Psychiatric, behavioral and emotional disorders in Polish children and adolescents with perinatal HIV infection.
The aims of the study were to evaluate the prevalence of psychiatric, behavioral and emotional disorders in children and adolescents with perinatal HIV infection and to establish their possible relationships with clinical and sociodemographic variables. 56 children with perinatal HIV infection (PHIV+ group), 24 healthy children perinatally HIV-exposed but uninfected (PHEU) and 43 healthy children of uninfected parents (HIV-nA), aged 6-18 years, were assessed. The Child Behavior Checklist (CBCL/4-18), completed by parents, and the Youth Self-Report (YSR) were used to assess behavioral and emotional disorders, while the semi-structured diagnostic interview K-SADS-PL was used to assess the symptoms of psychiatric disorders. Higher prevalence of psychiatric disorders was found in the PHIV+ group and the PHEU group compared to the HIV-nAgroup. Anxiety disorders and affective disorders were diagnosed most often. Prevalence of symptoms of emotional and behavioral disorders in the PHIV+ group and in the PHEU group was associated with similar sociodemographic variables (male, not living with the biological caregiver, the experience of stressful life events). Psychiatric disorders were noted more often among PHIV+ subjects whose ARV treatment was started after 12 months of age. Positive correlations were observed between the results of some YSR and CBCL/4-18 problem scales and CD4 counts at the time of the study, higher logarithm of viral load at the start of ARV treatment and at the time of HIV diagnosis. The prevalence of psychiatric disorders in PHIV+ group and the PHEU group is higher in comparison with HIV-nAgroup. Amore serious course of HIV infection and its severity before treatment are associated with the severity of internalizing problems.


A Reevaluation of the Ozone Budget with HALOE UARS Data: No Evidence for the Ozone Deficit.
Recently, additional ozone production mechanisms have been proposed to resolve the ozone deficit problem, which arises from greater ozone destruction than production in several photochemical models of the upper stratosphere and lower mesosphere. A detailed ozone model budget analysis was performed with simultaneous observations of O(3), HCl, H(2)O, CH(4), NO, and NO(2) from the Halogen Occultation Experiment (HALOE) on the Upper Atmosphere Research Satellite (UARS) under conditions with the strongest photochemical control of ozone. The results indicate that an ozone deficit may not exist. On the contrary, the use of currently recommended photochemical parameters leads to insufficient ozone destruction in the model.


Remote and interdisciplinary research in surgical knowledge production.
Surgical knowledge production has changed dramatically in the last 30 y, moving away from investigations by individual surgeon researchers and toward remote and interdisciplinary research. We investigated how surgeons make decisions about engaging in research and identify motivators, facilitators, and barriers to conducting research in an increasingly challenging environment. We performed a qualitative analysis of semistructured interviews with surgeons from academic medical centers across the United States. We asked participants to describe their experiences and opinions regarding remote and interdisciplinary collaborations. Of 64 surgeon researchers invited, 21 (33%) agreed and participated in semistructured interviews. Each interview lasted an average (standard deviation) of 29 min (12). Surgeons were motivated by both internal and external factors, including some that might be identified as barriers. The internal desire to improve care and the need for collaboration to address increasingly complex questions requiring larger samples sizes emerged as most significant to interview participants. Social networks were identified as the dominant facilitator of multisite research, with technology playing a supporting role. Barriers to remote and interdisciplinary research ranged from individual, "micro" level barriers, through structural barriers that include institutional level challenges and competing priorities, to macrolevel system and policy-level barriers. Surgeons clearly recognize the importance of high-quality research aligned with current paradigms of clinical care and are using remote and interdisciplinary collaboration to improve the quality of the science they produce and align their work with the demand for increasingly high levels of evidence.


Glycopeptides bind MHC molecules and elicit specific T cell responses.
Carbohydrates are T cell independent antigens because they do not bind to MHC molecules. However, glycopeptides might potentially bind to MHC molecules via their peptide component for presentation to T cells. We have conjugated the disaccharide galabiose [Gal alpha (1-4)Gal beta] to the amino terminus of a T cell peptide determinant from hen egg-white lysozyme [HEL(52-61)]. The resulting glycopeptide (Gal2-52-61) and a nonglycosylated analogue containing tyrosine and glutamic acid at the amino-terminus (YE-52-61) bound equally well to purified I-Ak. T cell hybridomas were produced after immunization with Gal2-52-61. Many of the T cell hybridomas were glycopeptide-specific and responded to Gal2-52-61 but not to nonglycosylated synthetic peptides or to HEL presented by APC, indicating that the carbohydrate moiety influenced T cell recognition. Recognition was lost with the amino terminal attachment of the disaccharide to a peptide six amino acids longer at the amino terminus than HEL(52-61). Recognition also was lost with peptides containing only a single galactosyl residue or with galabiose bound to a different I-Ak binding peptide. T cells directed to Gal2-52-61 recognized glycopeptides having significant variation in the disaccharide structure, such as HEL(52-61) glycopeptides carrying lactose, cellobiose, or hepta-o-acetylated galabiose. Peptide residues were important features of the T cell epitope; Ala substitutions of two critical T cell contact residues of HEL(52-61) (Tyr53 and Leu56) abrogated T cell reactivity to the glycopeptides without affecting binding to I-Ak. In conclusion, we propose that these T cells recognize a peptide conformation specific to glycopeptide-I-Ak complexes and that this recognition does not involve specific interaction between the carbohydrate moiety and the T cell receptor.


Opioid Prescribing Practices in Pediatric Acute Care Settings.
Deaths due to prescription opioid overdoses are at record-high levels. Limiting the amount of opioid prescribed has been suggested as a prevention strategy. The purpose of this study was to describe the opioid prescribing practices in the emergency departments and urgent care sites of a Midwestern tertiary care children's hospital system. This retrospective medical record review examined the visits from the 2 pediatric emergency departments and 2 pediatric urgent care sites in the system from June 1, 2012, to May 31, 2013, during which an outpatient opioid prescription was written. The primary outcome was number of days of opioid prescribed. Other data collected included patient demographics, diagnosis, and prescriber information; factors associated with prescriptions written for more than 5 days were identified. A total of 4075 opioid prescriptions were included in the 1-year study period, and 3991 of these had complete data for analysis. The median amount prescribed was 3.3 days with an interquartile range of 2.5 days. Odds of receiving a prescription of more than 5 days' duration were higher for children younger than 1 year (odds ratio [OR], 12.3; 95% confidence interval [CI], 7.3-21.0), 1 to 4 years of age (OR, 7.7; 95% CI, 5.5-10.8), and 5 to 9 years of age (OR, 2.4; 95% CI, 1.7-3.4); for children with noninjury diagnoses (OR, 1.4; 95% CI, 1.2-1.7); or if prescribed by a resident physician (OR, 1.4; 95% CI, 1.1-1.8) or from the urgent care (OR, 1.4; 95% CI, 1.1-1.7). Opioid prescriptions of more than 5 days were more frequently prescribed for younger patients, noninjury diagnoses, or if prescribed by a resident physician or from the urgent care. We need to focus on medical student, resident, and provider education as well as further opioid research in order to decrease unnecessary prescribing.


[Importance of a self-care system in diabetes mellitus in preventing complications and preserving the patient's work capacity].
A system of self-control of the patients nutrition using the V. S. Vorobyov calculator was introduced to prevent early complications in diabetes mellitus patients, 112 patients were followed up during 5 months. 35 of them were administered insulin, 65 sugar-reducing drugs per os, and 12 patients were given diets. Introduction of the self-control system in the nutrition of diabetes mellitus patients made it possible to achieve stable compensation in 89.4% patients, reduction of the dose or withdrawal of oral sugar-reducing drugs, and reduction of the insulin dose. It is suggested to devise a unified system for training diabetes mellitus patients, with a special section on training self-control methods in nutrition.


Number of symptoms, quantification, and qualification of depression.
Current classification systems (ICD-10 and DSM-IV) require a quantitative criterion for differentiating depressive states, suggesting a correlation between the number of symptoms, i.e., the pervasiveness of the syndrome, and the subtype of the illness. All the symptoms (within those contained in the diagnostic lists) are assumed to have comparable value. To investigate the relevance of the number and the type of symptoms reported by 196 patients suffering from depression, we compared the symptoms using independent indicators of severity such as the Clinical Global Index (CGI) and the social functioning subscale of the Global Assessment of Functioning (GAF). A second comparison using the same indicators was made between qualitatively distinct categories of DSM-IV and ICD-10 (i.e., melancholic v nonmelancholic, somatic v nonsomatic, and psychotic v nonpsychotic). There was evidence that increasing numbers of symptoms actually reflect higher levels of severity, but the categorizations that were mainly based on qualitative criteria (e.g., melancholia, somatic syndrome, etc.) usually attained better discrimination compared with those based on the number of symptoms. Moreover, certain symptoms (usually those indicated as endogenous) were more likely to be associated with greater severity and pervasiveness. Finally, the results clearly showed that different symptoms had different weight in establishing the gradient of severity.


Probing Sizes and Shapes of Nobelium Isotopes by Laser Spectroscopy.
Until recently, ground-state nuclear moments of the heaviest nuclei could only be inferred from nuclear spectroscopy, where model assumptions are required. Laser spectroscopy in combination with modern atomic structure calculations is now able to probe these moments directly, in a comprehensive and nuclear-model-independent way. Here we report on unique access to the differential mean-square charge radii of ^{252,253,254}No, and therefore to changes in nuclear size and shape. State-of-the-art nuclear density functional calculations describe well the changes in nuclear charge radii in the region of the heavy actinides, indicating an appreciable central depression in the deformed proton density distribution in ^{252,254}No isotopes. Finally, the hyperfine splitting of ^{253}No was evaluated, enabling a complementary measure of its (quadrupole) deformation, as well as an insight into the neutron single-particle wave function via the nuclear spin and magnetic moment.


