The faecal flora in ulcerative colitis.
Differential counts of the faecal flora of patients with ulcerative colitis showed a dysbiotic flora with a 100-fold increase of group-D streptococci and a reduction of bifidobacteria in comparison with the stable eubiotic flora of healthy subjects. The increase in number in group-D streptococci was accompanied by an increase in variety. About four different varieties of enterococci were found in faeces from patients compared with one or two in samples from healthy subjects. The strains isolated from patients were more active in mucin breakdown, and only strains from patients were able to break down hyaluronic acid. Lactic acid could be formed from these substrates. The increased secretion of mucin in colitis and the presence of unprotected hyaluronic acid in ulcers seem to select these organisms which are probably the cause of the high lactic-acid content of the faeces in such patients.


Preparing Social Services and Public Services Professionals for Meaningful Roles in Disaster Services.
This manuscript reviews the importance of disaster preparedness for the social services and public services professional. The value in separating fact from fiction in regard to probabilities for biological, chemical, and nuclear terrorism is highlighted. The various phases of disaster preparedness are elucidated along with the components of the effective all-hazards plan. Consideration of the psychological impact of disasters is presented in conjunction with the role of the mental health worker in the amelioration of outcomes. The role of electronic technology in disaster preparedness is elaborated, and useful websites are cited to facilitate disaster planning.


Extended follow up of high-dose melphalan and autologous stem cell transplantation after vincristine, doxorubicin, dexamethasone induction in amyloid light chain amyloidosis of the prospective phase II HOVON-41 study by the Dutch-Belgian Co-operative Trial Group for Hematology Oncology.
In a prospective multicenter phase II study, we evaluated the effect of three courses of vincristine, doxorubicin and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation on an intention-to-treat basis. Sixty-nine newly diagnosed patients with amyloid light chain amyloidosis were included between November 2000 and January 2006: 37 men and 32 women with a median age of 56 years, including 46% of patients with cardiac and 22% of patients with involvement of 3 or 4 organs. Initial results presented in 2008 showed a 4-year overall survival rate of 62% among all the patients, while the 4-year survival rate after transplantation was 78%. Here we report the long-term follow-up data after a median follow up of 115 months of the patients still alive. Median survival of all patients was 96 months from registration and for the transplanted patients ten years from the date of transplantation. Twelve (12%) patients died during induction therapy with vincristine, doxorubicin and dexamethasone, including 8 patients (12%) due to treatment-related mortality. Two patients died within one month following high-dose melphalan. We conclude that vincristine, doxorubicin and dexamethasone should not be applied as induction therapy for intensification in amyloid light chain amyloidosis. However, a 2-step approach consisting of a non-intensive less toxic induction therapy followed by high-dose melphalan and autologous stem cell transplantation may result in extended survival in newly diagnosed patients with amyloid light chain amyloidosis (clinicaltrials.gov identifier: 01207094).


[Phenolic constituents of licorice. IV. Correlation of phenolic constituents and licorice specimens from various sources, and inhibitory effects of licorice extracts on xanthine oxidase and monoamine oxidase].
The roots and/or rhizomes of Glychyrrhiza uralensis, G. glabra and G. inflata, and commercial licorice specimens from various regions or countries were analyzed by high-performance liquid chromatography (HPLC), and classified into three types based on their phenolic constituents. i) Type A: The roots and rhizomes of G. uralensis, commercial licorice specimens from northwestern region of China (Seihoku-kanzo) and from northeastern region of China (Tohoku-kanzo) in Japanese markets, and also several licorice specimens from Chinese markets. They contain licopyranocoumarin (6), glycycoumarin (7) and/or licocoumarone (8), which were not found in G. glabra and G. inflata. ii) Type B: The root and rhizome of G. glabra, and the licorice specimens imported from the Soviet Union and Afghanistan. They contain glabridin (9) and glabrene (10), which were not found in the samples of the other two Glycyrrhiza species. A root sample of Glycyrrhiza species from Turkey also contains 9 and 10. iii) Type C: The root sample of G. inflata. They contain licochalcones A (11) and B (12), which were not found in the samples of the other two Glycyrrhiza species. Commercial licorice specimens obtained in Japan, which were imported from Sinkiang of China (Shinkyo-kanzo), and some licorice specimens obtained from Chinese markets, have also been found to contain 11 and 12. The phenolics 6-12, characteristic constituents of types A, B or C, were not found in a specimen of cortex-free licorice from a Japanese market (kawasari-kanzo). Extracts of some licorice specimens of types A and B, and all of the licorice specimens of type C inhibited 40-56% of the xanthine oxidase activity at the concentration of 30 micrograms/ml. Extracts of some licorice specimens of types A and B also showed inhibitory effects on monoamine oxidase (44-64% inhibition, at the concentration of 30 micrograms/ml), which were slightly weaker than that of harmane hydrochloride.


Cardiac 18F-Dopamine Positron Emission Tomography Predicts the Type of Phenoconversion of Pure Autonomic Failure.
Pure autonomic failure (PAF) is a rare disease characterized clinically by neurogenic orthostatic hypotension (nOH) and biochemically by peripheral noradrenergic deficiency. Clinically diagnosed PAF can evolve ("phenoconvert") to a central Lewy body disease (LBD, e.g., Parkinson's disease (PD) or dementia with Lewy bodies (DLB)) or to the non-LBD synucleinopathy multiple system atrophy (MSA). We examined whether cardiac 18F-dopamine positron emission tomography (PET) predicts the trajectory of phenoconversion in PAF. Since cardiac 18F-dopamine-derived radioactivity always is decreased in LBDs with nOH and usually is normal in MSA, we hypothesized that PAF patients with low cardiac 18F-dopamine-derived radioactivity may phenoconvert to a central LBD but do not phenoconvert to MSA. We reviewed data from all the patients seen at the National Institutes of Health Clinical Center from 1994 to 2023 with a clinical diagnosis of PAF and data about serial 18F-dopamine PET. Twenty patients met the above criteria. Of 15 with low cardiac 18F-dopamine-derived radioactivity, 6 (40%) phenoconverted to PD or DLB and none to MSA. Of 5 patients with consistently normal 18F-dopamine PET, 4 phenoconverted to MSA, and the other at autopsy had neither a central LBD nor MSA. In this case series, 40% of patients with nOH and low cardiac 18F-dopamine-derived radioactivity phenoconverted to PD or DLB during follow-up; none phenoconverted to MSA. Cardiac 18F-DA PET therefore can predict the type of phenoconversion in PAF. This capability could refine eligibility criteria for entry into disease-modification trials aiming to prevent evolution of PAF to symptomatic central LBDs.


[The effect of blood serum polyreactive immunoglobulins on serum antibody affinity determination].
The presence of polyreactive immunoglobulins in sera may substantially influence on the accuracy of antibody affinity determination. In order to obtain precise values of antibody affinity one should apply one of two following ways. First, one should block polyreactive immunoglobulins with high concentration of Twin 20 and high concentration of any antigen which does not interact with studying antibody. After this antibody affinity may be determined by traditional methods. Another way is the application of the method suggested by us earlier, which allow determining affinity of two antibodies in a mixture and the relation of their concentrations.


Sex differences in the characteristics and short-term prognosis of patients presenting with acute symptomatic pulmonary embolism.
We sought to examine sex-related differences in the characteristics and outcome in patients presenting with acute symptomatic pulmonary embolism (PE). We conducted a retrospective cohort study of 2,096 patients diagnosed with acute PE. The characteristics were recorded at presentation. Treatment was at the discretion of patients' physicians. The primary study outcome, all-cause mortality, and the secondary outcomes of PE-specific mortality, recurrent venous thromboembolism, and major bleeding were assessed during the first month of follow-up after PE diagnosis. Overall, the women were older than the men and had significantly higher rates of immobilization. They had significantly lower rates of chronic obstructive pulmonary disease and cancer. Women had a higher prevalence of syncope and elevated brain natriuretic peptide levels. Thirty-day all-cause mortality was similar between women and men (7.1% versus 6.2%; P = 0.38). Male gender was not independently significantly associated with PE-related death (adjusted odds ratio [OR] 1.02; 95% CI, 0.50 to 2.07; P = 0.96). Restricting the analyses to haemodynamically stable patients (n = 2,021), female gender was an independent predictor of all-cause (adjusted OR 1.56; 95% CI, 1.07 to 2.28; P = 0.02) and PE-specific mortality (adjusted OR 1.85; 95% CI, 1.02 to 3.33; P = 0.04). Compared with men, women were 2.05 times more likely to experience a major bleed. Women and men with PE had different clinical characteristics, presentation, and outcomes. Women receiving anticoagulation have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.


Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis.
Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.


Chemotherapy of schistosomiasis: present and future.
Schistosomiasis is a chronic parasitic disease in tropical and subtropical regions and is associated with a variety of clinical syndromes that may lead to severe morbidity. Over the past 25 years, therapy and control of schistosomiasis has come to rely heavily on one drug, praziquantel (PZQ). This reliance is of concern should widespread treatment failure arise, particularly as measures are being undertaken to increase PZQ's availability. This review summarizes the use, possible modes of action and limitations of PZQ, and recent attempts to derive synthetic analogs. Alternative artemisinin-based chemotherapies that have shown applicability in certain disease settings are also similarly examined. Looking forward, the review highlights some of the more experimental anti-schistosomals being evaluated (e.g. the trioxolanes), including those where knowledge of the parasite target (e.g. cysteine proteases and hemozoin formation) is more defined.


Genetic structure of Pileolaria pseudomilitaris (Polychaeta: Spirorbidae).
The genetic structure of Pileolaria pseudomilitaris was studied by means of gene-diversity analysis of allozyme frequencies. At an esterase locus, most of the gene diversity was due to subdivision of the population into colonies and subpopulations separated by less than 100 meters. Gene frequencies at a phosphoglucose isomerase locus were similar over many kilometers, but differed between two habitat types. Differences between colonies are attributed to drift and founder effect; similarities over greater distances are attributed to similar selection pressures. A mathematical appendix details the method of gene diversity analysis for a multi-leveled, hierarchically subdivided population.


