Biochemical characterization and application of a new lipase and its cognate foldase obtained from a metagenomic library derived from fat-contaminated soil.
LipMF3 is a new lipase isolated from a metagenomic library derived from a fat-contaminated soil. It belongs to the lipase subfamily I.1 and has identities of 68% and 67% with lipases of Chromobacterium violaceum and C. amazonense, respectively. Genes encoding LipMF3 and its cognate foldase, LifMF3, were cloned and co-expressed in Escherichia coli. The highest hydrolytic activity of purified Lip-LifMF3 was at 40 °C and pH 6.5. Under these conditions, the highest activity was against tributyrin (1650 U mg-1), but it also had high activity against olive oil (862 U mg-1). It was stable in hydrophilic organic solvents (25%, v/v in water) with residual activity around 100% after 24 h. It also showed stability over a wide pH range (5.5 to 11) with residual activity above 80% after 24 h. Lip-LifMF3 was immobilized by covalent bonding onto Immobead 150P and by adsorption onto Sepabeads FP-BU. The latter preparation gave the best results, producing 94% conversion after 5 h for the synthesis of ethyl oleate and a 90% enantiomeric excess of the product (R)‑1‑phenylethyl acetate for the kinetic resolution of (R,S)‑1‑phenyl‑1‑ethanol. The results obtained in this work provide a basis for the development of applications of Lip-LifMF3 in biocatalysis.


Women's Sexual Issues After Myocardial Infarction: A Literature Review.
Sexual activity after myocardial infarction (MI) is a concern for patients and often a challenge for health care professionals to address. It is widely recognized that most patients, of both sexes, report sexual problems or concerns after MI. However, there are reported differences between men and women. Women with sexual concerns may seek less help from health care providers and are more inclined to conceal them because of cultural barriers. The aim of the current study is to present a comprehensive review of the literature describing women's sexual issues after MI. A systematic search of the relevant literature was performed within international databases, including PubMed/Medline, Scopus, ScienceDirect, and ProQuest, as well as Google Scholar using relevant keywords. Also, Persian electronic databases such as Magiran, Scientific Information Databases, and Iran Medex were searched from the inception to October 2014. Articles focusing on the sexual issues after MI only in women, as well as articles on both sexes where women's results could be separated, were included in this review. A total of 8 articles were included in the final dataset. The main themes of women's sexual concerns after MI were "loss or decrease of sexual activity," "dissatisfaction of sexual relationship," "doubt about resumption time of sexual activity," "fear of reinfarction or sudden death during sexual activity after MI," "knowledge deficit regarding sexual activity after MI," and "poor performance of health care providers in sexual counseling." The results of this review demonstrate that women's post-MI sexual activity is affected by many concerns. The concerns may be a knowledge deficit related to not receiving necessary consultation on this topic. Nurses, as first-line care givers, can provide appropriate consultation and education for patients post-MI. As a result, breaking taboo imposed by cultural barriers, personal assumptions, or lack of confidence on giving sexual consultation may ultimately help patients to improve their quality of life.


Integration of Ecology and Environmental Metagenomics Conceptual and Methodological Frameworks.
Although from its origin metagenomics was concerned with composition of communities of microbial OTUs (Operational Taxonomic Units) living in a given habitat and their diversity and functional heterogeneity (concepts already well rooted in ecology), the new field was more 'environmentally' than 'ecologically' oriented. Probably by circumstantial reasons, metagenomics and ecology followed rather independent trajectories and conceptual and methodological gaps appeared. Recently, calls for the need of integrating the theoretical basis and methodologies coming from metagenomics (and other meta-omics) and ecology have been made. Here I will address some of the principles and methods of field ecology that, although useful in the context of environmental metagenomic studies, have been rather disregarded. In particular, I will emphasize the contribution of some well established concepts and methods of field ecology to a an appropriate field sampling and experimental design of environmental metagenomic studies.


[Does the Residual Regurgitation on Intraoperative Transesophageal Echocardiography after Valve Surgery Deteriorate in Early Postoperative Period?].
Residual regurgitation after valve surgery affects patients' long-term prognosis. Whether post-repair regurgitation deteriorates postoperatively or not remains unclear, but this issue is a primary concern of the anesthesiologists responsible for intraoperative evaluation by transesophageal echocardiography (TEE). This study was conducted to assess changes in the severity of residual regurgitation during the early postoperative period. Among 160 consecutive patients who underwent valve repair or valve replacement surgery during April 2010-June 2013 at our institution, 38 (24%) were found to have residual regurgitation by intraoperative TEE. We retrospectively evaluated these patients by reviewing follow-up transthoracic echocardiographic examination records. Residual regurgitation improved in 14 (37%), remained unchanged in 21 (55%), and worse in 3 (8%). All three patients showing worse regurgitation had undergone valve repair. Of them, one had reoperation one year later. No worsening of regurgitation, including perivalvular leakage, was found in patients who had undergone valve replacement. In valve repair, even mild residual regurgitation deteriorates postoperatively. Therefore, it should be observed cautiously. In valve replacement mild residual regurgitation did not deteriorate, irrespective of the regurgitation mechanism.


Cohabitating Partners and Domestic Labor in Low-Income Black Families.
This article examines the division of domestic labor in low-income cohabiting Black stepfamilies. We analyze survey data collected from 136 such families in order to understand how stepparent gender and relationship length impact the distribution of domestic labor. We hypothesize that women do more domestic work than men across all three family types, and that stepfathers are more involved in domestic labor in established relationships compared to new relationships. Findings indicate that cohabiting stepfathers in both new and established cohabiting Black stepfamilies make substantial contributions to domestic labor. These families demonstrate a division of labor consistent with traditional gender roles, though both partners agree on how much work each does. Parents, regardless of gender, are more involved in domestic labor than stepparents.


The role of highlighting in visual search through maps.
Two experiments were conducted in which participants performed a vehicle dispatching task. The intensity of one information source (vehicles in Experiment 1, destinations in Experiment 2) was varied to examine the effects of salience and discrimination on both searching for and processing the information in a cluttered display. Response times were recorded for questions either requiring focused attention on or divided attention between the different information domains in the map. The results of the present experiments indicate that it is possible to declutter a display without erasing any information. By 'lowlighting' one information domain and keeping the other domain at a fairly high intensity level, dividing attention between the information sources is optimal, as is focusing attention on either of the information domains exclusively. These results are discussed in conjunction with a computational model of confusion and salience which serves to predict search and integration performance in a cluttered display with separate domains of information displayed at different intensities.


Stability, Molecular Sieving, and Ion Diffusion Selectivity of a Lamellar Membrane from Two-Dimensional Molybdenum Disulfide.
Two-dimensional (2D) subnanometer channels allow unique mass transport promising for molecular sieving. New 2D channels of MoS2 nanosheets allow one to understand molecular transmission and separation, unlike the graphene oxide counterpart containing various defects and cationic metal contaminants. Membranes from layered MoS2 platelets show extraordinary stability in an aqueous environment and compatibility with polymer filters, both beneficial to efficient manufacturing. Sharing gas-tightness and unimpeded water vapor permeation with a graphene oxide membrane, our lamellar MoS2 membrane demonstrates a molecular sieving property for organic vapor for the first time. The MoS2 membrane also reveals diffusion selectivity of aqueous ions, attributable to the energy penalty in bulk-to-2D dimensional transition. These newly revealed properties of the lamellar membrane full of angstrom-sized 2D channels point to membrane technology applications for energy and environment.


Expression and distribution of prolactin receptor in normal, fibrotic, and cirrhotic human liver.
Liver cirrhosis is often associated with elevated levels of prolactin (PRL). This is commonly attributed to impaired hepatic metabolism of estrogens. However, there is evidence suggesting that PRL may be an important factor in hepatic tissue regeneration. To investigate the role of PRL in the pathogenesis of liver cirrhosis, we used RT-PCR and immunhistochemical staining to analyze changes in the expression and the histological distribution of the prolactin receptor (PRLR) in normal, fibrotic and cirrhotic hepatic tissue. Liver tissue was obtained from 29 surgically explanted human livers. The histological examination demonstrated normal liver tissue (n=9) as well as different grades of fibrosis (n=10) and cirrhosis (n=10). In liver cirrhosis and fibrosis, PRLR-mRNA was expressed at a higher level compared to normal liver specimens. Immunohistochemical staining of normal liver tissue demonstrated homogeneous distribution of the PRLR in the hepatocytes and in the epithelial cells of the bile ducts. This pattern of distribution was lost in fibrosis, where an accumulation of the PRLR was observed in the damaged hepatocytes. As no PRL-mRNA was detectable in normal, fibrotic or cirrhotic tissue, PRL does not act through autocrine or paracrine mechanisms. These data confirm previous results, which we obtained using an animal model for experimental liver cirrhosis in rats suggesting a metabolic function of PRL in normal liver and a regenerative function in fibrotic and cirrhotic liver. In conclusion, PRL might be involved in the pathogenesis of liver cirrhosis.


Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01.
It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists.


Intersectoral approaches to neglected diseases.
The neglected diseases are a diverse group of communicable diseases that affect principally the world's poorest people. They are linked to poverty, as both a cause and a consequence of same, and affect community security and family productivity. The neglected diseases cause acute and chronic illness, disability, and sometimes death, and they may carry stigma for those infected. Current interventions for neglected diseases emphasize the health sector, but to achieve sustainability and simultaneously combat poverty, an intersectoral approach to their prevention and control is needed. This chapter outlines some concepts for an intersectoral approach, including interventions from the nutrition and food security, education, and environmental sectors.


