What distinguishes clinicians who better support patients for chronic disease self-management?
Many frequent readmissions due to acute exacerbations of chronic disease could be prevented if patients self-managed. This study explored factors involved in patient activation for chronic disease self-management by qualitative analysis of interview data from hospital and community-based clinicians and patients. All clinicians reported that many frequently readmitted patients did not readily take up referral to chronic disease self-management services. This reluctance was compounded by system or access barriers. Clinicians who had a defined role in chronic disease management and patient-centred and behaviour change skills reported that although some patients were more resistant than others, patients could be persuaded to adopt self-management behaviours. Hospital clinicians and GPs were more inclined to attribute blame to clinical, social and personal patient factors, such as difficulty with support at home, social circumstances and reluctance to take responsibility. Investment in extending the skills and role of hospital clinicians and GPs to take a more supportive role in patient uptake of referrals to chronic disease self-management services would reduce hospital readmissions. Improvements in access to chronic disease self-management and GP services are also needed to address failure to take up chronic disease self-management.


New Molecular Insights of Insulin in Diabetic Cardiomyopathy.
Type 2 diabetes mellitus (T2DM) is a highly prevalent disease worldwide. Cardiovascular disorders generated as a consequence of T2DM are a major cause of death related to this disease. Diabetic cardiomyopathy (DCM) is characterized by the morphological, functional and metabolic changes in the heart produced as a complication of T2DM. This cardiac disorder is characterized by constant high blood glucose and lipids levels which eventually generate oxidative stress, defective calcium handling, altered mitochondrial function, inflammation and fibrosis. In this context, insulin is of paramount importance for cardiac contractility, growth and metabolism and therefore, an impaired insulin signaling plays a critical role in the DCM development. However, the exact pathophysiological mechanisms leading to DCM are still a matter of study. Despite the numerous questions raised in the study of DCM, there have also been important findings, such as the role of micro-RNAs (miRNAs), which can not only have the potential of being important biomarkers, but also therapeutic targets. Furthermore, exosomes also arise as an interesting variable to consider, since they represent an important inter-cellular communication mechanism and therefore, they may explain many aspects of the pathophysiology of DCM and their study may lead to the development of therapeutic agents capable of improving insulin signaling. In addition, adenosine and adenosine receptors (ARs) may also play an important role in DCM. Moreover, the possible cross-talk between insulin and ARs may provide new strategies to reverse its defective signaling in the diabetic heart. This review focuses on DCM, the role of insulin in this pathology and the discussion of new molecular insights which may help to understand its underlying mechanisms and generate possible new therapeutic strategies.


Refined structure of baboon alpha-lactalbumin at 1.7 A resolution. Comparison with C-type lysozyme.
The solution of the structure of alpha-lactalbumin from baboon milk (Papio cynocephalus) at 4.5 A resolution using the isomorphous replacement method has been reported previously. Initial refinement on the basis of these low-resolution studies was not successful because of the poor isomorphism of the best heavy-atom derivative. Because of the striking similarity between the structure of lysozyme and alpha-lactalbumin, a more cautious molecular replacement approach was tried to refine the model. Using hen egg-white lysozyme as the starting model, preliminary refinement was performed using heavily constrained least-squares minimization in reciprocal space. The model was further refined using stereochemical restraints at 1.7 A resolution to a conventional crystallographic residual of 0.22 for 1141 protein atoms. In the final model, the root-mean-square deviation from ideality for bond distances is 0.015 A, and for angle distances it is 0.027 A. The refinement was carried out using the human alpha-lactalbumin sequence and "omit maps" calculated during the course of refinement indicated eight possible sequence changes in the baboon alpha-lactalbumin X-ray sequence. During the refinement, a tightly bound calcium ion and 150 water molecules, of which four are internal, have been located. Some of the water molecules were modelled for disordered side-chains. The co-ordination around the calcium is a slightly distorted pentagonal bipyramid. The Ca-O distances vary from 2.2 A to 2.6 A, representing a tight calcium-binding loop in the structure. The calcium-binding fold only superficially resembles the "EF-hand" and presumably has no evolutionary relationship with other EF-hand structures. The overall structure of alpha-lactalbumin is very similar to that of lysozyme. All large deviations occur in the loops where all sequence deletions and insertions are found. The C terminus appears to be rather flexible in alpha-lactalbumin compared to lysozyme. The experimental evidence supports the earlier predictions for the alpha-lactalbumin structure that were based upon the assumption that alpha-lactalbumin and lysozyme have similar three-dimensional structures, with minimal deletions and insertions. A detailed comparison of the two structures shows striking features as well as throwing some light on the evolution of these two proteins from a common precursor.


Linking climate change projections for an Alaskan watershed to future coho salmon production.
Climate change is predicted to dramatically change hydrologic processes across Alaska, but estimates of how these impacts will influence specific watersheds and aquatic species are lacking. Here, we linked climate, hydrology, and habitat models within a coho salmon (Oncorhynchus kisutch) population model to assess how projected climate change could affect survival at each freshwater life stage and, in turn, production of coho salmon smolts in three subwatersheds of the Chuitna (Chuit) River watershed, Alaska. Based on future climate scenarios and projections from a three-dimensional hydrology model, we simulated coho smolt production over a 20-year span at the end of the century (2080-2100). The direction (i.e., positive vs. negative) and magnitude of changes in smolt production varied substantially by climate scenario and subwatershed. Projected smolt production decreased in all three subwatersheds under the minimum air temperature and maximum precipitation scenario due to elevated peak flows and a resulting 98% reduction in egg-to-fry survival. In contrast, the maximum air temperature and minimum precipitation scenario led to an increase in smolt production in all three subwatersheds through an increase in fry survival. Other climate change scenarios led to mixed responses, with projected smolt production increasing and decreasing in different subwatersheds. Our analysis highlights the complexity inherent in predicting climate-change-related impacts to salmon populations and demonstrates that population effects may depend on interactions between the relative magnitude of hydrologic and thermal changes and their interactions with features of the local habitat.


Availability of tanning beds on US college campuses.
Indoor tanning is widespread among young adults in the United States despite evidence establishing it as a risk factor for skin cancer. The availability of tanning salons on or near college campuses has not been formally evaluated. To evaluate the availability of indoor tanning facilities on US college and university campuses (colleges) and in off-campus housing surrounding but not owned by the college. This observational study sampled the top 125 US colleges and universities listed in US News and World Report. Investigators searched websites of the colleges and nearby housing and contacted them by telephone inquiring about tanning services. Frequency of indoor tanning facilities on college campus and in off-campus housing facilities, as well as payment options for tanning. Of the 125 colleges, 48.0% had indoor tanning facilities either on campus or in off-campus housing, and 14.4% of colleges allow campus cash cards to be used to pay for tanning. Indoor tanning was available on campus in 12.0% of colleges and in off-campus housing in 42.4% of colleges. Most off-campus housing facilities with indoor tanning (96%) provide it free to tenants. Midwestern colleges had the highest prevalence of indoor tanning on campus (26.9%), whereas Southern colleges had the highest prevalence of indoor tanning in off-campus housing facilities (67.7%). Presence of on-campus tanning facilities was significantly associated with enrollment (P = .01), region (P = .02), and presence of a school of public health (P = .01) but not private vs public status (P = .18) or presence of a tobacco policy (P = .16). Presence of tanning facilities in off-campus housing was significantly associated with region (P = .002) and private vs public status (P = .01) but not enrollment (P = .38), tobacco policy (P = .80), or presence of a school of public health (P = .69). Reducing the availability of indoor tanning on and around college campuses is an important public health target.


Cue-dependent interference in comprehension.
The role of interference as a primary determinant of forgetting in memory has long been accepted, however its role as a contributor to poor comprehension is just beginning to be understood. The current paper reports two studies, in which speed-accuracy tradeoff and eye-tracking methodologies were used with the same materials to provide converging evidence for the role of syntactic and semantic cues as mediators of both proactive (PI) and retroactive interference (RI) during comprehension. Consistent with previous work (e.g., Van Dyke & Lewis, 2003), we found that syntactic constraints at the retrieval site are among the cues that drive retrieval in comprehension, and that these constraints effectively limit interference from potential distractors with semantic/pragmatic properties in common with the target constituent. The data are discussed in terms of a cue-overload account, in which interference both arises from and is mediated through a direct-access retrieval mechanism that utilizes a linear, weighted cue-combinatoric scheme.