[Complications after total hip replacement (author's transl)].
Alloarthroplastic replacement of the hip comprises certain risks. Therefore good apparative and instrumental equipment and biological understanding of the post operative phase are necessary. Our rate of operative complications was 1.3% of all cases. In this number fat embolism after implantation of acrylic cement is of special interest. Reference is made of animal experiments on the pathogenesis of this phenomenon. Early complications comprise luxation of the prosthesis, bleeding and hematoma formation, iliotibial-nerve syndrome, phlebothrombosis, embolism, early infection. Late complications comprise infection and loosening of the prosthesis. In a total of 1200 implantations we had early complications in 1.8% and late complications in 0.9%. Reference is made of clinical and X-ray signs of loosening of the implant. Arthrography proved to be the most dependable method. We found periarticular calcifications in 30% of all cases. Fractures of the prosthesis were extremely rare: in few cases we found fractures of the polyestercup. In all cases the aggressive granuloma will leed to rarefication of bone sooner or later going along with loosening of the implant.


The effects of smoking on the lungs.
The literature relating to tobacco smoking has been reviewed and is discussed under a number of headings. The smoking habits of Australians and people of other countries, the constituents of tobacco smoke and the different types of tobacco are discussed. The effects of tobacco smoke on lung defences and and function are outlined and the evidence relating cigarette smoking to lung cancer in Australia, the UK and the USA is reviewed. The relationship between cigarette smoking and diseases which chronic air flow obstruction is outlined. Differences in smoking-related diseases in males and females and the effects of stopping smoking are included in the discussion.


Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment.
We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is Salmonella typhimurium strain chi8937, with deletions of asdA and arabinose-regulated expression of murA, two genes required for peptidoglycan synthesis and additional mutations to enhance complete lysis and antigen delivery. The second component is plasmid pYA3681, which encodes arabinose-regulated murA and asdA expression and C2-regulated synthesis of antisense asdA and murA mRNA transcribed from the P22 P(R) promoter. An arabinose-regulated c2 gene is present in the chromosome. chi8937(pYA3681) exhibits arabinose-dependent growth. Upon invasion of host tissues, an arabinose-free environment, transcription of asdA, murA, and c2 ceases, and concentrations of their gene products decrease because of cell division. The drop in C2 concentration results in activation of P(R), driving synthesis of antisense mRNA to block translation of any residual asdA and murA mRNA. A highly antigenic alpha-helical domain of Streptococcus pneumoniae Rx1 PspA was cloned into pYA3681, resulting in pYA3685 to test antigen delivery. Mice orally immunized with chi8937(pYA3685) developed antibody responses to PspA and Salmonella outer membrane proteins. No viable vaccine strain cells were detected in host tissues after 21 days. This system has potential applications with other Gram-negative bacteria in which biological containment would be desirable.


A novel protein ubiquitination-related five-gene signature predicts overall survival in patients with lung adenocarcinoma.
Protein ubiquitination has been reported to be involved in many biological processes that affect cancer cell growth or death. In this study, we identified differentially expressed E3s/DUB-related genes associated with the prognosis of lung adenocarcinoma and then constructed an E3s/DUB enzyme signature prediction model for the training group and validated its accuracy for prognosis prediction in the validation group. According to our constructed model, all patients were divided into the high- or low-risk group, and a comparison of the two groups revealed that the high-risk group had poorer survival and higher mortality than the low-risk group. The calculated risk score was also an independent prognostic factor when analyzed together with other clinical factors. To explore the functions of the signature genes, we predicted the substrate proteins with which they interact and then performed enrichment analysis. Interestingly, we found that the signature genes were enriched in multiple treatment resistance and immune-related pathways. Therefore, we continued to analyze immune infiltration in the samples and found a variety of differences in immune cell infiltration. According to our constructed model, these differences in immune cell infiltration may predict different immune statuses after grouping and are associated with worse prognosis in high-risk patients.


The potential of training specialist oncology nurses in real-life reporting of adverse drug reactions.
Specialist oncology nurses (SONs) have the potential to play a major role in monitoring and reporting adverse drug reactions (ADRs); and reduce the level of underreporting by current healthcare professionals. The aim of this study was to investigate the long term clinical and educational effects of real-life pharmacovigilance education intervention for SONs on ADR reporting. This prospective cohort study, with a 2-year follow-up, was carried out in the three postgraduate schools in the Netherlands. In one of the schools, the prescribing qualification course was expanded to include a lecture on pharmacovigilance, an ADR reporting assignment, and group discussion of self-reported ADRs (intervention). The clinical value of the intervention was assessed by analyzing the quantity and quality of ADR-reports sent to the Netherlands Pharmacovigilance Center Lareb, up to 2 years after the course and by evaluating the competences regarding pharmacovigilance of SONs annually. Eighty-eight SONs (78% of all SONs with a prescribing qualification in the Netherlands) were included. During the study, 82 ADRs were reported by the intervention group and 0 by the control group. This made the intervention group 105 times more likely to report an ADR after the course than an average nurse in the Netherlands. This is the first study to show a significant and relevant increase in the number of well-documented ADR reports after a single educational intervention. The real-life pharmacovigilance educational intervention also resulted in a long-term increase in pharmacovigilance competence. We recommend implementing real-life, context- and problem-based pharmacovigilance learning assignments in all healthcare curricula.


Tomato Sl3-MMP, a member of the Matrix metalloproteinase family, is required for disease resistance against Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMPs have been characterized in detail in mammals and shown to play key roles in many physiological and pathological processes. Although MMPs in some plant species have been identified, the function of MMPs in biotic stress responses remains elusive. A total of five MMP genes were identified in tomato genome. qRT-PCR analysis revealed that expression of Sl-MMP genes was induced with distinct patterns by infection of Botrytis cinerea and Pseudomonas syringae pv. tomato (Pst) DC3000 and by treatment with defense-related hormones such as salicylic acid, jasmonic acid and ethylene precursor 1-amino cyclopropane-1-carboxylic acid. Virus-induced gene silencing (VIGS)-based knockdown of individual Sl-MMPs and disease assays indicated that silencing of Sl3-MMP resulted in reduced resistance to B. cinerea and Pst DC3000, whereas silencing of other four Sl-MMPs did not affect the disease resistance against these two pathogens. The Sl3-MMP-silenced tomato plants responded with increased accumulation of reactive oxygen species and alerted expression of defense genes after infection of B. cinerea. Transient expression of Sl3-MMP in leaves of Nicotiana benthamiana led to an enhanced resistance to B. cinerea and upregulated expression of defense-related genes. Biochemical assays revealed that the recombinant mature Sl3-MMP protein had proteolytic activities in vitro with distinct preferences for specificity of cleavage sites. The Sl3-MMP protein was targeted onto the plasma membrane of plant cells when transiently expressed in onion epidermal cells. VIGS-based knockdown of Sl3-MMP expression in tomato and gain-of-function transient expression of Sl3-MMP in N. benthamiana demonstrate that Sl3-MMP functions as a positive regulator of defense response against B. cinerea and Pst DC3000.


Satellite glial cells in sensory ganglia play a wider role in chronic pain via multiple mechanisms.
Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons. An increasing body of evidence suggests that in the presence of inflammation and nerve damage, a significant number of satellite glial cells become activated, thus triggering a series of functional changes. This suggests that satellite glial cells are closely related to the occurrence of chronic pain. In this review, we first summarize the morphological structure, molecular markers, and physiological functions of satellite glial cells. Then, we clarify the multiple key roles of satellite glial cells in chronic pain, including gap junction hemichannel Cx43, membrane channel Pannexin1, K channel subunit 4.1, ATP, purinergic P2 receptors, and a series of additional factors and their receptors, including tumor necrosis factor, glutamate, endothelin, and bradykinin. Finally, we propose that future research should focus on the specific sorting of satellite glial cells, and identify genomic differences between physiological and pathological conditions. This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.


Live and Let Die? Life Cycle Human Health Impacts from the Use of Tire Studs.
Studded tires are used in a number of countries during winter in order to prevent accidents. The use of tire studs is controversial and debated because of human health impacts from increased road particle emissions. The aims of this study are to assess whether the use of tire studs in a Scandinavian studded passenger car actually avoids or causes health impacts from a broader life cycle perspective, and to assess the distribution of these impacts over the life cycle. Life cycle assessment is applied and the disability-adjusted life years indicator is used to quantify the following five types of health impacts: (1) impacts saved in the use phase, (2) particle emissions in the use phase, (3) production system emissions, (4) occupational accidents in the production system, and (5) conflict casualties from revenues of cobalt mining. The results show that the health benefits in the use phase in general are outweighed by the negative impacts during the life cycle. The largest contribution to these negative human health impacts are from use phase particle emissions (67⁻77%) and occupational accidents during artisanal cobalt mining (8⁻18%). About 23⁻33% of the negative impacts occur outside Scandinavia, where the benefits occur. The results inform the current debate and highlight the need for research on alternatives to tire studs with a positive net health balance.


Spirals and paracrystals induced by Vinca alkaloids: evidence that microtubule-associated proteins act as polycations.
Formation of the vinca-induced spirals from tubulin and microtubules is dependent upon the presence of microtubule-associated proteins. Formation of paracrystals visualized in thin-sectioned material is also shown to require the presence of microtubule-associated proteins. The polycationic behaviour of the latter in stabilizing microtubules and spirals is demonstrated in experiments where assembly of tubulin in their absence was stimulated by polylysine or high Mg2+ and addition of vincristine caused spirals to form. Spirals were stable to cold, Ca2+, and colchicine, but polyadenylic acid caused their depolymerization.