Safety and efficacy of an indigenous human recombinant interferon alpha 2b (Shanferon) in patients with chronic hepatitis B.
Interferon treatment is the established option for the treatment of patients with chronic hepatitis B without decompensated liver disease. However, such treatment is expensive. We report here our data of a multi-center, open-label trial of the use of an indigenously produced interferon in the treatment of chronic HBeAg-positive chronic hepatitis B. Adult patients with chronic HBeAg-positive hepatitis B with elevated serum transaminase activity and positive serum HBV DNA test were treated with 5 MU/day of an indigenously produced interferon (Shanferon; Shantha Biotechnics, Hyderabad, India) for 4 months, and were then followed up for 6 months. Of the 39 patients enrolled, 36 completed the treatment and 33 completed the post-treatment follow-up. Of the 33 patients who completed the study, end-of-treatment biochemical and virological responses were observed in 10 (30%) and 5 (15%) respectively. Sustained biochemical and virological responses were observed in 15 (45%) and 7 (21%), patients respectively. Adverse effects led to the discontinuation of treatment in only one patient. Our data suggest that safety and efficacy of the indigenously produced interferon were similar to those previously reported results with interferon from other sources.


Headlice eradication as everyday engagement with science: An analysis of online parenting discussions.
This paper focuses on the way in which people deploy scientific knowledge alongside other resources in everyday interactions. In the UK headlice are common amongst schoolchildren, and treatment is viewed as a parental responsibility. Choice between treatment options lies with individual parents, with official guidance giving no clear steer. In the face of this combination of responsibility and uncertainty, users of an online parenting forum justify their actions using a variety of resources, including claims to scientific knowledge of both headlice and the action of various treatments, but also drawing on the authority of having direct experience, trust in brand-named products and generalised suspicion of "chemical" treatments. These discussions occasion expression of knowledge as part of portraying oneself as a responsible parent, and thus while they do not necessarily represent public knowledge about science more generally, they do offer a useful site to explore what people do with science.


Orthogonal polynomials describing polarization aberration for rotationally symmetric optical systems.
Optical lithography has approached a regime of high numerical aperture and wide field, where the impact of polarization aberration on imaging quality turns to be serious. Most of the existing studies focused on the distribution rule of polarization aberration on the pupil, and little attention had been paid to the field. In this paper, a new orthonormal set of polynomials is established to describe the polarization aberration of rotationally symmetric optical systems. The polynomials can simultaneously reveal the distribution rules of polarization aberration on the exit pupil and the field. Two examples are given to verify the polynomials.


Point-of-use water treatment and diarrhoea reduction in the emergency context: an effectiveness trial in Liberia.
Communicable diseases are of particular concern in conflict and disaster-affected populations that reside in camp settings. In the acute emergency phase, diarrhoeal diseases have accounted for more than 40% of deaths among camp residents. Clear limitations exist in current water treatment technologies, and few products are capable of treating turbid water. We describe the findings of a 12-week effectiveness study of point-of-use water treatment with a flocculant-disinfectant among 400 households in camps for displaced populations in Monrovia, Liberia. In intervention households, point-of-use water treatment with the flocculant-disinfectant plus improved storage reduced diarrhoea incidence by 90% and prevalence by 83%, when compared with control households with improved water storage alone. Among the intervention group, residual chlorine levels met or exceeded Sphere standards in 85% (95% CI: 83.1-86.8) of observations with a 95% compliance rate.


Individual-level predictors of nonparticipation and dropout in a life-skills HIV prevention program for adolescents in foster care.
The purpose of this study is to identify individual-level characteristics of foster care adolescents who are more likely to not participate in, and drop out of, a life-skills HIV prevention program delivered over 8 months. Structured interviews were conducted with 320 foster care adolescents (15-18 years). Logistic regression and survival analyses (Cox Proportional Hazards Regression) determined the influence of demographics, HIV sexual risk behaviors, substance use, mental health problems, and other individual-level risk factors on nonparticipation and dropout. Older age and having vaginal intercourse without a condom were significant predictors of nonparticipation. Older age and marijuana use significantly increased the hazard of dropping out of the program. Foster care adolescents at increased risk for HIV infection were more likely to never participate in and drop out of the program. To improve initial and ongoing participation, HIV prevention efforts for adolescents in foster care should be tailored to individual-level HIV risk behaviors and incorporate early and ongoing engagement and retention strategies.


Massachusetts' approach to the prevention of heart disease, cancer, and stroke.
Heart disease, cancer, and cerebrovascular disease together cause more than two out of three deaths in the United States annually. These three diseases are largely a result of widespread risk factors such as smoking, unhealthy diet, high blood pressure, physical inactivity, and environmental toxic exposure. The prevalence of these risk factors can be significantly lowered, resulting in major reductions in mortality rates for these diseases. Thus far, there have been no statewide disease prevention efforts to reduce deaths from all three diseases simultaneously. The Massachusetts Department of Public Health recently began an aggressive statewide program to prevent deaths from these three causes through a reduction in their underlying risk factors. Within 5 years, this program will save at least 2,000 lives annually. Similar efforts by public health agencies and health care practitioners in the rest of the United States could save many thousands of lives.


Ephedrine-induced mitophagy via oxidative stress in human hepatic stellate cells.
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown. In this study, we investigated hepatotoxicity and key regulation of mitophagy in ephedrine-treated LX-2 cells. Ephedrine triggered mitochondrial oxidative stress and depolarization. Mitochondrial swelling and autolysosome were observed in ephedrine-treated cells. Ephedrine also inhibited mitochondrial biogenesis, and the mitochondrial copy number was decreased. Parkin siRNA recovered the ephedrine-induced mitochondrial damage. Excessive mitophagy lead to cell death through imbalance of autophagic flux. Moreover, antioxidants and reducing Parkin level could serve as therapeutic targets for ephedrine-induced hepatotoxicity.


Survey for selected diseases in nutria (Myocastor coypus) from Louisiana.
Thirty-two trapper-caught nutria (Myocastor coypus) from East Baton Rouge, Iberville, Tangipahoa, and St. Helena Parishes in Louisiana (USA) were sampled for several disease agents. Antibodies against Toxoplasma gondii, Chlamydia psittaci, Francisella tularensis, Leptospira spp., and encephalomyocarditis virus were detected in 7%, 14%, 0%, 7%, and 0% of nutria, respectively. Both animals seropositive for leptospirae were positive for L. interrogans serovar canicola. No Salmonella spp. were isolated from feces, and no Giardia spp. were seen in trichrome-stained fecal preparations.


The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye.
Transthyretin (TTR), or prealbumin, is a 55-kD tetrameric protein which plays an important role in the plasma transport of thyroxine, and through its interaction with retinol-binding protein, of retinol. Four major sources of TTR synthesis have been identified in the mammal: liver hepatocytes, visceral yolk sac endoderm, choroid plexus epithelium, and the eye. We now report in situ hybridization studies demonstrating that in the rat eye, the retinal pigment epithelium is the unique source of TTR synthesis. This finding underscores the developmental, structural, and functional homology between the choroid plexus epithelium and the retinal pigment epithelium. Although the functional significance of ocular TTR synthesis is unclear, it is likely that it serves to transport thyroxine or retinol across the blood-retina barrier, thereby facilitating their effects on differentiation and morphogenesis. Considering the importance of retinol in the biochemistry of the visual process, we propose that TTR may play a role in the intraocular cycling of retinol.


Impact of Chinese one-child policy on sibling structure: experience from rural areas in three provinces.
To study the influence of population policy and boy preference on the sibling structure, that is, in which order and combinations boys and girls are born into families. A population-based survey with a representative sample of new mothers in 2008-2009 in rural China. Two provinces (Anhui and Shaanxi) where authorisation for a second child was usually given if the first birth was a daughter and one province (Chongqing) where only one child was authorised. The mothers giving birth in 2008-2009 were identified from family planning and hospital birth registers (including births outside hospitals) (n=5049). Of them, 3673 were interviewed by trained medical university staff members and students using structured questionnaire (response rate 73%). Children's distribution by sex and families' distribution by children's birth order and sex composition were calculated and compared with theoretical values based on the assumption that family planning policy is fully followed. The recommended family policy was varyingly followed in the three provinces. In all provinces, there were more second children than allowed. If the policy allowing a second child only after a first-born girl were fully followed, it would result in a sibling structure in which the one-child family is always with a boy and in the two-child family the first one is always a girl. This sibling structure was partly seen in Anhui but weakly in Shaanxi. The policy allowing only one child would result in an equal number of boys and girls, but in Chongqing, there were more boys. In Anhui, unlike the other provinces, there were many more first-born girls than boys, which the authors could not fully explain. Population policy and boy preference influence the actual and relative number of girls and boys and also sibling structure.