Endovascular recanalization of total occlusions of the mesenteric and celiac arteries.
To evaluate our experience with the endovascular treatment of total occlusions of the mesenteric and celiac arteries. We performed a retrospective review of endovascular stenting of 27 nonembolic total occlusions of the superior mesenteric artery (SMA) and celiac artery (CA) between July 2004 and July 2011 (26 patients, 16 females; mean age, 62 ± 13 years). A variety of demographic, lesion-related and procedure-related variables were evaluated for potential impact of technical success and patency. The follow-up protocol included clinical assessment, and color and spectral Doppler evaluation of the stented vessel(s). The clinical presentation was chronic mesenteric ischemia in 12 patients, acute mesenteric vascular syndromes in 10 patients, foregut ischemia/ischemic pancreatitis in three patients, and prior to endovascular repair of aortic aneurysm in one patient. The treated vessel was SMA in 22 procedures, CA in three, and both SMA and CA in one. Technical success was achieved in 23 of the 27 attempted recanalizations (85%). Three patients who failed the attempt underwent open bypass, and another one underwent retrograde recanalization and stenting of the SMA. Procedure success was only significantly related to patient age <70 years or procedure performance after the year 2006. Notably, the presence of a stump, ostial plaque, extensive vascular calcification, recanalization route (intraluminal vs subintimal), occlusion length, and vessel diameter had no significant impact on procedure success. Traditional duplex criteria proved unreliable in predicting restenosis. Life table analysis of freedom from symptom recurrence showed a primary and assisted rates of 58% and 80% at 1 year, and 33% and 60% at 2 years, respectively. Clinical recurrences developed in six patients (four presented with abdominal angina and weight loss, two presented with abdominal catastrophe). There were six access-related complications and no procedural deaths. Four delayed deaths occurred during follow-up (two cardiac causes, two due to abdominal sepsis). Endovascular recanalization of mesenteric artery occlusion is both feasible and successful, provided careful planning is used.


Botulinum Toxin Confers Radioprotection in Murine Salivary Glands.
Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of xerostomia in patients with head and neck cancer.


The intelligence paradox; will ET get the metabolic syndrome? Lessons from and for Earth.
Mankind is facing an unprecedented health challenge in the current pandemic of obesity and diabetes. We propose that this is the inevitable (and predictable) consequence of the evolution of intelligence, which itself could be an expression of life being an information system driven by entropy. Because of its ability to make life more adaptable and robust, intelligence evolved as an efficient adaptive response to the stresses arising from an ever-changing environment. These adaptive responses are encapsulated by the epiphenomena of "hormesis", a phenomenon we believe to be central to the evolution of intelligence and essential for the maintenance of optimal physiological function and health. Thus, as intelligence evolved, it would eventually reach a cognitive level with the ability to control its environment through technology and have the ability remove all stressors. In effect, it would act to remove the very hormetic factors that had driven its evolution. Mankind may have reached this point, creating an environmental utopia that has reduced the very stimuli necessary for optimal health and the evolution of intelligence - "the intelligence paradox". One of the hallmarks of this paradox is of course the rising incidence in obesity, diabetes and the metabolic syndrome. This leads to the conclusion that wherever life evolves, here on earth or in another part of the galaxy, the "intelligence paradox" would be the inevitable side-effect of the evolution of intelligence. ET may not need to just "phone home" but may also need to "phone the local gym". This suggests another possible reason to explain Fermi's paradox; Enrico Fermi, the famous physicist, suggested in the 1950s that if extra-terrestrial intelligence was so prevalent, which was a common belief at the time, then where was it? Our suggestion is that if advanced life has got going elsewhere in our galaxy, it can't afford to explore the galaxy because it has to pay its healthcare costs.


A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression.
The high heritability of plasma renin activity was confirmed in recent investigations. A variation located near the strong enhancer of the human renin gene (REN), C-5312T, has been shown to have different transcription activity levels depending on its allele: the 5312T allele shows transcription levels that are 45% greater than those of the 5312C allele. The purpose of this study was to confirm the hypothesis that variations in the enhancer region of the REN gene are involved in regulating renal expression of renin. Sixty-four subjects with biopsy-proven renal diseases were included in this study (male/female: 35/29, age 41.9 ± 20.9 years, SBP/DBP 123.1 ± 23.7/73.4 ± 14.8 mmHg, s-Cr 0.93 ± 0.63 mg/dl). A genetic variant of REN, C-5312T, was assayed by PCR-RFLP and the TaqMan method. Total RNAs from a small part of the renal cortex were reverse-transcribed and amplified for REN and GAPDH with a real-time PCR system. Logarithmically transformed expression values of the relative ratio of REN to GAPDH (10-3) were as follows (mean ± SE): CC (26 cases), 0.016 ± 0.005; CT (33 cases), 0.047 ± 0.021 (p = 0.41 vs. CC); TT (5 cases), 0.198 ± 0.194 (p = 0.011 vs. CC, p < 0.031 vs. CT). Thus, significant differences in REN expression were observed among the genetic variants. The results suggest that variants in the enhancer region of the human renin gene have an effect on the expression levels of renin in renal tissue; this observation is in good accordance with the results of the transcriptional assay.


Transplantation of photoreceptors labeled with tritiated thymidine into RCS rats.
Tritiated thymidine was administered to newborn rats to label photoreceptors, about 50% of which are still dividing. These photoreceptors were enzymatically dissociated and separated from the remainder of the retina after the infant rat matured. These labeled photoreceptors were then transplanted into a foreign host retina in the region of the outer nuclear layer. The hosts were ocular, albinotic, Royal College of Surgeons (RCS) rats, congenic to the normal donors and at least 4 months old, a time when virtually all the photoreceptors have degenerated from their retinas. The transplant site was examined at various times after transplantation by light microscope autoradiography. Labeled photoreceptor cell bodies were found in clusters in the outer nuclear layer region for as long as 3 months after transplantation surgery.


Subcutaneous pellet testosterone replacement therapy: the "first steps" in treating men with spinal cord injuries.
The authors describe the case of a 36-year-old man who presented with hormone level concerns 6 months after a rock climbing accident that resulted in paraplegia. Hypogonadism was diagnosed, and the patient received subcutaneous pellet testosterone replacement therapy. Within 6 months, the patient had substantial improvement in muscle function and was able to take several steps with the assistance of crutches or a walker. This case highlights the potential improvement in quality of life and overall prognosis resulting from the subcutaneous pellet form of testosterone when used as part of the overall treatment plan in such patients. Considering the overwhelming preponderance of hypogonadism in men with spinal cord injuries, the standard of care for such patients should include screening, laboratory hormone evaluation, and prompt treatment for testosterone deficiency.


Cortical dynamics of feature binding and reset: control of visual persistence.
An analysis of the reset of visual cortical circuits responsible for the binding or segmentation of visual features into coherent visual forms yields a model that explains properties of visual persistence. The reset mechanisms prevent massive smearing of visual percepts in response to rapidly moving images. The model simulates relationships among psychophysical data showing inverse relations of persistence to flash luminance and duration, greater persistence of illusory contours than real contours, a U-shaped temporal function for persistence of illusory contours, a reduction of persistence due to adaptation with a stimulus of like orientation, an increase of persistence with spatial separation of a masking stimulus. The model suggests that a combination of habituative, opponent, and endstopping mechanisms prevent smearing and limit persistence. Earlier work with the model has analyzed data about boundary formation, texture segregation, shape-from-shading, and figure-ground separation. Thus, several types of data support each model mechanism and new predictions are made.


Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-month time point.
Treat-to-target (T2T) is a widely accepted management strategy for rheumatoid arthritis (RA) with a key decision point at 3 months after treatment initiation. At this time point, it remains unclear which patients will benefit from treatment adaptation or from continuation of existing treatment. We performed a pooled analysis of patient-level clinical trial data of patients with RA. We used a diagnostic testing methodology and a probabilistic approach employing logistic regression to investigate which levels of response at 3 months can inform treatment decisions in regard to achieving the target at 6 months. To be at least 80% sensitive for achieving the low disease activity (LDA) target at 6 months, a change at 3 months in Simplified Disease Activity Index/Clinical Disease Activity Index (SDAI or CDAI) of 58% needs to be observed at 3 months. Higher changes are needed to sensitively predict remission (REM). Not reaching the (minor) SDAI 50% response level is afflicted with very low negative likelihood ratios (LRs) (0.28 for LDA and 0.07 for REM at 6 months). Experiencing (major) SDAI 85% response has substantial positive LRs of 9.2 for reaching LDA and 6.2 for reaching REM at 6 months. In logistic regression, the change at 3 months is significantly associated with reaching of the target at 6 months. The 3-month time point is a critical decision point. Not achieving minor responses at 3 months makes reaching of the treatment target at 6 months highly unlikely, while reaching major responses is highly predictive of reaching the treatment target.


Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients.
To determine whether men with Klinefelter syndrome (KS) have the same phenotype as men with mosaic KS. Subject identification via prospectively collected database. Male infertility specialty clinic. Men undergoing a fertility evaluation from 2005 to 2012 at a single male infertility specialty clinic and having a karyotype demonstrating KS (mosaic or non-mosaic). None. Testicular size, and semen and hormone parameters, genetic evaluation, and signs of testosterone (T) deficiency using validated questionnaires. Of 86 men identified with KS, 6 (6.7%) were mosaic KS, and 80 (93.3%) were non-mosaic KS. Men with mosaic KS had lower baseline luteinizing hormone (LH) levels (10.31 IU/L ± 5.52 vs. 19.89 IU/L ± 6.93), lower estradiol levels (58.71 ± 31.10 pmol/L vs. 108.57 ± 43.45 pmol/L), larger mean testicular volumes (11 ± 7.3 mL vs. 6.35 ± 3.69 mL), and a higher mean total sperm count (4.43 ± 9.86 M/mL vs. 0.18 ± 1.17 M/mL). A higher proportion of men with mosaic KS had sperm in the ejaculate: 3 (50%) of 6 versus 3 (3.75%) of 80. The Sexual Health Inventory for Men (SHIM) and Androgen Deficiency in the Aging Male (ADAM) questionnaire scores were not different between groups. Men with mosaic KS seem to be more well androgenized than their non-mosaic KS counterparts, both with respect to hormones and sperm in the ejaculate.


Knowledge of HIV antibody status and decisions to continue or terminate pregnancy among intravenous drug users.
We studied decisions to continue or terminate pregnancy among human immunodeficiency virus (HIV)-seropositive (+) and -seronegative (-) intravenous drug users informed of HIV antibody status before 24 weeks' gestation. Fourteen (50%) of 28 HIV+ vs 16 (44%) of 36 HIV- women chose to terminate their pregnancies. In retrospective interviews, HIV+ women were more likely to have perceived their risk of perinatal HIV transmission to be greater than or equal to 50% and, among those who terminated pregnancy, to cite this concern as an important factor in their decision. However, decisions to terminate pregnancy were predicted more readily by pregnancy-related variables such as prior elective abortion, a negative emotional reaction to pregnancy, and whether the pregnancy had been unplanned. Women who were HIV+ and chose to continue their pregnancies cited the desire for a child, religious beliefs, and family pressure as the most important factors in their decisions. Results indicate that while concerns about perinatal transmission of HIV may lead to decisions to terminate pregnancy in certain cases, there may be other determinants of pregnancy decisions in this population. Counseling of HIV-infected women must address not only perinatal transmission but also the sociocultural and behavioral context in which pregnancy decision making takes place.


Biosafety and risk assessment framework for selectable marker genes in transgenic crop plants: a case of the science not supporting the politics.
Selectable marker gene systems are vital for the development of transgenic crops. Since the creation of the first transgenic plants in the early 1980s and their subsequent commercialization worldwide over almost an entire decade, antibiotic and herbicide resistance selectable marker gene systems have been an integral feature of plant genetic modification. Without them, creating transgenic crops is not feasible on purely economic and practical terms. These systems allow the relatively straightforward identification and selection of plants that have stably incorporated not only the marker genes but also genes of interest, for example herbicide tolerance and pest resistance. Bacterial antibiotic resistance genes are also crucial in molecular biology manipulations in the laboratory. An unprecedented debate has accompanied the development and commercialization of transgenic crops. Divergent policies and their implementation in the European Union on one hand and the rest of the world on the other (industrialized and developing countries alike), have resulted in disputes with serious consequences on agricultural policy, world trade and food security. A lot of research effort has been directed towards the development of marker-free transformation or systems to remove selectable markers. Such research has been in a large part motivated by perceived problems with antibiotic resistance selectable markers; however, it is not justified from a safety point of view. The aim of this review is to discuss in some detail the currently available scientific evidence that overwhelmingly argues for the safety of these marker gene systems. Our conclusion, supported by numerous studies, most of which are commissioned by some of the very parties that have taken a position against the use of antibiotic selectable marker gene systems, is that there is no scientific basis to argue against the use and presence of selectable marker genes as a class in transgenic plants.


Diagnostic reference levels for computed tomography examinations in pediatric population - A systematic review.
Computed tomography (CT) has vital role in diagnosis of various pathologies using cross sectional images. Besides the advantages of CT in pediatric radiology, radiation dose has a significant adverse effect as children are more vulnerable than adults. Establishing Diagnostic Reference levels (DRLs) will determine unusual increase in radiation doses and therefore helps in optimizing the radiation dose by maintaining optimum diagnostic image quality. The objective of the review is to explore the literature on DRLs in pediatric CT examinations and techniques that have been used to establish them. Detailed search was done in PubMed-Medline, Scopus CINAHL, Web of Science, and the Cochrane Library databases to find studies that have established DRLs for pediatric CT examinations. The Preferred Reporting Items for Systematic Review and Meta-Analyses methodology was used to assess the relevant articles. The articles which assessed DRLs in pediatric CT examinations were included. A total of 501 articles were identified, of which 21 articles were included after a detailed screening process. Our review showed increased in pediatric patient dose surveys across the world and also increased in awareness for establishing DRLS among pediatric CT examinations. The review also demonstrated wide variation in DRLs and also deviation in the scanning techniques, protocols used and categorization methods used for establishing DRLs. As the pediatric population is more sensitive to radiation, the current review emphasizes the need for optimization of protocols and international standardization for establishing DRLs to facilitate a more feasible way of comparison of dose globally across CT sites.


Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice.
The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS) against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic mice was studied. The influence of these agents on the plasma levels of fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-alpha), and on the activity of plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected diabetic mice was examined. To induce diabetes, mice were treated intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA isolates obtained from infected patients were used in this study. Diabetic mice were infected by injecting 200 microl MRSA/PBS suspension containing 10(7) c.f.u. via the tail vein. At day 4 post-infection, 200 microl DAS or DADS was administrated twice orally with an interval of 12 h. Eight hours after each administration, the blood and organs of mice were collected. Results showed that DAS and DADS significantly decreased MRSA viability in the kidney (P<0.05), with administration of each agent twice showing a greater inhibitory effect than when given once (P<0.05). MRSA infection in diabetic mice significantly elevated the plasma levels of IL-6 and TNF-alpha (P<0.05). DAS or DADS given once did not affect the plasma levels of IL-6 and TNF-alpha (P>0.05); however, DAS or DADS given twice significantly decreased the plasma levels of both IL-6 and TNF-alpha (P<0.05). DAS and DADS treatments also significantly reduced the plasma levels of CRP, fibronectin and fibrinogen (P<0.05). DAS or DADS treatment did not affect PAI-1 activity (P>0.05), but DAS or DADS given twice significantly increased AT-III activity (P<0.05). DADS given twice elevated protein C activity (P<0.05). MRSA infection significantly increased malondialdehyde levels in the kidney and spleen (P<0.05), and these levels were significantly decreased by treatment with DAS or DADS (P<0.05). These data suggest that DAS and DADS could provide multiple protective functions against MRSA infection in diabetic mice.


