6 severity), and nausea (60.3% frequency, mean value 1.0, s = 0.7 severity) were the most common symptoms. Among race finishers, 43.9% reported that GI symptoms affected their race performance, with nausea being the most common symptom (86.0%). Among race non-finishers, 35.6% reported that GI symptoms were a reason for dropping out of the race, with nausea being the most common symptom (90.5%). For both finishers and non-finishers, nausea was greatest during the most challenging and hottest part of the race. GI symptoms are very common during ultramarathon running, and in particular, nausea is the most common complaint for finishers and non-finishers.


PSMD12 haploinsufficiency in a neurodevelopmental disorder with autistic features.
Protein homeostasis is tightly regulated by the ubiquitin proteasome pathway. Disruption of this pathway gives rise to a host of neurological disorders. Through whole exome sequencing (WES) in families with neurodevelopmental disorders, we identified mutations in PSMD12, a core component of the proteasome, underlying a neurodevelopmental disorder with intellectual disability (ID) and features of autism spectrum disorder (ASD). We performed WES on six affected siblings from a multiplex family with ID and autistic features, the affected father, and two unaffected mothers, and a trio from a simplex family with one affected child with ID and periventricular nodular heterotopia. We identified an inherited heterozygous nonsense mutation in PSMD12 (NM_002816: c.367C>T: p.R123X) in the multiplex family and a de novo nonsense mutation in the same gene (NM_002816: c.601C>T: p.R201X) in the simplex family. PSMD12 encodes a non-ATPase regulatory subunit of the 26S proteasome. We confirm the association of PSMD12 with ID, present the first cases of inherited PSMD12 mutation, and demonstrate the heterogeneity of phenotypes associated with PSMD12 mutations.


The effects of repeated intra-amygdala CRF injections on rat behavior and HPA axis function after stress.
Patients diagnosed with certain anxiety disorders or depression show symptoms of a dysregulated HPA-axis secondary to increased release of corticotropin releasing factor (CRF). Male Wistar rats were injected with CRF (100 ng/microL) in the basolateral amygdala (BLA) for 5 days. Measurement of behavior was performed on the elevated plus maze and open field test. Behavioral and neuroendocrine response to restraint stress was also evaluated. Chronic treatment of CRF resulted in a significant increase in grooming after restraint stress in the Open Field test. Basal plasma corticosterone concentrations were significantly lower in the CRF-injected rats. These animals also showed greater and longer increase in corticosterone levels following the restraint stress than controls, but had comparable ACTH responses to restraint stress. Our results indicate that chronic administration of CRF into the basolateral amygdala may promote stress-induced grooming behavior in rats. In addition the data suggests that increased CRF in the amygdala may contribute to the dysregulation of corticosterone secretion. These findings may have important implications for patients suffering from psychiatric illnesses such as posttraumatic stress disorder and depression that are characterized by abnormalities in cortisol release.


Gamma Knife radiosurgery of saccular aneurysms in a rabbit model.
OBJECTIVEIntracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation. The aim of this study was to determine the efficacy of GKRS treatment in a saccular aneurysm animal model.METHODSAneurysms were surgically produced using an elastase-induced aneurysm model in the right common carotid artery of 10 New Zealand white rabbits. Following initial observation for 4 years, each rabbit aneurysm was treated with a conformal GKRS isodose of 25 Gy to the 50% margin. Longitudinal MRI studies obtained over 2 years and terminal measures obtained at multiple time points were used to track aneurysm size and shape index modifications.RESULTSAneurysms did not rupture or involute during the observation period. Whole aneurysm and blood volume averages decreased with a linear trend, at rates of 1.7% and 1.6% per month, respectively, over 24 months. Aneurysm wall percent volume increased linearly at a rate of 0.3% per month, indicating a relative thickening of the aneurysm wall during occlusion. Nonsphericity of the average volume, aspect ratio, and isoperimetric ratio of whole aneurysm volume all remained constant. Histopathological samples demonstrated progressive reduction in aneurysm size and wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate stable aneurysm patency and maintenance of minimal rupture risk following treatment.CONCLUSIONSThe data indicate that GKRS targeted to saccular aneurysms is associated with histopathological changes and linear reduction of aneurysm size over time. The results suggest that GKRS may be a viable, minimally invasive treatment option for intracranial aneurysm obliteration.


Population structure and local selection yield high genomic variation in Mimulus guttatus.
Across western North America, Mimulus guttatus exists as many local populations adapted to site-specific environmental challenges. Gene flow between locally adapted populations will affect genetic diversity both within demes and across the larger metapopulation. Here, we analyse 34 whole-genome sequences from the intensively studied Iron Mountain population (IM) in conjunction with sequences from 22 Mimulus individuals sampled from across western North America. Three striking features of these data address hypotheses about migration and selection in a locally adapted population. First, we find very high levels of intrapopulation polymorphism (synonymous π = 0.033). Variation outside of genes is likely even higher but difficult to estimate because excessive divergence reduces the efficiency of read mapping. Second, IM exhibits a significantly positive genomewide average for Tajima's D. This indicates allele frequencies are typically more intermediate than expected from neutrality, opposite the pattern observed in many other species. Third, IM exhibits a distinctive haplotype structure with a genomewide excess of positive associations between rarer alleles at linked loci. This suggests an important effect of gene flow from other Mimulus populations, although a residual effect of population founding might also contribute. The combination of multiple analyses, including a novel tree-based analytic method, illustrates how the balance of local selection, limited dispersal and metapopulation dynamics manifests across the genome. The overall genomic pattern of sequence diversity suggests successful gene flow of divergent immigrant genotypes into IM. However, many loci show patterns indicative of local adaptation, particularly at SNPs associated with chromosomal inversions.