Establishment of a mouse primary co-culture of endometrial epithelial cells and peripheral blood leukocytes: effect on epithelial barrier function and leukocyte survival.
This study aimed to establish an in vitro co-culture model that would allow us to study the interaction between endometrial epithelial cells and immune cells. Flow cytometry analysis and cell surface marker staining were used to identify suitable immune leukocytes from a range of sources, such as intraepithelial lymphocytes (IEL), thymocytes, splenocytes and peripheral blood leukocytes. Optimizing culture conditions such as cell viabilities, cell seeding ratios and densities and co-culture methods were examined and determined. Results showed that co-culture of mouse endometrial epithelial cells (EEC) with peripheral blood leukocytes (PBL) at seeding densities of 3.0 x 10(6) and 1.0 x 10(6)cells/ml, respectively, appeared to affect both the survival of leukocytes and epithelial barrier function. Cell viability counts of immune cells showed 95% and 72.5% cell survival after isolation and after 4 days in co-culture with EEC, respectively, but only 11% cell survival when cultured alone for 4 days without EEC. Short-circuit current (I(sc)) results also showed that EEC and PBL co-culture exhibited a four-fold increase in the transepithelial resistance (TER) as compared to EEC culture alone, indicating enhanced protective barrier function. Taken together, the currently established in vitro co-culture model of endometrial epithelial cells and immune cells may provide a means to investigate local cellular immune responses upon uterine infections.


The effect of ratios upon improving patient-based real-time quality control (PBRTQC) performance.
Large biological variation hinders application of patient-based real-time quality control (PBRTQC). The effect of analyte ratios on the ability of PBRTQC to improve error detection was investigated. Four single analyte-ratio pairs (alanine aminotransferase [ALT] vs. ALT to aspartate aminotransferase ratio [RALT]; creatinine [Cr] vs. Cr to cystatin C ratio [RCr]; lactate dehydrogenase [LDH] vs. LDH to hydroxybutyrate dehydrogenase ratio [RLDH]; total bilirubin [TB] vs. TB to direct bilirubin ratio [RTB]) were chosen for comparison. Various procedures, including four conventional algorithms (moving average [MA], moving median [MM], exponentially weighted moving average [EWMA] and moving standard deviation [MSD]) were assessed. A new algorithm that monitors the number of defect reports per analytical run (NDR) was also evaluated. When a single analyte and calculated ratio used the same PBRTQC parameters, fewer samples were needed to detect systematic errors (SE) by taking ratios (p<0.05). Application of ratios in MA, MM and EWMA significantly enhanced their ability to detect SE. The influence of ratio on random error (RE) detection depended upon the analytes and PBRTQC parameters, as consistent advantage was not demonstrated. The NDR method performed well when appropriate parameters were used, but was only effective for unilateral SE. Rearrangement of sample order led to a significant deterioration of conventional algorithms' performance, while NDR remained almost unaffected. For analytes with large variation and poor PBRTQC performance, using ratios as PBRTQC indexes may significantly improve performance and achieve better anti-interference ability, providing a new class of monitoring indicators for PBRTQC.


[Evaluation of condition and factors affecting activity effectiveness and visual performance of pilots who use night vision goggles during the helicopter flights].
According to analysis of questionnaire authors revealed factors, which affect activity effectiveness, and visual performance of pilots who use night vision goggles during the helicopter flights. These are: difficulty of flight tasks, flying conditions, illusion of attitude. Authors gave possible ways to reduce an impact of these factors.


Rewarming and cardiac surgery: a review.
Patients undergoing cardiac surgery are mildly hypothermic by the completion of the surgical procedure. They need to return to a normothermic state if enzymatic functions are to proceed in their normal manner. The body can produce heat by elevating metabolic rate or by activating the shivering mechanism. Metabolic rate peaks shortly after separation of the patient from cardiopulmonary bypass, and therefore contributes to heat production. Because of the effects of neuromuscular blockage administered both during and after surgery; these patients may be unable to generate heat by shivering, and shivering is usually undesirable. This eliminates the major heat production mechanism available to the body. Therefore, heat must be transferred down its gradient by means of convection and conduction. External and internal methods accomplish these goals. External methods, which minimize additional heat loss, include the use of warming lights, elevation of room temperature, and the use of blankets. Internal methods, which transfer heat by convection, may be used to help actively reverse hypothermia. Such techniques include warmed inhalation gases and intravenous fluids, warmed nasogastric lavage fluid, and warmed peritoneal dialysis fluid for patients with end-stage renal failure with severe electrolyte disorders after surgery.


Our brotherhood and your sister: building anti-rape community in the fraternity.
Research shows that male peer influence is a significant predictor of violent sexual behavior. However, men challenging sexual violence within their male peer communities may exert a counter-influence, shifting community norms and behaviors. Using the Fraternity Peer Rape Education Program as a case study, this article examines the ways that fraternity men in a peer rape education program make sense of and interact within their communities. Through coded interviews, this article examines participants' perceptions of change within themselves, within their interactions with fraternity brothers, and within their fraternities. Learning about sexual violence altered participants' worldview and created a communal sense of partnership and responsibility, while simultaneously limiting the traditional ways that fraternal communities are maintained. This experience provides lessons for how we may begin creating communities of men against sexual violence, as well as what support may be required for such messy, nonlinear change processes.


High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis.
Patients with RA display greater occult coronary atherosclerosis burden and experience higher cardiovascular morbidity and mortality compared with controls. We here explored whether pro-inflammatory cytokines and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, correlated with plaque burden and cardiovascular events (CVEs) in RA. We evaluated 150 patients with 64-slice coronary CT angiography. Coronary artery calcium, number of segments with plaque (segment involvement score), stenotic severity and plaque burden were assessed. Lesions were described as non-calcified, mixed or fully calcified. Blood levels of hs-cTnI and pro-inflammatory cytokines were assessed during coronary CT angiography. Subjects were followed over 60 (s.d. 26) months for both ischaemic [cardiac death, non-fatal myocardial infarction (MI), stroke, peripheral arterial ischaemia] and non-ischaemic (new-onset heart failure hospitalization) CVEs. Plasma hs-cTnI correlated with all coronary plaque outcomes (P < 0.01). Elevated hs-cTnI (⩾1.5 pg/ml) further associated with significant calcification, extensive atherosclerosis, obstructive plaque and any advanced mixed or calcified plaques after adjustments for cardiac risk factors or Framingham D'Agostino scores (all P < 0.05). Eleven patients suffered a CVE (1.54/100 patient-years), eight ischaemic and three non-ischaemic. Elevated hs-cTnI predicted all CVE risk independent of demographics, cardiac risk factors and prednisone use (P = 0.03). Conversely, low hs-cTnI presaged a lower risk for both extensive atherosclerosis (P < 0.05) and incident CVEs (P = 0.037). Plasma hs-cTnI independently associated with occult coronary plaque burden, composition and long-term incident CVEs in patients with RA. Low hs-cTnI forecasted a lower risk for both extensive atherosclerosis as well as CVEs. hs-cTnI may therefore optimize cardiovascular risk stratification in RA.


Molecular epidemiology of rotavirus in cats in the United Kingdom.
Rotaviruses are leading causes of gastroenteritis in the young of many species. Molecular epidemiological studies in children suggest that interspecies transmission contributes to rotavirus strain diversity in people. However, population-based studies of rotaviruses in animals are few. We investigated the prevalence, risk factors for infection, and genetic diversity of rotavirus A in a cross-sectional survey of cats housed within 25 rescue catteries across the United Kingdom. Morning litter tray fecal samples were collected during the winter and summer in 2012 from all pens containing kittens and a random sample of those housing adult cats. Group A rotavirus RNA was detected by real-time reverse transcription-PCR, and positive samples were G and P genotyped using nested VP4 and VP7 PCR assays. A total of 1,727 fecal samples were collected from 1,105 pens. Overall, the prevalence of rotavirus was 3.0% (95% confidence interval [CI], 1.2 to 4.9%). Thirteen out of 25 (52%; 95% CI, 31.3 to 72.2%) centers housed at least one rotavirus-positive cat. The prevalence of rotavirus was associated with season (odds ratio, 14.8 [95% CI, 1.1 to 200.4]; P = 0.04) but not age or diarrhea. It was higher during the summer (4.7%; 95% CI, 1.2 to 8.3%) than in winter (0.8%; 95% CI, 0.2 to 1.5%). Asymptomatic epidemics of infection were detected in two centers. G genotypes were characterized for 19 (33.3%) of the 57 rotavirus-positive samples and P genotypes for 36 (59.7%). Two rotavirus genotypes were identified, G3P[9] and G6P[9]. This is the first population-based study of rotavirus in cats and the first report of feline G6P[9], which questions the previous belief that G6P[9] in people is of bovine origin.


[Incidence of osteomyelitis and septic arthritis in a neonatal pathology unit].
During a five years period 8 newborns on 2035 admissions developed septic arthritis representing a very low incidence of 4%. Umbilical catheters were used in 3 patients. Staphylococcus aureus was the most frequent etiologic agent and in 6/8 cases blood cultures were positive for the same pathogen agent. Because of the paucity of clinical signs in the first period in the sick neonate, detection of the disorder by the radiologist assumes great importance in the neonatal intensive care unit, as early recognition and therapy may prevent residual deformity.


[Variety of symptoms after drug use of gamma-hydroxybutyric acid (GHB)].
Gamma-hydroxybutyric acid (GHB, "liquid ecstasy") and its legal prodrugs gamma-butyrolactone and 1,4-butanediol are gaining importance as recreational drugs in Germany. Because of the wide availability of GHB and its prodrugs physicians are increasingly being confronted with cases of intoxication. The effect of GHB intoxication is comparable with those of alcohol and/or benzodiazepines. Likewise, symptoms of withdrawal may occur. In this review, we summarise current data regarding the history, pharmacodynamics and pharmacokinetics of the drug as well as the relevant symptoms of intoxication or withdrawal as they pertain to neurology and psychiatry.