Pattern of fall injuries in Pakistan: the Pakistan National Emergency Department Surveillance (Pak-NEDS) study.
We aimed to analyse the frequency and patterns of fall-related injuries presenting to the emergency departments (EDs) across Pakistan. Pakistan National Emergency Departments surveillance system collected data from November 2010 to March 2011 on a 24/7 basis using a standardized tool in seven major EDs (five public and two private hospitals) in six major cities of Pakistan. For all patients presenting with fall-related injuries, we analysed data by intent with focus on unintentional falls. Simple frequencies were run for basic patient demographics, mechanism of falls, outcomes of fall injuries, mode of arrival to ED, investigations, and procedures with outcomes. There were 3335 fall-related injuries. In cases where intent was available, two-thirds (n = 1186, 65.3%) of fall injuries were unintentional. Among unintentional fall patients presenting to EDs, the majority (76.9%) were males and between 15-44 years of age (69%). The majority of the unintentional falls (n = 671, 56.6%) were due to slipping, followed by fall from height (n = 338, 28.5%). About two-thirds (n = 675, 66.6%) of fall injuries involved extremities, followed by head/neck (n = 257, 25.4%) and face (n = 99, 9.8%). Most of the patients were discharged from the hospital (n = 1059, 89.3%). There were 17 (1.3%) deaths among unintentional fall cases. Falls are an important cause of injury-related visits to EDs in Pakistan. Most of the fall injury patients were men and in a productive age group. Fall injuries pose a burden on the healthcare system, especially emergency services, and future studies should therefore focus on safety measures at home and in workplaces to reduce this burden.


[Detection and differentiation of Entamoeba histolytica and Entamoeba dispar by polymerase chain reaction in a community in Zulia State, Venezuela].
Differential identification of Entamoeba histolytica and Entamoeba dispar is essential for both appropriate patient treatment and epidemiological purposes. To determine the prevalence of these amoeba infections in Santa Rosa de Agua (Maracaibo, Zulia State, Venezuela), a PCR assay using specific primers for each species was standardized and applied. 204 stool samples were analyzed through direct microscopic examination with SSF (0.85%) and lugol, formol-ether concentration, and PCR. Under direct microscopy, 42 individuals (20.58%) presented the E. histolytica/E. dispar complex. Meanwhile PCR showed 47 positive cases for these amoebas: 22 E. histolytica (10.78%), 16 E. dispar (7.84%), and 9 (4.41%) mixed infections. There was no significant difference in the presence of E. histolytica and/or E. dispar according to either gender or age. There were no cases of these amoebas in children under 2 years of age. Observed frequency of E. histolytica (31/204) shows the endemic nature of amoeba infection in this community.


Associations between television viewing and physical activity and low back pain in community-based adults: A cohort study.
Two systematic reviews concluded that there was limited evidence to support an association between physical activity and sedentary behavior and developing low back pain (LBP). The aim of this study was to examine the associations of physical activity and television viewing time with LBP intensity and disability in community-based adults.Five thousand fifty-eight participants (44% men) of the Australian Diabetes, Obesity and Lifestyle Study had physical activity and television viewing time measured in 1999 to 2000, 2004 to 2005, and 2011 to 2012, and LBP intensity and disability assessed in 2013 to 2014 using the Chronic Pain Grade Questionnaire. Multinomial logistic regressions were used to estimate the odds ratio for LBP intensity and disability associated with physical activity and television viewing time. Analyses were adjusted for age, education, smoking, dietary guideline index score, body mass index, and mental component summary score. To test whether associations of physical activity or television viewing time with LBP intensity and disability were modified by sex, obesity, or age, interactions were tested using the likelihood ratio test.As gender modified the associations between physical activity and television viewing time and LBP disability (P = 0.05), men and women were examined separately. A total of 81.7% men and 82.1% women had LBP. Most men (63.6%) and women (60.2%) had low intensity LBP with fewer having high intensity LBP (18.1% men, 21.5% women). Most participants had no LBP disability (74.5% men, 71.8% women) with the remainder reporting low (15.8% men, 15.3% women) or high (9.7% men, 12.9% women) LBP disability. Insufficient physical activity (<2.5 hours/week) was not associated with LBP intensity or disability. High television viewing time (≥2 hours/day) was associated with greater prevalence of LBP disability in women (low disability OR 1.35, 95% CI 1.04-1.73; high disability OR 1.29, 95% CI 1.01-1.72).Although it needs to be confirmed in RCTs our findings suggest that targeting time spent watching television and possibly other prolonged sedentary behaviors may have the potential to reduce LBP disability in community-based adults, particularly in women.


Multiple phosphorylation sites of DNA polymerase alpha-primase cooperate to regulate the initiation of DNA replication in vitro.
DNA polymerase alpha-primase (pol-prim) is the only enzyme that can start DNA replication de novo. The 180-kDa (p180) and 68-kDa (p68) subunits of the human four-subunit enzyme are phosphorylated by Cyclin-dependent kinases (Cdks) in a cell cycle-dependent manner. Cyclin A-Cdk2 physically interacts with pol-prim and phosphorylates N-terminal amino acids of the p180 and the p68 subunits, leading to an inhibition of pol-prim in initiating cell-free SV40 DNA replication. Mutation of conserved putative Cdk phosphorylation sites in the N terminus of human p180 and p68 reduced their phosphorylation by Cyclin A-Cdk2 in vitro. In contrast to wild-type pol-prim these mutants were no longer inhibited by Cyclin A-Cdk2 in the initiation of viral DNA replication. Importantly, rather than inhibiting it, Cyclin A-Cdk2 stimulated the initiation activity of pol-prim containing a triple N-terminal alanine mutant of the p180 subunit. Together these results suggest that Cyclin A-Cdk2 executes both stimulatory and inhibitory effects on the activity of pol-prim in initiating DNA replication.


A walking programme and a supervised exercise class versus usual physiotherapy for chronic low back pain: a single-blinded randomised controlled trial. (The Supervised Walking In comparison to Fitness Training for Back Pain (SWIFT) Trial).
Chronic low back pain (CLBP) is a persistent disabling condition with rising significant healthcare, social and economic costs. Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery. While international clinical guidelines and systematic reviews for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost, barriers to their delivery include space and time restrictions in healthcare settings and poor patient attendance. The European Clinical Guidelines have identified the need for research in the use of brief/minimal contact self-activation interventions that encourage participation in physical activity for CLBP. Walking may be an ideally suited form of individualized exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all ages with little risk of injury, but its effectiveness for LBP is unproven. This study will be an assessor-blinded randomized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy, which will act as the control group, in people with chronic low back pain. A sample of 246 patients will be recruited in Dublin, Ireland through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP. Patients will be randomly allocated to one of the three groups in a concealed manner. The main outcomes will be functional disability, pain, quality of life, fear avoidance, back beliefs, physical activity, satisfaction and costs, which will be evaluated at baseline, and 3, 6 and 12 months [follow-up by pre-paid postage]. Qualitative telephone interviews and focus groups will be embedded in the research design to obtain feedback about participants' experiences of the interventions and trial participation, and to inform interpretation of the quantitative data. Planned analysis will be by intention to treat (quantitative data) and thematic analysis (qualitative data) The trial will evaluate the effectiveness of a walking programme and a supervised general exercise programme compared to usual physiotherapy in people with CLBP. Current controlled trial ISRCTN17592092.