Long-term nicotine exposure-induced chemoresistance is mediated by activation of Stat3 and downregulation of ERK1/2 via nAChR and beta-adrenoceptors in human bladder cancer cells.
Previous reports suggested that bladder cancer patients who continue to smoke while receiving chemotherapy have poorer outcomes than their nonsmoking counterparts. Nicotine, the major addictive compound in cigarette smoke, is known to induce chemoresistance in some cancer cells. Chemoresistance has been linked to the activation of Stat3 (signal transducer and activator of transcription). The objective of this study was to identify the role of Stat3 in chemoresistance induced by nicotine in human bladder cancer cell line, T24 cells. Chemoresistant T24 cells were established by persistent nicotine treatment. Apoptosis and cell cycle parameters were analyzed by Annexin V staining, poly(ADP-ribose) polymerase degradation, caspase activity, and propidium iodide staining. Signal transduction mediating the chemoresistance was detected by Western blotting and small interfering RNA (siRNA) transfection. We provide evidence for the first time that nicotine strongly activated Stat3, leading to Cyclin D1 overexpression, cell cycle perturbations, and chemoresistance. Furthermore, nicotine mobilized Stat3 signaling, resulting in the loss of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) activation and reduced chemosensitivity via nicotinic acetylcholine receptors and beta-adrenoceptors. Inhibition of Stat3 by siRNA or a specific inhibitor restored chemosensitivity in T24 cells. Stat3 could be the major target for increasing chemosensitivity in patients who develop chemoresistance during chemotherapy, and avoidance of cigarette smoking or nicotine-based treatments may increase the efficacy of chemotherapy.


Brain pathological changes during neurodegenerative diseases and their identification methods: How does QSM perform in detecting this process?
The presence of iron is essential for many biological processes in the body. But sometimes, for various reasons, the amount of iron deposition in different areas of the brain increases, which leads to problems related to the nervous system. Quantitative susceptibility mapping (QSM) is one of the newest magnetic resonance imaging (MRI)-based methods for assessing iron accumulation in target areas. This Narrative Review article aims to evaluate the performance of QSM compared to other methods of assessing iron deposition in the clinical field. Based on the results, we introduced related basic definitions, some neurodegenerative diseases, methods of examining iron deposition in these diseases, and their advantages and disadvantages. This article states that the QSM method can be introduced as a new, reliable, and non-invasive technique for clinical evaluations.


[Antibacterial effect of self-etching adhesive systems on Streptococcus mutans].
To investigate the antibacterial effect of different self-etching adhesive systems against Streptococcus mutans (S. mutans). Six reagents Clearfil(TM) SE Bond primer (SP), Clearfil(TM) SE Bond adhesive (SA),Clearfil(TM) Protect Bond primer (PP), which contained antibacterial monomer methacryloyloxydodecylpyridinium bromide (MDPB), ClearfilTM Protect Bond adhesive (PA), positive control chlorhexidine acetate [CHX, 1% (mass fraction)], and negative control phosphate buffer solution (PBS) were selected. They were mixed with S. mutans for 30 s respectively, then colony-forming units (CFU) were counted after incubated for 48 h on brain heart infusion (BHI) agar medium. The 6 reagents were applied to the sterile paper discs, and distributed onto the BHI agar medium with S. mutans and incubated for 24 h, then the inhibition zones were observed. CHX, PBS, PP, and SP were added on the dentin with artificial caries induced by S. mutans and kept for 30 s, then confocal laser scanning microscope (CLSM) was used to observe the live and dead bacteria after staining. The ratio of live to dead bacteria was calculated. PP+PA and SP+SA were applied on the dentin according to the manual and light cured. S. mutans were incubated on the samples for 2 h, ultrasonically treated and incubated on BHI agar medium for 48 h, then CFU was counted. The data were analyzed by non-parametric analysis and one-way ANOVA. Compared with PBS, the PP, SP, PA, SA and CHX showed the antibacterial effect on free S. mutans (P<0.05); SP and PP showed stronger antibacterial effect than PA, SA and CHX (P<0.05). CHX, SP and PP presented inhibition zones, while PBS, SA and PA did not. Compared with PBS, the CHX, SP and PP could lower the ratio of the live to dead bacteria significantly (P<0.05). Cured self-etching adhesive systems did not show any antibacterial effect on the free S. mutans. The primer of self-etching adhesives Clearfil(TM) SE Bond and Clearfil(TM) Protect Bond showed significant antibacterial effect on free and attached S. mutans. The adhesive only showed antibacterial effect on free S. mutans before light-cured polymerization. After being cured, the self-etching adhesive systems did not show antibacterial effect anymore.