Prenatally diagnosed cystic neuroblastoma: a report of two cases.
We report two cases of prenatally diagnosed cystic neuroblastoma (PDCN). In the first case, prenatal ultrasonography (US) at 33 weeks' gestation showed a 30 x 20 mm cyst at the upper pole of the right kidney. The size and content of the mass demonstrated no change during pregnancy. Postnatal US showed no change in the cystic mass 4 weeks after birth compared to the prenatal findings. The infant underwent total resection of the tumour at 28 days of age. In the second case, a left cystic mass measuring 50 x 40 mm was detected in a fetus in the 37th week of pregnancy. Postnatal US showed a cystic mass in the left adrenal gland. The US findings showed no change 18 days after birth and the infant underwent total resection of the tumour at 19 days of age. In both cases, pathological examination revealed a neuroblastoma and all of the biological prognostic factors were favourable. Surgical intervention was necessary for a final histological and biological diagnosis to be made. We recommend that prenatally suspected neuroblastomas should normally undergo surgical intervention, unless tumour size decreases within about 1 month after birth.


MOFabric: Electrospun Nanofiber Mats from PVDF/UiO-66-NH2 for Chemical Protection and Decontamination.
Textiles capable of capture and detoxification of toxic chemicals, such as chemical-warfare agents (CWAs), are of high interest. Some metal-organic frameworks (MOFs) exhibit superior reactivity toward CWAs. However, it remains a challenge to integrate powder MOFs into engineered materials like textiles, while retaining functionalities like crystallinity, adsorptivity, and reactivity. Here, we present a simple method of electrospinning UiO-66-NH2, a zirconium MOF, with polyvinylidene fluoride (PVDF). The electrospun composite, which we refer to as "MOFabric", exhibits comparable crystal patterns, surface area, chlorine uptake, and simulant hydrolysis to powder UiO-66-NH2. The MOFabric is also capable of breaking down GD (O-pinacolyl methylphosphonofluoridae) faster than powder UiO-66-NH2. Half-life of GD monitored by solid-state NMR for MOFabric is 131 min versus 315 min on powder UiO-66-NH2.


Fabrication of 2D metal-organic framework nanosheet@fiber composites by spray technique.
A feasible and rapid one-step strategy has been developed to fabricate 2D metal-organic framework nanosheet (MOF-NS)@fiber composites at room temperature by spray technique, through which five kinds of MOF-NS@fiber were successfully prepared. The representative nanoscale CuBDC were synthesized on the surface of carbon fibers with homogeneous dispersion and high coverage.


Alogliptin and Gliclazide Similarly Increase Circulating Endothelial Progenitor Cells in Type 2 Diabetes Patients.
We investigated the effect of alogliptin and gliclazide on endothelial progenitor cells (EPCs) in type 2 diabetes. Eighty patients with type 2 diabetes and HbA1c between 7.5% and 8.5% were randomized to receive either alogliptin (25 mg/daily) or gliclazide extended-release (30 mg/daily for HbA1c 7.5-8.0% and 60 mg/daily for HbA1c 8.0-8.5%) in combination with metformin for 4 months. At baseline and 4 months, clinical and laboratory parameters of EPCs were determined. After 4 months of treatment, alogliptin and gliclazide resulted in a similar significant reduction in HbA1c (%) (8.0±0.3 vs. 7.1±0.2, and 8.0±0.3 vs. 7.0±0.2, respectively; P<0.05) and a similar and significant increase in EPC count (cells/106 WBC) (CD45-CD133+KDR+ : 2.2±1.2 vs. 3.7±1.6, CD45-CD34+KDR+: 3.3±1.8 vs. 4.9±1.8; P<0.05 for alogliptin; CD45-CD133+KDR+: 2.3±1.3 vs. 3.6±1.5, CD45-CD34+KDR+: 3.1±1.3 vs. 4.6±1.7; P<0.05 for gliclazide). Both alogliptin and gliclazide demonstrated a beneficial effect in increasing EPCs in poorly controlled type 2 diabetes. As alogliptin and gliclazide exhibit different mechanisms of action, the observed increase in EPCs seems to be due to their glucose-lowering effect.


The Effect of Continuous Care on the Lifestyle of Patients with Multiple Sclerosis: A Randomized Clinical Trial.
Multiple sclerosis is a common debilitating chronic disease of the central nervous system with a progressive and prolonged nature. Patients need an adjusted lifestyle and continuous care in order to prevent its recurrence and progressive disabilities. This study aimed to assess the effect of continuous care on lifestyle in patients suffering from multiple sclerosis. A randomized clinical trial was conducted among 72 patients with multiple sclerosis who referred to the Farshchian Educational Hospital in Hamadan, Iran in 2013. The patients were allocated to intervention and control groups using balanced block randomization with blocks of four. The steps of continuous care (orientation, sensitization, control, and evaluation) were implemented in the case group for 2 months. The patients' lifestyle was assessed before and 1 and 2 months after continuous care using the researcher-developed Lifestyle Questionnaire. The data were analyzed using the Chi-square test, t-test, and repeated-measures analysis of variance. The mean score of lifestyle and its dimensions were significantly higher in the intervention group 1 and 2 months after the intervention compared to the baseline (P = 0.001). In contrast, the mean score of lifestyle and its dimensions had no significant difference in the control group 1 and 2 months after routine care compared to the baseline. Continuous care improved the patients' lifestyle. It could be designed as an appropriate care system into the hospitals or other health care centers. This care system could be used widely in order to improve adherence to suitable lifestyle in patients with chronic diseases.


[The commonest therapeutic methods for laser irradiation of blood].
One of the most widely employed methods of laser therapy is laser irradiation of blood (LIB). There are two modifications of this technique, one being intravenous low-intensity laser irradiation of blood (ILIB), the other non-invasive blood irradiation(NLIB). The two methods have been developing independently since either has its advantages and disadvantages. The present article was designed to review the main currently available techniques for laser irradiation of blood which are presented in the form of tables (charts). Replacing the UV irradiation of blood with UV lamps by laser ultraviolet irradiation of blood (LUVIB®) has made it possible to significantly simplify the technique and enhanced its efficiency. The most effective options for ILIB are the combined techniques: ILIB-635 + LUVIB® and ILIB-525 + LUVIB. The most effective technique for ELIB is believed to be the use of low-intensity pulsed laser light with a wavelength of 635 nm and output power up to 40 W.


The promise of autologous and allogeneic cellular therapies in the clinical trials of autism spectrum disorder.
Autism spectrum disorder (ASD) is a consortium of developmental conditions. As scientists have not yet identified the exact underlying cause for these disorders, it is not easy to narrow down a singular therapy to propose a reliable cure. The preponderance of research suggests that stem-cell therapy improves aspects of outcome measure scales in patients with ASD; therefore, future studies should give us more confidence in the results. This overview considers the data that have emerged from the small set of published trials conducted using different approaches in stem-cell therapy for ASD, evaluates their results and proposes additional steps that could be taken if this field of endeavor is to be pursued further.


[Acquired long QT syndrome: a dominant problem?].
QT prolongation is essentially of pharmacologic origin. It is principally linked to a block of the outward potassium current Ikr, with as a consequence a prolongation of the repolarisation causing early after potentials and re-entry. The term "repolarisation reserve" expresses the variable risk of arrhythmia among individuals under the same drug blocking Ikr. This reserve can be altered under various pathologic or genetic conditions. A series of risk factors (bradycar-Torsades de pointes} were described in 1966 by Dessertenne. They are due to a perturbation of ventricular repolarisation causing QT prolongation on surface ECG. Acquired dia, electrolytic disorders, cardiac disease, neurologic disorders, nutrition troubles, female gender) can play a role as well as the metabolic processing of pharmacological agents by Cytochrome P450 and various inhibitors or inductors of this system which can influence the half life of drugs. The list of drugs involved is continuously increasing: antiarrhythmics, antihistamines, psychotropics, anti-infectious are the main categories involved. Risk prediction is difficult particularly for non cardiovascular drugs and a low risk incidence. An other risk is to exclude patients from the benefit of an efficient drug for a serious but not frequent risk, at last an industrial risk for the manufacturer when a drug is withdrawn lately when important quantities of money have already been invested for its development. The diagnosis of torsades is easy on standard ECG although QT measurement and its heart rate variation remain uneasy. The treatment of the arrhythmias is based on heart rate acceleration by Isoprenaline or intravenous pacing and on intravenous administration of magnesium.


[Double umbilical cord knot in mono-amniotic twin pregnancy as the cause of intrauterine fetal death of both twins].
In cases of rare monoamniotic-monochronic geminie pregnancies there is a high risk of complications by real umbilical cord knots, including the cords of both gemini. In these cases fetal mortality is very high. Modern examination techniques (Colour doppler sonography) are able to detect such cord knots in monoamniotic twins. Therefore it is necessary in all twin pregnancies, especially following fertility treatment, to examine precisely by a routine examinator the question of mono - or diamniotic pregnancy. In monoamniotic pregnancy there should be a look for real knots of umbilical cord in regular intervals. In such a case, if a knot is present, the pregnant woman had to be supervised by CTG, to react immediately at first signs of hypoxia.