Is combined atrial volumetrics by two-dimensional echocardiography a suitable measure for quantitative assessment of the hemodynamic significance of patent ductus arteriosus in neonates and infants?
Patent ductus arteriosus (PDA) is a common cardiac problem in neonates and infants, but determination of its hemodynamic significance can be challenging. We hypothesized that combined left (LA) and right atrial (RA) volumes physiologically best reflect hemodynamically significant patent ductus arteriosus (HSPDA), and utilized two-dimensional echocardiography (2DE) derived atrial volumes to test this hypothesis. 2DE examinations with good-quality images in 138 neonates <3 months corrected gestational age with PDA, and 50 normal neonates without PDA were selected. Measurements of LA, RA, and combined atrial volumes were performed, in addition to transductal diameters, left atrial to aortic dimension (LA:Ao), and left ventricular end-diastolic to aortic dimension ratios. An experienced cardiologist, blinded to 2DE images of atria and ventricles and to the above measurements, independently assessed HSPDA based only on images and Doppler data of the ductus itself, thus identifying each PDA as of low hemodynamic significance or HSPDA. Receiver operating characteristic (ROC) curves showed indexed LA volumes and LA/RA volume ratios to have moderate power to discriminate HSPDA from low hemodynamic burden PDA. Classic LA:Ao ratio, combined atrial volumes, and RA volumes yielded ROC areas that appeared less promising as discriminators for HSPDA. Atrial volume measurements in neonates and infants have a linear association with body surface area and show acceptable inter- and intraobserver agreement. Indexed LA volume and LA/RA volume ratio are potentially useful markers for HSPDA. RA dilation due to left to right shunting through the patent foramen ovale as quantified by RA volume measurements does not appear to be an important marker for HSPDA.


Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis.
We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.


High-range-resolution velocity-estimation techniques for coherent Doppler lidars with exponentially shaped laser pulses.
On the basis of an analysis of the autocovariance of the complex heterodyne signal, some novel algorithms are derived and investigated for recovering the nonuniform Doppler-velocity coherent-lidar profiles within the lidar resolution interval conditioned by the sensing laser-pulse length. The case of exponentially shaped sensing laser pulses is considered. The algorithm performance and efficiency are studied and illustrated by computer simulations (based on the use of pulse models and real laser pulses), taking into account the influence of additive noise and radial-velocity fluctuations. It is shown that, at some reasonable number of signal realizations used and with appropriate data processing to suppress the noise effects, the Doppler-velocity profiles can be determined with a considerably shorter resolution interval in comparison with that (usually accepted as a lower bound) determined by the pulse length.


A chinese mind-body exercise improves self-control of children with autism: a randomized controlled trial.
Self-control problems commonly manifest as temper outbursts and repetitive/rigid/impulsive behaviors, in children with autism spectrum disorders (ASD), which often contributes to learning difficulties and caregiver burden. The present study aims to compare the effect of a traditional Chinese Chan-based mind-body exercise, Nei Yang Gong, with that of the conventional Progressive Muscle Relaxation (PMR) technique in enhancing the self-control of children with ASD. Forty-six age- and IQ-matched ASD children were randomly assigned to receive group training in Nei Yang Gong (experimental group) or PMR (control group) twice per week for four weeks. The participants' self-control was measured by three neuropsychological tests and parental rating on standardized questionnaires, and the underlying neural mechanism was assessed by the participants' brain EEG activity during an inhibitory-control task before and after intervention. The results show that the experimental group demonstrated significantly greater improvement in self-control than the control group, which concurs with the parental reports of reduced autistic symptoms and increased control of temper and behaviors. In addition, the experimental group showed enhanced EEG activity in the anterior cingulate cortex, a region that mediates self-control, whereas the PMR group did not. The present findings support the potential application of Chinese Chan-based mind-body exercises as a form of neuropsychological rehabilitation for patients with self-control problems. Chinese Clinical Trial Registry; Registration No.: ChiCTR-TRC-12002561; URL: www.chictr.org.


Mesenchymal stem cells reverse trauma and hemorrhagic shock-induced bone marrow dysfunction.
Lung contusion (LC) followed by hemorrhagic shock (HS) causes persistent bone marrow (BM) dysfunction lasting up to 7 d after injury. Mesenchymal stem cells (MSCs) are multipotent cells that can hasten healing and exert protective immunomodulatory effects. We hypothesize that MSCs can attenuate BM dysfunction after combined LCHS. Male Sprague-Dawley rats (n = 5-6 per group) underwent LC plus 45 min of HS (mean arterial pressure of 30-35). Allogeneic MSCs (5 × 10(6) cells) were injected intravenously after resuscitation. At 7 d, BM was analyzed for cellularity and growth of hematopoietic progenitor cell (HPC) colonies (colony-forming unit-erythroid; burst-forming unit-erythroid; and colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte). Flow cytometry measured %HPCs in peripheral blood; plasma granulocyte colony-stimulating factor (G-CSF) levels were measured via enzyme-linked immunosorbent assay. Data were analyzed by one-way analysis of variance followed by the Tukey multiple comparison test. As previously shown, at 7 d, LCHS resulted in 22%, 30%, and 24% decreases in colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte, burst-forming unit-erythroid, and colony-forming unit-erythroid colony growth, respectively, versus naive. Treatment with MSCs returned all BM parameters to naive levels. There was no difference in %HPCs in peripheral blood between groups; however, G-CSF remained increased up to 7 d after LCHS. MSCs returned G-CSF to naive levels. Plasma from animals receiving MSCs was not suppressive to the BM. One week after injury, the persistent BM dysfunction observed in animals undergoing LCHS is reversed by treatment with MSCs with an associated return of plasma G-CSF levels to normal. Plasma from animals undergoing LCHS plus MSCs was not suppressive to BM cells in vitro. Treatment with MSCs after injury and shock reverses BM suppression and returns plasma G-CSF levels to normal.


Complete genome sequence provides insights into the biodrying-related microbial function of Bacillus thermoamylovorans isolated from sewage sludge biodrying material.
To enable the development of microbial agents and identify suitable candidate used for biodrying, the existence and function of Bacillus thermoamylovorans during sewage sludge biodrying merits investigation. This study isolated a strain of B. thermoamylovorans during sludge biodrying, submitted it for complete genome sequencing and analyzed its potential microbial functions. After biodrying, the moisture content of the biodrying material decreased from 66.33% to 50.18%, and B. thermoamylovorans was the ecologically dominant Bacillus, with the primary annotations associated with amino acid transport and metabolism (9.53%) and carbohydrate transport and metabolism (8.14%). It contains 96 carbohydrate-active- enzyme-encoding gene counts, mainly distributed in glycoside hydrolases (33.3%) and glycosyl transferases (27.1%). The virulence factors are mainly associated with biosynthesis of capsule and polysaccharide capsule. This work indicates that among the biodrying microorganisms, B. thermoamylovorans has good potential for degrading recalcitrant and readily degradable components, thus being a potential microbial agent used to improve biodrying.


Saprophytic intracellular rhizobia in alfalfa nodules.
In indeterminate alfalfa nodules, the establishment of the senescent zone IV, in which both symbionts undergo simultaneous degeneration, has been considered, until now, as the end point of the symbiotic interaction. However, we now describe an additional zone, zone V, proximal to the senescent zone IV and present in alfalfa nodules more than 6 weeks old. In zone V, a new round of bacterial release occurs from remaining infection threads, leading to the reinvasion of plant cells that have completely senesced. These intracellular rhizobia are rod shaped and do not display the ultrastructural differentiation features of bacteroids observed in the more distal zones of the nodule. Interestingly, we have found that oxygen is available in zone V at a concentration compatible with both bacterial development and nitrogen fixation gene expression in newly released rhizobia. However, this expression is not correlated with acetylene reduction. Moreover, the pattern of nifH expression in this zone, as well as new data relating to expression in zone II, strongly suggest that nifH transcription in the nodule is under the control of a negative regulator in addition to oxygen. Our results support the conclusion that zone V is an ecological niche where intracellular rhizobia take advantage of the interaction for their exclusive benefit and live as parallel saprophytic partners. The demonstration of such an advantage for rhizobia in nodules was the missing evidence that Rhizobium-legume interactions are indeed symbiotic and, in particular, suggests that benefits to the two partners are associated with different developmental stages within the nodule.