Nutraceutical formulation, characterisation, and in-vitro evaluation of methylselenocysteine and selenocystine using food derived chitosan:zein nanoparticles.
Selenoamino acids (SeAAs) have been shown to possess antioxidant and anticancer properties. However, their bioaccessibility is low and they may be toxic above the recommended nutritional intake level, thus improved targeted oral delivery methods are desirable. In this work, the SeAAs, Methylselenocysteine (MSC) and selenocystine (SeCys2) were encapsulated into nanoparticles (NPs) using the mucoadhesive polymer chitosan (Cs), via ionotropic gelation with tripolyphosphate (TPP) and the NPs produced were then coated with zein (a maize derived prolamine rich protein). NPs with optimized physicochemical properties for oral delivery were obtained at a 6: 1 ratio of Cs:TPP, with a 1:0.75 mass ratio of Cs:zein coating (diameter ~260 nm, polydispersivity index ~0.2, zeta potential >30 mV). Scanning Electron Microscopy (SEM) analysis showed that spheroidal, well distributed particles were obtained. Encapsulation Efficiencies of 80.7% and 78.9% were achieved, respectively, for MSC and SeCys2 loaded NPs. Cytotoxicity studies of MSC loaded NPs showed no decrease in cellular viability in either Caco-2 (intestine) or HepG2 (liver) cells after 4 and 72 h exposures. For SeCys2 loaded NPs, although no cytotoxicity was observed in Caco-2 cells after 4 h, a significant reduction in cytotoxicity was observed, compared to pure SeCys2, across all test concentrations in HepG2 after 72 h exposure. Accelerated thermal stability testing of both loaded NPs indicated good stability under normal storage conditions. Lastly, after 6 h exposure to simulated gastrointestinal tract environments, the sustained release profile of the formulation showed that 62 ± 8% and 69 ± 4% of MSC and SeCys2, had been released from the NPs respectively.


Thirty-day complication and readmission rates associated with resection of metastatic spinal tumors: a single institutional experience.
This study aims to assess 30-day complication and unplanned readmission rates associated with resection of metastatic spinal tumors. Medical records were reviewed for 135 adults who underwent elective resection of a spinal cord tumor. Patient demographics, comorbidities, and tumor characteristics were collected. Tumor pathology was analyzed and diagnosed by a pathologist. The primary outcomes were intra- and 30-day post-operative complication and readmission rates. Of the 135 spinal tumor resections, 30 (22.2%) cases were metastatic. The most common tumor pathology was bone (13.3%) and the most common locations were thoracic (45.2%), and cervical (32.7%). Most patients had an open surgery (96.7%), with a mean laminectomy/laminoplasty level of 1.9±1.5 and mean operative time of 328.4±658.0 min. There was a 3.3% incidence rate of intraoperative durotomies, with no spinal cord or nerve root injuries. Post-operatively, 44.8% of patients were transferred to the intensive care unit (ICU). The most common post-operative complications were weakness (20.0%), new sensory deficits (16.7%), and hypotension (13.3%). The mean length of stay was 8.8±7.6 days, with the majority of patients discharged home (96.7%). The 30-day readmission rate was 9.7%, with the most common 30-day complications being uncontrolled pain (16.7%), sensory-motor deficits (13.3%), and fever (10.0%). Our study suggests that weakness, sensory deficits, and uncontrolled pain are the most common complications after resection of spinal metastases, with a relatively high associated 30-day readmission rate. Further studies are necessary to corroborate our findings and identify strategies to reduce complication and readmission rates after resection of spinal metastases.


Health-related Quality of Life in Infants With Chronic Liver Disease.
The objective of the present study was to report on the health-related quality of life (HRQOL) of infants with chronic liver disease using the PedsQL (Pediatric Quality of Life Inventory) Infant Scales. The 36-item (ages 1-12 months) and 45-item (ages 13-24 months) PedsQL Infant Scales (physical functioning, physical symptoms, emotional functioning, social functioning, cognitive functioning) were completed by 50 parents of infants with chronic liver disease. Infants ages 1 to 12 months had significantly lower HRQOL scores compared with a matched healthy sample. Infants 13 to 24 months trended to lower physical HRQOL scores that did not reach statistical significance. Recent hospitalizations had an impact on the majority of HRQOL subscales, as did ascites, and failure to thrive. Infants ages 1 to 12 months with chronic liver disease demonstrate lower HRQOL compared with healthy children with physical subscales being most severely affected. The PedsQL Infant Scales allow the definition of HRQOL during a critical period of an infants' development that has been heretofore difficult to measure.