[Enterococci as a cause of infectious complications after surgery].
Self-obtained data about study of enterococci as etiologic agents of infectious complications after cardiovascular and transplantation surgery are presented in the article. 465 strains of enterococci were isolated from different biosubstrates. Isolation rate of different species of enterococci in blood, urine, fromwounds, trachea, cardiacvalves, as well as in the environment and on wear of healthcare workers were determined. Most frequently enterococci were isolated from urine (47.7% of cases) and from trachea (24.3% of cases). Enterococcal bacteremia was determined in 9.7% of cases and represented a significant part in Grampositive microflora--38.5% of all isolates. High resistance of enterococci to antibiotics and well lysis by phages were noted.


Determination of electron transfer kinetic parameters by fourier transform electrochemical impedance spectroscopic analysis.
A new attempt to obtain electron transfer kinetic parameters at an electrified electrode/electrolyte interface using Fourier transform electrochemical impedance spectroscopic (FTEIS) analyses of small potential step chronoamperometric currents is presented. The kinetic parameters thus obtained allowed mass transport free voltammograms to be constructed in an overpotential region, where the diffusion limits the electron transfer reaction, using the Butler-Volmer (B-V) relation. The B-V voltammograms clearly distinguish electrode reactions that are not much different in their electron transfer kinetic parameters, thus showing very similar normal linear sweep voltammetric (SCV) behaviors. Electrochemical reduction of p-benzoquinone, which displays nearly the same SCV responses at a gold electrode regardless whether the electrode is covered by a thiolated beta-cyclodextrin self-assembled monolayer, was taken as an example for the demonstration. The results show that the two voltametrically similar systems display very different electron transfer characteristics.


STING agonists induce an innate antiviral immune response against hepatitis B virus.
Chronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.


Effects of HIV and childhood trauma on brain morphometry and neurocognitive function.
A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.


Quantitative Proteomics Analysis Confirmed Oxidative Metabolism Predominates in Streptomyces coelicolor versus Glycolytic Metabolism in Streptomyces lividans.
Recent physiological studies indicated that S. lividans metabolism was mainly glycolytic, whereas S. coelicolor metabolism was mainly oxidative. To determine whether such metabolic characteristics were correlated with consistent proteomics features, a comparative label-free, shotgun proteomics analysis of these strains was carried out. Among 2024 proteins identified, 360 showed significant differences in abundance between the strains. This study revealed that S. coelicolor catabolized glucose less actively than S. lividans, whereas the amino acids present in the medium were catabolized less actively by S. lividans than by S. coelicolor. The abundance of glycolytic proteins in S. lividans was consistent with its high glycolytic activity, whereas the abundance of proteins involved in the catabolism of amino acids in S. coelicolor provided an explanatory basis for its predominantly oxidative metabolism. In this study, conducted under conditions of low O2 availability, proteins involved in resistance to oxidative stress and those belonging to a DosR-like dormancy regulon were abundant in S. coelicolor, whereas tellurium resistance proteins were abundant in S. lividans. This indicated that the strains reacted differently to O2 limitation. Proteins belonging to the CDA, RED, and ACT pathways, usually highly expressed in S. coelicolor, were not detected under these conditions, whereas proteins of siderophores, 5-hydroxyectoine, and terpenoid biosynthetic pathways were present.


Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.
Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.


Normalization of cytoplasmic calcium response in pancreatic beta-cells of spontaneously diabetic GK rat by the treatment with T-1095, a specific inhibitor of renal Na+-glucose co-transporters.
Chronic hyperglycemia is known to lead to a progressively further impaired insulin response and to hasten the development of complications in patients with type 2 diabetes, a notion referred as glucose toxicity. T-1095, a derivative of phlorizin, is a newly developed oral hypoglycemic agent that acts as a specific inhibitor of renal Na(+)-glucose co-transporters, reducing circulating blood glucose levels by promoting glucose excretion into urine. The effects of glycemic improvement by T-1095 on secretory function and cytoplasmic calcium response in pancreatic beta-cells were investigated using spontaneously diabetic GK rats. After four weeks of treatment with T-1095 (age 4 to 8 week rats), serum glucose and HbA1c levels were significantly improved (serum glucose level, GK vs. GK T-1095, 277.3 +/- 11.8 vs. 204.7 +/- 6.4 mg/dl; HbA1c level, GK vs. GK T-1095, 6.2 +/- 0.2 vs. 4.8 +/- 0.1 %). Insulin secretion induced by 16.7 mM glucose was also significantly increased in the T-1095-treated group compared to the untreated group. The [Ca(2+)]i response induced by 16.7 mM glucose in GK beta-cells was characterized by the loss of the steep first peak of [Ca(2+)]i elevation, and the lost first peak of [Ca(2+)]i reappeared in T-1095-treated beta-cells in 32 of 34 observations. In T-1095-treated beta-cells, the time lag to peak [Ca(2+)]i levels in the 16.7 mM glucose stimulation was significantly reduced (259.1 +/- 15.3 sec, p < 0.01) compared to untreated GK rats (524.7 +/- 52.9 sec). Thus, improvement of hyperglycemia by T-1095 ameliorates beta-cell function by relieving [Ca(2+)]i response.


What care should be covered?
The answer to the question of what health care services should be covered by a managed care plan is straightforward; the plan should cover whatever the consumer is willing to pay for. From the plan's perspective, the consumer is the payer, that is, the employer who negotiates the plan; not the individual patient whose personal preferences and interests may be quite different. Since managed care organizations contract with payers to arrange for health care services within a defined set of benefits, there is a broader question as well: Within the benefits chosen by the payer, what actually is covered? Criteria for determining "medical necessity," which managed care plans frequently use as the basis for coverage, are discussed.


"Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial.
Among randomized controlled trials (RCTs), trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]). Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants' perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test (P=0.64, not significant). Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial "short blanket syndrome". Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased results on account of large proportions of drop-outs. Our experience suggests that participants do not change their mind depending on the allocation group (intervention or control). There is no single answer to sort out the short blanket syndrome.


[Nephrolithiasis--rational etiological assessment].
Although underlying metabolic abnormalities do not differ fundamentally in patients with either first or recurrent nephrolithiasis and 35% of patients with a first event may have to face a recurrence 5 years later, extended metabolic investigations in patients with a first renal calculus should be restricted to particular, exceptional cases. However, in patients with a first calculus basic investigations with respect to specific causes for a concrement such as primary hyperparathyroidism, incomplete renal-tubular acidosis, recurrent urinary tract infection and cystinuria are mandatory. This includes, in addition to a laboratory investigation of blood and urine after a 2-hour-fasting period, analysis of the stone and a urography. The extended metabolic investigation in patients with recurrences or a first occurrence in a patients with a risk constellation includes evaluation of the most important lithogenic (calcium, oxalate, phosphate, uric acid) and inhibiting components (citrate) in the 24-hour urine, in patients with cystine calculi quantitation of cystine. A metabolic investigation should never be undertaken in the hospital or under standardized diet, but always under accustomed, unrestricted nutrition. At least 2 urine samples should be investigated from each patient, preferably not prior to 3-4 months after the event when homeostasis of the patient is restored analogously to the onset of concrement development.


Preaortic paraganglioma mimicking a hypervascular tumor of the pancreas.
Paragangliomas are rare tumors that arise from neuroepithelial cells. They are most frequently located in the para-aortic region and they may be confused with other retroperitoneal tumors, especially pancreatic tumors. We present a case of a secreting preaortic paraganglioma in a young patient which was mimicking a hypervascular tumor of the pancreas, and that was completely resected 5 years after the failure of a first attempt to remove the tumor.


A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice.
Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines are employed to prevent disease, but with limited effectiveness. Development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing influenza virus prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines to intradermally deliver a combination of conserved influenza virus antigens (hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein) and induce strong immune responses with substantial breadth and potency in a murine model. The immunity conferred by nucleoside-modified mRNA-lipid nanoparticle vaccines provided protection from challenge with pandemic H1N1 virus at 500 times the median lethal dose after administration of a single immunization, and the combination vaccine protected from morbidity at a dose of 50 ng per antigen. The broad protective potential of a single dose of combination vaccine was confirmed by challenge with a panel of group 1 influenza A viruses. These findings support the advancement of nucleoside-modified mRNA-lipid nanoparticle vaccines expressing multiple conserved antigens as universal influenza virus vaccine candidates.


The gene repertoire and the common evolutionary history of glutamate, pheromone (V2R), taste(1) and other related G protein-coupled receptors.
Glutamate receptors (also known as clan C) are one of the main groups of GPCRs with many subgroup linked through complex evolutionary relationships. We performed thorough searches for genes coding for proteins belonging to this family in the human, mouse, Fugu, and zebrafish genomes, as well as in four invertebrate species. We assembled over 70 new full-length sequences from protein predictions excluding pseudogenes. This resulted in a total of 22 full-length sequences from the human genome, 79 from the mouse genome, 30 from the Fugu genome, and 32 from the zebrafish genome (pseudogenes are not included in these numbers). We show that the vertebrate Glutamate GPCRs form four main phylogenetic groups with a total of eight subgroups (Group I: V2R, TAS1R, GPRC6A, and CASR, Group II: GRM, Group III: GABA together with previously unpublished GPR158 and GPR158L and Group IV: GPRC5). All eight receptor subgroups are present both in mammals and fish, except for GPRC5 and GPR158. The pheromone (V2R), GPRC6, and sweet taste (TAS1) receptors were not found in invertebrates while GRM, GABA, and CASR were found in both C. elegans and C. intestinalis. The pheromone receptors are found in high numbers in mouse, zebrafish and Fugu but are only found as pseudogenes in the human genome. This report provides a comprehensive overview of the expansion/deletions of the groups within the Glutamate receptor family.


Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer.
The survival times of patients with advanced colorectal cancer (CRC) have increased due to the introduction of chemotherapy involving irinotecan and cetuximab. However, further studies are required on the effective pretreatment methods for identifying patients with CRC who would respond to particular treatments. The aim of the present study was to identify biomarkers for predicting the efficacy of chemotherapy for CRC. A total of 123 serum samples were collected from 31 patients with CRC just prior to each of the first four rounds of chemotherapy. Serum metabolome analysis was performed using a multiplatform metabolomics system, and univariate Cox regression hazards analysis of the time to disease progression was conducted. Octanoic acid and 1,5-anhydro-D-glucitol were identified as biomarker candidates. In addition, the serum level of octanoic acid was indicated to be significantly associated with the time to disease progression (hazard ratio, 3.3; 95% confidence interval, 1.099-11.840; P=0.033). The serum levels of fatty acids, in particular polyunsaturated fatty acids, tended to be downregulated in the partial response group. The findings of the present study suggest that the serum level of octanoic acid may serve as a useful predictor for the prognosis of CRC.


Workplace Violence and Perceptions of Safety Among Emergency Department Staff Members: Experiences, Expectations, Tolerance, Reporting, and Recommendations.
Workplace violence (WPV) is a widely recognized problem in emergency departments (EDs). The majority of WPV studies do not include nonclinical staff and do not address expectations of violence, tolerance to violence, or perceptions of safety. Among a multidisciplinary sample of ED staff members, specific study aims were to (a) describe exposure to WPV; (b) describe perceptions of safety, tolerance to violence, and expectation of violence; (c) describe reporting behaviors and perceived barriers to reporting violence; (d) examine relationships between demographic variables, experiences of violence, tolerance to violence, perceptions of safety, and reporting behaviors; and (e) identify perceptions of viable interventions to improve workplace safety. A cross-sectional design was used to survey ED staff members in a Level 1 Shock Trauma center. Eleven disciplines were represented in 147 completed surveys; 88% of respondents reported exposure to WPV in the previous 6 months. Members of every discipline reported exposure to WPV; 98% of the sample felt safe at work and 64% felt violence was an expected part of the job. Most violence was not reported, primarily because "nobody was hurt." Emergency department staff members expected and experienced violence; nevertheless, there was a widespread perception of safety. Perceptions of safety and reasons for not reporting did not mirror previous findings. The WPV exposure is not isolated to clinical staff members and occurs even when prevention strategies are in place. The definition of WPV and the individual's interpretation of the event might preclude reporting.


Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids.
To determine whether calcium-permeable channels are targets for the oxidized phospholipids: 1-palmitoyl-2-glutaroyl-phosphatidylcholine (PGPC) and 1-palmitoyl-2-oxovaleroyl-phosphatidylcholine (POVPC). Oxidized phospholipids are key factors in inflammation and associated diseases, including atherosclerosis; however, the initial reception mechanisms for cellular responses to the factors are poorly understood. Low micromolar concentrations of PGPC and POVPC evoked increases in intracellular calcium in human embryonic kidney 293 cells that overexpressed human transient receptor potential canonical 5 (TRPC5) but not human TRP melastatin (TRPM) 2 or 3. The results of electrophysiological experiments confirmed stimulation of TRPC5. To investigate relevance to endogenous channels, we studied proliferating vascular smooth muscle cells from patients undergoing coronary artery bypass surgery. PGPC and POVPC elicited calcium entry that was inhibited by anti-TRPC5 or anti-TRPC1 antibodies or dominant-negative mutant TRPC5. Calcium release did not occur. The effect was functionally relevant because it enhanced cell migration. The actions of PGPC and POVPC depended on G(i/o) proteins but not on previously identified G protein-coupled receptors for oxidized phospholipids. Stimulation of calcium-permeable TRPC5-containing channels may be an early event in cellular responses to oxidized phospholipids that couples to cell migration and requires an unidentified G protein-coupled receptor.


Interleukin-6 in the fever and multiorgan crisis of pheochromocytoma.
A 31-y-old black man with neurofibromatosis, alcoholism and hypertension was admitted because of abdominal pain, hematemesis and cough. In the hospital he had prolonged fever and developed a multiorgan crisis. Despite thorough investigation, no infectious cause for fever was found. Urinary catecholamines and metabolites were markedly elevated. Computerized tomography revealed a mass abutting the left kidney. A diagnosis of pheochromocytoma was made, and as soon as treatment with phenoxybenzamine and propranolol was begun, the fever resolved. Serum interleukin-6 (IL-6) concentration was initially elevated, decreased after the start of adrenergic blockade, and gradually fell to an undetectable level after surgery. These observations suggest that interleukin-6 might have been causally related to the patient's fever and possibly the multiorgan crisis.


Gene cloning and characterization of KdeA, a multidrug efflux pump from Klebsiella pneumoniae.
We cloned a gene related to multidrug resistance from a drug-resistant Klebsiella pneumoniae strain MGH78578. We designated the gene kdeA, which encodes a protein possessing 12 hydrophobic regions. The deduced amino acid sequence of KdeA is similar to that of MdfA, a well-characterized multidrug efflux pump from Escherichia coli. Introduction of the kdeA gene into cells of the drug-hypersusceptible E. coli strain KAM32 resulted in elevated minimum inhibitory concentrations of chloramphenicol, norfloxacin, acriflavine, and ethidium bromide. We observed elevated energy-dependent ethidium efflux activity with cells carrying kdeA compared with control cells. We also observed expression of kdeA in cells of K. pneumoniae under normal growth conditions.


Sapphire ball lensed fiber probe for common-path optical coherence tomography in ocular imaging and sensing.
We describe a novel common-path optical coherence tomography (CP-OCT) fiber probe design using a sapphire ball lens for cross-sectional imaging and sensing in retina vitrectomy surgery. Single mode Gaussian beam (TEM00) simulation was used to optimize lateral resolution and working distance (WD) of the common-path probe. A theoretical sensitivity model for CP-OCT was prosed to assess its optimal performance based an unbalanced photodetector configuration. Two probe designs with working distances (WD) 415μm and 1221μm and lateral resolution 11μm and 18μm, respectively were implemented with sensitivity up to 88dB. The designs are also fully compatible with conventional Michelson interferometer based OCT configurations. The reference plane of the probe, located at the distal beam exit interface of the single mode fiber (SMF), was encased within a 25-gauge hypodermic needle by the sapphire ball lens facilitates its applications in bloody and harsh environments. The performances of the fiber probe with 11μm of lateral resolution and 19μm of axial resolution were demonstrated by cross-sectional imaging of a cow cornea and retina in vitro with a 1310nm swept source OCT system. This probe was also attached to a piezoelectric motor for active compensation of physiological tremor for handheld retinal surgical tools.


Etiology, clinical characteristics, and outcome of infective endocarditis: 10-year experience from a tertiary care center in Pakistan.
This study was conducted to assess the clinical characteristics, causative agents, complications, and outcomes of infective endocarditis (IE) among patients presenting to our tertiary care center over the last decade. This retrospective cohort study included all adult patients admitted to the Aga Khan University Hospital with the diagnosis of IE over a ten-year period from 2010 to 2020. Outcomes variables included complications during hospitalization, surgical intervention, mortality, and length of stay. We identified a total of 305 cases out of which 176 (58%) were males and 129 (42%) were females. The mean age of the patients was 46.9±18.8 years. 95 (31%) had prosthetic valves in place. Staphylococcus aureus was isolated in 54 (39%) patients followed by coagulase-negative Staphylococcus in 23 (17%). Echocardiography revealed vegetations and abscesses in 236 (77%) and 4 (1%) patients, respectively. The most common valvular complication was mitral valve regurgitation found in 26 (9%) patients, followed by tricuspid valve regurgitation in 13 (4%) patients and aortic valve regurgitation in 11 (3%) patients. Furthermore, 81 (27%) patients suffered from heart failure and 66 (22%) from a stroke during hospitalization. The mean hospital length of stay was 10.4 ± 10.6 days. 64 (21%) patients required surgical repair and the overall mortality rate was 25%. Prosthetic valve endocarditis (OR = 3.74, 95% CI = 2.15-6.50, p<0.001), chronic kidney disease (OR = 2.51, 95% CI = 1.15-5.47, p=0.036), previous stroke (OR = 2.42, 95% CI = 1.18-4.96, p=0.026), and ischemic heart disease (OR = 3.04, 95% CI = 1.50-6.16, p=0.003) were significantly associated with an increased risk of mortality. In conclusion, our study provided valuable data on the clinical characteristics and outcomes of patients with IE in a developing country. S. aureus was the most common causative agent. Heart failure and stroke were the most common complications. The presence of prosthetic valves, history of chronic kidney disease, ischemic heart disease and previous stroke were associated with a significantly increased risk of mortality. Surgical management was not associated with improved outcomes.