Inpatient care for children, ages 1-20 years, with spina bifida in the United States.
To describe the inpatient health service use and insurance types for hospitalized children with spina bifida compared to children generally and to evaluate hospital discharge and insurance type trends over a 10-year study period. The cross-sectional secondary data analyses were conducted using the 2000, 2003, 2006 and 2009 Kid's Inpatient Databases. Diagnoses were identified by ICD-9 codes and hospital type was categorized based on the National Association of Children's Hospitals and Related Institutions designations. Chi-squared tests and the Wald test of trend were used for the statistical analyses. Children with spina bifida are more likely to receive their inpatient care in children's hospitals or pediatric units compared to all children. Children with spina bifida were most commonly admitted for shunt malfunction and repair. The percentage of children covered by Medicaid rose during the study period for both children with spina bifida and children generally. This study is the first of its kind to document longitudinal trends in inpatient utilization, insurance type, and reason for admission for children with spina bifida. The changing trends in insurance coverage should be closely monitored because insurance is closely linked to health care access, which is linked to health outcomes.


Efficient use of strong light for high photosynthetic productivity: interrelationships between the optical path, the optimal population density and cell-growth inhibition.
The interrelationships between the optical path in flat plate reactors and photosynthetic productivity were elucidated. In preliminary works, a great surge in photosynthetic productivity was attained in flat plate photoreactors with an ultra short (e.g. 1.0 cm) optical path, in which extremely high culture density was facilitated by vigorous stirring and strong light. This surge in net photosynthetic efficiency was associated with a very significant increase in the optimal population density facilitated by the very short optical path (OP). A salient feature of these findings concerns the necessity to address growth inhibition (GI) which becomes increasingly manifested as cell concentration rises above a certain, species-specific, threshold (e.g. 1-2 billion cells of Nannochloropsis sp. ml(-1)). Indeed, ultrahigh cell density cultures may be established and sustained only if growth inhibition is continuously, or at least frequently, removed. Nannochloropsis culture from which GI was not removed, yielded 60 mg(-1) h(-1), yielding 260 mg l(-1) h(-1) when GI was removed. Two basic factors crucial for obtaining maximal photosynthetic productivity and efficiency in strong photon irradiance are defined: (1) areal cell density must be optimal, as high as possible (cell growth inhibition having been eliminated), insuring the average photon irradiance (I(av)) available per cell is falling at the end of the linear phase of the PI(av) curve, relating rate of photosynthesis to I(av), i.e. approximately photon irradiance per cell. (2) The light-dark (L-D) cycle period, which is determined by travel time of cells between the dark and the light volumes along the optical path, should be made as short as practically feasible, so as to approach, as much as possible the photosynthetic unit turnover time. This is obtainable in flat plate reactors by reducing the OP to as small a magnitude as is practically feasible.


Identification and Assessment of Cardiac Amyloidosis by Myocardial Strain Analysis of Cardiac Magnetic Resonance Imaging.
We explored the usefulness of myocardial strain analysis on cardiac magnetic resonance imaging (CMR) scans for the identification of cardiac amyloidosis.Methods and Results:The 61 patients with systemic amyloidosis underwent 3.0-T CMR, including CMR tagging and late-gadolinium enhanced (LGE) imaging. The circumferential strain (CS) of LGE-positive and LGE-negative patients was measured on midventricular short-axis images and compared. Logistic regression modeling of CMR parameters was performed to detect patients with LGE-positive cardiac amyloidosis. Of the 61 patients with systemic amyloidosis 48 were LGE-positive and 13 were LGE-negative. The peak CS was significantly lower in the LGE-positive than in the LGE-negative patients (-9.5±2.3 vs. -13.3±1.4%, P<0.01). The variability in the peak CS time was significantly greater in the LGE-positive than in the LGE-negative patients (46.1±24.5 vs. 21.2±20.1 ms, P<0.01). The peak CS significantly correlated with clinical biomarkers. The sensitivity, specificity, and accuracy of the diagnostic model using CS parameters for the identification of LGE-positive amyloidosis were 93.8%, 76.9%, and 90.2%, respectively. Myocardial strain analysis by CMR helped detect LGE-positive amyloidosis without the need for contrast medium. The peak CS and variability in the peak CS time may correlate with the severity of cardiac amyloid deposition and may be more sensitive than LGE imaging for the detection of early cardiac disease in patients with amyloidosis.


SH2 mutants of c-src that are host dependent for transformation are trans-dominant inhibitors of mouse cell transformation by activated c-src.
The c-src gene encodes a membrane-associated protein-tyrosine kinase, pp60c-src, whose substrates and regulators have not been identified. In an effort to obtain mutants that might assist the search for proteins that interact with pp60c-src, we have generated by site-directed mutagenesis two alleles of chicken c-src that are host dependent for transformation and inhibit transformation of mouse cells by activated c-src in a trans-dominant manner. These alleles, named M6 and M9, encode nonconservative changes within the highly conserved FLVRES sequence in the src homology-2 (SH2) region of pp60c-src, as well as an activating change, Y527F, near the carboxyl terminus. M6 and M9 transform chicken embryo fibroblasts (CEF) more efficiently than the parental allele (Y527F c-src), but fail to transform mouse NIH-3T3 cells. The product of M6-src is less stable than activated pp60c-src in NIH-3T3 cells and shows decreased protein tyrosine kinase activity on all tested substrates; the product of M9-src, however, is stable, has a novel pattern of substrate preference for tyrosine phosphorylation in vitro, and induces a pattern of phosphotyrosine-containing proteins in mouse cells that is similar to that induced by Y527F c-src, even though it fails to transform these cells. Both M6 and M9 inhibit transformation of NIH-3T3 cells by activated c-src in a dose-dependent manner, as assayed by resistance of M6- or M9-expressing cells to transformation by Y527F c-src or by morphological reversion of cells previously transformed by activated c-src following introduction of M6 or M9. When reversion occurs, the concentration of protein encoded by the active allele declines, without change in level of src mRNA or rate of src protein synthesis, implying that the products of M6 and M9, when present at adequate levels, can destabilize transformation-competent src protein. These alleles offer new opportunities for interfering with the actions of src-related genes and for isolating cellular factors required for the functions of those genes.


The effect of urban green on small-area (healthy) life expectancy.
Several epidemiological studies have investigated the effect of the quantity of green space on health outcomes such as self-rated health, morbidity and mortality ratios. These studies have consistently found positive associations between the quantity of green and health. However, the impact of other aspects, such as the perceived quality and average distance to public green, and the effect of urban green on population health are still largely unknown. Linear regression models were used to investigate the impact of three different measures of urban green on small-area life expectancy (LE) and healthy life expectancy (HLE) in The Netherlands. All regressions corrected for average neighbourhood household income, accommodated spatial autocorrelation, and took measurement uncertainty of LE, HLE as well as the quality of urban green into account. Both the quantity and the perceived quality of urban green are modestly related to small-area LE and HLE: an increase of 1 SD in the percentage of urban green space is associated with a 0.1-year higher LE, and, in the case of quality of green, with an approximately 0.3-year higher LE and HLE. The average distance to the nearest public green is unrelated to population health. The quantity and particularly quality of urban green are positively associated with small-area LE and HLE. This concurs with a growing body of evidence that urban green reduces stress, stimulates physical activity, improves the microclimate and reduces ambient air pollution. Accordingly, urban green development deserves a more prominent place in urban regeneration and neighbourhood renewal programmes.


Foot and ankle experience in orthopaedic residency.
Dedicated orthopaedic residency training in the musculoskeletal discipline of foot and ankle is an important contribution to the development of a well-rounded orthopaedic surgeon. Current residency training guidelines are vague and do not require specific experience or proficiency in this discipline. A one-page questionnaire on commitment to foot and ankle education in American Orthopaedic Surgery residency training programs was completed by all 148 program directors. Eighty of the programs (54.1%) had a single faculty member dedicated to foot and ankle orthopaedics, while 21 (14.2%) did not have a faculty member with a specific interest or commitment to problems related to the foot and ankle. Fifteen programs (10.1%) did not have a committed faculty member, nor did their residents have a clinical rotation dedicated to foot and ankle. Ninety-six programs (64.9%) had at least one clinical rotation dedicated to foot and ankle. Fifty-two (35.1%) did not. Thirty-three (34.7%) of those programs with a dedicated foot and ankle experience assigned residents during at least two periods of their training. Of those programs with a single foot-specific rotation, the most common year for training was in the PGY3 year (27 of 63, 42.9%). Of the 60 months' duration of most orthopaedic residency programs, 39 of 96 (40.6%) programs with a dedicated clinical foot and ankle rotation allocated an average of 12 weeks to foot and ankle. Twenty-six (27.1%) allocated less than 3 total months, and 31 (32.3%) allocated 16 to 24 weeks of dedicated foot and ankle experience. Current residency training in the United States does not universally require a commitment to foot and ankle education. A large number of residency programs do not have a faculty member committed to foot and ankle education, and almost one-third have no time specifically allocated to foot and ankle education.