Molecular analysis of the serotyping antigens of Neisseria meningitidis.
Molecular approaches to the rapid analysis of the serotyping antigens of Neisseria meningitidis, the class 2 and 3 outer membrane proteins (OMPs), were developed, evaluated, and used to study 12 antigenic variants of these proteins. A primer set for the polymerase chain reaction (PCR) amplification of the genes encoding these antigens was devised. Low-stringency amplification of meningococcal chromosomal DNA with this primer set resulted in the amplification of two products from each strain, whereas at higher stringencies only one product was amplified in most strains. Southern hybridization techniques and restriction analyses were used to differentiate the PCR products amplified at high stringencies from strains expressing class 2 or class 3 OMPs; these PCR products were further characterized by the determination of their nucleotide sequences, confirming that they represented the amplified class 2 and class 3 OMP genes. Analyses of these and other nucleotide sequences enabled the construction of a phenogram illustrating the interrelationships between Neisseria OMP genes. The comparative analysis of deduced amino acid sequences revealed conserved and variable regions of the proteins; the latter probably correspond to surface loops on the protein and hence are potentially exposed to the immune system. Further analyses of the primary structures of these related porins from Neisseria species enabled construction of models of the secondary structure of these antigens and comparison of these models with those previously published. The methods reported in the present work are rapid reproducible procedures for the analysis of antigenic variants of these proteins.


Poaching and human encroachment reverse recovery of African savannah elephants in south-east Angola despite 14 years of peace.
With populations of African savannah elephants (Loxodonta africana) declining across the continent, assessing the status of individual elephant populations is important for conservation. Angola's elephant population represents a key linkage between the larger populations of Namibia and Botswana. Elephants in Angola were decimated during the 1975-2002 Angolan civil war, but a 2005 survey showed that populations were recolonizing former habitats. Between 2005 and 2015, no research was permitted on elephants in Angola, but elsewhere in Africa many elephant populations experienced a poaching crisis. In 2015, we were able to resume elephant research in Angola. We used aerial surveys and satellite monitoring of collared elephants to determine the current status of elephant populations in Angola and to learn how human populations may be affecting elephant habitat usage. The aerial survey revealed a population of 3,395 ± SE of 797 elephants, but populations had declined 21% from the 2005 estimate. The high number of carcasses observed on the survey suggests that populations may have increased after the 2005 survey but were declining rapidly as of 2015. Satellite-collared elephants avoided areas <6 km from human indicators but preferred areas nearer humans at scales of 6-40 km, suggesting that humans may be displacing elephants from preferred habitats near rivers. Taken together, these results suggest that Angola's elephant population is experiencing intense poaching and may be losing habitat to human settlements. Without action to conserve their populations, Angola's elephants face an uncertain future.


Combined inactivation and expression strategy to study gene function under physiological conditions: application to identification of new Escherichia coli adhesins.
In bacteria, whereas disruption methods have been improved recently, the use of plasmid complementation strategies are still subject to limitations, such as cloning difficulties, nonphysiological levels of gene expression, or a requirement for antibiotics as plasmid selection pressure. Moreover, because of the pleiotropic modifications of cell physiology often induced by plasmid-based complementation, these strategies may introduce biases when biological process such as adhesion or biofilm formation are studied. We developed a plasmid-free approach that combines the lambda-red linear DNA recombination method with site-directed insertion of a repression and expression (RExBAD) cassette which places a functional pBAD promoter upstream of a target gene. We showed that this method permits both inactivation and modulation of most Escherichia coli gene expression, including expression of toxin and essential genes. We used this strategy to study adhesion and bacterial biofilms by placing the RExBAD cassette in front of the tra operon, encoding the DNA transfer and pilus genes on the F conjugative plasmid, and in front of flu, the antigen 43 (Ag43) autotransporter adhesin-encoding gene. In silico analysis revealed the existence of 10 genes with homology to the Ag43 gene that were good candidates for genes that encode putative new adhesins in E. coli. We used the RExBAD strategy to study these genes and demonstrated that induction of expression of four of them is associated with adhesion of E. coli to abiotic surfaces. The potential use of the RExBAD approach to study the function of cryptic or uncharacterized genes in large-scale postgenomic functional analyses is discussed.


The role of ecology, neutral processes and antagonistic coevolution in an apparent sexual arms race.
Some of the strongest examples of a sexual 'arms race' come from observations of correlated evolution in sexually antagonistic traits among populations. However, it remains unclear whether these cases truly represent sexually antagonistic coevolution; alternatively, ecological or neutral processes might also drive correlated evolution. To investigate these alternatives, we evaluated the contributions of intersex genetic correlations, ecological context, neutral genetic divergence and sexual coevolution in the correlated evolution of antagonistic traits among populations of Gerris incognitus water striders. We could not detect intersex genetic correlations for these sexually antagonistic traits. Ecological variation was related to population variation in the key female antagonistic trait (spine length, a defence against males), as well as body size. Nevertheless, population covariation between sexually antagonistic traits remained substantial and significant even after accounting for all of these processes. Our results therefore provide strong evidence for a contemporary sexual arms race.


Molecular breast imaging: advantages and limitations of a scintimammographic technique in patients with small breast tumors.
Preliminary studies from our laboratory showed that molecular breast imaging (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work to a larger patient population and examines the technical factors that influence the ability of MBI to detect small breast tumors. Following injection of 740 MBq Tc-99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a lesion suspicious for malignancy that measured <2 cm on mammography or sonography. Using a small field of view gamma camera, patients were imaged in the standard mammographic views using light pain-free compression. Subjective discomfort, breast thickness, the amount of breast tissue in the detector field of view, and breast counts per unit area were measured and recorded. Follow-up was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity was 29%, 86%, and 97% for tumors <5, 6-10, and > or =11 mm in diameter, respectively. In seven patients, MBI identified eight additional mammographically occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery, there were 36 true negative and 11 false positive scans on MBI. MBI has potential for the regular detection of malignant breast tumors less than 2 cm in diameter. Work in progress to optimize the imaging parameters and technique may further improve sensitivity and specificity.


