Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

SLC37A1 and SLC37A2 Are Phosphate-Linked, Glucose-6-Phosphate Antiporters

Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (Pi). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a Pi-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis

Attitudes towards chiropractic: an analysis of written comments from a survey of north american orthopaedic surgeons

<p>Abstract</p> <p>Background</p> <p>There is increasing interest by chiropractors in North America regarding integration into mainstream healthcare; however, there is limited information about attitudes towards the profession among conventional healthcare providers, including orthopaedic surgeons.</p> <p>Methods</p> <p>We administered a 43-item cross-sectional survey to 1000 Canadian and American orthopaedic surgeons that inquired about demographic variables and their attitudes towards chiropractic. Our survey included an option for respondants to include written comments, and our present analysis is restricted to these comments. Two reviewers, independantly and in duplicate, coded all written comments using thematic analysis.</p> <p>Results</p> <p>487 surgeons completed the survey (response rate 49%), and 174 provided written comments. Our analysis revealed 8 themes and 24 sub-themes represented in surgeons' comments. Reported themes were: variability amongst chiropractors (n = 55); concerns with chiropractic treatment (n = 54); areas where chiropractic is perceived as effective (n = 43); unethical behavior (n = 43); patient interaction (n = 36); the scientific basis of chiropractic (n = 26); personal experiences with chiropractic (n = 21); and chiropractic training (n = 18). Common sub-themes endorsed by surgeon's were diversity within the chiropractic profession as a barrier to increased interprofessional collaboration, endorsement for chiropractic treatment of musculoskeletal complaints, criticism for treatment of non-musculoskeletal complaints, and concern over whether chiropractic care was evidence-based.</p> <p>Conclusions</p> <p>Our analysis identified a number of issues that will have to be considered by the chiropractic profession as part of its efforts to further integrate chiropractic into mainstream healthcare.</p

Low-value care practice in headache: a Spanish mixed methods research study

Background Headache is one of the most prevalent diseases. The Global Burden of Disease Study ranks it as the seventh most common disease overall and the second largest neurological cause of disability in the world. The "Do Not Do" recommendations are a strategy for increasing the quality of care and reducing the cost of care for headache. This study aimed to identify specific low-value practices in headache care, determine their frequency, and estimate the cost overrun that they represent, in order to establish "Do not Do" recommendations specifically for headache by consensus and according to scientific evidence. Methods This was a mixed methods research study that combined qualitative consensus-building techniques, involving a multidisciplinary panel of experts to define the "Do Not Do" recommendations in headache care, and a retrospective observational study with review of a randomized set of patient records from the past 6 months in four hospitals, to quantify the frequency of these "Do Not Do" practices. We calculated the sum of direct costs of medical consultations, medicines, and unnecessary diagnostic tests. Results Seven "Do Not Do" recommendations were established for headache. In total, 3507 medical records were randomly reviewed. Low-value practices had a highly variable occurrence, depending on the hospital and type of headache. Overall, 34.1% of low-value practices were related to treatment, 21% were related to overuse of imaging in consultation, and 19% were related to emergency care. The estimated cost of low-value practices in the four hospitals was 203,520.47 euros per 1000 patients. Conclusions This study identified low-value headache practices that need to be eradicated and provided data on their frequency and cost overruns

Acinic cell carcinoma in pregnancy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>We report an observational study on the etiology and recurrence of acinic cell carcinoma of the parotid gland that seemed to be related to pregnancy. The medical literature has never reported such an association; therefore, our case report is probably the first to mention this observation.</p> <p>Case presentation</p> <p>This report is of a 25-year-old Arabic female patient from the United Arab Emirates, who, during her first pregnancy, developed acinic cell carcinoma of the right parotid gland that was managed with surgical excision in the form of superficial parotidectomy. During her second pregnancy, which occurred four years later, she had a recurrence of the same malignant neoplasm associated with ipsilateral malignant cervical lymphadenopathy. The patient was managed with total parotidectomy and neck dissection, as well as postoperative adjuvant radiotherapy. Our observation on this particular case of acinic cell carcinoma is that the initial onset of her neoplasm was during her first pregnancy, and the recurrence of the same malignant disease was during a subsequent pregnancy. This chronologic association raised our suspicion that there might be a possible etiologic effect of pregnancy or its associated hormonal or physiologic changes or both on the pathogenesis or etiology of acinic cell carcinoma.</p> <p>Conclusion</p> <p>Some association might exist between pregnancy and the pathogenesis or etiology of acinic cell carcinoma.</p

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Illegal Substance Use among Italian High School Students: Trends over 11 Years (1999–2009)

Purpose: To monitor changes in habits in drug use among Italian high school students. Methods: Cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) carried out in Italy annually for 11 years (1999-2009) with representative samples of youth attending high school. The sample size considered ranges from 15,752 to 41,365 students and response rate ranged from 85.5% to 98.6%. Data were analyzed to obtain measures of life-time prevalence (LT), use in the last year (LY), use in the last 30 days (LM), frequent use. Comparisons utilized difference in proportion tests. Tests for linear trends in proportion were performed using the Royston p trend test. Results: When the time-averaged value was considered, cannabis (30% LT) was the most, and heroin the least (2%) frequently used, with cocaine (5%), hallucinogens (2%) and stimulants (2%) in between. A clear gender gap is evident for all drugs, more obvious for hallucinogens (average M/F LY prevalence ratio 2, range 1.7-2.4, p,0.05), less for cannabis (average M/F LY prevalence ratio 1.3, range 1.2-1.5, p,0.05). Data shows a change in trend between 2005 and 2008; in 2006 the trend for cannabis use and availability dropped and the price rose, while from 2005 cocaine and stimulant use prevalence showed a substantial increase and the price went down. After 2008 use of all substances seems to have decreased. Conclusions: Drug use is widespread among students in Italy, with cannabis being the most and heroin the least prevalent. Girls are less vulnerable than boys to illegal drug use. In recent years, a decrease in heroin use is overbalanced by a marked rise in hallucinogen and stimulant use.-