Yasmin: the reason why.
Oral contraceptives have been available for a little over 40 years and, during that time, many different formulations have been introduced. There have been dramatic dosage reductions of both the estrogen and progestogen components and various progestogens have been introduced over time. The properties of most progestogens used in oral contraceptives are very similar, differing mainly in potency. Oral contraceptives with progestogens having new and unique properties are needed. World-wide, around 20-30% of women of childbearing age use oral contraceptives and their use declines after the age of 35 years, with an accompanying increase in the rates of unintended pregnancy and elective termination. Incorrect use likewise gives rise to high unintended pregnancy rates. Use in Europe is higher than in other regions. Discontinuation because of unwanted effects and misperceptions is very common. Common misperceptions that prevent women from initiating oral contraceptive use are weight gain, cancer risks and that bleeding indicates a significant problem. Unwanted effects that commonly give rise to discontinuation are bleeding, nausea, weight gain, mood changes, breast tenderness and headaches. Discontinuation rates are high, particularly in the first year, and adolescents have the highest rates of discontinuation. Correct consistent use must be encouraged by taking pills at a regular time each day and by reinforcing that bleeding and other unwanted effects are not medically serious. Reinforcement of the non-contraceptive health benefits is very important and it needs to be emphasized that long-term use enhances these non-contraceptive benefits. Most non-contraceptive benefits are due to the progestogen component and its inhibition of ovulation. The new drospirenone-containing oral contraceptive (Yasmin, Schering AG, Berlin, Germany) offers the traditional non-contraceptive benefits; however, due to its unique antimineralocorticoid and antiandrogenic properties, new and unique benefits have been observed. Acne is well controlled, as would be expected from its inhibition of ovulation, antiandrogenic activity and lack of attenuation of the estrogen-mediated increase in sex hormone binding globulin. Its antimineralocorticoid activity gives rise to a reduction in fluid-related symptoms. The oral contraceptive containing 3 mg drospirenone with 30 microg ethinylestradiol DRSP/EE) has excellent efficacy since drospirenone is a potent progestogen, the corrected Pearl index being 0.09. This index is lower than those of many other oral contraceptives. Cycle control is excellent and comparable to that experienced with other oral contraceptives. A significant and consistent weight loss was seen with DRSP/EE compared to a reference preparation containing desogestrel. Day-to-day compliance and the duration of intake of an oral contraceptive are dependent on the woman's satisfaction with the pill she is taking. DRSP/EE meets these expectations and, with its new and unique non-contraceptive benefits, offers a real new choice to women.


Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria.
Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase-dependent cell death associated with mitochondrial depolarization. Since casp8p41 does not contain the catalytic cysteine at position 360, the mechanism by which casp8p41 initiates apoptosis is unclear. We demonstrate that casp8p41 directly causes mitochondrial depolarization and release of cytochrome c with downstream caspase 9 activation. Moreover, death induced by casp8p41 requires the presence of mitochondria, and in intact cells, casp8p41 colocalizes with mitochondria. These results illuminate a novel mechanism of cell death induced by a caspase 8 cleavage fragment whereby mitochondrial interaction leads to depolarization and cytochrome c release.


Skimming for barcodes: rapid production of mitochondrial genome and nuclear ribosomal repeat reference markers through shallow shotgun sequencing.
DNA barcoding is critical to conservation and biodiversity research, yet public reference databases are incomplete. Existing barcode databases are biased toward cytochrome oxidase subunit I (COI) and frequently lack associated voucher specimens or geospatial metadata, which can hinder reliable species assignments. The emergence of metabarcoding approaches such as environmental DNA (eDNA) has necessitated multiple marker techniques combined with barcode reference databases backed by voucher specimens. Reference barcodes have traditionally been generated by Sanger sequencing, however sequencing multiple markers is costly for large numbers of specimens, requires multiple separate PCR reactions, and limits resulting sequences to targeted regions. High-throughput sequencing techniques such as genome skimming enable assembly of complete mitogenomes, which contain the most commonly used barcoding loci (e.g., COI, 12S, 16S), as well as nuclear ribosomal repeat regions (e.g., ITS1&2, 18S). We evaluated the feasibility of genome skimming to generate barcode references databases for marine fishes by assembling complete mitogenomes and nuclear ribosomal repeats. We tested genome skimming across a taxonomically diverse selection of 12 marine fish species from the collections of the National Museum of Natural History, Smithsonian Institution. We generated two sequencing libraries per species to test the impact of shearing method (enzymatic or mechanical), extraction method (kit-based or automated), and input DNA concentration. We produced complete mitogenomes for all non-chondrichthyans (11/12 species) and assembled nuclear ribosomal repeats (18S-ITS1-5.8S-ITS2-28S) for all taxa. The quality and completeness of mitogenome assemblies was not impacted by shearing method, extraction method or input DNA concentration. Our results reaffirm that genome skimming is an efficient and (at scale) cost-effective method to generate all mitochondrial and common nuclear DNA barcoding loci for multiple species simultaneously, which has great potential to scale for future projects and facilitate completing barcode reference databases for marine fishes.


Sex under the influence of drugs or alcohol: common for men in substance abuse treatment and associated with high-risk sexual behavior.
Sex under the influence of drugs or alcohol is associated with high-risk sexual behavior. Heterosexual men (n = 505) in substance abuse treatment completed a computer-administered interview assessing sexual risk behaviors. Most men (73.3%) endorsed sex under the influence in the prior 90 days, and 39.1% endorsed sex under the influence during their most recent sexual event. Sex under the influence at the most recent event was more likely to involve anal intercourse, sex with a casual partner, and less condom use. Patients might benefit from interventions targeting sexual behavior and substance use as mutual triggers. (Am J Addict 2010;00:1-9).


Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity.
Cyclic nucleotides are second messengers that are essential in vision, muscle contraction, neurotransmission, exocytosis, cell growth, and differentiation. These molecules are degraded by a family of enzymes known as phosphodiesterases, which serve a critical function by regulating the intracellular concentration of cyclic nucleotides. We have determined the three-dimensional structure of the catalytic domain of phosphodiesterase 4B2B to 1.77 angstrom resolution. The active site has been identified and contains a cluster of two metal atoms. The structure suggests the mechanism of action and basis for specificity and will provide a framework for structure-assisted drug design for members of the phosphodiesterase family.


Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease. Gastroenterology 1995; 108:1056-67.
The efficacy of enteral nutrition as primary therapy of active Crohn's disease is controversial. The aim of the study was to compare by meta-analysis the likelihood of clinical response to liquid diet therapy vs. corticosteroids and to assess the importance of formula composition to efficacy. Randomised controlled trials comparing exclusive enteral nutrition with corticosteroids and elemental with non-elemental formulas were identified through a combination of computerised and hand-searching techniques. Rates of clinical remission of active Crohn's disease, based on the intention to treat principle, were extracted from the studies by two independent reviewers. Odds ratios for the likelihood of clinical response were calculated. In eight trials comprising 413 patients, enteral nutrition was inferior to corticosteroids (pooled odds ratio 0.35; 95% confidence interval 0.23-0.53). In five trials comprising 134 patients, there was no difference in the efficacy of elemental versus non-elemental formulas (pooled odds ratio 0.87; 95% confidence interval 0.41-1.83). Corticosteroids are more effective than enteral nutrition in the treatment of active Crohn's disease. Limited sample size precludes definite conclusions about the importance of formula composition in the efficacy of enteral nutrition; however, data analysed in this study do not support an advantage to elemental feedings compared with a polymeric formulation.


De novo concurrent papillary renal cell carcinoma and angiomyolipoma in a kidney allograft: evidence of donor origin.
In the general population, renal cell carcinoma (RCC) is a relatively common neoplasm; however, the papillary RCC subtype is infrequent and represents only 10 to 15% of all RCC. Angiomyolipoma is a well-known common benign tumor. The occurrence of RCC in association with angiomyolipoma is a rare event, with only approximately 50 cases reported in the nontransplantation setting. In transplant recipients, RCC can develop in native kidneys, but its occurrence "de novo" in the renal allograft is very rare with an estimated incidence of less than 0.5%. We report here the case of a 39-year-old woman who underwent cadaveric renal transplantation in 1990. No lesion was observed in the allograft during the pre- and perioperative period or on early postoperative ultrasounds. No graft rejection occurred under a standard triple immunosuppressive therapy. Thirteen years later, during a routine ultrasonography, 2 solid masses were discovered in the allograft, both of them richly vascularized. She underwent allograft nephrectomy and the histologic findings revealed that one of the tumors was a chromophilic (type 1) papillary RCC (2.5 cm in diameter) and the other, an angiomyolipoma (1.5 cm). Microsatellite analysis of the allograft, as compared with the recipient peripheral blood leukocytes, demonstrated that the 2 tumors (1 malignant and 1 benign) were of donor origin. To our knowledge, this is the first report of de novo concurrent papillary RCC and angiomyolipoma in a renal allograft.


Comparison between the viral transforming gene (src) of recovered avian sarcoma virus and its cellular homolog.
Recovered avian sarcoma viruses are recombinants between transformation-defective mutants of Rous sarcoma virus and the chicken cellular gene homologous to the src gene of Rous sarcoma virus. We have constructed and analyzed molecular clones of viral deoxyribonucleic acid from recovered avian sarcoma virus and its transformation-competent progenitor, the Schmidt-Ruppin A strain of Rous sarcoma virus. A 2.0-megadalton EcoRI fragment containing the entire src gene from each of these clones was subcloned and characterized. These fragments were also used as probes to isolate recombinant phage clones containing the cellular counterpart of the viral src gene, termed cellular src, from a lambda library of chicken deoxyribonucleic acid. The structure of cellular src was analyzed by restriction endonuclease mapping and electron microscopy. Restriction endonuclease mapping revealed extensive similarity between the src regions of Rous sarcoma virus and recovered avian sarcoma virus, but striking differences between the viral src's and cellular src. Electron microscopic analysis of heteroduplexes between recovered virus src and cellular src revealed a 1.8-kilobase region of homology. In the cellular gene, the homologous region was interrupted by seven nonhomologous regions which we interpret to be intervening sequences. We estimate the minimum length of cellular src to be about 7.2 kilobases. These findings have implications concerning the mechanism of formation of recovered virus src and possibly other cell-derived retrovirus transforming genes.