Developing clinical leaders: the impact of an action learning mentoring programme for advanced practice nurses.
To determine whether a formal mentoring programme assists nurse practitioner candidates to develop competence in the clinical leadership competencies required in their advanced practice roles. Nurse practitioner candidates are required to show evidence of defined clinical leadership competencies when they apply for endorsement within the Australian health care system. Aiming to assist the candidates with the development or enhancement of these leadership skills, 18 nurse practitioner candidates participated in a mentoring programme that matched them with senior nurse mentors. A pre-postlongitudinal intervention study. Eighteen nurse practitioner candidates and 17 senior nurses participated in a voluntary mentoring programme that incorporated coaching and action learning over 18 months in 2012 and 2013. Participants completed a pen and paper questionnaire to document baseline measures of self-reported leadership practices prior to commencement of the programme and again at the end of the programme. The mentors and the nurse practitioner candidates qualitatively evaluated the programme as successful and quantitative data illustrated significant improvement in self-reported leadership practices among the nurse practitioner candidates. In particular, the nurse practitioner candidates reported greater competence in the transformational aspects of leadership, which is directly related to the nurse practitioner candidate clinical leadership standard. A formal, structured mentoring programme based on principles of action learning was successful in assisting Australian advanced practice nurses enhance their clinical leadership skills in preparation for formal endorsement as a nurse practitioner and for success in their advanced practice role. Mentoring can assist nurses to transition to new roles and develop knowledge and skills in clinical leadership essential for advanced practice roles. Nurse managers should make greater use of mentoring programmes to support nurses in their transition to new roles.


Addressing Long-Term Services and Supports Reform via Medicare. Yes, Medicare, That Post-Acute Care Program.
Reform of the U.S. long-term services and supports (LTSS) financing system has been historically difficult to achieve. This article outlines several recent reform proposals and offers a path forward on achieving LTSS reform. These proposals include the Commonwealth Fund's Medicare Help at Home proposal, the work of the Bipartisan Policy Center, as well as the State of Minnesota to develop an LTSS benefit. All three proposals focus on an expansion of Medicare to cover the LTSS needs of Americans. While Medicare increasingly pays for LTSS, these approaches ensure that the role of Medicare in LTSS financing is much more coordinated. Enhancing Medicare's role reduces the current reliance on Medicaid, the default payer of LTSS, while providing an opportunity for a more robust private insurance market to develop. This would help provide for the immediate LTSS needs of Americans while building a more sustainable and equitable financing system for future generations.


Assessing iodine status and monitoring progress of iodized salt programs.
Despite remarkable progress in the control of the iodine deficiency disorders (IDD), they remain a significant global public health problem. Assessing the severity of IDD and monitoring the progress of salt iodization programs are cornerstones of a control strategy. Because thyroid size decreases only gradually in response to iodized salt, the goiter rate in children may be a poor IDD monitoring indicator for several years after the introduction of salt iodization. During this period, the goiter rate reflects chronic iodine deficiency, and will be inconsistent with measurements of urinary iodine. Thyroglobulin is a promising new biochemical indicator for monitoring thyroid function after the introduction of iodized salt. Recent development of a dried blood spot thyroglobulin assay makes sample collection practical even in remote areas. Interpretation of thyroid volume data from ultrasound surveys requires valid references from iodine-sufficient populations, but defining normal values for thyroid size in children has been difficult. New international reference criteria for thyroid volume were published recently and can be used for goiter screening in the context of IDD monitoring. Ensuring sustainability is one of the great remaining challenges in the global fight to eliminate IDD. A recent cohort study demonstrated the vulnerability of children in IDD-affected areas to even short-term lapses in iodized salt programs.


Expression and purification of the immunogenically active fragment B of the Park Williams 8 Corynebacterium diphtheriae strain toxin.
The construction of a hexahistidine-tagged version of the B fragment of diphtheria toxin (DTB) represents an important step in the study of the biological properties of DTB because it will permit the production of pure recombinant DTB (rDTB) in less time and with higher yields than currently available. In the present study, the genomic DNA of the Corynebacterium diphtheriae Park Williams 8 (PW8) vaccine strain was used as a template for PCR amplification of the dtb gene. After amplification, the dtb gene was cloned and expressed in competent Escherichia coli M15 cells using the expression vector pQE-30. The lysate obtained from transformed E. coli cells containing the rDTB PW8 was clarified by centrifugation and purified by affinity chromatography. The homogeneity of the purified rDTB PW8 was confirmed by immunoblotting using mouse polyclonal anti-diphtheria toxoid antibodies and the immune response induced in animals with rDTB PW8 was evaluated by ELISA and dermonecrotic neutralization assays. The main result of the present study was an alternative and accessible method for the expression and purification of immunogenically reactive rDTB PW8 using commercially available systems. Data also provided preliminary evidence that rabbits immunized with rDTB PW8 are able to mount a neutralizing response against the challenge with toxigenic C. diphtheriae.


Aza-annulation of enynyl azides: a new approach to substituted pyridines.
Synthesis of substituted pyridines through a novel aza-annulation of 2-en-4-ynyl azides, derived from MBH-acetates of acetylenic aldehydes, is described. A variety of enynyl azides having aryl, heteroaryl, and alkyl groups on the alkyne functionality successfully participated in the Ag-mediated annulation reaction to provide the corresponding 3,6-disubstituted pyridines. I2-mediated cyclization was found to be controlled by the substituent on the alkyne functionality, which offered the 5-iodo-3,6-disubstituted pyridines from enynyl azides having an electron-rich substituent on the alkyne functionality.


The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant.
The S protein of bovine coronavirus (BCV) has been isolated from the viral membrane and purified by gradient centrifugation. Purified S protein was identified as a viral hemagglutinin. Inactivation of the cellular receptors by sialate 9-O-acetylesterase and generation of receptors by sialylation of erythrocytes with N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) indicate that S protein recognizes 9-O-acetylated sialic acid as a receptor determinant as has been shown previously for intact virions. The second glycoprotein of BCV, HE, which has been thought previously to be responsible for the hemagglutinating activity of BCV, is a less efficient hemagglutinin; it agglutinates mouse and rat erythrocytes, but in contrast to S protein, it is unable to agglutinate chicken erythrocytes, which contain a lower level of Neu5,9Ac2 on their surface. S protein is proposed to be responsible for the primary attachment of virus to cell surface. S protein is proposed to be responsible for the primary attachement of virus to cell surface receptors. The potential of S protein as a probe for the detection of Neu5,9Ac2-containing glycoconjugates is demonstrated.


[Prevention of severe infections in asplenic patients].
The lifetime risk of dying from sepsis is approximately 2-3% in persons with (functional) asplenia. Both patients and their physicians are not always fully aware of these risks and the implementation of preventive measures is insufficient. Physicians should inform both patients and colleagues on the consequences of lost splenic function. Primary care physicians should screen their lists for patients with (functional) asplenia and offer these patient adequate preventive measures when needed.


[Recurrent and alternating peripheral facial paralysis. Report of a case with 5 episodes].
The clinic case of a 36 years-old woman with five episodes of relapsing and alternating Bell's palsy in the last 24 years is reported. The definitive etiology could not be demonstrated. The possibility of an immunologic factor is denoted. The literature was reviewed and other etiopathogenic theories are commented on.


Developing Internet-based health interventions: a guide for public health researchers and practitioners.
Researchers and practitioners interested in developing online health interventions most often rely on Web-based and print resources to guide them through the process of online intervention development. Although useful for understanding many aspects of best practices for website development, missing from these resources are concrete examples of experiences in online intervention development for health apps from the perspective of those conducting online health interventions. This study aims to serve as a series of case studies in the development of online health interventions to provide insights for researchers and practitioners who are considering technology-based interventional or programmatic approaches. A convenience sample of six study coordinators and five principal investigators at a large, US-based land grant university were interviewed about the process of developing online interventions in the areas of alcohol policy, adolescent health, medication adherence, and human immunodeficiency virus prevention in transgender persons and in men who have sex with men. Participants were asked questions that broadly addressed each of the four phases of the User-Centered Design Process Map from the US Department of Health and Human Services' Research-Based Web Design & Usability Guidelines. Interviews were audio recorded and transcribed. Qualitative codes were developed using line-by-line open coding for all transcripts, and all transcripts were coded independently by at least 2 authors. Differences among coders were resolved with discussion. We identified the following seven themes: (1) hire a strong (or at least the right) research team, (2) take time to plan before beginning the design process, (3) recognize that vendors and researchers have differing values, objectives, and language, (4) develop a detailed contract, (5) document all decisions and development activities, (6) use a content management system, and (7) allow extra time for testing and debugging your intervention. Each of these areas is discussed in detail, with supporting quotations from principal investigators and study coordinators. The values held by members of each participating organization involved in the development of the online intervention or program, as well as the objectives that are trying to be met with the website, must be considered. These defined values and objectives should prompt an open and explicit discussion about the scope of work, budget, and other needs from the perspectives of each organization. Because of the complexity of developing online interventions, researchers and practitioners should become familiar with the process and how it may differ from the development and implementation of in-person interventions or programs. To assist with this, the intervention team should consider expanding the team to include experts in computer science or learning technologies, as well as taking advantage of institutional resources that will be needed for successful completion of the project. Finally, we describe the tradeoff between funds available for online intervention or program development and the complexity of the project.