History of forced sex and recent sexual risk indicators among young adult males.
It is unclear whether young adult men who have ever been forced to have sex are at increased risk for sexual risk-taking, and whether their risk differs according to the gender of the perpetrator. Data from 1,400 males aged 18-24 who participated in the 2002 National Survey of Family Growth were used to determine the prevalence of a history of forced sex and the context of each respondent's most recent experience with such assaults. Logistic regression analyses were conducted to examine the relationship between victimization and having a recent indicator of sexual risk (e.g., having had sex in the past year with five or more female partners, a female injection-drug user or an HIV-positive female). Separate analyses were performed for coercion by females and coercion by males. Six percent of men reported having been forced by a female perpetrator to have vaginal intercourse, while 1% said they had been forced by a male perpetrator to have oral or anal sex. Men had an elevated likelihood of having had one or more recent sexual risk indicators if they had ever been forced to have sex by a male (odds ratio, 6.9) or female (3.3). Verbal and physical forms of coercion and provision of alcohol and drugs were commonly used by perpetrators of both genders. A better understanding of the pathways linking sexual victimization to sexual risk-taking among men is needed. Clinicians working with young men should screen them for victimization and provide STD testing and referrals for counseling if abuse is suspected or disclosed.


Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study.
To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16-8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29-26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34-0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13-4.03) and sudden deaths (HR 1.94, 95% CI 1.06-3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16-0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria-based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.


Improved metabolic health among the obese in six population surveys 1986 to 2009: the Northern Sweden MONICA study.
The incidence of CVD is decreasing in spite of increasing BMI in the population. We examined trends in metabolic health among overweight and obese individuals and the influence of lifestyle and socioeconomic status. Six cross sectional population surveys in the Northern Sweden MONICA Study between 1986 and 2009. 8 874 subjects 25 to 64 years participated (74% participation rate). Metabolic health was defined as a total cholesterol level below 5.0 mmol/l, blood pressure below 140/90 mmHg and not having diabetes. In 2009 the age span 25 to 74 years was studied. The prevalence of metabolic health among obese subjects increased by 7.9 % per year (95% confidence interval 5.4; 10.5), reaching 21.0% in 2009. The corresponding figures for overweight subjects were 5.9% per year (4.6; 7.3), reaching 18% in 2009, whereas for the normal-weight subjects, the increase was 6.2% per year (5.3; 7.2), reaching 39% in 2009. The prevalence of metabolic health among subjects with abdominal obesity increased by 5.8% (4.6; 7.0) per year, reaching 17.3% in 2009. Among those with no abdominal obesity the increase was 6.2% (5.2; 7.1), reaching 38% in 2009 (p = <0.001 for all groups). Only among non-obese men and obese women did the increase continue between 2004 and 2009. In the other groups a slight decline or levelling off was noted. In 2009 women had a 27% higher prevalence of metabolic health than men. The prevalence of metabolic health among the obese was 19.8% which declined to 15.8% if subjects treated for hypertension or hypercholesterolemia were classified as not healthy. Overweight and obese subjects were less often metabolically healthy (odds ratio 0.54 and 0.59 respectively) compared with normal-weight subjects, independent of sex and age as were subjects with abdominal obesity (odds ratio 0.52). Adjustments for smoking, physical activity and education level did not influence any estimates. This report shows a large increase in prevalence of metabolic health from 1986 to 2009 for all anthropometric categories. Metabolic health remains considerably less prevalent among overweight and obese subjects than among those with normal weight.


Updating a model of pulp and paper wastewater treatment in a partial-mix aerated stabilization basin system.
A relatively simple set of calculations was presented in 1994 to evaluate the effectiveness of each ASB cell as reactor, clarifier, and digester. The steady-state model, which incorporated estimates of solids settling and benthal feedback of BOD5 and nutrients, has been a reasonable diagnostic tool for municipal and industrial applications. Results have aided in understanding normal system function, the nature of chronic inefficiencies of individual systems, and appropriate modifications to meet changes in discharge requirements. For applications in the pulp and paper industry, several changes have been incorporated recently. Nitrogen limitation is not needed in modeling pulp and paper ASB reactions. Slowly biodegradable material is modeled as a contributor to soluble BOD5, and this contribution becomes a significant factor in the latter segments of an ASB. Phosphorus availability is modeled as a stoichiometric control of soluble BOD5 uptake. Anoxic microorganisms are assumed to be responsible for a portion of the soluble BOD5 consumption in the first ASB aeration zone. Finally, the long-term nutrient capture in ASBs is modeled as 3% for nitrogen and 28% for phosphorus.


Association Between Health Symptoms and Particulate Matter from Traffic and Residential Heating - Results from RHINE III in Tartu.
Traffic and residential heating are the main sources of particulate matter (PM) in Northern Europe. Wood is widely used for residential heating and vehicle numbers are increasing. Besides traffic exhaust, studded tires produce road dust that is the main source of traffic-related PM10. Several studies have associated total PM mass with health symptoms; however there has been little research on the effects of PM from specific sources. To study the health effects resulting from traffic and local heating PM. Data on respiratory and cardiac diseases were collected within the framework of RHINE III (2011/2012) in Tartu, Estonia. Respondents' geocoded home addresses were mapped in ArcGIS and linked with local heating-related PM2.5, traffic-related PM10 and total PM2.5 concentrations. Association between self-reported health and PM was assessed using multiple logistic regression analysis. The annual mean modelled exposure for local heating PM2.5 was 2.3 μg/m3, for traffic PM10 3.3 μg/m3 and for all sources PM2.5 5.6 μg/m3. We found relationship between traffic induced PM10 as well as all sources induced PM2.5 with cardiac disease, OR=1.45 (95% CI 1.06-1.93) and 1.42 (95% CI 1.02-1.95), respectively. However, we did not find any significant association between residential heating induced particles and self-reported health symptoms. People with longer and better confirmed exposure period were also significantly associated with traffic induced PM10, all sources induced PM2.5 and cardiac diseases. Traffic-related PM10 and all sources induced PM2.5 associated with cardiac disease; whereas residential heating induced particles did not.


Making unhealthy places: The built environment and non-communicable diseases in Khayelitsha, Cape Town.
In this paper, we examine how economic, social and political forces impact on NCDs in Khayelitsha (a predominantly low income area in Cape Town, South Africa) through their shaping of the built environment. The paper draws on literature reviews and ethnographic fieldwork undertaken in Khayelitsha. The three main pathways through which the built environment of the area impacts on NCDs are through a complex food environment in which it is difficult to achieve food security, an environment that is not conducive to safe physical activity, and high levels of depression and stress (linked to, amongst other factors, poverty, crime and fear of crime). All of these factors are at least partially linked to the isolated, segregated and monofunctional nature of Khayelitsha. The paper highlights that in order to effectively address urban health challenges, we need to understand how economic, social and political forces impact on NCDs through the way they shape built environments.