Evaluation of a novel pulsatile extracorporeal life support system synchronized to the cardiac cycle: effect of rhythm changes on hemodynamic performance.
Arrhythmias are a frequent complication during extracorporeal life support (ECLS). A new ECLS system can provide pulsatile flow synchronized to the patient's intrinsic cardiac cycle based upon the R wave of the electrocardiogram (ECG). It is unclear how the occurrence of arrhythmias may alter the hemodynamic performance of the system. This in vitro study evaluated the effect of simulated arrhythmias on hemodynamics during R wave-triggered pulsatile ECLS. The ECLS circuit with an i-cor diagonal pump and iLA membrane ventilator was primed with whole blood at room temperature. Flow and pressure data were collected at 2.5 and 4 L/min for each condition using a customized data acquisition system. Pulsatile ECLS flow was R wave synchronized to an ECG simulator using 1:1, 1:2, and 1:3 assist ratios. Conditions tested included sinus rhythm at 45 and 90 bpm, supraventricular tachycardia (SVT), ventricular tachycardia (VT), and irregular rhythms such as ventricular fibrillation. Pulsatile mode was successfully triggered by ECG signals of normal sinus rhythm, SVT, VT, atrial fibrillation, atrial flutter, and ventricular bigeminy with assist ratios 1:1, 1:2, and 1:3. Regular rhythm at 90 bpm generated the best surplus hemodynamic energy (SHE). For SVT and VT, an assist ratio of 1:2 resulted in maximum pulsatile flow waveforms with optimal SHE at 2.5 L/min flow rate. At 4 L/min, SHE declined and the pressure drop increased independent of arrhythmia condition. Irregular rhythms still produced adequate pulsatile wave forms at lower pulsatile frequency. This study demonstrated the feasibility of generating pulsatile ECLS flow with the novel ECG-synchronized i-cor system during various simulated rhythms. The optimal rate for pulsatile flow was 90 bpm. During irregular rhythms, the lower pulsatile frequency was the more reliable synchronization mode for generating pulsatile flow.


[Efficacy of sanatorium treatment to patients with consequences of cerebrovascular disease].
To estimate the efficacy of the introduction of Russian standard of the sanatorium treatment of patients with cerebrovascular diseases. We examined 480 neurological patients. Efficacy of treatment was estimated according to conclusions of the physician on the basis of dynamic supervision and the scale "The Rehabilitation Profile of Activity" (Rehabilitation Activities Profile). The general for all patients was physiotherapy exercises and diet therapy. The majority of patients received medical shower (62.9±2.2%), psychotherapy (83.5±1.7%) and used terrainkur (52.1±2.3%). Frequencies of separate methods of treatment effects in groups of patients with positive and negative outcomes did not differ. The reliability of distinction was noted only for frequencies of dry-air bathtubs (36 and 16%), local bathtubs (39 and 14%), medical shower (76 and 52%), sinusoidal modulated currents (36 and 18%), reflex therapy (36 and 18%), massage (58 and 38%), psychotherapy (100 and 76%), naftalan therapy (44 and 24%). The significance of the ratio between sensitivity and specificity of treatment methods is emphasized.


Liner malseating is rare with two modular dual-mobility designs.
The aim of this study was to evaluate the incidence of liner malseating in two commonly used dual-mobility (DM) designs. Secondary aims included determining the risk of dislocation, survival, and clinical outcomes. We retrospectively identified 256 primary total hip arthroplasties (THAs) that included a DM component (144 Stryker MDM and 112 Zimmer-Biomet G7) in 233 patients, performed between January 2012 and December 2019. Postoperative radiographs were reviewed independently for malseating of the liner by five reviewers. The mean age of the patients at the time of THA was 66 years (18 to 93), 166 (65%) were female, and the mean BMI was 30 kg/m2 (17 to 57). The mean follow-up was 3.5 years (2.0 to 9.2). Three liners (1.2%) were malseated, including two MDMs (1.4%) and one G7 (0.9%). No clinical consequence was identified from malseating. The five-year survival free of dislocation was 97.1%, including two DM and one intraprosthetic dislocation. The five-year survival free of revision was 95.4%, with seven revisions. The mean Harris Hip Scores increased from 46 (24 to 69) preoperatively to 81 (40 to 100) at two years postoperatively (p < 0.001). The incidence of DM liner malseating after primary THA was low, with no known clinical consequences at mid-term follow-up. Malseating is not exclusive of design, and these findings emphasize the importance of careful evaluation of the liner after impaction to avoid this complication. Cite this article: Bone Joint J 2022;104-B(5):598-603.


Postoperative prostate-specific antigen as a prognostic indicator in patients with margin-positive prostate cancer, undergoing adjuvant radiotherapy after radical prostatectomy.
To identify a population of patients within the group with positive surgical margins after radical prostatectomy who would benefit in terms of improved local control of disease by the administration of adjuvant radiation therapy to the prostate bed. Postoperative prostate-specific antigen (PSA) values were evaluated in 45 patients with margin-positive (MP) disease who underwent adjuvant radiotherapy within 6 months of surgery. All patients were clinically T1-2 MO, and pNO. A cutoff of 0.5 ng/mL or less was used as the level below which PSA was considered undetectable. The mean follow-up time from date of radiation was 33 months. In 30 of 45 (67%) patients, PSA levels did drop to undetectable levels postoperatively. In 15 of 45 (33%) patients postoperative PSA levels did not drop to undetectable levels. In the group with detectable postoperative PSA, 12 of 15 (80%) failed adjuvant radiotherapy as determined by a progressive increase in PSA levels in a mean time of 0.95 years (range, 4 months to 2.02 years; median, 0.92 years). When postoperative PSA reached undetectable levels, only 10 of 30 (33%) failed treatment, with a mean time to failure of 2.1 years (range, 4 months to 7.8 years; median, 3.31 years). The data would suggest that patients who are MP, but attain an undetectable PSA level postoperatively accompanied by a progressive delayed increase in PSA, probably represent a group with local disease recurrence in the prostate fossa, whereas patients whose PSA levels are detectable postoperatively may represent a group with microscopic metastatic disease or a combination of local recurrence and distant disease or large volume local persistent disease. It is in the group of patients in whom the postoperative PSA decreased to undetectable levels that adjuvant radiotherapy may be effective in controlling local progression of prostate cancer through improved local control, as indicated by a durable decrease in PSA values to undetectable levels in roughly two thirds of these patients. Longer follow-up of these patients will be required to determine whether this improved local control will translate into improved survival.


[Newborn ventilation: comparison between a T-piece resuscitator and self-infating bags in a neonatal preterm simulator].
Although the provision of effective assisted ventilation is the most effective intervention in delivery room resuscitation of depressed newborn infants, there is still limited evidence about which is the optimal device to deliver positive pressure ventilation (PPV). To compare the accuracy of pressures and ventilation rate (VR) delivered to a neonatal simulator with three devices: 240 ml and 450 ml self-infating bags (SIB) and a T-piece resuscitator, and to evaluate the variability in terms of providers' experience. 76 health care providers divided in two groups according to experience were asked to provide positive pressure ventilation to a neonatal simulator through a facial mask or an endotracheal tube with three ventilating devices: a T-piece resuscitator, a 240 ml and a 450 ml self-infating bags. Participants used each combination of device and interface randomly on 2 consecutive occasions. Mean and maximum PIP and respiratory rate were recorded. Statistical analyses were performed using two-factor analysis of variance for repeated measures. SIB 240 and 450 were similar in the mean target peak inspiratory pressure (PIP) but both were significantly different (p < 0.001) from T-piece, although all values were close to the target. Mean VR was over the target for all the devices (p < 0.001). The highest difference found was 7 ± 1.7 breaths/minute with the 240 ml bag when compared with the T-piece using a mask. Experienced operators were closer than novice operators to target VR, regardless of the device or interface. The accuracy for the devices was comparable in the variables measured regardless operator´s experience. Overall, the T-piece provided lower PIP while both SIB, higher than the target. The VR was over the target for all the devices. Both SIB and novice participants were associated with higher VR. The intraoperator consistency was comparable in the variables measured with all devices.


Renal cell-to-cell communication via extracellular ATP.
In the kidney, macula densa cells communicate with the mesangial cell-afferent arteriolar smooth muscle cell complex through ATP signaling. This signaling process involves release of ATP across the macula densa basolateral membrane through a maxi anion channel and the interaction of ATP with purinergic P2 receptors.


Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease.
We report results of a phase 1 multicenter stem cell transplantation (SCT) trial from HLA-matched (n = 7) or one-antigen-mismatched (n = 7) unrelated donors (URD) using bone marrow or cord blood as stem cell source, following reduced-intensity conditioning (RIC) in severe sickle cell disease (SCD). Conditioning included distal alemtuzumab, fludarabine, and melphalan (matched donors), with thiotepa (mismatched donors). Abatacept, a selective inhibitor of T cell costimulation, was added to tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis to offset GVHD risks, and was administered for longer duration in bone marrow recipients than in cord blood recipients because of increased incidence of chronic GVHD with bone marrow. Median age at transplant was 13 years (range, 7-21 years). The incidence of grades II to IV and grades III to IV acute GVHD at day +100 was 28.6% and 7%, respectively. One-year incidence of chronic GVHD was 57% and mild/limited in all but 1 patient who received abatacept for a longer duration. Only 1 patient developed reversible posterior encephalopathy syndrome and recovered. With a median follow-up of 1.6 years (range, 1-5.5 years), the 2-year overall and disease-free survival was 100% and 92.9%, respectively. The encouraging results from the phase 1 portion of this RIC SCT trial, despite risk factors such as older age, URD, and HLA-mismatch, support further evaluation of URD SCT in clinical trial settings. The phase 2 portion of the trial is in progress. This trial was registered at www.clinicaltrials.gov as NCT03128996.