Natural killer T-cell autoreactivity leads to a specialized activation state.
Natural killer T (NKT) cells are innate-like T cells that recognize specific microbial antigens and also display autoreactivity to self-antigens. The nature of NKT-cell autoreactive activation remains poorly understood. We show here that the mitogen-activated protein kinase (MAPK) pathway is operative during human NKT-cell autoreactive activation, but calcium signaling is severely impaired. This results in a response that is biased toward granulocyte macrophage colony-stimulating factor (GM-CSF) secretion because this cytokine requires extracellular signal-regulated kinase (ERK) signaling but is not highly calcium dependent, whereas interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-2 production are minimal. Autoreactive activation was associated with reduced migration velocity but did not induce arrest; thus, NKT cells retained the ability to survey antigen presenting cells (APCs). IL-12 and IL-18 stimulated autoreactively activated NKT cells to secrete IFN-gamma, and this was mediated by Janus kinase-signal transducers and activators of transcription (JAK-STAT)-dependent signaling without induction of calcium flux. This pathway did not require concurrent contact with CD1d(+) APCs but was strictly dependent on preceding autoreactive stimulation that induced ERK activation. In contrast, NKT-cell responses to the glycolipid antigen alpha-galactosyl ceramide (alpha-GalCer) were dampened by prior autoreactive activation. These results show that NKT-cell autoreactivity induces restricted cytokine secretion and leads to altered basal activation that potentiates innate responsiveness to costimulatory cytokines while modulating sensitivity to foreign antigens.


Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality.
Older adults get lost, in many cases because of recognized or incipient Alzheimer disease (AD). In either case, getting lost can be a threat to individual and public safety, as well as to personal autonomy and quality of life. Here we compare our previously described real-world navigation test with a virtual reality (VR) version simulating the same navigational environment. Quantifying real-world navigational performance is difficult and time-consuming. VR testing is a promising alternative, but it has not been compared with closely corresponding real-world testing in aging and AD. We have studied navigation using both real-world and virtual environments in the same subjects: young normal controls (YNCs, n = 35), older normal controls (ONCs, n = 26), patients with mild cognitive impairment (MCI, n = 12), and patients with early AD (EAD, n = 14). We found close correlations between real-world and virtual navigational deficits that increased across groups from YNC to ONC, to MCI, and to EAD. Analyses of subtest performance showed similar profiles of impairment in real-world and virtual testing in all four subject groups. The ONC, MCI, and EAD subjects all showed greatest difficulty in self-orientation and scene localization tests. MCI and EAD patients also showed impaired verbal recall about both test environments. Virtual environment testing provides a valid assessment of navigational skills. Aging and Alzheimer disease (AD) share the same patterns of difficulty in associating visual scenes and locations, which is complicated in AD by the accompanying loss of verbally mediated navigational capacities. We conclude that virtual navigation testing reveals deficits in aging and AD that are associated with potentially grave risks to our patients and the community.


Autonomic neuropathy in chronic renal insufficiency. Comparative analysis of diabetic and nondiabetic patients.
Disturbances of peripheral and autonomic nervous system function were evaluated in 37 normal subjects, in 52 patients with non diabetic chronic renal insufficiency (25 predialysis patients, 27 dialysis patients), and in 21 patients with diabetic chronic renal failure (10 predialysis patients, 11 dialysis patients). In nondiabetic patients, the predialysis group showed abnormal test results indicating parasympathetic lesions, in dialysis patients these derangements were nearly normalized. In predialysis diabetic patients, the autonomic alterations were much more extensive, corresponding to alterations of electroneurographical findings; in addition to parasympathetic lesions, sympathetic disturbances were seen. In contrast to the nondiabetic groups, in dialysis patients a deterioration of autonomic lesions was observed. In conclusion, these data indicate that deranged autonomic functions are common in uremia; they improve in dialysis patients with nondiabetic renal failure in contrast to diabetic patients; in this group the autonomic functions worsen in dialysis patients as a function of duration of diabetes and hemodialysis.


A Simplified Preoperative Assessment Predicts Complete Cytoreduction and Outcomes in Patients with Low-Grade Mucinous Adenocarcinoma of the Appendix.
Complete cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve survival in patients with low-grade mucinous adenocarcinoma (LGMA). However, incomplete cytoreduction exposes patients to significant morbidity without a similar survival benefit. Preoperative assessment of the ability to achieve CRS is therefore a critical step in selecting patients for CRS/HIPEC. The aim of this study was to develop and validate a preoperative scoring system to accurately predict the ability to achieve complete cytoreduction in patients with LGMA of the appendix. A simplified preoperative assessment for appendix tumor (SPAAT) score was developed based on computed tomography scan findings thought to predict incomplete cytoreduction. We applied the SPAAT score to patients with LGMA to determine the ability of the score to predict complete cytoreduction. This scoring system was then applied to a separate cohort of patients from a different institution. Sensitivity and specificity were determined for the SPAAT score. Survival was calculated and correlated with the SPAAT score and the completeness of cytoreduction score. A SPAAT score of <3 is a significant predictor of complete cytoreduction in the derivation cohort. In the validation cohort, 40 of 42 patients with a SPAAT score <3 achieved a complete cytoreduction, for a positive predictive value of 95.2 % and a negative predictive value of 100 %. Additionally, the SPAAT score was a significant predictor of disease-free survival. The SPAAT score is a useful tool in the preoperative assessment of patients with LGMA who are under consideration for cytoreductive surgery. Prospective analysis of this scoring system is warranted to appropriately select patients who will benefit from CRS/HIPEC.


Breast cancer prognosis predicted by nuclear receptor-coregulator networks.
Although molecular signatures based on transcript expression in breast cancer samples have provided new insights into breast cancer classification and prognosis, there are acknowledged limitations in current signatures. To provide rational, pathway-based signatures of disrupted physiology in cancer tissues that may be relevant to prognosis, this study has directly quantitated changed gene expression, between normal breast and cancer tissue, as a basis for signature development. The nuclear receptor (NR) family of transcription factors, and their coregulators, are fundamental regulators of every aspect of metazoan life, and were rigorously quantified in normal breast tissues and ERα positive and ERα negative breast cancers. Coregulator expression was highly correlated with that of selected NR in normal breast, particularly from postmenopausal women. These associations were markedly decreased in breast cancer, and the expression of the majority of coregulators was down-regulated in cancer tissues compared with normal. While in cancer the loss of NR-coregulator associations observed in normal breast was common, a small number of NR (Rev-ERBβ, GR, NOR1, LRH-1 and PGR) acquired new associations with coregulators in cancer tissues. Elevated expression of these NR in cancers was associated with poorer outcome in large clinical cohorts, as well as suggesting the activation of ERα -related, but ERα-independent, pathways in ERα negative cancers. In addition, the combined expression of small numbers of NR and coregulators in breast cancer was identified as a signature predicting outcome in ERα negative breast cancer patients, not linked to proliferation and with predictive power superior to existing signatures containing many more genes. These findings highlight the power of predictive signatures derived from the quantitative determination of altered gene expression between normal breast and breast cancers. Taken together, the findings of this study identify networks of NR-coregulator associations active in normal breast but disrupted in breast cancer, and moreover provide evidence that signatures based on NR networks disrupted in cancer can provide important prognostic information in breast cancer patients.


The Skin-Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain.
Recent discovery of an association of low serum melatonin levels with relapse in multiple sclerosis (MS) opens a new horizon in understanding the pathogenesis of this disease. Skin is the main organ for sensing seasonal changes in duration of sunlight exposure. Level of melatonin production is dependent on light exposure. The molecular mechanisms connecting peripheral (skin) sensing of the light exposure and developing brain inflammation (MS) have not been investigated. We hypothesize that there is a connection between the reaction of skin to seasonal changes in sunlight exposure and the risk of MS and that seasonal changes in light exposure cause peripheral (skin) inflammation, the production of cytokines, and the subsequent inflammation of the brain. In skin of genetically predisposed individuals, cytokines attract memory cutaneous lymphocyte-associated antigen (CLA+) T lymphocytes, which then maintain local inflammation. Once inflammation is resolved, CLA+ lymphocytes return to the circulation, some of which eventually migrate to the brain. Once in the brain these lymphocytes may initiate an inflammatory response. Our observation of increased CC chemokine ligand 27 (CCL27) in MS sera supports the involvement of skin in the pathogenesis of MS. Further, the importance of our data is that CCL27 is a chemokine released by activated keratinocytes, which is upregulated in inflamed skin. We propose that high serum levels of CCL27 in MS are the result of skin inflammation due to exposure to seasonal changes in the sunlight. Future studies will determine whether CCL27 serum level correlates with seasonal changes in sunlight exposure, MS exacerbation, and skin inflammation.


Baboon placental heparin-binding epidermal growth factor-like growth factor.
Placental extravillous trophoblast remodeling of the uterine spiral arteries is important for promoting blood flow to the placenta and fetal development. Heparin-binding EGF-like growth factor (HB-EGF), an EGF family member, stimulates differentiation and invasive capacity of extravillous trophoblasts in vitro. Trophoblast expression and maternal levels of HB-EGF are reduced at term in women with preeclampsia, but it is uncertain whether HB-EGF is downregulated earlier when it may contribute to placental insufficiency. A nonhuman primate model has been established in which trophoblast remodeling of the uterine spiral arteries is suppressed by shifting the rise in estrogen from the second to the first trimester of baboon pregnancy. In the present study, we used this model to determine if placental HB-EGF is altered by prematurely elevating estrogen early in baboon gestation. Uterine spiral artery remodeling and placental expression of HB-EGF and other EGF family members were assessed on day 60 of gestation in baboons treated with estradiol (E2) daily between days 25 and 59 of gestation (term = 184 days). The percentages of spiral artery remodeling were 90, 84 and 70% lower (P < 0.01), respectively, for vessels of 26-50, 51-100 and >100 µm diameter in E2-treated compared with untreated baboons. HB-EGF protein quantified by immunocytochemical staining/image analysis was decreased three-fold (P < 0.01) in the placenta of E2-treated versus untreated baboons, while amphiregulin (AREG) and EGF expression was unaltered. Therefore, we propose that HB-EGF modulates the estrogen-sensitive remodeling of the uterine spiral arteries by the extravillous trophoblast in early baboon pregnancy.