Hypoxia prevents induction of aromatase expression in human trophoblast cells in culture: potential inhibitory role of the hypoxia-inducible transcription factor Mash-2 (mammalian achaete-scute homologous protein-2).
The human placenta has a remarkable capacity to aromatize C19-steroids, produced by the fetal adrenals, to estrogens. This reaction is catalyzed by aromatase P450 (P450arom), encoded by the CYP19 gene. In placenta, CYP19 gene expression is restricted to the syncytiotrophoblast layer. Cytotrophoblasts isolated from human placenta, when placed in monolayer culture in 20% O2, spontaneously fuse to form syncytiotrophoblast. These morphological changes are associated with a marked induction of aromatase activity and CYP19 gene expression. When cytotrophoblasts are cultured in an atmosphere containing 2% O2, they manifest increased rates of DNA synthesis and fail to fuse and form syncytiotrophoblast. The objective of the present study was to utilize cytotrophoblasts isolated from midterm human placenta to analyze the effects of O2 on CYP19 gene expression and the molecular mechanisms that mediate these effects. We observed that when trophoblast cells were maintained in 2% O2, there was only a modest induction of CYP19 expression as a function of time in culture, and aromatase activity was barely detectable. However, when cytotrophoblasts that had been maintained in 2% O2 for 3 days were placed in a 20% O2 environment, there was a rapid onset of cell fusion and induction of P450arom mRNA and aromatase activity. In addition, mRNAs for the helix-loop-helix factors Mash-2 (mammalian achaete-scute homologous protein-2) and Id1 (inhibitor of differentiation 1) were readily detectable in freshly isolated cytotrophoblasts and were markedly decreased upon differentiation to syncytiotrophoblast in 20% O2. By contrast, when cytotrophoblasts were cultured in 2% O2, mRNA levels for Mash-2 and Id1 remained elevated. Interestingly, overexpression of Mash-2 in primary cultures of human trophoblast cells markedly inhibited cell fusion and the spontaneous induction of P450arom mRNA levels and caused a marked decrease in expression of co-transfected fusion gene constructs containing either 125, 201, 246, or 501 bp of DNA flanking the 5'-end of the placenta-specific exon (exon I.1) of the human CYP19 gene linked to the human GH (hGH) structural gene, as reporter. In studies using BeWo, a human choriocarcinoma cell line, overexpression of Mash-2 also inhibited expression of cotransfected CYP19I.1:hGH fusion gene constructs. The findings that Mash-2 had no effect on the expression of a CYP19I.1(-42):hGH fusion gene in primary cultures of human trophoblast and BeWo cells suggest that Mash-2 exerts its inhibitory effects directly or indirectly though CYP19I.1 5'-flanking sequences that lie between -42 and -125 bp. By contrast, neither Id1 nor Id2 had an effect on CYP19I. 1 promoter activity in the transfected BeWo cells. These findings suggest that Mash-2 may serve as a hypoxia-induced transcription factor that prevents differentiation to syncytiotrophoblast and aromatase induction in human trophoblast cultured under low O2 conditions.


The Long-Term Development of Training, Technical, and Physiological Characteristics of an Olympic Champion in Nordic Combined.
Nordic combined requires high technical skills and vertical impulse for the ski-jumping event and aerobic endurance, ski efficiency and finish-sprint abilities to succeed in the subsequent cross-country race. The main aim of this study was to investigate the development of training, technical, and physiological characteristics during the last four seasons preceding the Olympic Games in a Nordic Combined Champion [∼74 kg (63 kg lean-mass)]. During the first season of the 4-year cycle, the development of lower-body muscle-mass and vertical jump velocity was prioritized, after which the emphasis on developing the technical abilities were increased over the following three seasons. While maintaining his vertical velocity in countermovement jump at ∼3 m⋅s-1, despite an increase of 7 kg overall body-mass, the participant improved his vertical velocity in sport-specific ski jump imitation with 0.31 m⋅s-1 coincidentally with high technical focus, including use of systematic mental training to enhance skill acquisition, and an almost twofold increase of annual imitation jumps in the four-season cycle. Endurance training increased from 462 h⋅season-1 in season one to 635 h⋅season-1 in season three, which was mainly due to more low-intensity training. Thereafter, endurance training in the Olympic season was reduced by 12% and more focus was placed on quality of each session and sufficient recovery. The highest V˙ O2peak (5.36 L⋅min-1 and 72.0 ml⋅kg-1⋅min-1) was measured in the third season and thereafter maintained, although competition results were further improved toward the Olympics. The amount of moderate- (31.9 ± 2.8 h⋅season-1, 43.0 ± 3.9 sessions⋅season-1) and high-intensity (28.3 ± 3.1 h⋅season-1, 52.3 ± 2.7 sessions⋅season-1) endurance training was stable throughout the four-season period, with >65% being performed as skiing or roller ski skating. Development of finish-sprint ability was an important strategy throughout the entire period, and both Olympic gold medals were won in a finish-sprint. Altogether, this study provides unique data from the four-season cycle of a two-time Olympic gold medal winner in Nordic Combined, where high amounts of strength/power and endurance training is successfully combined toward a peak in the Olympic season. This knowledge shows how the combination of long-term endurance and strength/power may be optimized, and generates new hypotheses to be tested in future research.


Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats.
Osteoporosis is a systemic disease characterized by bone degradation and decreased bone mass that promotes increased bone fragility and eventual fracture risk. Studies have investigated the use of sodium fluoride (NaF) for the treatment of osteoporosis. However, fluoride can alter glucose homeostasis. The aim of this study was to evaluate the effects of NaF intake (50 mg/L) from water on the following parameters of ovariectomized (OVX) rats: (1) tyrosine phosphorylation status of insulin receptor substrate (pp185 (IRS-1/IRS-2)) in white adipose tissue; (2) insulin sensitivity; (3) plasma concentrations of glucose, insulin, total cholesterol, triglyceride, TNF-α, IL-6, osteocalcin, calcium, and fluoride; (4) bone density and biomechanical properties in the tibia; and (5) tibia histomorphometric analysis. Fifty-two Wistar rats (2 months old) were ovariectomized and distributed into two groups: control group (OVX-C) and NaF group (OVX-F), which was subjected to treatment with NaF (50 mg/L) administered in drinking water for 42 days. The chronic treatment with NaF promoted (1) a decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin infusion in white adipose tissue and in insulin sensitivity; (2) an increase in the plasma concentration of insulin, fluoride, osteocalcin, calcium, triglyceride, VLDL-cholesterol, TNF-α, and IL-6; (3) a reduction in the trabecular width, bone area, stiffness, maximum strength, and tenacity; (4) no changes in body weight, food and water intake, plasma glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, bone mineral content, and bone mineral density. It was concluded that chronic treatment with NaF (50 mg/L) in OVX rats causes a decrease in insulin sensitivity, insulin signaling transduction, and biochemical, biomechanical, and histomorphometric bone parameters.


Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California.
We conducted a retrospective cohort study to examine cancer risk in a large cohort of systemic lupus erythematosus (SLE) patients in California. The cohort consisted of individuals with SLE derived from statewide patient discharge data during the period 1991-2002. SLE patients were followed using cancer registry data to examine patterns of cancer development. Standardized incidence ratios (SIRs) and 95% CI were calculated to compare the observed to expected numbers of cancers based on age-, race-, and sex-specific incidence rates in the California population. The 30,478 SLE patients were observed for 157,969 person-years. A total of 1,273 cancers occurred within the observation interval. Overall cancer risk was significantly elevated (SIR = 1.14, 95% CI = 1.07-1.20). SLE patients had higher risks of vagina/vulva (SIR = 3.27, 95% CI = 2.41-4.31) and liver cancers (SIR = 2.70, 95% CI = 1.54-4.24). Elevated risks of lung, kidney, and thyroid cancers and several hematopoietic malignancies were also observed. Individuals had significantly lower risks of several screenable cancers, including breast, cervix, and prostate. These data suggest that risks of several cancer types are elevated among SLE patients. Detailed studies of endogenous and exogenous factors that drive these associations are needed.


Modulation of tracheal smooth muscle responses in inducible T-cell kinase knockout mice.
It has been shown that the Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) plays a role in the activation of naive T cells and in the differentiation of T helper (TH2)-type cells producing cytokines in a model of allergic inflammation, thereby possibly indirectly mediating hyperresponsivenes of airway smooth muscle tone. Using excised tracheae from wild type (WT) mice and those lacking ITK, we conducted a series of in vitro experiments in which isometric smooth muscle tones were assessed in response to several agonists to determine whether the absence of ITK would affect the responsiveness of tracheal smooth muscle cells. The resulting change in contractile responses was evaluated by measuring agonist cumulative concentration-response curves (CCRC). Our results indicate that the cholinergic agonist acetylcholine (ACh) and its analog carbachol (CCh) exhibited comparable CCRC profiles in contracting isolated tracheae from both WT and ITK-/- mice, with no alteration in their efficacies. However, the EC50 values for the two agonists were found to be significantly higher in ITK-/- tracheae than in those from WT mice, suggesting an alteration of the potencies of these cholinergic agonists in the trachea of ITK-/- mice. Moreover, we found that the depolarizing agent potassium chloride (KCl) had a significantly lower efficacy in contracting ITK-/- tracheae compared to those from WT mice. This difference in KCl efficacy was abolished in the presence of a calcium (Ca2+) voltage-dependent channel (VDC) agonist, Bay K8644, suggesting a modulation of the KCl induced permeability of VDC Ca2+ channels in the trachea of ITK-/- mice. Taken together, these results suggest that the presence of ITK may play a modulating role in the pharmacomechanical as well as in the electromechanical coupling of airway smooth muscle contraction.