The relationship of total progressive motile sperm count with the outcome of IUI? An analysis of 5171 cycles.
Background: The role of motile sperm count in intrauterine insemination (IUI) success rate is controversial. This retrospective cohort study performed among unselected infertile couples undergoing IUI was to explore the association between the total progressive motile sperm count (TPMSC) and the live birth rate (LBR) following IUI.Methods: The total cohort of 5363 cycles, 2666 infertile couples between January 2015 and December 2018 and finally 5171 cycles, 2647 couples were included for analysis in Sun Yat-sen memorial hospital of Sun Yat-sen University. The primary outcome was LBR per cycle. And the secondary outcome measure was clinical pregnancy rate (CPR) per cycle.Results: From the receiver operating characteristic (ROC) analysis of female age predicting live birth, female age cutoff was defined as 28 years. With a female age of ≤28 years, the CPRs were 11.5%, 14.9%, 16.1%, and 15.8% in quartile groups of pre-wash TPMSC, respectively. For the LBRs the values were 9.4%, 12.9%, 14.4%, and 11.3%, and there were also no significant differences in quartile groups of pre-wash TPMSC with ≤24 million (M), [24M-50M], [50M-97M], >97M. No statistically significant differences in the CPRs (p = .051) and LBRs (p = .088) were also observed in the quartiles groups of post-wash TPMSC. With a female age of >28 years, the CPR in couples with post-wash TPMSC ≤22.32 M was significantly lower than with post-wash TPMSC >81.0 M (p = .007). There was an obvious trend in which CPRs and LBRs increased with the post-wash TPMSC during the <81 M interval in women >28 years.Conclusions: The optimal female age cutoff for live birth was 28 years in IUI cycles. Pre-wash and post-wash TPMSC were not significantly associated with CPR and LBR per cycle. When female age >28 years, there was a better outcome with post-wash TPMSC >22.32 million.


Anterior intercostal artery perforator flap in immediate breast reconstruction: Anatomical study and clinical application.
Although the use of lateral intercostal artery perforator (ICAP) flaps for immediate breast reconstruction has been widely described, data on the use of the anterior ICAP (AICAP) flaps for this indication are limited. In this context, we describe the results of anatomical study and our clinical experience with AICAP flaps for breast reconstruction. In this study, the location and characteristics of the AICAPs were dissected in 12 female adult formalin-preserved hemitrunks and two fresh-frozen cadavers. Fourteen patients (mean BMI 23) underwent partial breast resection for a quadrant breast cancer followed by breast reconstruction with an intercostal perforator flap. The mean resection size was 6 × 5 × 5.5 cm (range 3-8 × 3.5-7 × 4-8 cm).The main outcome measures were pre-operative and postradiotherapy health-related quality of life assessed with the BREAST-Q reconstruction survey. According to anatomical study, at least one perforator was found in each third of hemitrunks dissected. The mean of perforator size was in diameter 0.42 ± 0.05 mm and in length 3.1 ± 0.36 cm. In clinical outcomes, the mean of flap size was 16 × 5 × 3 cm (range 14-19 × 3-8 × 2-5 cm). The mean surgical time was 120 min (range 109-125 min). Only one partial flap failure was detected. No postoperative changes in breast size were observed, although soft tissue changes were observed in four patients after radiotherapy. The mean BREAST-Q scores changes were 0 in satisfaction with the breast, 5 in satisfaction with outcome, 0 in psychosocial well-being, 6.15 in sexual well being, and 34.69 in physical well-being. Based on this anatomical and clinical study, we found AICAP flap has a consistent vascularization with good perforators. And moreover, it is suitable for partial breast reconstruction (quadrantectomy) and does not appear to negatively impact patient satisfaction.


Detection and quantification of 8-methoxypsoralen-DNA adducts.
8-Methoxypsoralen (8-MOP) is a photoactivated drug used clinically in the treatment of psoriasis and cutaneous T-cell lymphoma (CTCL). We have developed monoclonal antibodies which specifically recognize 8-MOP-modified DNA and do not cross-react with unmodified DNA or free 8-MOP. Highly sensitive, competitive enzyme-linked immunosorbent assays (ELISA) have been developed with both colour and fluorescence endpoint detection for quantification of DNA adducts in biological samples. In addition, immunofluorescence and flow cytometric techniques have been developed to visualize adducts in tissues and cells. These techniques have been validated in keratinocytes treated in culture and in animals treated in vivo with 8-MOP and ultraviolet A (UVA) light. Adduct levels have also been monitored in skin biopsies and lymphocytes of patients with psoriasis and lymphoma.


Proteome profile of the MCF7 cancer cell line: a mass spectrometric evaluation.
The development of novel proteomic technologies that will enable the discovery of disease specific biomarkers is essential in the clinical setting to facilitate early diagnosis and increase survivability rates. We are reporting a shotgun two-dimensional (2D) strong cationic exchange/reversed-phase liquid chromatography/electrospray ionization tandem mass spectrometry (SCX/RPLC/ESI-MS/MS) protocol for the analysis of proteomic constituents in cancerous cells. The MCF7 breast cancer cell line was chosen as a model system. A series of optimization steps were performed to improve the LC/MS experimental setup, sample preparation, data acquisition and database search protocols, and a data filtering strategy was developed to enable confident identification of a large number of proteins and potential biomarkers. This research has resulted in the identification of >2000 proteins using multiple filtering and p-value sorting. Approximately 1600-1900 proteins had p < 0.001, and, of these, approximately 60% were matched by >or=2 unique peptides. Alternatively, >99% of the proteins identified by >or=2 unique peptides had p < 0.001. When searching the data against a reversed database of proteins, the rate of false positive identifications was 0.1% at the peptide level and 0.4% at the protein level. The typical reproducibility in detecting overlapping proteins across replicate runs exceeded 90% for proteins matched by >or=2 unique peptides. According to their biological function, approximately 200 proteins were involved in cancer-relevant cellular processes, and over 25 proteins were previously described in the literature as putative cancer biomarkers, as they were found to be differentially expressed between normal and cancerous cell states. Among these, biomarkers such PCNA, cathepsin D, E-cadherin, 14-3-3-sigma, antigen Ki-67, TP53RK, and calreticulin were identified. These data were generated by subjecting to MS analysis approximately 42 microg of sample, analyzing 16 SCX peptide fractions, and interpreting approximately 55,000 MS2 spectra. Total MS time required for analysis was 40 h.


Mutations causing achondroplasia and thanatophoric dysplasia alter bFGF-induced calcium signals in human diploid fibroblasts.
Mutations in the fibroblast growth factor receptor (FGFR) gene family recently have been shown to underlie several hereditary disorders of bone development, with specific FGFR3 mutations causing achondroplasia (Ach) and thanatophoric dysplasia (TD). However, for none of these mutations has the defect in receptor function been demonstrated directly and, therefore, for none has the pathophysiological mechanism of the disease been defined. Using our established techniques for single-cell ratiometric real-time calcium image analysis, we defined the nature of the basic fibroblast growth factor (bFGF)-induced calcium signal in human diploid fibroblasts, and, in blinded studies, have analyzed the bFGF-induced signals from 18 independent fibroblast cell lines, including multiple lines from patients with known mutant alleles of FGFR3 and syndromes of Ach or TD. Control cells responded with transient increases in intracellular calcium, with many cells showing oscillatory calcium waves. Homozygous Ach cell lines failed to signal, whereas heterozygous Ach lines responded nearly normally. We observed heterogeneous signals in TD heterozygotes: the unresponsive lines all turned out to carry TD1 alleles, whereas all responsive lines had TD2 alleles. Since FGFR1, 2 and 3 receptors are known to be expressed in fibroblasts, our results suggest that specific mutant FGFR3 alleles can function in a dosage-dependent dominant-negative fashion to inactivate FGFR signaling.


Next-to-Next-to-Leading Order Event Generation for Top-Quark Pair Production.
The production of top-quark pairs in hadronic collisions is among the most important reactions in modern particle physics phenomenology and constitutes an instrumental avenue to study the properties of the heaviest quark observed in nature. The analysis of this process at the Large Hadron Collider relies heavily on Monte Carlo simulations of the final state events, whose accuracy is challenged by the outstanding precision of experimental measurements. In this Letter we present the first matched computation of top-quark pair production at next-to-next-to-leading order in QCD with all-order radiative corrections as implemented via parton-shower simulations. Besides its intrinsic relevance for LHC phenomenology, this work also establishes an important step towards the simulation of other hadronic processes with color charges in the final state.


Mercury bioaccumulation and isotopic relation between Trichiurus lepturus (Teleostei) and its preferred prey in coastal waters of southeastern Brazil.
The trophic transfer of total mercury (THg) and its bioaccumulation from prey species to the predator fish Trichiurus lepturus was analysed in coastal waters of southeastern Brazil to evaluate the trace element dynamic in this predator-prey system. The isotopic (δ13C and δ15N) relation between this predator and its prey allowed inferences on prey assimilation and predator feeding habits. The THg increment varied from 4.5 to 19.5 times between prey and predator, with a biomagnification power of 0.59. The prey species could be divided into three groups regarding δ15N values: i) 13.6 to 13.2‰ (juvenile conspecifics, Pellona harroweri, and Peprilus paru); ii) 12.5 to 11.8‰ (Chirocentrodon bleekerianus, Lycengraulis grossidens, and Dorytheuthis plei); and iii) 10.5‰ (Xiphopenaeus kroyeri). Based on δ13C values, the prey groups were: i) -15.3‰ (X. kroyeri); ii) -17.6 to -16.8‰ (C. bleekerianus, D. plei, P. harroweri, P. paru, and juvenile conspecifics); and iii) -18.7‰ (L. grossidens). The values of THg and δ15N highlighted juvenile conspecifics as the main via of this trace element and the most assimilated prey. The isotopic relation between predator and its prey species showed a feeding activity preferably coastal and pelagic.