Sources and circulation of water and arsenic in the Giant Mine, Yellowknife, NWT, Canada.
Recovery of gold from arsenopyrite-hosted ore in the Giant Mine camp, Yellowknife, NWT, Canada, has left a legacy of arsenic contamination that poses challenges for mine closure planning. Seepage from underground chambers storing some 237,000 tonnes of arsenic trioxide dust, has As concentrations exceeding 4000 ppm. Other potential sources and sinks of As also exist. Sources and movement of water and arsenic are traced using the isotopes of water and sulphate. Mine waters (16 ppm As; AsV/AsIII approximately 150) are a mixture of two principal water sources--locally recharged, low As groundwaters (0.5 ppm As) and Great Slave Lake (GSL; 0.004 ppm As) water, formerly used in ore processing and discharged to the northwest tailings impoundment (NWTP). Mass balance with delta18O shows that recirculation of NWTP water to the underground through faults and unsealed drillholes contributes about 60% of the mine water. Sulphate serves to trace direct infiltration to the As2O3 chambers. Sulphate in local, low As groundwaters (0.3-0.6 ppm As; delta34SSO4 approximately 4% and delta18OSO4 approximately -10%) originates from low-temperature aqueous oxidation of sulphide-rich waste rock. The high As waters gain a component of 18O-enriched sulphate derived from roaster gases (delta18OSO4) = + 3.5%), consistent with their arsenic source from the As2O3 chambers. High arsenic in NWTP water (approximately 8 ppm As; delta18OSO4 = -2%) derived from mine water, is attenuated to close to 1 ppm during infiltration back to the underground, probably by oxidation and sorption by ferrihydrite.


Symposium on surgical manpower in the smaller community. The advantages and disadvantages of practising surgery in a small community.
The advantages of practice in a community encompassing a population of about 35 000 include readily available beds and operating rooms, a relative diversity of surgical problems, increased job satisfaction and solid community support through service clubs and other volunteer organizations. Disadvantages in some situations can include lack of investigational facilities and of internists for consultation. A lack of surgical assistants, anesthetists and intensive-care-unit support are other potential negative factors. The quest for continuing medical education requires definite resolve, and practice finesse must be well honed.


Be vigilant for skin manifestations of inherited cancer syndromes.
More than 200 hereditary cancer susceptibility syndromes have been described, and it is thought that they account for 5-10% of all cancers. Many have dermatological manifestations (usually lesions, occasionally rashes) which frequently precede other systemic pathology. Dermatological signs are usually non-specific and often trivial in appearance, making their significance easy to overlook and a clinical diagnosis challenging. Histological examination is often required to differentiate lesions. They are usually benign and pathologically unrelated to the primary tumours, with the exception of the atypical moles of the dysplastic naevus syndrome, and may present simply as a cosmetic problem for the patient. However, a number of cancer syndromes exhibit an increased risk of developing malignant skin lesions. For instance, Gorlin syndrome (nevoid basal cell carcinoma syndrome) which typically results in the development of multiple basal cell carcinomas, within the first few decades of life. The majority of cancer syndromes with skin signs are inherited in an autosomal dominant pattern demonstrating complete penetrance before the age of 70. Once a cancer syndrome has been diagnosed, the cornerstone of management is frequent surveillance for the early detection and treatment of malignancy. Genetic testing and counselling should be offered to family members.


Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice.
Bullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times. Rabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice. Collagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies. This novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease.


Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.
Acute intermittent porphyria (AIP) results from a partial deficiency of porphobilinogen deaminase (PBGD). Symptomatic AIP patients, most of whom are women, experience acute attacks characterized by severe abdominal pain and abrupt increases in blood pressure. Here, we characterized the reactivity of mesenteric arteries from male and female AIP mice with ~30% of normal PBGD activity and wild type C57BL/6 mice. An acute porphyric attack was induced in AIP mice by treatment with phenobarbital. Vascular responses to K+, phenylephrine (PE), acetylcholine (ACh), and hemin were determined (Wire Multi Myograph). Maximal contraction to PE was increased in arteries from male and female AIP mice (p < .05) during an induced attack of acute porphyria. Female AIP arteries had increased sensitivity to PE (p < .05) even after nitric oxide (NO) blockade with Nω-nitro-L-arginine methyl ester (L-NAME) (p < .05). Maximal relaxation to ACh was similar in males and females with lower sensitivity in female AIP arteries (p < .05). Hemin induced greater relaxation in AIP arteries in both males and females (p < .05). Sex differences in this AIP mouse model include a pro-contractile response in females. These alterations may contribute to the increased blood pressure during an acute attack and provide a novel mechanism of action whereby heme ameliorates the attacks.


Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction.
Modulation of the autonomic nervous system (ANS) has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI. Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT) and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study. Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05). Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05). The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05). However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV), left atrial diameter (LA), ejection fraction (EF). Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.


Living with hepatitis C: qualitative interviews with hepatitis C-infected veterans.
Chronic hepatitis C (HCV) infection affects millions of people in the USA and prevalence rates are higher in US veterans. The consequences of HCV infection include reduced quality of life, liver damage, and reduced longevity. Our objective was to describe the experiences of US veterans living with chronic HCV infection and use this information in the development of an HCV self-management intervention. Twenty-two male HCV-infected veterans completed qualitative interviews. Participants were recruited via flyers and hepatitis C clinic providers at a major VA medical center. Participants were asked about their medical history, being diagnosed with HCV, and general experiences living with HCV. The study gathered the following findings: the impact of HCV on interpersonal relationships was pronounced, recovery from substance use disorders and getting care for HCV were connected, receiving the HCV diagnosis was more troubling to non-IV drug users, participants had misconceptions about HCV and its treatment, psychological problems were prevalent as were barriers to participating in antiviral treatment and HCV care in general. The themes derived from our analysis indicate that affected veterans may benefit from interventions or support to improve HCV-related health education, social/relationship issues, psychological issues, and exploration of the connection between substance use recovery and motivation to get care for HCV infection.


Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay.
Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Elevated ADMA plasma levels have been reported in connection with diseases associated with an impaired endothelial L-arginine-NO pathway and endothelial dysfunction, such as atherosclerosis, hypercholesterolemia, chronic heart failure, diabetes mellitus, and hypertension. NO production by NOS is decreased due to elevated ADMA levels. In fact, there is increasing interest in determination of ADMA levels in samples of various origins. The aim of this work was to develop a precise and easy immunoassay in contrast to the existing methods, such as HPLC, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS. We determined cross-reactivity in our immunoassay of 1.2% for symmetric dimethylarginine and <0.02% for L-arginine. The limit of quantitation was 0.05 micromol/l. We found good correlation of the values measured when we compared our assay with LC-tandem MS (n = 29; r = 0.984; p < 0.0001). We determined ADMA levels in human serum and plasma, mouse and rat plasma, and cell culture supernatant. For human plasma we found a mean of 0.65 micromol/l in healthy subjects. In the plasma of mice and rats we found mean concentrations of 1.05 and 1.09 micromol/l, respectively.


Generation of gas-phase ions from charged clusters: an important ionization step causing suppression of matrix and analyte ions in matrix-assisted laser desorption/ionization mass spectrometry.
Ionization in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a very complicated process. It has been reported that quaternary ammonium salts show extremely strong matrix and analyte suppression effects which cannot satisfactorily be explained by charge transfer reactions. Further investigation of the reasons causing these effects can be useful to improve our understanding of the MALDI process. The dried-droplet and modified thin-layer methods were used as sample preparation methods. In the dried-droplet method, analytes were co-crystallized with matrix, whereas in the modified thin-layer method analytes were deposited on the surface of matrix crystals. Model compounds, tetrabutylammonium iodide ([N(Bu)4 ]I), cesium iodide (CsI), trihexylamine (THA) and polyethylene glycol 600 (PEG 600), were selected as the test analytes given their ability to generate exclusively pre-formed ions, protonated ions and metal ion adducts respectively in MALDI. The strong matrix suppression effect (MSE) observed using the dried-droplet method might disappear using the modified thin-layer method, which suggests that the incorporation of analytes in matrix crystals contributes to the MSE. By depositing analytes on the matrix surface instead of incorporating in the matrix crystals, the competition for evaporation/ionization from charged matrix/analyte clusters could be weakened resulting in reduced MSE. Further supporting evidence for this inference was found by studying the analyte suppression effect using the same two sample deposition methods. By comparing differences between the mass spectra obtained via the two sample preparation methods, we present evidence suggesting that the generation of gas-phase ions from charged matrix/analyte clusters may induce significant suppression of matrix and analyte ions. The results suggest that the generation of gas-phase ions from charged matrix/analyte clusters is an important ionization step in MALDI-MS. Copyright © 2016 John Wiley & Sons, Ltd.