Prognostic value of proadrenomedullin in severe sepsis and septic shock patients with community-acquired pneumonia.
Midregional proadrenomedullin (proADM) is a novel biomarker with potential prognostic utility in patients with community-acquired pneumonia. The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in severe sepsis and septic shock due to CAP. Prospective observational study including 49 patients admitted to ICU with both a clinical and radiologic diagnosis of pneumonia and fulfilling criteria for severe sepsis or septic shock. The prognostic accuracy of proADM levels was compared with those of pneumonia severity index and of procalcitonin (PCT) and C-reactive protein (CRP). 49 patients with severe sepsis or septic shock due to CAP were included in the study. Mortality was 24.5% for ICU and 34.7% for hospital mortality. In all cases proADM values at ICU admission were pathological (considering normal proADM levels <4 nmol/L). ProADM consistently rose as PSI class advanced from II to V (p = 0.02). Median proADM levels were higher (p <0.01) in hospital non-survivors 5.0 (1.9-10.1) nmol/L vs. survivors 1.7 (1.3-3.1) nmol/L. These differences were also significant with respect to ICU mortality. The receiver-operating characteristic curve for proADM yielded an AUC of 0.72; better than the AUC for PCT and CRP (0.40 and 0.44 respectively) and similar to PSI (0.74). In our study MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients.


Role of triiodothyronine in down-regulation and recovery of lymphocyte beta-adrenoceptors in thyroidectomized patients.
Thyroid function modulates beta-adrenergic sensitivity through the regulation of beta-adrenoceptor density. In particular, thyroidectomy decreases and thyroid hormone injections increase beta-adrenoceptor density on human lymphocytes. In the present paper the relationship between receptor modifications and thyroid hormone levels has been studied in human lymphocytes from patients after thyroidectomy. The patterns of early changes as well as recovery trends have been investigated. Results show a statistically significant fall in receptor density, parallelled by a decrease in T3 levels, 1-3 days after thyroidectomy. Recovery of receptor density is observed 5-8 days after surgical intervention and is accompanied by increased T3 levels. There is a positive correlation between receptor density and T3 levels. On the contrary, no statistically significant correlation was observed for receptor density and T4 levels. The time course of disappearance and recovery of receptor density and that of T3 levels have also been analyzed with the aid of a mathematical model fitting experimental data. On this basis, the hypothesis that both down-regulation and subsequent recovery of beta-adrenoceptor density are driven by the fall and rise of T3 is suggested. Data are also discussed in relation to experimental results we have obtained in animal studies.


Evaluation of freezing in arterial microsurgical anastomosis.
In this work, the authors discuss the effect of freezing on vascular anastomosis performed in the femoral arteries of the rat. For this purpose, they utilize dimethyl propane ether (-60 degrees C). Two experiments were performed independently from each other. On the right side, they froze the artery before cutting and anastomosing it. On the left side, the artery was first transected and then frozen before anastomosis was performed. Patency was studied at 7 days. Changes in diameter of the vascular lumen were measured both in the experimental as well in the control group. Permeability of the arteries frozen before being cut was greater than in those in which freezing was performed subsequently. On the other hand, the authors found some cases of thrombosed vessels, which have not been previously described in the literature. They also noticed proximal and distal vasospasm when cool was applied locally. They conclude that freezing of microarteries before cutting them produces vasodilatation with a low incidence of thrombotic phenomena. However, the presence of a significant proximal and distal vasospasm leads them to believe that further studies are necessary before this technique is applied in the clinical setting.


[Digestive changes in cholecystectomized patients].
An important number of cholecystectomized patients after some years of complete well-being, begin complaining of symptoms such as periodic diarrhea or constipation, abdominal pain, regurgitation, vomiting, etc. The purpose of this study is to try to identify an alteration or lesion in the stomach or colon in cholecystectomized patients of more than five years standing, which may be causing the aforementioned condition. The forty patients under observation, free of biliary tract post-operative lesions, were subjected to: hemogram, amylasemia, either infusion cholangiograph or ERCP, fecal parasitological-tests, upper digestive and colon X Ray series, esophagus, stomach and duodenal endoscopy with biopsies. Additionally, ten underwent a colonoscopy which also included biopsy. The result of the radiological, amylasemia and hemogram studies was normal in all cases. The parasitological tests were negative. In every case, a moderate to severe superficial, chronic gastritis was found as well as minor histopathological alterations in the colon mucosa. The presence of bile in both duodenum and colon in interdigestive periods, alterations in the enterohepatic circulation as well as in the biliary composition itself, are suggested as the possible causes of the patients symptoms.


Retinol conversion to retinoic acid is impaired in breast cancer cell lines relative to normal cells.
The bioactivity of retinol (vitamin A) is in part dependent on its metabolism to retinoic acid (RA). We investigated the ability of breast epithelial cells to synthesize RA when challenged with a physiological retinol dose (2 microM). Normal human mammary epithelial cells (HMEC) cultured from reduction mammoplasties were competent in RA synthesis and the ability to synthesize RA was retained by immortal, nontumorigenic breast epithelial cell lines (MTSV1.7, MCF-10F, and 184B5). In contrast, most (five of six) breast cancer cell lines could not synthesize RA or did so at low rates relative to normal cells. A notable exception was the MDA-MB-468 cell line, which was fully competent in RA synthesis. Most (>/=68%) of the RA synthesized by breast cells was recovered from the culture medium. Cellular retinol binding protein and cellular RA binding protein II, both expressed in HMEC, had various expression patterns in the cell lines that did not correlate with the observed differences in RA synthesizing ability. Strong RA induction of the RA hydroxylase P450RAI (CYP26) was confined to ERalpha-positive T47D and MCF-7 breast cancer cells and did not appear to explain the lack of detectable RA levels in these cells since RA remained undetectable when the cells were treated with 5-10 microM liarozole, a P450RAI inhibitor. We hypothesize that retinol bioactivity is impaired in breast cancer cells that cannot synthesize RA. In preliminary support of this hypothesis, we found that retinol (0.5-2 microM) inhibited MCF-10F but not T47D or MCF-7 cell growth.


Accelerated evolution and Muller's rachet in endosymbiotic bacteria.
Many bacteria live only within animal cells and infect hosts through cytoplasmic inheritance. These endosymbiotic lineages show distinctive population structure, with small population size and effectively no recombination. As a result, endosymbionts are expected to accumulate mildly deleterious mutations. If these constitute a substantial proportion of new mutations, endosymbionts will show (i) faster sequence evolution and (ii) a possible shift in base composition reflecting mutational bias. Analyses of 16S rDNA of five independently derived endosymbiont clades show, in every case, faster evolution in endosymbionts than in free-living relatives. For aphid endosymbionts (genus Buchnera), coding genes exhibit accelerated evolution and unusually low ratios of synonymous to nonsynonymous substitutions compared to ratios for the same genes for enterics. This concentration of the rate increase in nonsynonymous substitutions is expected under the hypothesis of increased fixation of deleterious mutations. Polypeptides for all Buchnera genes analyzed have accumulated amino acids with codon families rich in A+T, supporting the hypothesis that substitutions are deleterious in terms of polypeptide function. These observations are best explained as the result of Muller's ratchet within small asexual populations, combined with mutational bias. In light of this explanation, two observations reported earlier for Buchnera, the apparent loss of a repair gene and the overproduction of a chaperonin, may reflect compensatory evolution. An alternative hypothesis, involving selection on genomic base composition, is contradicted by the observation that the speedup is concentrated at nonsynonymous sites.


Surveillance for waterborne disease and outbreaks associated with drinking water and water not intended for drinking--United States, 2005-2006.
Since 1971, CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists have maintained a collaborative Waterborne Disease and Outbreak Surveillance System (WBDOSS) for collecting and reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs) and cases of waterborne disease. This surveillance system is the primary source of data concerning the scope and effects of waterborne disease in the United States. Data presented summarize 28 WBDOs that occurred during January 2005--December 2006 and four previously unreported WBDOs that occurred during 1979--2002. The surveillance system includes data on WBDOs associated with recreational water, drinking water, water not intended for drinking (WNID) (excluding recreational water), and water use of unknown intent. Public health departments in the states, territories, localities, and Freely Associated States (FAS) (i.e., the Republic of the Marshall Islands, the Federated States of Micronesia, and the Republic of Palau, formerly parts of the U.S.-administered Trust Territory of the Pacific Islands) are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC by a standard form. Only cases and outbreaks associated with drinking water, WNID (excluding recreational water), and water of unknown intent (WUI) are summarized in this report. Cases and outbreaks associated with recreational water are reported in a separate Surveillance Summary. Fourteen states reported 28 WBDOs that occurred during 2005--2006: a total of 20 were associated with drinking water, six were associated with WNID, and two were associated with WUI. The 20 drinking water-associated WBDOs caused illness among an estimated 612 persons and were linked to four deaths. Etiologic agents were identified in 18 (90.0%) of the drinking water-associated WBDOs. Among the 18 WBDOs with identified pathogens, 12 (66.7%) were associated with bacteria, three (16.7%) with viruses, two (11.1%) with parasites, and one (5.6%) mixed WBDO with both bacteria and viruses. In both WBDOs where the etiology was not determined, norovirus was the suspected etiology. Of the 20 drinking water WBDOs, 10 (50) were outbreaks of acute respiratory illness (ARI), nine (45%) were outbreaks of acute gastrointestinal illness (AGI), and one (5.0%) was an outbreak of hepatitis. All WBDOs of ARI were caused by Legionella, and this is the first reporting period in which the proportion of ARI WBDOs has surpassed that of AGI WBDOs since the reporting of Legionella WBDOs was initiated in 2001. A total of 23 deficiencies were cited in the 20 WBDOs associated with drinking water: 12 (52.2%) deficiencies fell under the classification NWU/POU (deficiencies occurred at points not under the jurisdiction of a water utility or at the point-of-use), 10 (43.5%) deficiencies fell under the classification SWTDs (contamination at or in the source water, treatment facility, or distribution system), and for one (4.3%) deficiency, classification was unknown. Among the 12 NWU/POU deficiencies, 10 (83.3%) involved Legionella spp. in the drinking water system. The most frequently cited SWTD deficiencies were associated with a treatment deficiency (n = four [40.0%]) and untreated ground water (n = four [40.0%]). Three of the four WBDOs with treatment deficiencies used ground water sources. Approximately half (52.2%) of the drinking water deficiencies occurred outside the jurisdiction of a water utility. The majority of these WBDOs were associated with Legionella spp, which suggests that increased attention should be targeted towards reducing illness risks associated with Legionella spp. Nearly all of WBDOs associated with SWTD deficiencies occurred in systems using ground water. EPA's new Ground Water Rule might prevent similar outbreaks in the future in public water systems. CDC and EPA use surveillance data to identify the types of water systems, deficiencies, and etiologic agents associated with WBDOs and to evaluate the adequacy of current technologies and practices for providing safe drinking water. Surveillance data also are used to establish research priorities, which can lead to improved water-quality regulation development. The majority of drinking water deficiencies are now associated with contamination at points outside the jurisdiction of public water systems (e.g., regrowth of Legionella spp. in hot water systems) and water contamination that might not be regulated by EPA (e.g., contamination of tap water at the POU). Improved education of consumers and plumbers might help address these risk factors.