[Etiology and epidemiological characterization of non-malarial febrile syndrome in three municipalities of Urabá (Antioquia), Colombia].
Urabá, a region on the northern coast of Colombia, is endemic to several acute febrile illnesses of infectious origin; however, only patients with malaria may have access to quick and effective diagnosis. For this reason, many non-malarial febrile patients go without a clear etiologic diagnosis. To establish the etiology and clinical signs of acute febrile non-malaria syndromes and explore some of the likely risk factors in patients originating in the municipalities of Necocli, Turbo and Apartado who exhibit these symptoms. We obtained acute and convalescent sera from 220 non-malarial febrile patients from the rural and urban zones of Necocli, Turbo and Apartado during 2007 and 2008. Serologic tests for dengue (IgM by ELISA), leptospirosis (IgM and IgG by IFA), rickettsiosis (IgG by IFI), hanta and arenavirus (IgG by ELISA) were performed. We found that the frequency of infection for dengue, leptospirosis, rickettsiosis and arenavirus, was 37.3%; 14.1%; 2.7% and 0.5%, respectively. There were 12 co-infection cases of leptospirosis-dengue and one of leptospirosis-rickettsiosis-dengue. Male gender and relative humidity were considered risk factors for dengue, and the beginning of clinical signs in February of 2008 was associated with the infection of dengue and leptospirosis. This study confirms previous records that underline the importance of Rickettsia spp, dengue virus and Leptospira spp as causal agents of febrile syndrome in this region of Colombia.


Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.
Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion.


The serotonin transporter gene (5-HTT) variant and psychiatric disorders: review of current literature.
Both serotonin and the serotonin transporter, which transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons, play an important role in the pathophysiology of several psychiatric disorders. Mutations associated with the serotonin transporter gene may result in changes in serotonin transporter function. The serotonin transporter gene promoter variant, consisting of a long (L) and a short (S) variant, is one of the major factors which contribute to the etiology of many psychiatric disorders. In this regard, many studies have been published on association of this variant with various psychiatric disorders. This repeat length variant in the promoter region of this gene has been shown to affect the rate of serotonin uptake and may play a role in post-traumatic stress disorder and depression-susceptibility in people experiencing emotional trauma. Associations between a functional variant in the serotonin transporter anxiety-related personality traits were found, as well as the risk of developing depression, alcoholism or suicidal behavior. Understanding of possible associations of these variants and psychiatric disorders would bring progress in principles and treatment of many disorders.


An automatic method to generate domain-specific investigator networks using PubMed abstracts.
Collaboration among investigators has become critical to scientific research. This includes ad hoc collaboration established through personal contacts as well as formal consortia established by funding agencies. Continued growth in online resources for scientific research and communication has promoted the development of highly networked research communities. Extending these networks globally requires identifying additional investigators in a given domain, profiling their research interests, and collecting current contact information. We present a novel strategy for building investigator networks dynamically and producing detailed investigator profiles using data available in PubMed abstracts. We developed a novel strategy to obtain detailed investigator information by automatically parsing the affiliation string in PubMed records. We illustrated the results by using a published literature database in human genome epidemiology (HuGE Pub Lit) as a test case. Our parsing strategy extracted country information from 92.1% of the affiliation strings in a random sample of PubMed records and in 97.0% of HuGE records, with accuracies of 94.0% and 91.0%, respectively. Institution information was parsed from 91.3% of the general PubMed records (accuracy 86.8%) and from 94.2% of HuGE PubMed records (accuracy 87.0). We demonstrated the application of our approach to dynamic creation of investigator networks by creating a prototype information system containing a large database of PubMed abstracts relevant to human genome epidemiology (HuGE Pub Lit), indexed using PubMed medical subject headings converted to Unified Medical Language System concepts. Our method was able to identify 70-90% of the investigators/collaborators in three different human genetics fields; it also successfully identified 9 of 10 genetics investigators within the PREBIC network, an existing preterm birth research network. We successfully created a web-based prototype capable of creating domain-specific investigator networks based on an application that accurately generates detailed investigator profiles from PubMed abstracts combined with robust standard vocabularies. This approach could be used for other biomedical fields to efficiently establish domain-specific investigator networks.


Effects of kinesiotape on pain and disability in individuals with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.
To explore the effects of kinesiotape on pain and disability in individuals with chronic low back pain. PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched for English language publications from inception to 13 February 2018. This study was registered in PROSPERO (CRD42018089831). Our key search terms were ((kinesio taping) OR (kinesiotaping) OR (kinesiotape)) AND (low back pain). Randomized controlled trials evaluating the effects of kinesiotape published in English language were included in this review. The reference lists of retrieved studies and relevant reviews were also searched. Quality of the included trials was assessed according to 2015 updated Cochrane Back and Neck Review Group 13-Item criteria. A total of 10 articles were included in this meta-analysis. A total of 627 participants were involved, with 317 in the kinesiotape group and 310 in the control group. The effects of kinesiotape on pain and disability were explored. While kinesiotape was not superior to placebo taping in pain reduction, either alone ( P = 0.07) or in conjunction with physical therapy ( P = 0.08), it could significantly improve disability when compared to the placebo taping ( P < 0.05). Since kinesiotape is convenient for application, it could be used for individuals with chronic low back pain in some cases, especially when the patients could not get other physical therapy.