The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes.
Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive leukocyte invasion leads to heart failure and death during acute myocardial ischemia. We found that shortly and transiently after onset of ischemia, human and mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) that acts locally and distally to generate and recruit inflammatory and proteolytic cells. In the heart, fibroblast-derived GM-CSF alerts its neighboring myeloid cells to attract neutrophils and monocytes. The growth factor also reaches the bone marrow, where it stimulates a distinct myeloid-biased progenitor subset. Consequently, hearts of mice deficient in either GM-CSF or its receptor recruit fewer leukocytes and function relatively well, whereas mice producing GM-CSF can succumb from left ventricular rupture, a complication mitigated by anti-GM-CSF therapy. These results identify GM-CSF as both a key contributor to the pathogenesis of MI and a potential therapeutic target, bolstering the idea that GM-CSF is a major orchestrator of the leukocyte supply chain during inflammation.


PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome.
Cohesin is an important structural regulator of the genome, regulating both three-dimensional genome organization and gene expression. The core cohesin trimer interacts with various HEAT repeat accessory subunits, yielding cohesin complexes of distinct compositions and potentially distinct functions. The roles of the two mutually exclusive HEAT repeat subunits PDS5A and PDS5B are not well understood. Here, we determine that PDS5A and PDS5B have highly similar localization patterns across the mouse embryonic stem cell (mESC) genome and they show a strong overlap with other cohesin HEAT repeat accessory subunits, STAG1 and STAG2. Using CRISPR/Cas9 genome editing to generate individual stable knockout lines for PDS5A and PDS5B, we find that loss of one PDS5 subunit does not alter the distribution of the other PDS5 subunit, nor the core cohesin complex. Both PDS5A and PDS5B are required for proper gene expression, yet they display only partially overlapping effects on gene targets. Remarkably, gene expression following dual depletion of the PDS5 HEAT repeat proteins does not completely overlap the gene expression changes caused by dual depletion of the STAG HEAT repeat proteins, despite the overlapping genomic distribution of all four proteins. Furthermore, dual loss of PDS5A and PDS5B decreases cohesin association with NIPBL and WAPL, reduces SMC3 acetylation, and does not alter overall levels of cohesin on the genome. This work reveals the importance of PDS5A and PDS5B for proper cohesin function. Loss of either subunit has little effect on cohesin localization across the genome yet PDS5A and PDS5B are differentially required for gene expression.


[Effect of statins on activity of matrix metalloproteases and serum concentration of cystatin C in patients with various risk of development of ischemic heart disease and in patients after coronary artery bypass surgery].
We compared new non-lipid atherosclerosis indexes related to inflammation and macrophage stimulation (serum concentration of cystatin C, matrix metalloproteases and chitotriosidase activity) with common inflammatory (high sensitivity C reactive protein) and lipid markers in elderly persons and patients with atherosclerosis and ischemic heart disease who have undergone coronary bypass surgery.


Controlled porous structures of graphene aerogels and their effect on supercapacitor performance.
The design and optimization of 3D graphene nanostructures are critically important since the properties of electrochemical energy storages such as supercapacitors can be dramatically enhanced by tunable porous channels. In this work, we have developed porous graphene aerogels from graphene suspensions obtained via electrochemical exfoliation and explored their application as supercapacitor electrodes. By adjusting the content of the electrolyte in the exfoliation process, the aspect ratio of graphene sheets and the porosity of the graphene network can be optimized. Furthermore, the freezing temperature in the freeze drying step is also found to play a critical role in the resulting pore size distributions of the porous networks. The optimized conditions lead to meso- and macroporous graphene aerogels with a high specific surface area, extremely low densities and superior electrical properties. As a result, the graphene aerogel supercapacitors exhibit a specific capacitance of 325 F g(-1) at 1 A g(-1) and an energy density of 45 Wh kg(-1) in a 0.5 M H2SO4 aqueous electrolyte with high electrochemical stability and electrode uniformity required for practical usage. This research provides a practical method for lightweight, high-performance and low-cost materials in the effective use of energy storage systems.


Elucidating the Structural, Electronic, Elastic, and Optical Properties of Bulk and Monolayer MoS2 Transition-Metal Dichalcogenides: A DFT Approach.
Due to their outstanding properties for optoelectronic and versatile electronic applications, the atomically thin layers of transition-metal dichalcogenide (TMDC) materials have demonstrated a potential candidacy to succeed its analog silicon-based technology. Hence, the elucidation of the most important features of these materials is indispensable. In this study, we provide a theoretical elucidation of the structural, electronic, elastic, and optical characteristics of TMDCs. The study has been carried out by elucidating the material in its two particular forms, namely, bulk and two-dimensional (2D) layered (monolayer). The theoretical investigation was carried out within the framework of the density functional theory (DFT) method using first-principles calculations. The Perdew-Burke-Ernzerhof (PBE) variant of the generalized gradient approximation (GGA) scheme, as performed in the Quantum Espresso package, is used. Van der Waals density functional effects, involving the nonlocal correlation part from the rVV10 and vdW-DF2 methods, were treated to remedy the lack of the long-range vdW interaction. An illustration of the performance of both rVV10 and vdW-DF2 functionalities, with the popular PBE correlations, is elucidated. The Born stability criterion is employed to assess structural stability. The obtained results reveal an excellent stability of both systems. Furthermore, the theoretical results show that band-gap energy is in excellent agreement with experimental and theoretical data. Pugh's rule suggested that both the bulk and MoS2-2D layered systems are ductile materials. The refractive indices obtained herein are in good agreement with the available theoretical data. Moreover, the theoretical results obtained with the present approach demonstrate the ductility of both systems, namely, the bulk and the MoS2-2D layered. The results obtained herein hold promise for structural, elastic, and optical properties and pave the way for potential applications in electronic and optoelectronic devices.


Combined intra- and extraperitoneal urinary bladder rupture - a rare seat-belt injury: A case report.
While isolated traumatic urinary bladder injuries are rare, combined intra- and extraperitoneal traumatic urinary bladder ruptures without an underlying fracture are an absolute rarity. We report a case of combined intra- and extraperitoneal urinary bladder rupture without an underlying fracture resulting from blunt abdominal trauma during a high velocity car accident. A midline laparotomy was performed, and the intra- and extraperitoneal bladder ruptures were surgically treated. Based on the presented case the anatomical peculiarities of the urinary bladder and the different trauma mechanisms as well as the resulting lesions, the diagnostic modalities and the treatment options are discussed. Despite the rarity of traumatic urinary bladder injuries, and especially in the absence of an underlying fracture, physicians should maintain a high level of suspicion for urologic injuries in the presence of nonspecific lower abdominal pain, gross haematuria and the inability to urinate.


A quinoxaline based N-heteroacene interfacial layer for efficient hole-injection in quantum dot light-emitting diodes.
A series of N-heterocyclic quinoxaline derivatives was successfully synthesized and applied as hole transport layers in quantum dot light-emitting diodes (QLEDs). By inducing sp(2) N-atoms into the quinoxaline backbone, the electron affinity of the obtained material was enhanced, and its optical properties and bandgap became tunable. Quinoxaline based N-heteroacenes show a narrow bandgap, high thermal stability, and aligned film morphology. The resulting N-heteroacene polymer based QLED exhibits superior performance to poly(9-vinylcarbazole) based QLED. This study presents a strategy towards the design of novel N-rich molecules for the fabrication of QLEDs with improved performance.


Feasibility of e-Pain Reporter: A Digital Pain Management Tool for Informal Caregivers in Home Hospice.
Informal hospice caregivers often have difficulty managing patient pain at home. We developed a digital application, e-Pain Reporter, for informal caregivers to record and providers to monitor patient pain and pain management. The purpose of this study was (1) to assess the feasibility of informal caregivers using the e-Pain Reporter for 9 days in home hospice by investigating recruitment and retention and caregiver satisfaction with and frequency of use of the e-Pain Reporter and (2) describe patient pain characteristics and caregiver's barriers to pain management and self-efficacy in providing patient care in the home. One-group pre-post design was used. Patient-caregiver dyads were recruited from 1 hospice agency. Caregivers were asked to report all patient pain and pain management using the e-Pain Reporter. Feasibility of the e-Pain Reporter was assessed by the average number of times caregivers recorded breakthrough and daily pain and caregiver satisfaction with the app. The 27-item Barriers Questionnaire II and 21-item Caregiver Self-efficacy Scale were administered at baseline. Fourteen dyads enrolled, 2 patients died, and 12 dyads completed the study. Mean number of pain reports over 9 days was 10.5. Caregivers reported high overall satisfaction with the e-Pain Reporter. Barriers scores were moderately high, suggesting erroneous beliefs and misconceptions about pain reporting and use of analgesics, but self-efficacy in managing pain was also high (93% confidence). Findings suggest that the e-Pain Reporter is a feasible method to report and monitor caregiver management of pain at home. Caregiver high barriers and high overconfidence suggest the need for an educational component to the e-Pain Reporter to address misconceptions about pain and pain management.