Changes in the concentration of high-affinity oestradiol receptor in rat uterine supernatant preparations during the oestrous ycle, pseudopregnancy, pregnancy, maturation and after ovariectomy.
A quantitative method was used to determine the concentration of high-affinity oestradiol-receptor sites in rat uterine supernatant preparations under various physiological conditions. Cyclic changes in concentration were observed during the oestrous cycle, with a maximum occurring in late dioestrus. The changes followed a similar pattern in endometrium and myometrium, although concentrations were higher in the former. In pseudopregnancy the concentration was initially low, rising to a maximum on the tenth day. In early pregnancy a high concentration of receptor was found to be associated with the developing placenta, but this declined in later stages of pregnancy. After ovariectomy or combined ovariectomy and adrenalectomy the receptor concentration remained at a constant low value that could be increased by treatment with oestradiol. The receptor concentration was considerably higher in immature than in adult uteri.


Mianserin and lithium in the prophylaxis of depression.
Forty-one out-patients with a history of at least three attacks of depressive illness were randomly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets, or to lithium tablets once daily plus placebo mianserin tablets. After one year, the dosage of mianserin was increased to 30 mg t.d.s. for a further six months. All but three of the patients had previously been stabilized on prophylactic lithium therapy. Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT. The overall affective morbidity index, calculated from global rating, showed no significant difference between drugs, but the index of the mianserin group was higher in the second six months than in the first. The lithium group showed no such change. Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness.


Prospective evaluation of surgical management of sliding hiatal hernia and gastroesophageal reflux in dogs.
To evaluate response to surgical management of sliding hiatal hernia (SHH) and gastroesophageal reflux (GER) in dogs using standardized clinical scoring, videofluoroscopic swallow studies, and impedance planimetry. Prospective clinical trial. A total of 17 client-owned dogs. Dogs were included if they had clinical signs and videofluoroscopic evidence of SHH and/or GER. Owners were asked to complete a standardized canine dysphagia assessment tool (CDAT) preoperatively and postoperatively. Conscious videofluoroscopic swallowing studies and impedance planimetry (IP) were used to evaluate esophageal function and lower esophageal sphincter location and geometry preoperatively and in a subsection of dogs postoperatively. Preoperatively, 13/17 dogs included in the study had a history of regurgitation, and 4/17 had radiographic evidence of aspiration pneumonia. Postprandial regurgitation improved in 8/10 dogs with preoperative regurgitation, and for which completed preoperative and postoperative CDAT questionnaires were available (P < .01). The hiatal hernia severity score improved postoperatively (P = .046) in dogs with preoperative and postoperative videofluoroscopic swallowing studies (n = 12). However, hernia frequency score (P = .2) and IP parameters did not differ significantly between time points. Clinical signs of SHH generally improved with surgery but did not consistently resolve. Videofluoroscopic studies provide evidence that GER and SHH can persist postoperatively in some patients. Based on IP findings, clinical improvement may be attributed to a mechanism independent of lower esophageal sphincter attenuation.


Effects of extremely low-frequency magnetic field on caspase activities and oxidative stress values in rat brain.
This study was aimed to investigate the effect of extremely low-frequency magnetic field (ELF-MF) on apoptosis and oxidative stress values in the brain of rat. Rats were exposed to 100 and 500 µT ELF-MF, which are the safety standards of public and occupational exposure for 2 h/day for 10 months. Brain tissues were immunohistochemically stained for the active (cleaved) caspase-3 in order to measure the apoptotic index by a semi-quantitative scoring system. In addition, the levels of catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidative capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were measured in rat brain. Final score of apoptosis and MPO activity were not significantly different between the groups. CAT activity decreased in both exposure groups (p < 0.05), while TAC was found to be lower in ELF 500 group than those in ELF-100 and sham groups (p < 0.05). MDA, TOS, and OSI values were found to be higher in ELF-500 group than those in ELF-100 and sham groups (p < 0.05). In conclusion, apoptosis was not changed by long-term ELF-MF exposure, while both 100 and 500 µT ELF-MF exposure induced toxic effect in the rat brain by increasing oxidative stress and diminishing antioxidant defense system.


Analysis of molecular markers for metamorphic competency and their response to starvation or feeding in the mosquito, Aedes aegypti (Diptera: Culicidae).
The nutritional condition of fourth instar larvae of the yellow fever mosquito, Aedes aegypti, governs female longevity and egg production, both are key determinants of pathogen transmission. As well, nutrition provisions larval growth and development and attains its greatest pace in the last larval instar in preparation for metamorphosis to an adult. These developmental processes are regulated by a complex endocrine interplay of juvenile hormone, neuropeptides, and ecdysteroids that is nutrition sensitive. We previously determined that feeding for only 24h post-ecdysis was sufficient for fourth instar Ae. aegypti larvae to reach critical weight and accumulate sufficient nutritional stores to commit to metamorphosis. To understand the genetic basis of metamorphic commitment in Ae. aegypti, we profiled the expression of 16 genes known to be involved in the endocrine and nutritional regulation of insect metamorphosis in two ways. The first set is a developmental profile from the beginning of the fourth instar to early pupae, and the second set is for fourth instars starved or fed for up to 36 h. By comparing the two sets, we found that seven of the genes (AaegCYP302, AaegJHE43357, AaegBrCZ4, AaegCPF1-2, AaegCPR-7, AaegPpl, and AaegSlif) were expressed during metamorphic commitment in fourth instars and in fed but not starved larvae. Based on these results, the seven genes alone or in combination may serve as molecular indicators of nutritional and metamorphic status of fourth instar Ae. aegypti larvae and possibly other mosquito species in field and laboratory studies to gauge sub-lethal effects of novel and traditional cultural or chemical controls.


Trabecular bone score and its association with Cobb angle kyphosis in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) Study.
Hyperkyphosis (HK), or accentuated forward spinal curvature, commonly affects older people, although its causes are not completely understood. We tested whether a measure of bone quality, trabecular bone score (TBS), is associated with HK in 1997 older men, and determined that men with degraded TBS were more likely to have HK. While vertebral fractures and low bone mineral density (BMD) contribute to kyphosis progression, it is unknown whether the trabecular bone score (TBS) may provide additional information on bone quality that could influence the degree of kyphosis. We hypothesized that degraded TBS would be associated with hyperkyphosis (HK) defined as a Cobb angle > 50°. Using data from 1997 participants of the Osteoporotic Fractures in Men (MrOS) Study who had baseline TBS and Cobb angle kyphosis measured, we investigated whether men with degraded TBS were more likely to be hyperkyphotic, even after adjustment for BMD and prevalent vertebral fractures. Men were an average age of 74 ± 6 (mean ± SD) years with a mean kyphosis angle of 38.6 ± 11.5°, 295 (15%) were classified as hyperkyphotic, and 416 (21%) had degraded TBS. Compared with men with TBS > 1.2, men with degraded TBS were more likely to have HK (OR: 1.47, 95% CI: 1.06-2.06, p = 0.02) after adjusting for age, clinic, race, BMI, hip BMD, and prevalent vertebral fracture. If spine instead of hip BMD was included in the model, the odds ratio decreased to 1.35 (95% CI: 0.97-1.89, p = 0.08). Older men with degraded TBS are more likely to have HK not explained by underlying vertebral fractures.


Preferential association between childhood emotional abuse and bipolar disorder.
Childhood trauma has been suggested to be involved in the susceptibility to bipolar disorder. However, case-control studies are lacking, and the preferential implication and the dose-effect of different trauma subtypes remain poorly investigated. Two hundred six bipolar patients and 94 controls completed the Childhood Trauma Questionnaire (CTQ; Bernstein et al., 1994). The CTQ total score was higher for bipolar patients than for controls. The presence of multiple trauma was significantly more frequent in bipolar patients than in controls (63% vs. 33%). Multiple logistic regression suggested that only emotional abuse was associated with bipolar disorder with a suggestive dose-effect. Clinical practice should include systematic assessment of childhood trauma among bipolar patients with a particular focus on emotional abuse.


Hormonal regulation of proton secretion in rabbit medullary collecting duct.
With the exception of aldosterone, little is known about the hormonal regulation of distal nephron acidification. These experiments investigated the effects of prostaglandin E2, indomethacin, lysyl-bradykinin, 8-bromo-cyclic AMP, and forskolin on proton secretion in the major acidifying segment of the distal nephron, the medullary collecting duct from inner stripe of outer medulla. Using in vitro microperfusion and microcalorimetry, net bicarbonate reabsorption (proton secretion) was measured in rabbit medullary collecting ducts before, during, and after exposure to each test substance. PGE2 reduced proton secretion 12.2%, while the following substances stimulated proton secretion: indomethacin 14.2%; 8-bromo-cyclic AMP 34.5%; forskolin 39%. Lysyl-bradykinin was without effect. These studies demonstrate that distal nephron acidification, in addition to being stimulated by aldosterone, is significantly inhibited by the hormone PGE2. The stimulation of proton secretion by cAMP suggests that other hormones known to activate adenylate cyclase may also influence distal nephron acidification.