Problems with a great idea: referral by prehospital emergency services to a community-based falls-prevention service.
Falls are the leading cause of injury in older adults. Identifying people at risk before they experience a serious fall requiring hospitalisation allows an opportunity to intervene earlier and potentially reduce further falls and subsequent healthcare costs. The purpose of this project was to develop a referral pathway to a community falls-prevention team for older people who had experienced a fall attended by a paramedic service and who were not transported to hospital. It was also hypothesised that providing intervention to this group of clients would reduce future falls-related ambulance call-outs, emergency department presentations and hospital admissions. An education package, referral pathway and follow-up procedures were developed. Both services had regular meetings, and work shadowing with the paramedics was also trialled to encourage more referrals. A range of demographic and other outcome measures were collected to compare people referred through the paramedic pathway and through traditional pathways. Internal data from the Queensland Ambulance Service indicated that there were approximately six falls per week by community-dwelling older persons in the eligible service catchment area (south west Brisbane metropolitan area) who were attended to by Queensland Ambulance Service paramedics, but not transported to hospital during the 2-year study period (2008-2009). Of the potential 638 eligible patients, only 17 (2.6%) were referred for a falls assessment. Although this pilot programme had support from all levels of management as well as from the service providers, it did not translate into actual referrals. Several explanations are provided for these preliminary findings.


Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene.
von Hippel-Lindau (VHL) disease is a multisystem inherited cancer syndrome characterized by the development of highly vascular tumors including hemangioblastomas of the retina and central nervous system, pheochromocytomas, and clear cell renal carcinoma, which result from somatic inactivation of the wild-type VHL allele in cells harboring a germ-line VHL mutation. Homozygous inactivation of the VHL gene in mice resulted in embryonic lethality. To produce a mouse model that closely mimics human VHL disease and avoids embryonic lethality, we used Cre/lox site-specific recombination technology. We generated mice carrying conditional VHL alleles and a cre transgene under the control of the human beta-actin promoter, which directs cre expression in a mosaic pattern in multiple organs. VHL(f/d)/Cre mice developed multiple, hepatic hemangiomas that led to premature death, as well as angiectasis and angiogenesis in multiple organs. Interestingly, testes of male VHL(f/d)/Cre mice were unusually small with severely reduced sperm count resulting in infertility. Loss of pVHL function in this VHL conditional knockout mouse model results in an extensive abnormal vascular phenotype in multiple mouse organs, which will provide a useful animal model for testing potential antiangiogenic therapies for VHL disease treatment. Importantly, the phenotypic defects in sperm development observed in these mice support a novel role for VHL in spermatogenesis. This VHL conditional knockout mouse model will provide an in vivo system for studying the functional requirement of the VHL gene in reproductive biology.


Forced GATA-1 expression in the murine myeloid cell line M1: induction of c-Mpl expression and megakaryocytic/erythroid differentiation.
The "zinc-finger" transcription factor GATA-1 was first shown in cells of erythroid lineage. It is also expressed in cells of other hematopoietic lineages including megakaryocytes, mast cells, and eosinophils. GATA-1 is now considered to be one of the central regulators in hematopoietic cell differentiation. To further analyze the role of GATA-1 in controlling differentiation from hematopoietic stem cells, we investigated the phenotypic changes induced by the overexpression of murine GATA-1 in the murine myeloid leukemic cell line, M1. Forced expression of GATA-1 induced the appearance of erythroid cells and megakaryocytes as assessed by cellular morphology, acetylcholinesterase activity, and expression of platelet factor 4 and beta-globin mRNA synthesis. Because the c-mpl ligand, thrombopoietin, plays an important role in megakaryopoiesis, the expression of c-mpl and c-mpl ligand (thrombopoietin) mRNA was analyzed by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) in M1 cells overexpressing GATA-1. The c-mpl ligand mRNA was equally expressed both in parental M1 cells and in those transfected with the GATA-1 expression vector. In contrast, the mRNA expression of c-mpl was increased only in GATA-1 expressing M1 cells differentiated towards erythroid and megakaryocyte lineages. The increased expression of c-mpl mRNA induced by GATA-1 raised the question as to whether or not GATA-1 transactivated the c-mpl promoter. The activity of the c-mpl promoter in the presence of cotransfected GATA-1 was significantly increased compared with that of the control. A plasmid with the mutated GATA-binding site did not show transactivation ability in the cotransfection with a GATA expression vector. These findings suggest that the upregulation of c-mpl induced by GATA-1 expression in M1 cells is closely associated with erythroid and megakaryocytic differentiation.