The HEADS-ED: a rapid mental health screening tool for pediatric patients in the emergency department.
The American Academy of Pediatrics called for action for improved screening of mental health issues in the emergency department (ED). We developed the rapid screening tool home, education, activities/peers, drugs/alcohol, suicidality, emotions/behavior, discharge resources (HEADS-ED), which is a modification of "HEADS," a mnemonic widely used to obtain a psychosocial history in adolescents. The reliability and validity of the tool and its potential for use as a screening measure are presented. ED patients presenting with mental health concerns from March 1 to May 30, 2011 were included. Crisis intervention workers completed the HEADS-ED and the Child and Adolescent Needs and Strengths-Mental Health tool (CANS MH) and patients completed the Children's Depression Inventory (CDI). Interrater reliability was assessed by using a second HEADS-ED rater for 20% of the sample. A total of 313 patients were included, mean age was 14.3 (SD 2.63), and there were 182 females (58.1%). Interrater reliability was 0.785 (P < .001). Correlations were computed for each HEADS-ED category and items from the CANS MH and the CDI. Correlations ranged from r = 0.17, P < .05 to r = 0.89, P < .000. The HEADS-ED also predicted psychiatric consult and admission to inpatient psychiatry (sensitivity of 82% and a specificity of 87%; area under the receiver operator characteristic curve of 0.82, P < .01). The results provide evidence to support the psychometric properties of the HEADS-ED. The study shows promising results for use in ED decision-making for pediatric patients with mental health concerns.


Self-Assembled Hierarchical Formation of Conjugated 3D Cobalt Oxide Nanobead-CNT-Graphene Nanostructure Using Microwaves for High-Performance Supercapacitor Electrode.
Here we report the electrochemical performance of a interesting three-dimensional (3D) structures comprised of zero-dimensional (0D) cobalt oxide nanobeads, one-dimensional (1D) carbon nanotubes and two-dimensional (2D) graphene, stacked hierarchically. We have synthesized 3D self-assembled hierarchical nanostructure comprised of cobalt oxide nanobeads (Co-nb), carbon nanotubes (CNTs), and graphene nanosheets (GNSs) for high-performance supercapacitor electrode application. This 3D self-assembled hierarchical nanostructure Co3O4 nanobeads-CNTs-GNSs (3D:Co-nb@CG) is grown at a large scale (gram) through simple, facile, and ultrafast microwave irradiation (MWI). In 3D:Co-nb@CG nanostructure, Co3O4 nanobeads are attached to the CNT surfaces grown on GNSs. Our ultrafast, one-step approach not only renders simultaneous growth of cobalt oxide and CNTs on graphene nanosheets but also institutes the intrinsic dispersion of carbon nanotubes and cobalt oxide within a highly conductive scaffold. The 3D:Co-nb@CG electrode shows better electrochemical performance with a maximum specific capacitance of 600 F/g at the charge/discharge current density of 0.7A/g in KOH electrolyte, which is 1.56 times higher than that of Co3O4-decorated graphene (Co-np@G) nanostructure. This electrode also shows a long cyclic life, excellent rate capability, and high specific capacitance. It also shows high stability after few cycles (550 cycles) and exhibits high capacitance retention behavior. It was observed that the supercapacitor retained 94.5% of its initial capacitance even after 5000 cycles, indicating its excellent cyclic stability. The synergistic effect of the 3D:Co-nb@CG appears to contribute to the enhanced electrochemical performances.


Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies: a proof of concept study.
There are no suitable screening modalities for ovarian carcinomas (OC) and repeated imaging and CA-125 levels are often needed to triage equivocal ovarian masses. Definitive diagnosis of malignancy, however, can only be established by histologic confirmation. Thus, the ability to detect OC at early stages is low, and most cases are diagnosed as advanced disease. Since tumor cells expose phosphatidylserine (PS) on their plasma membrane, we predicted that tumors might secrete PS-positive exosomes into the bloodstream that could be a surrogate biomarker for cancer. To address this, we developed a highly stringent ELISA that detects picogram quantities of PS in patient plasma. Blinded plasma from 34 suspect ovarian cancer patients and 10 healthy subjects were analyzed for the presence of PS-expressing vesicles. The nonparametric Wilcoxon rank sum test showed the malignant group had significantly higher PS values than the benign group (median 0.237 vs. -0.027, p=0.0001) and the malignant and benign groups had significantly higher PS values than the healthy group (median 0.237 vs -0.158, p<0.0001 and -0.027 vs -0.158, p=0.0002, respectively). ROC analysis of the predictive accuracy of PS-expressing exosomes/vesicles in predicting malignant against normal, benign against normal and malignant against benign revealed AUCs of 1.0, 0.95 and 0.911, respectively. This study provides proof-of-concept data that supports the high diagnostic power of PS detection in the blood of women with suspect ovarian malignancies.


Engineered nanoparticles interact with nutrients to intensify eutrophication in a wetland ecosystem experiment.
Despite the rapid rise in diversity and quantities of engineered nanomaterials produced, the impacts of these emerging contaminants on the structure and function of ecosystems have received little attention from ecologists. Moreover, little is known about how manufactured nanomaterials may interact with nutrient pollution in altering ecosystem productivity, despite the recognition that eutrophication is the primary water quality issue in freshwater ecosystems worldwide. In this study, we asked two main questions: (1) To what extent do manufactured nanoparticles affect the biomass and productivity of primary producers in wetland ecosystems? (2) How are these impacts mediated by nutrient pollution? To address these questions, we examined the impacts of a citrate-coated gold nanoparticle (AuNPs) and of a commercial pesticide containing Cu(OH)2 nanoparticles (CuNPs) on aquatic primary producers under both ambient and enriched nutrient conditions. Wetland mesocosms were exposed repeatedly with low concentrations of nanoparticles and nutrients over the course of a 9-month experiment in an effort to replicate realistic field exposure scenarios. In the absence of nutrient enrichment, there were no persistent effects of AuNPs or CuNPs on primary producers or ecosystem productivity. However, when combined with nutrient enrichment, both NPs intensified eutrophication. When either of these NPs were added in combination with nutrients, algal blooms persisted for >50 d longer than in the nutrient-only treatment. In the AuNP treatment, this shift from clear waters to turbid waters led to large declines in both macrophyte growth and rates of ecosystem gross primary productivity (average reduction of 52% ± 6% and 92% ± 5%, respectively) during the summer. Our results suggest that nutrient status greatly influences the ecosystem-scale impact of two emerging contaminants and that synthetic chemicals may be playing an under-appreciated role in the global trends of increasing eutrophication. We provide evidence here that chronic exposure to Au and Cu(OH)2 nanoparticles at low concentrations can intensify eutrophication of wetlands and promote the occurrence of algal blooms.


The antibacterial efficacy of trovafloxacin against an experimental infection with Listeria monocytogenes in hydrocortisone-treated mice.
The efficacy of trovafloxacin in treating Listeria monocytogenes infections in glucocorticosteroid-treated mice was compared with the efficacy of amoxycillin. Swiss mice were treated with daily injections of 2.5 mg hydrocortisone s.c. and then infected i.v. with 1 x 10(7) cfu of L. monocytogenes. Untreated, this level of infection resulted in 100% mortality between day 3 and day 5 after infection. Both s.c. trovafloxacin and amoxycillin were effective in reducing the number of viable L. monocytogenes in the liver and spleen. Although the MIC of amoxycillin for this isolate of L. monocytogenes was lower than that of trovafloxacin (0.063 mg/L versus 0.5 mg/L, respectively), trovafloxacin was more efficacious in vivo after a single dose in the dose range between 12.5 and 100 mg/kg than was amoxycillin. After treatment with trovafloxacin at 100 mg/kg bodyweight od for 3 days, a mean log10 cfu of 1.58 and 2.52 L. monocytogenes could be recovered from the spleens and livers, respectively, whereas after treatment with amoxycillin at 100 mg/kg bodyweight every 8 h for 3 days, the mean 1og10 cfu values were 2.36 and 2.02, respectively. These differences were statistically not significant. Results of the present study show that the antibacterial efficacy of trovafloxacin against L. monocytogenes in our animal model is equivalent to that of amoxycillin.


Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome.
The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on human DNMT1. Functional studies in human and mouse cells further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that preferentially occurs at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.


Morphometric evaluation of oesophageal wall in patients with nutcracker oesophagus and ineffective oesophageal motility.
The pathogenesis of nutcracker oesophagus (NE) and ineffective oesophageal motility (IEM) is unclear. Damage to the enteric nervous system or smooth muscle can cause oesophageal dysmotility. We tested the hypothesis that NE and IEM are associated with abnormal muscular or neural constituents of the oesophageal wall. Oesophageal manometry was performed in patients prior to total gastrectomy for gastric cancer. The oesophageal manometries were categorized as normal (n = 7), NE (n = 13), or IEM (n = 5). Histologic examination of oesophageal tissue obtained during surgery was performed after haematoxylin and eosin (H&E) and trichrome staining. Oesophageal innervation was examined after immunostaining for protein gene product-9.5 (PGP-9.5), choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS). There were no significant differences in inner circular smooth muscle thickness or degree of fibrosis among the three groups. Severe muscle fibre loss was found in four of five patients with IEM. The density of PGP-9.5-reactive neural structures was not different among the three groups. The density of ChAT immunostaining in the myenteric plexus (MP) was significantly greater in patients with NE (P < 0.05) and the density of nNOS immunostaining in the circular muscle (CM) was significantly greater in IEM patients (P < 0.05). The ChAT/nNOS ratio in both MP and CM was significantly greater in NE patients. NE may result from an imbalance between the excitatory and inhibitory innervation of the oesophagus, because more than normal numbers of ChAT-positive myenteric neurones are seen in NE. Myopathy and/or increased number of nNOS neurones may contribute to the hypocontractile motor activity of IEM.


Optical absorption signature of a self-assembled dye monolayer on graphene.
A well-organized monolayer of alkylated perylene-3,4,9,10-tetracarboxylic-3,4,9,10-diimide (PTCDI) has been formed onto CVD graphene transferred on a transparent substrate. Its structure has been probed by scanning tunnelling microscopy and its optical properties by polarized transmission spectroscopy at varying incidence. The results show that the transition dipoles of adsorbed PTCDI are all oriented parallel to the substrate. The maximum absorption is consistent with the measured surface density of molecules and their absorption cross section. The spectrum presents mainly a large red-shift of the absorption line compared with the free molecules dispersed in solution, whereas the relative strengths of the vibronic structures are preserved. These changes are attributed to non-resonant interactions with the graphene layer and the neighbouring molecules.