Fabrication of TiO2-Reduced Graphene Oxide Nanorod Composition Spreads Using Combinatorial Hydrothermal Synthesis and Their Photocatalytic and Photoelectrochemical Applications.
This study is the first to employ combinatorial hydrothermal synthesis and facile spin-coating technology to fabricate TiO2-reduced graphene oxide (rGO) nanorod composition spreads. The features of this study are (1) the development of a self-designed spin-coating wedge, (2) the systemic investigation of the structure-property relationship of the system, (3) the high-throughput screening of the optimal ratio from a wide range of compositions for photocatalytic and photoelectrochemical (PEC) applications, and (4) the effective coupling between the density gradient TiO2 nanorod array and the thickness gradient rGO. The formation of rGO in the fabricated TiO2-rGO sample was monitored through Fourier transform infrared spectrometry. Transmission electron microscopy images also suggested that the TiO2 nanorod surfaces were covered with a thin layer of amorphous rGO. The rutile TiO2 plane evolution along the composition variation was verified through X-ray diffraction. 7% TiO2-93% rGO on the nanorod composition spread exhibited the most promising photocatalytic ability; the corresponding photodegradation kinetics, denoted by the photodegradation rate constant (k), was determined to be approximately 12.7 × 10-3 min-1. The excellent performance was attributed to the effective coupling between the TiO2 and rGO, which improved the charge carrier transport, thus inhibiting electron-hole pair recombination. A cycling test implied that 7% TiO2-93% rGO is a reliable photocatalyst. A photoluminescence spectroscopy study also supported the superior photocatalytic ability of the sample, which was attributed to its markedly poorer recombination behavior. In addition, without further treatment, the sample exhibited excellent PEC stability; the photocurrent density was more than three times higher than that exhibited by the density gradient TiO2 nanorods.


Integrated care: meaning, logic, applications, and implications--a discussion paper.
Integrated care is a burgeoning field. As is often the case in new areas of inquiry and action, conceptual clarification is demanded. Without such attention, it would be difficult to advance theory and practice in this increasingly important professional arena. In the following discussion paper, the authors explore the intellectual territory of integrated care, and underscore the need for a patient-centric imperative and meaning. They also examine the practical applications and implications arising from their views. The intention is to stimulate fruitful dialogue and debate about what 'integrated care' could and should be.


Intervention for Feeding Difficulties in Children With a Complex Medical History: A Randomized Clinical Trial.
This study aimed to compare outcomes of different multidisciplinary feeding therapy approaches in children with feeding difficulties. Children aged 2 to 6 years with feeding difficulties and a medically complex history (MC) were recruited. Children with feeding difficulties and a nonmedically complex history (NMC) were included as a comparison group. Participants attended a clinical assessment, and eligible participants were randomized to receive targeted feeding intervention incorporating either operant conditioning or systematic desensitization. Parents could elect to receive intervention in an intensive (10 sessions in a week) or weekly (10 sessions during 10 weeks) format. Both groups received immersive parent training. A review was completed 3 months post-intervention. In total, 98 participants were eligible to participate (MC, n = 43; NMC, n = 55). Data from 20 children from the MC group (47%) and 41 children from the NMC group (75%) were included in the final analysis. Clinically significant improvements were observed following both arms of therapy, consistent with previous research. Parents of children in the MC arm were significantly more likely to elect for intensive intervention than weekly (MC = 12/20, 60%; 12/41, 29%; P = 0.02). Both therapy protocols were considered clinically effective. The difference in attrition rates between the etiological groups suggests primary differences in how service delivery should be managed. Progress for the medically complex child may be slower while medical issues are stabilized, or while the focus for parents shifts to other developmental areas. In planning services for a medically complex group, therefore, it is essential that consideration be given to medical and family needs.


Persistent organochlorines in human breast milk from major metropolitan cities in India.
The present study was carried out to understand the current contamination status of organochlorine compounds (OCs) in human breast milk from three metropolitan cities in India (New Delhi, Mumbai and Kolkata). Among the OCs analyzed, DDTs were predominant followed by HCHs and PCBs. CHLs and HCB levels were much lower. Contamination patterns were different in human milk found in our previous study in Chennai, a metropolitan city in southern India, indicating region specific exposure routes and variable sources. In comparison with previous data, levels of DDTs and HCHs generally declined with time, implying the effect of various bans and restrictions on their usage. No association between concentrations of OCs and demographic characteristics such as parity and age of mothers was observed which might be due to narrow range of mother's age. Estimated daily intake shows that some infants are exposed to OCs to a greater extent, particularly HCHs than the guideline standard.


[Management of complications related to intraduodenal infusion of levodopa/carbidopa in patients with Parkinson's disease].
Continuous infusion of intraduodenal levodopa/carbidopa is an effective treatment that improves the motor complications and the quality of life of patients in the advanced stages of Parkinson's disease. However, it is not free of complications. These may present in the post-operative period following surgery (gastrostomy) or in the long-term during the follow-up period and can be related with the medication (levodopa/carbidopa), the stoma, the gastrostomy or the device (pump, enteral tube, parts of the FREKA system). The aim of this review is to report on the management of the complications that can be observed in patients with advanced Parkinson's disease treated with continuous infusion of intraduodenal levodopa/carbidopa.


Insulin receptor binding and protein kinase activity in muscles of trained rats.
Exercise has been shown to increase insulin sensitivity, and muscle is quantitatively the most important tissue of insulin action. Since the first step in insulin action is the binding to a membrane receptor, we postulated that exercise training would change insulin receptors in muscle and in this study we have investigated this hypothesis. Female rats initially weighing approximately 100 g were trained by treadmill running for 2 h/day, 6 days/wk for 4 wk at 25 m/min (0 grade). Insulin receptors from vastus intermedius muscles were solubilized by homogenizing in a buffer containing 1% Triton X-100 and then partially purified by passing the soluble extract over a wheat germ agglutinin column. The 4 wk training regimen resulted in a 65% increase in citrate synthase activity in red vastus lateralis muscle, indicating an adaptation to exercise. Insulin binding by the partially purified receptor preparation s was approximately doubled in muscle of trained rats at all insulin concentrations, suggesting an increase in the number of receptors. Training did not alter insulin receptor structure as evidenced by electrophoretic mobility under reducing and nonreducing conditions. Basal insulin receptor protein kinase activity was higher in trained than untrained animals and this was likely due to the greater number of receptors. However, insulin stimulation of the protein kinase activity was depressed by training. These results demonstrate that endurance training does alter receptor number and function in muscle and these changes may be important in increasing insulin sensitivity after exercise training.


Applied anatomy of pelvic lymph nodes and its clinical significance for prostate cancer:a single-center cadaveric study.
Pelvic lymph node dissection (PLND) is one of the most important steps in radical prostatectomy (RP). Not only can PLND provide accurate clinical staging to guide treatment after prostatectomy but PLND can also improve the prognosis of patients by eradicating micro-metastases. However, reports of the number of pelvic lymph nodes have generally come from incomplete dissection during surgery, there is no anatomic study that assesses the number and variability of lymph nodes. Our objective is to assess the utility of adopting the lymph node count as a metric of surgical quality for the extent of lymph node dissection during RP for prostate cancer by conducting a dissection study of pelvic lymph nodes in adult male cadavers. All 30 adult male cadavers underwent pelvic lymph node dissection (PLND), and the lymph nodes in each of the 9 dissection zones were enumerated and analyzed. A total of 1267 lymph nodes were obtained. The number of lymph nodes obtained by limited PLND was 4-22 (14.1 ± 4.5), the number obtained by standard PLND was 16-35 (25.9 ± 5.6), the number obtained by extended PLND was 17-44 (30.0 ± 7.0), and the number obtained by super-extended PLDN was 24-60 (42.2 ± 9.7). There are substantial inter-individual differences in the number of lymph nodes in the pelvic cavity. These results have demonstrated the rationality and feasibility of adopting lymph node count as a surrogate for evaluating the utility of PLND in radical prostatectomy, but these results need to be further explored.


Thoracoscopic right S6 sleeve segmentectomy for squamous-cell carcinoma arising from the B6 central bronchus.
We describe a patient with low respiratory function who underwent thoracoscopic sleeve segmentectomy to preserve lung function as much as possible. The patient had already used home oxygen therapy because of chronic obstructive lung disease. There was a squamous-cell carcinoma at inlet of right B6 bronchus, and cT1aN0M0 disease was diagnosed. Because respiratory function was poor, right S6 segmentectomy was scheduled. Moreover, to preserve the respiratory muscles as much as possible, a thoracoscopic approach was selected. We performed S6 sleeve segmentectomy, and sutured the lower bronchus and basal bronchus. There were some limitations in handling needles during thoracoscopy. To resolve these difficulties, we devised two techniques. One was to suture the bronchus with continuous sutures on the mediastinal side and simple interrupted sutures on the other side. The other was to create a working space for handling the needles to avoid entanglement of the sutures. These techniques allowed us to suture the bronchi relatively easily.


[Regional anesthesia practice in Chile: an online survey].
To conduct a survey to profile the practice of regional anesthesia in Chile and determine the limitations on its use. A link to an online questionnaire was sent by e-mail to anesthesiologists who were members of their national professional association (Sociedad Chilena de Anestesiologia). The survey was processed anonymously. Multiple choice items elicited responses concerning general demographic information, professional experience as an anesthetist, academic degree, hospital size, and the use of regional anesthesia in clinical practice (number of procedures and types of techniques). Finally, the questionnaire focused on the use of nerve and plexus blocks. A total of 209 completed questionnaires were received, for a response rate of 54%. Regional anesthesia was part of routine practice for 97% of the respondents; 68% reported that regional techniques were used in more than 30% of their caseload. Most performed neuraxial techniques: 98.1% were spinal blocks, 96.2% lumbar epidural blocks, and 66.9% thoracic epidural blocks. Routine use of peripheral nerve blockade was reported by 73.7%. Upper limb anesthesia was provided significantly more often than lower limb anesthesia (P =.011). The most common technique involved use of a peripheral nerve stimulator (64%). Skills were mainly acquired through residency programs (68.9%) and self-teaching (20.1%). Peripheral nerve blocks were never performed by 26.3% of the respondents; the reason given most often was lack of training. Although regional anesthesia is commonly used in Chile, neuraxial blocks remain the most frequently used types. Peripheral nerve blocks are used fairly often, mostly on an upper limb. Training should stimulate attempts to promote more widespread use of all forms of regional anesthesia.