Astroglial monoacylglycerol lipase controls mutant huntingtin-induced damage of striatal neurons.
Cannabinoids exert neuroprotection in a wide array of preclinical models. A number of these studies has focused on cannabinoid CB1 receptors in striatal medium spiny neurons (MSNs) and the most characteristic MSN-degenerative disease, Huntington's disease (HD). Accruing evidence supports that astrocytes contribute to drive HD progression, and that they express CB1 receptors, degrade endocannabinoids, and modulate endocannabinergic transmission. However, the possible role of the astroglial endocannabinoid system in controlling MSN integrity remains unknown. Here, we show that JZL-184, a selective inhibitor of monoacylglycerol lipase (MGL), the key enzyme that deactivates the endocannabinoid 2-arachidonoylglycerol, prevented the mutant huntingtin-induced up-regulation of the pro-inflammatory cytokine tumor necrosis factor-α in primary mouse striatal astrocytes via CB1 receptors. To study the role of astroglial MGL in vivo, we injected stereotactically into the mouse dorsal striatum viral vectors that encode mutant or normal huntingtin under the control of the glial fibrillary acidic protein promoter. We observed that, in wild-type mice, pharmacological blockade of MGL with JZL-184 (8 mg/kg/day, i.p.) conferred neuroprotection against mutant huntingtin-induced striatal damage, as evidenced by the prevention of MSN loss, astrogliosis, and motor coordination impairment. We next found that conditional mutant mice bearing a genetic deletion of MGL selectively in astroglial cells (MGLfloxed/floxed;GFAP-Cre/+ mice) were resistant to mutant huntingtin-induced MSN loss, astrogliosis, and motor coordination impairment. Taken together, these data support that astroglial MGL controls the availability of a 2-arachidonoylglycerol pool that ensues protection of MSNs in the mouse striatum in vivo, thus providing a potential druggable target for reducing striatal neurodegeneration.


Characterization of Ferroplasma isolates and Ferroplasma acidarmanus sp. nov., extreme acidophiles from acid mine drainage and industrial bioleaching environments.
Three recently isolated extremely acidophilic archaeal strains have been shown to be phylogenetically similar to Ferroplasma acidiphilum Y(T) by 16S rRNA gene sequencing. All four Ferroplasma isolates were capable of growing chemoorganotrophically on yeast extract or a range of sugars and chemomixotrophically on ferrous iron and yeast extract or sugars, and isolate "Ferroplasma acidarmanus" Fer1(T) required much higher levels of organic carbon. All four isolates were facultative anaerobes, coupling chemoorganotrophic growth on yeast extract to the reduction of ferric iron. The temperature optima for the four isolates were between 35 and 42 degrees C and the pH optima were 1.0 to 1.7, and "F. acidarmanus" Fer1(T) was capable of growing at pH 0. The optimum yeast extract concentration for "F. acidarmanus" Fer1(T) was higher than that for the other three isolates. Phenotypic results suggested that isolate "F. acidarmanus" Fer1(T) is of a different species than the other three strains, and 16S rRNA sequence data, DNA-DNA similarity values, and two-dimensional polyacrylamide gel electrophoresis protein profiles clearly showed that strains DR1, MT17, and Y(T) group as a single species. "F. acidarmanus" Fer1(T) groups separately, and we propose the new species "F. acidarmanus" Fer1(T) sp. nov.


Ultrafast vibration and laser acoustics in thin transparent films.
Picosecond laser pulses are used to excite and detect stress pulses in thin transparent films on opaque substrates. The reflectance variation, measured for silica films, is modeled as a sum of different contributions: an echo contribution from stress-induced modulation of the substrate reflectance, an interference contribution from light reflected by the stress pulse in the transparent film, and a contribution from stressinduced vibrations of the order of 10(-3)nm of the film surface, observed for what is to our knowledge the first time. We show how both the thickness and sound velocity of the film can be determined, provided that its refractive index is known.


The molecular genetic analysis of hemophilia A: a directed search strategy for the detection of point mutations in the human factor VIII gene.
A directed-search strategy for point mutations in the factor VIII gene causing hemophilia A was used to screen eight potentially hypermutable CpG dinucleotides occurring at sites deemed to be of functional importance. Polymerase chain reaction-amplified DNA samples from 793 unrelated individuals with hemophilia A were screened by discriminant oligonucleotide hybridization. Point mutations were identified in 16 patients that were consistent with a model of 5-methylcytosine (5mC) deamination. Four new examples of recurrent mutation were demonstrated at the following codons: 336 (CGA----TGA), 372 (CGC----TGC), 372 (CGC----CAC), and 1689 (CGC----TGC). These are functionally important cleavage sites for either activated protein C or thrombin. Further novel C----T transitions were identified in the remaining arginine codons screened (-5, 427, 583, 795, and 1696), resulting in the creation of TGA termination codons. Differences in mutation frequency were found both within and between the CpG sites and between ethnic groups. These differences are assumed to be due to differences in the level of cytosine methylation at these sites, although direct evidence for this inference is lacking.


Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients.
Elbow tenderness and pain with resisted wrist extension are common manifestations of lateral epicondylar tendinopathy, also known as tennis elbow. Previous studies have suggested platelet-rich plasma (PRP) to be a safe and effective therapy for tennis elbow. To evaluate the clinical value of tendon needling with PRP in patients with chronic tennis elbow compared with an active control group. Randomized controlled trial; Level of evidence, 2. A total of 230 patients with chronic lateral epicondylar tendinopathy were treated at 12 centers over 5 years. All patients had at least 3 months of symptoms and had failed conventional therapy. There were no differences in patients randomized to receive PRP (n = 116) or active controls (n = 114). The PRP was prepared from venous whole blood at the point of care and contained both concentrated platelets and leukocytes. After receiving a local anesthetic, all patients had their extensor tendons needled with or without PRP. Patients and investigators remained blinded to the treatment group throughout the study. A successful outcome was defined as 25% or greater improvement on the visual analog scale for pain. Patient outcomes were followed for up to 24 weeks. At 12 weeks (n = 192), the PRP-treated patients reported an improvement of 55.1% in their pain scores compared with 47.4% in the active control group (P = .163). At 24 weeks (n = 119), the PRP-treated patients reported an improvement of 71.5% in their pain scores compared with 56.1% in the control group (P = .019). The percentage of patients reporting significant elbow tenderness at 12 weeks was 37.4% in the PRP group versus 48.4% in the control group (P = .143). Success rates for patients at 12 weeks were 75.2% in the PRP group versus 65.9% in the control group (P = .104). At 24 weeks, 29.1% of the PRP-treated patients reported significant elbow tenderness versus 54.0% in the control group (P = .009). Success rates for patients with 24 weeks of follow-up were 83.9% in the PRP group compared with 68.3% in the control group (P = .037). No significant complications occurred in either group. No significant differences were found at 12 weeks in this study. At 24 weeks, however, clinically meaningful improvements were found in patients treated with leukocyte-enriched PRP compared with an active control group.


Frontiers in electronic structure theory.
Current and emerging research areas in electronic structure theory promise to greatly extend the scope and quality of quantum chemical computations. Two particularly challenging problems are the accurate description of electronic near-degeneracies (as occur in bond-breaking reactions, first-row transition elements, etc.) and the description of long-range dispersion interactions in density functional theory. Additionally, even with the emergence of reduced-scaling electronic structure methods and basis set extrapolation techniques, quantum chemical computations remain very time-consuming for large molecules or large basis sets. A variety of techniques, including density fitting and explicit correlation methods, are making rapid progress toward solving these challenges.


Unwrapping a First Aid Tourniquet From Its Plastic Wrapper With and Without Gloves Worn: A Preliminary Study.
The purpose of this study was to gather data about unwrapping a packaged limb tourniquet from its plastic wrapper while wearing different types of gloves. Because already unwrapped tourniquets require no time to unwrap, unwrapping data may provide insights into the issue of having tourniquets unwrapped when stowed in a first aid kit of a Serviceperson at war. In a laboratory setting, 36 tests of nine glove groups were performed in which four people, gloved and ungloved, unwrapped tourniquets. Other tourniquets were environmentally exposed for 3 months. All the users successfully unwrapped each tourniquet. Mean times to unwrap by glove group were not significantly different (p = .0961). When mean values of eight experimental groups were compared with that of one control group (i.e., bare hands), results showed no significant difference (p > .07). Mean time was least for bare hands (12 seconds) and most for cold gloves layered under mittens (22 seconds). Among the 36 pairwise comparisons of difference between glove group means, after adjustment for multiple comparisons, no comparison was noted to be statistically significant (p > .052, all 36 pairs). Glove thickness ranged from 0 mm for bare hands to 2.5 mm for cold gloves layered under mittens. By glove group, the thickness-time association was moderate, as tested by linear regression (R2 = 0.6096). The tourniquets exposed to the environment had evidence of rapid photodegradation due to direct exposure to sunlight. Such exposure also destroyed the wrappers. In a preliminary study, different gloves performed similarly when wearers unwrapped a tourniquet from its wrapper. The tourniquet wrappers gave no visible protection from sunlight, and environmental exposure destroyed the wrappers.


Challenges in surveillance of dementias in New York State.
Prevalence of dementia is expected to increase three- to four-fold in the next 50 years. In 1986, New York State established the Alzheimer's Disease and Other Dementias Registry, one of a few such registries in the United States. We identify surveillance challenges within the Registry. Data quality--specifically, the attributes of completeness and accuracy--is the primary challenge to the New York State dementias registry. Completeness may be undermined when hospitals and nursing homes fail to report data, and hospital charts do not record dementia diagnoses. Failure to record diagnoses may occur because of diagnosis uncertainty, perceived stigma, clinical attention on the primary reason for hospitalization, and financial disincentives. Dementia is well recorded in nursing home data because care planning requires frequent resident evaluations. The accuracy of recording specific forms of dementia is limited because coding terminology has not kept pace with physicians' perspectives on dementias. Hospitals and nursing homes document dementia and comorbidities more effectively among frail individuals and those with advanced dementias than among individuals who appear to be relatively healthy. One way to overcome challenges of data quality is to form partnerships with organizations that have expertise in managing medical records and coding dementias. As medical advances make early diagnoses more possible outside the hospital or nursing home setting, we will need to redesign the current surveillance system to capture this additional dementia data and ensure a representative system.