Enhanced proliferation of fibroblasts and endothelial cells treated with an extract of the leaves of Chromolaena odorata (Eupolin), an herbal remedy for treating wounds.
Burns are a major problem in many developing countries. Eupolin ointment is a topical agent used in the treatment of soft-tissue wounds and burns in Vietnam and is made from an aqueous extract of the leaves of Chromolaena odorata (formerly Eupatorium odoratum). Clinical studies using this extract have shown antimicrobial and anticoagulation effects as well as the promotion of tissue remodeling in the wound healing process. However, the mechanism by which this agent affects cells involved in the wound healing process is unknown. In our research, fibroblasts and endothelial cells, two cell types that play a crucial role in wound healing, were used to investigate some of the effects of Eupolin extract in vitro. Cell growth was estimated by a colorimetric assay at different time intervals. Enhanced growth of fibroblasts and endothelial cells was found at concentrations of 10 microg/ml and 100 microg/ml of Eupolin extract. This was particularly evident in medium supplemented with only 0.5% fetal calf serum where the cells were quiescent. Toxicity of the extract to fibroblasts was observed at 250 microg/ml in Dulbecco's modified Eagle's medium/0.5% fetal calf serum, but there was no significant damage at this dose to the endothelial cells. The results of the study demonstrated that Eupolin extract increased fibroblast and endothelial cell growth, and this could explain in part the beneficial clinical effects that have been observed.


The incidence of gross proteinuria in people with insulin-dependent diabetes mellitus.
Epidemiologic data on the incidence of gross proteinuria in people with diabetes are important in medical counseling, in projecting estimates of needs and costs of health care, and for developing approaches to prevent renal complications. We performed a population-based incidence study in southern Wisconsin of insulin-taking diabetic persons diagnosed before 30 years of age. The presence of gross proteinuria (greater than or equal to 0.30 g/L) was determined by means of a reagent strip. The incidence of proteinuria in a 4-year interval was 14.4% (95% confidence interval, 11.7% to 17.0%). The relative risk of developing proteinuria after 4 years for those with glycosylated hemoglobin levels in the highest quartile compared with those in the lowest quartile was 3.0 (95% confidence interval, 1.6 to 5.3). The incidence of proteinuria was also associated with higher diastolic blood pressure, being male, taking more insulin, and having more severe retinopathy at the baseline examination. The relationship between glycosylated hemoglobin level and the incidence of proteinuria was significant even after controlling for these other risk variables. These data suggest that hyperglycemia, as measured by glycosylated hemoglobin level, is a significant risk factor for the development of gross proteinuria.


[Therapy of patients with chronic pancreatitis of alcoholic etiology by dalagrin and laser therapy of the blood].
Effectiveness of dalargin and intravenous laser blood beaming (ILBB) in combined treatment of chronic alcoholic pancreatitis (CAP) was studied in 105 patients (8 females and 97 males) with CAP duration 1 to 25 years. Pancreatic function and treatment effects were studied by routine clinical investigations, advanced laboratory, biochemical tests, radioimmunossays. Pancreatic disorders in alcoholics present with high blood levels of trypsin and lipase, low levels of insulin and C-peptide. Serum concentrations of hydrocortisone and gastrin were elevated. Combined treatment of CAP with adjuvant dalargin and ILBB not only relieves clinical symptoms but also promotes normalization of pancreatic function.


Thyroid cancers amongst goiter population in a Nigerian tertiary hospital: surgical and radiographic perspective.
Goiters are commonly benign, but cases of malignancy can develop. Thyroid cancer is known to be commoner in whites than in blacks and in females than in males. Bone metastasis is a common occurrence and may be the initial manifestation in a small subset. We hope to determine the incidence and the cervical radiographic patterns of thyroid cancer amongst goiter population in Nigeria. Surgical, histological and radiographic findings in patients with goiter who had thyroidectomy in our hospital from 1999 to 2006 were reviewed. Those with proven cancer were analyzed for sex, age and radiographic changes using SPSS 11.0 for windows. Thirteen (8.2%) cases out of the 160 goiters were malignant and distant metastases were present in 1.3% at presentation. The histological sub-types of malignant goiters were follicular (5.0%), papillary (1.9%) and poorly differentiated or anaplastic thyroid carcinoma (1.3%). As much as 30% of thyroid cancers demonstrated calcification on plain neck radiograph, which were commonly scattered or diffused. Carcinomatous goiters occurred in 9.3% of the goiter population studied with predominance of follicular variant. Surgery remains the main stay but was inappropriate in about 1.2% of population with goitre. Aside evidence of bony destruction, TC should be suspected in goiters with mixed (diffused or scattered) calcifications.


Early lactate and glucose kinetics following return to spontaneous circulation after out-of-hospital cardiac arrest.
Lactate has been shown to be preferentially metabolized in comparison to glucose after physiological stress, such as strenuous exercise. Derangements of lactate and glucose are common after out-of-hospital cardiac arrest (OHCA). Therefore, we hypothesized that lactate decreases faster than glucose after return-to-spontaneous-circulation (ROSC) after OHCA. We included 155 OHCA patients in our analysis. Within the first 8 h of presentation to the emergency department, 843 lactates and 1019 glucoses were available, respectively. Lactate decreased to 50% of its initial value within 1.5 h (95% CI [0.2-3.6 h]), while glucose halved within 5.6 h (95% CI [5.4-5.7 h]). Also, in the first 8 h after presentation lactate decreases more than glucose in relation to their initial values (lactate 72.6% vs glucose 52.1%). In patients with marked hyperlactatemia after OHCA, lactate decreased expediently while glucose recovered more slowly, whereas arterial pH recovered at a similar rapid rate as lactate. Hospital non-survivors (N = 82) had a slower recovery of lactate (P = 0.002) than survivors (N = 82). The preferential clearance of lactate underscores its role as a prime energy substrate, when available, during recovery from extreme stress.


Hybrid retinal imager using line-scanning laser ophthalmoscopy and spectral domain optical coherence tomography.
We demonstrate for the first time the integration of two technologies, Spectral Domain Optical Coherence Tomography (SDOCT) and Line-Scanning Laser Ophthalmoscopy (LSLO) into a single compact instrument that shares the same imaging optics and line scan camera for both OCT and LSLO imaging. Co-registered high contrast wide-field en face retinal LSLO and SDOCT images are obtained non-mydriatically with less than 600 microwatts of broadband illumination at 15 frames/sec. The LSLO/SDOCT hybrid instrument could have important applications in clinical ophthalmic diagnostics and emergency medicine.


Inoculation of blood culture bottles with ascitic fluid. Improved detection of spontaneous bacterial peritonitis.
The observation that only 42% of the cases of suspected spontaneous bacterial peritonitis at the University of New Mexico, Albuquerque, had positive cultures prompted a change in ascitic fluid culture technique such that a large volume (10 mL in toto) of ascitic fluid was inoculated into blood culture bottles at the bedside. This new method of culture increased the percentage of cases with positive cultures to 91% and decreased the interval between inoculation of the culture and detection of bacterial growth. This is a more sensitive method of culture than the conventional method in detecting spontaneous bacterial peritonitis.


Technical note: simultaneous identification of CSN1S2 A, B, C, and E alleles in goats by polymerase chain reaction-single strand conformation polymorphism.
Most variability in goat caseins originates from the high number of genetic polymorphisms often affecting the specific protein expression, with strong effects on milk composition traits and technological properties. At least 7 alleles have been found in the goat alpha(S2)-CN gene (CSN1S2). Five of them (CSN1S2*A, CSN1S2*B, CSN1S2*C, CSN1S2*E, and CSN1S2*F) are widespread in most breeds, whereas the other 2 (CSN1S2*D and CSN1S2*0) are rarer alleles. Four different PCR-RFLP tests are needed to detect all of these variants at the DNA level. The objective of this study was to develop and validate a rapid method for typing 4 of the 5 most-common goat CSN1S2 alleles by means of PCR-single strand conformation polymorphism (SSCP). The method was validated by analyzing 37 goat samples at the protein and DNA level, respectively, by milk isoelectrofocusing and PCR-RFLP methods already described. The genotypes obtained using the PCR-SSCP approach were in full agreement with those obtained by the validation analyses. The newly developed PCR-SSCP approach provides an accurate and inexpensive assay highly suitable for genotyping goat CSN1S2.


Long-term effects of meloxicam in the treatment of respiratory disease in fattening cattle.
The long-term effects of a single dose of meloxicam (Metacam 20 mg/ml; Boehringer Ingelheim Vetmedica) in conjunction with antibiotic therapy in cattle with clinical signs of bovine respiratory disease (BRD) was evaluated in a blind, controlled, randomised study. Two hundred animals with clinical signs of brd received a single subcutaneous injection of 20 mg/kg oxytetracycline; 100 of them also received a subcutaneous injection of 0.5 mg/kg meloxicam, and the other 100 received an injection of isotonic saline. The animals were weighed before they were treated and seven, 35, 70 and 105 days later, and finally before they were slaughtered. The mean bodyweight of the meloxicam-treated animals was significantly higher from day 70 until slaughter, and the mean average daily weight gain until slaughter and the mean carcase weight of the animals treated with meloxicam were significantly higher. In the animals with lung lesions, significantly less lung tissue was affected in those that had been treated with meloxicam.