Objective measures of sleep and dim light melatonin onset in adolescents and young adults with delayed sleep phase disorder compared to healthy controls.
Delayed sleep phase disorder is characterized by a delay in the timing of the major sleep period relative to conventional norms. The sleep period itself has traditionally been described as normal. Nevertheless, it is possible that sleep regulatory mechanism disturbances associated with the disorder may affect sleep duration and/or architecture. Polysomnographic data that may shed light on the issue are scarce. Hence, the aim of this study was to examine polysomnographic measures of sleep in adolescents and young adults with delayed sleep phase disorder, and to compare findings to that of healthy controls. A second aim was to estimate dim light melatonin onset as a marker of circadian rhythm and to investigate the phase angle relationship (time interval) between dim light melatonin onset and the sleep period. Data from 54 adolescents and young adults were analysed, 35 diagnosed with delayed sleep phase disorder and 19 healthy controls. Results show delayed timing of sleep in participants with delayed sleep phase disorder, but once sleep was initiated no group differences in sleep parameters were observed. Dim light melatonin onset was delayed in participants with delayed sleep phase disorder, but no difference in phase angle was observed between the groups. In conclusion, both sleep and dim light melatonin onset were delayed in participants with delayed sleep phase disorder. The sleep period appeared to occur at the same circadian phase in both groups, and once sleep was initiated no differences in sleep parameters were observed.


Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: a meta-analysis.
Although carotid bruits are deemed to be markers of generalised atherosclerosis, they are poor predictors of cerebrovascular events. We investigated whether a carotid bruit predicts myocardial infarction and cardiovascular death. In this meta-analysis, we searched Medline (1966 to August, 2007) and Embase (1974 to August, 2007) with the terms "carotid" and "bruit". Bibliographies of all the retrieved articles were also searched. Articles were included if they reported the incidence of myocardial infarction or cardiovascular death in adults. Outcome variables were extracted in duplicate and included the rate of myocardial infarction and cardiovascular mortality. Quality of the articles was independently assessed with the Hayden rating scheme. Data were pooled with a random effects model. Of the 22 articles included, 20 (91%) used prospective cohorts. Our analysis included 17,295 patients with 62 413.5 patient-years of follow-up, with a median sample size of 273 patients (range 38-4736) followed up for 4 years (2-7). The rate of myocardial infarction in patients with carotid bruits was 3.69 (95% CI 2.97-5.40) per 100 patient-years (eight studies) compared with 1.86 (0.24-3.48) per 100 patient-years in those without bruits (two studies). Yearly rates of cardiovascular death were also higher in patients with bruits (16 studies) than in those without (four studies) (2.85 [2.16-3.54] per 100 patient-years vs 1.11 [0.45-1.76] per 100 patient-years). In the four trials in which direct comparisons of patients with and without bruits were possible, the odds ratio for myocardial infarction was 2.15 (1.67-2.78) and for cardiovascular death 2.27 (1.49-3.49). Auscultation for carotid bruits in patients at risk for heart disease could help select those who might benefit the most from an aggressive modification strategy for cardiovascular risk.


Epidemiology of dengue in Nepal: History of incidence, current prevalence and strategies for future control.
Dengue is now established as one of the most important arboviral infections. As the epidemic continues unabated globally, this Aedes mosquito-transmitted pathogen is considered a major re-emerging tropical disease and significant public health concern. Four well-established distinct serotypes of dengue virus, with a fifth one recently proposed, are responsible for causing a spectrum of clinical symptoms in humans ranging from mild fever to severe haemorrhagic manifestations. Indigenous cases of dengue were first recognised in Nepal, a Himalayan country bordered by India and China, just a decade ago in a cluster of tropical and subtropical areas. Subsequently, the range of infection has extended all over the country and now comprises not only low lying regions, but also hilly locations including the capital city Kathmandu. The two major epidemics to date, in 2010 and 2013, have demonstrated the capacity of infection outbreaks to be explosive and challenging to currently available disease control measures. There is a pressing need to undertake effective vector surveillance studies supported by provision of well-equipped diagnostic virology laboratories. However, sincere efforts are being made to map the nationwide prevalence and understand the epidemiology of dengue infection. Yet, the precise burden of dengue in Nepal remains unknown, since most reports are confined to economically affluent areas and do not account for regions of relative social deprivation in which disease is more likely to occur. This review presents a current overview of dengue in Nepal and discusses future prospects for control of this debilitating disease in the country.


Mechanism of acyl transfer by the class A serine beta-lactamase of Streptomyces albus G.
Optimization by energy minimization of stable complexes occurring along the pathway of hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase has highlighted a proton shuttle that may explain the catalytic mechanism of the beta-lactamases of class A. Five residues, S70, S130, N132, T235 and A237, are involved in ligand binding. The gamma-OH group of T235 and, in the case of benzylpenicillin, the gamma-OH group of S130 interact with the carboxylate group, on one side of the ligand molecule. The side-chain NH2 group of N132 and the carbonyl backbone of A237 interact with the exocyclic CONH amide bond, on the other side of the ligand. The backbone NH groups of S70 and A237 polarize the carbonyl group of the scissile beta-lactam amide bond. Four residues, S70, K73, S130 and E166, and two water molecules, W1 and W2, perform hydrolysis of the bound beta-lactam compound. E166, via W1, abstracts the proton from the gamma-OH group of S70. While losing its proton, the O-gamma atom of S70 attacks the carbonyl carbon atom of the beta-lactam ring and, concomitantly, the proton is delivered back to the adjacent nitrogen atom via W2, K73 and S130, thus achieving formation of the acyl-enzyme. Subsequently, E166 abstracts a proton from W1. While losing its proton, W1 attacks the carbonyl carbon atom of the S70 ester-linked acyl-enzyme and, concomitantly, re-entry of a water molecule W'1 replacing W1 allows E166 to deliver the proton back to the same carbonyl carbon atom, thus achieving hydrolysis of the beta-lactam compound and enzyme recovery. The model well explains the differences found in the kcat. values for hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase. It also explains the effects caused by site-directed mutagenesis of the Bacillus cereus beta-lactamase I [Gibson, Christensen & Waley (1990) Biochem J. 272, 613-619].


Professional carers' struggle to be confirmed. Narratives within the care of the elderly and disabled.
Twenty-seven members of staff working in special types of housing in Sweden narrated 95 narratives about their experience of being in problematic situations during the working day. The narratives were interpreted using a phenomenological-hermeneutic approach inspired by the philosophy of Ricoeur. The narratives mainly concerned interactions with colleagues and very few narratives concerned interactions with residents and relatives. On the relationship level of communication there is evidence that many interactions among the staff, residents and relatives were of a receptive and disconfirming nature. The results indicate that the staff feel lonely, and struggled to maintain self-esteem and to be confirmed.


Vernakalant hydrochloride for the treatment of atrial fibrillation.
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Rhythm control strategy for AF is limited by drug toxicity and side effects, and recent trials have shown that this strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance rhythm control, with the possibility of sinus rhythm restoration and maintenance. A promising find in the search for new antiarrhythmic therapies is atrial-tissue specific ion channels. The findings that the ultrarapid delayed rectifier (I(Kur)) and the inwardly rectifying, acetylcholine-regulated current (I(K-Ach)) exist in atrial but not ventricular tissue increase the probability that atrioselective drugs without ventricular proarrhythmic toxicity can be developed for treatment of patients with AF. There are also other potential targets for atrial-selective therapy: transient outward current (I(to)), rapidly and slowly activating delayed rectifier currents (I(Kr) and I(Ks)), atrial sodium current (I(Na)) and atrially expressed connexins. New drugs under development with promising atrial-selectivity include: tertiapin, NIP-142, NIP-141, JTV-519, AVE0118, AVE1231, DPO-1, AZD7009 and many others. Among such new agents, vernakalant hydrochloride is currently in an advanced phase of development and has already been evaluated in clinical trials. In this overview, we describe the history and current state of developmental process of the drug, as well as its mechanism of action and influence on electrophysiological parameters. Vernakalant seems to be effective in terminating recent-onset AF, but is not efficacious in long-lasting AF and atrial flutter. The drug may be relatively free of proarrhythmic effects, and exerts a protective effect on ventricular tissue and ventricular repolarization. It is expected that the intravenous formulation will soon be approved for the pharmacological termination of recent-onset AF.


Characterization of reproduction-specific genes in a marine bivalve mollusc: influence of maturation stage and sex on mRNA expression.
Numerous studies have investigated the reproduction mechanisms in mollusc species at a biochemical and physiological level; few have described these mechanisms at a molecular level, despite great commercial interest in several mollusc species. We investigated genes involved in gonad maturation of the marine scallop Argopecten purpuratus. A cDNA library was made from gonad tissue. After sequence analysis, 418 unique genes were characterized, of these, about 80% were of unknown function. Among the identified sequences, we analyzed the mRNA expression by real-time PCR of 7 genes involved in reproduction mechanisms, either directly: testis-specific serine/threonine-protein kinase (TSSK), vitellogenin (Vg), and spermatogenesis and centriole associated 1 (SCA) or indirectly: calcineurin A (CNA), centrin, RNA-specific adenosine deaminase (ADAR), and cytidine deaminase (CDA). The real-time PCR analyses were conducted on different tissues of mature and immature scallops (testis, ovary, immature gonad, gill, digestive gland and mantle). The genes studied, presented (1) a strong tissue-dependent expression pattern (higher expression in gonad tissues than in all other tissues) and (2) a sex- and maturation-specific expression pattern (except centrin). This is the first time that the expression of specific genes involved in reproduction mechanisms in a marine mollusc has been described at the molecular level.