Effects of Nitrogen and Phosphorus Addition on Soil Extracellular Enzyme Activity and Stoichiometry in Chinese Fir (Cunninghamia lanceolata) Forests.
Soil extracellular enzymes play an important role in microbial functions and soil nutrient cycling in the context of increasing N deposition globally. This is particularly important for Chinese fir (Cunninghamia lanceolata) forests because of the decline in soil fertility induced by successive rotation. In this study, we aimed to determine the effects of simulated N deposition (N30: 30 kg ha-2 year-1; N60: 60 kg ha-2 year-1) and phosphorus addition (P20: 20 mg kg-1; P40: 40 mg kg-1) on the activity and stoichiometry of soil extracellular enzymes related to soil C, N, and P cycling in Chinese fir. The results showed that N addition alone increased the activity of soil β-1,4 glucosidase (BG) but decreased the activity of N-acetyl-β-d-glucosidase (NAG) and leucine aminopeptidase (LAP). N addition increased the ratios of soil enzymes, C:N and C:P, alleviated microbial N-limitation, and aggravated microbial C-limitation. P addition alone increased enzyme activity, and P40 addition increased the ratio of BG to soil microbial biomass carbon (MBC), and (NAG + LAP):MBC activity ratio, thereby aggravating C restriction. N and P co-addition significantly affected soil extracellular enzyme activity and stoichiometry. For instance, BG activity and BG:MBC activity ratio increased significantly under the N30 + P40 treatment, which intensified C-limitation. Soil pH was the main factor influencing enzyme activity, and these variables were positively correlated. The stoichiometric relationships of enzyme reactions were coupled with soil pH, total nitrogen (TN), and available phosphorus (AP). Our results indicate that changes in soil characteristics induced by N and P inputs influence the activities of soil microorganisms and result in changes in microbial resource acquisition strategies. This study provides useful insights into the development of management strategies to improve the productivity of Chinese fir forests under scenarios of increasing N deposition.


Assessing physical and respiratory distress in children with bronchiolitis admitted to a community hospital emergency department: A retrospective chart review.
Bronchiolitis is a leading cause of infant hospitalization with wide variation in its diagnosis and management, especially in smaller community hospitals. The objective of this study is to describe children admitted to a community-based hospital emergency department (ED) for bronchiolitis and explore alternate assessments of illness severity. A retrospective chart review (January to September 2014) of 100 children, < 2 years old and meeting International Classification of Diseases 10 for bronchiolitis. Outcomes included demographics, symptoms, and interventions. In addition, the Respiratory Distress Assessment Instrument (RDAI) score was calculated using documented assessments of wheezing and retractions. Descriptive and comparative statistics were completed with p < 0.05 considered significant. The mean (standard deviation) age 10.6 (8.4) months, n = 41 females. Sixty-seven percent had a chest X-ray (CXR), 17% oral antibiotics, 65% bronchodilators, and 19% oral steroids; 19% were admitted in hospital. There was a significant difference in RDAI score between those given oral antibiotics (mean (95% CI), 6.35 (4.96-7.75)) versus not (4.70 (4.20-5.20)), p = 0.01. Those who received a CXR had a significantly higher oxygen flowrate (1.4 (0.6-2.1) litres per minute (lpm)) and worse physical appearance (tri-pod position, head bobbing) versus those who did not (0.15 (-0.05 to 0.35) lpm), p = 0.002 and p = 0.04, respectively. A large number of children admitted to a community-based ED for bronchiolitis received unnecessary CXR and medications. Assessing physical and respiratory distress may be more effective at determining illness severity compared with radiological or laboratory testing. Local clinical practice guidelines may aid in optimal management of bronchiolitis for community-based EDs.


Changes in keratin expression of human vaginal epithelium during different female generation phases. Polyclonal antibody studies.
Distinct expression patterns of keratins reflect different epithelial prototypes and different epithelial differentiation pathways. In order to get evidence of the expression of keratins in a hormone-dependent tissue in man, we investigated 70 epithelial tissue specimens by means of SDS-gel electrophoresis and immunoblot. Every tissue probe belonged to different generation phases such as sexual maturity, climacteric and postmenopausal period and pregnancy. Keratins 1(avb), 4(avb), 5(avb), 10(avb), 13, 14 were detected regularly whereas keratins 6, 16, and 19 are expressed irregularly. During all generation phases, with the exception of pregnancy, the keratins 1 and 10, associated with the epidermal differentiation, and keratins 4 and 13, associated with the differentiation to a non-keratinizing stratified epithelium, are synthesized simultaneously. However in pregnancy, i.e. pregnancy at term of delivery, only K4/K13 are expressed, while K1/K10 are below the detection limit. In terms of keratin expression vaginal epithelium represents a mosaic of differentiation. Only in pregnancy the 'pure' type of a nonkeratinizing epithelium is seen, apparently as a result of the high concentration of estrogens.


[Perfluorochemical emulsion as a perfusate in 24-hour liver preservation prior to transplantation in the rat].
Perfluorochemical (PFC) emulsion as a perfusate of liver preservation prior to transplantation was evaluated in continuous hypothermic perfusion for 24 hours followed by orthotopic transplantation in inbred male Lewis rat. Three different contents of PFC emulsion that is, 20% (original Fluosol DA), 10% and 0% PFC solution were prepared as a perfusate. Isolated liver was stored for up to 24 hours using a continuous non-pulsatile perfusion technique of closed circuit with each perfusate. Gas content, GOT, GPT, LDH, potassium and glucose of the perfusate were measured. Oxygen consumption of perfused liver was higher in PFC emulsion than non PFC perfusate. Biochemical analysis of perfusate suggested that liver was preserved best in 10% PFC emulsion. Histological findings, especially, acid phosphatase staining, showed better result in PFC groups. One week survival rates after liver graft were 4/6 (66.7%) in 10% PFC solution, 1/6 (16.7%) in 20% and 0/6 (0%) in 0% solution. In spite of the highest oxygen consumption of perfused liver in early phase, 20% PFC emulsion did not bring the good preservation of perfused liver because of impaired circulation due to higher viscosity in low temperature. Ten percent PFC solution is considered the best in hypothermic preservation of the liver.


[Multidirectional atlantoaxial instability of an os odontoideum in an adult].
Increasing neck pain in a 29 year old woman after a frontal car collision gave reason for a conventional x-ray that presented a traumatically displaced os odontoideum positioned at the top of the dens axis. No neurological defect was seen. Dynamic flexion/extension film showed a movement to an atlantoaxial dislocation with a shift of the os odontoideum. The sclerotic structure of the corresponding bony surfaces was confirmed by computed tomography, whereas magnetic resonance imaging demonstrated a posttraumatic signal change in front of the base of dens axis and os odontoideum. Fusion was achieved by computed navigation with C1/C2 transfacetal screws as described by Magerl and interspinal fusion with a bicortical autologous iliac crest graft and a posterior tension band as described by Brooks. An exact positioning of screws past the asymmetric course of both arteria vertebrales was possible by navigation. The patient was free of pain 5 months after the fusion.


A single-center, retrospective study of COVID-19 features in children: a descriptive investigation.
Compared to adults, there are relatively few studies on COVID-19 infection in children, and even less focusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report the results from patients at Wuhan Children's Hospital, located within the initial center of the outbreak. Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with the Fisher exact test and Cox regression statistical methods. Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction (PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) with thrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) with below standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the 43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity (67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes (65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleural area (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15 patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatric patients had CT lesions that were either unchanged or worse. There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge. These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge criteria.


Computational Power of Symmetry-Protected Topological Phases.
We consider ground states of quantum spin chains with symmetry-protected topological (SPT) order as resources for measurement-based quantum computation (MBQC). We show that, for a wide range of SPT phases, the computational power of ground states is uniform throughout each phase. This computational power, defined as the Lie group of executable gates in MBQC, is determined by the same algebraic information that labels the SPT phase itself. We prove that these Lie groups always contain a full set of single-qubit gates, thereby affirming the long-standing conjecture that general SPT phases can serve as computationally useful phases of matter.


Direct in situ hybridization for rapid detection of cytomegalovirus in bronchoalveolar lavage.
Rapid detection of cytomegalovirus (CMV) from pulmonary specimens in immunosuppressed persons may provide an origin for pneumonia. In situ DNA hybridization has been effective for detection of CMV in otherwise nondiagnostic histologic material. Studies comparing bronchoalveolar lavage (BAL) with open-lung biopsy have shown the former to be superior in detecting most pulmonary pathogens affecting immunocompromised patients. Fifty consecutive BAL specimens were studied to compare direct in situ DNA hybridization, routine tissue culture, and conventional cytologic examination to assess the efficacy of the hybridization technic to rapidly detect CMV. Using tissue culture as the standard, a sensitivity of 90% (28 of 31) and specificity of 63% (12 of 19) were observed with the CMV probe. Discrepant results between the probe and tissue culture were present in ten cases. There were seven probe-positive, culture-negative cases, three of which had systemic CMV infection, including two patients with inclusions noted by conventional cytologic examination. Three probe-negative, culture-positive cases were found. In the authors' laboratory, the predictive value of a positive CMV probe is 80% (28 of 35). In contrast to the probe, conventional cytologic examination revealed CMV inclusions in only 23% (7 of 31) of the culture-positive cases. An average of 21 days was required for CMV cultures to become positive; probe results were available within 24 hours. The authors conclude direct in situ DNA hybridization is a useful rapid method for the detection of CMV in BAL specimens submitted for cytologic examination.