Overcoming immunological barriers in regenerative medicine.
Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists.


Genome-wide association study of concentrations of iron and other minerals in longissimus muscle of Angus cattle.
The objective of this study was to characterize variation and identify SNP and chromosomal regions associated with mineral concentrations in LM of Angus beef cattle. Samples of LM from 2,285 Angus cattle were obtained, and concentrations of 7 minerals, including iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc, were quantified. Genomic DNA extracted from the ground beef sample used for mineral composition was genotyped with the Bovine SNP50 Infinium II BeadChip, and effects of SNP on each trait were estimated using the Bayes-Cπ module of GenSel software. Pedigree-based estimates of heritabilities and corresponding genetic variances indicate iron was the only mineral concentration that could be considered a good candidate for manipulation by genomic selection. The amount of variation that could be accounted for by SNP genotypes was concordant with pedigree-based heritabilities and varied from very low for potassium and sodium (<0.09) to medium high (0.37) for iron. Although significant chromosomal regions were identified for all minerals analyzed in this study, further study focused on iron. Seven regions on 6 chromosomes (1, 2, 7, 10, 15, and 28) were identified to have a major effect on the iron content of LM in Angus cattle. The accuracy of direct genomic values (DGV) for iron concentration was estimated using a 5-fold cross-validation strategy. The accuracy of DGV estimated as the genetic correlation between DGV and the phenotype (iron concentration) adjusted for contemporary groups was 0.59. A bivariate animal model was used to estimate genetic correlations between iron concentrations and a reduced set of economically important carcass traits: HCW, rib eye area, calculated USDA yield grade, percent KPH, and marbling score. The genetic correlations between iron concentration and HCW, percentage KPH, marbling score, and rib eye area were small (-0.19 to 0.15) and nonsignificant. Although still weak (0.22), a positive significant genetic correlation was identified between iron content and USDA calculated yield grade. Beef is a major contributor of iron and zinc in the human diet, and this study found that iron content might be effectively manipulated through marker-assisted selection programs, without compromising other carcass and palatability traits.


Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases.
N-acetylcysteine (NAC), which is an acetylated cysteine compound, has aroused scientific interest for decades due to its important medical applications. It also represents a nutritional supplement in the human diet. NAC is a glutathione precursor and shows antioxidant and anti-inflammatory activities. In addition to the uses quoted in the literature, NAC may be considered helpful in therapies to counteract neurodegenerative and mental health diseases. Furthermore, this compound has been evaluated for its neuroprotective potential in the prevention of cognitive aging dementia. NAC is inexpensive, commercially available and no relevant side effects were observed after its administration. The purpose of this paper is to give an overview on the effects and applications of NAC in Parkinson's and Alzheimer's disorders and in neuropathic pain and stroke.


The ethical framing of personalized medicine.
Personalized medicine encompasses the use of biological information such as genomics to provide tailored interventions for patients. The review explores the ethical, legal, and social issues that have emerged with personalized medicine and must be considered because of the complex nature of providing individualized care within a clinical setting. Recent studies found that the use of personalized medicine presents challenges in multiple areas: biobanking and informed consent, confidentiality, genetic discrimination, return of results, access to treatment, clinical translation, direct-to-consumer genetic testing, emerging duties, and knowledge mobilization. Although personalized medicine provides benefits in treating patients in a manner that is more suited to their genetic profile, there are challenges that must be discussed to ensure the protection and fair treatment of individuals. The issues concerning personalized medicine are widespread, and range from individual privacy to the stratification and discrimination of sub-populations based on ethnicity. These issues have considerable impact on the individual and society. A thorough exploration of these ethical issues may identify novel challenges as well as potential avenues for resolution.


Sex-specific effects of stress on metabolic and cardiovascular disease: are women at higher risk?
Cardiovascular disease (CVD) has traditionally been viewed as a male disease; however, the relative risk for obesity and hypertension morbidity and mortality, major risk factors for CVD, is higher for women in the United States. Emerging epidemiological data strongly support stressful experiences as a modifiable risk factor for obesity, insulin resistance, and heart disease in women at all ages. Therefore, primary prevention of these diseases may be associated with both identifying and increasing the knowledge regarding the sex differences in emotional functioning associated with physiological responses to stress. The purpose of this review is to highlight the growing body of clinical and experimental studies showing that stress, obesity-associated metabolic disturbances, and CVD comorbidities are more prevalent in females. Overall, this review reveals the need for investigations to decipher the early origins of these comorbidities. Targeting the sources of behavioral/emotional stress through the trajectory of life has the potential to reduce the alarming projected rates for chronic disease in women.


Mouthing activity data for children aged 7 to 35 months in Taiwan.
Young children's mouthing activities thought to be among the most important exposure pathways. Unfortunately, mouthing activity studies have only been conducted in a few countries. In the current study, we used videotaping and computer-based translating method to obtain mouthing activity data for 66 children aged 7-35 months in Taiwan. The median indoor hand-to-mouth and object-to-mouth frequencies were 8.91 and 11.39 contacts/h, respectively. The median indoor hand-to-mouth and object-to-mouth hourly contact durations were 0.34 and 0.46 min/h, respectively. The indoor object-to-mouth activities were significantly and negatively correlated with age. Children aged 12 to <24 months in the current study had lower indoor hand-to-mouth and object-to-mouth frequencies than children of same age group in the United States. We also found that indoor mouthing duration with pacifier was significantly and negatively correlated with indoor mouthing duration with other non-dietary objects. The results of the current study indicate that the mouthing behaviors may be different between different countries or populations with different ethnic or lifestyle characteristics. We conclude that using hand-to-mouth frequency values from the current literature may not be most reliable for estimating non-dietary exposures of young children living in Taiwan or even in other similar Asian countries.


Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats.
Methylphenidate (MPH) is a central stimulant, prescribed for the treatment of attention deficit/hyperactivity disorder. The long-term behavioral consequences of MPH treatment are unknown. In this study, the oxidative stress and neuroinflammation induced by various doses of MPH were investigated. Forty adult male rats were divided into 5 groups; and treated with different doses of MPH for 21 days. Twenty four hours after drug treatment, Open Field Test (OFT) was performed in all animals. At the end of the study, blood cortisol level (BCL) was measured and hippocampus was isolated and oxidative stress and inflammation parameters and histological changes were analyzed. Chronic MPH at all doses decreased central square entries, number of rearing, ambulation distance and time spent in central square in OFT. BCL increased in doses 10 and 20mg/kg of MPH. Furthermore, MPH in all doses markedly increased lipid peroxidation, mitochondrial oxidized glutathione (GSSG) level, Interleukin 1β (IL-1β) and Tumor Necrosis Factor α (TNF-α) in isolated hippocampus. MPH (10 and 20mg/kg) treated groups had decreased mitochondrial reduced glutathione (GSH) content, and reduced superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) activities. 10 and 20mg/kg of MPH change cell density and morphology of cells in Dentate Gyrus (DG) and CA1 areas of hippocampus. Chronic treatment with high doses of MPH can cause oxidative stress, neuroinflammation and neurodegeneration in hippocampus of adult rats.


Ex vivo effects of ibogaine on the activity of antioxidative enzymes in human erythrocytes.
Ibogaine is a naturally occurring alkaloid with psychotropic and metabotropic effects, derived from the bark of the root of the West African Tabernanthe iboga plant. The tribes of Kongo basin have been using iboga as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. Besides, it has been found that this drug has anti-addictive effects. Previous studies have demonstrated that ibogaine changed the quantity of ATP and energy related enzymes as well as the activity of antioxidant enzymes in cells thus altering redox equilibrium in a time manner. In this work, the mechanism of its action was further studied by measuring the effects of ibogaine in human erythrocytes in vitro on ATP liberation, membrane fluidity and antioxidant enzymes activity. Heparinized human blood samples were incubated with ibogaine (10 and 20 μM) at 37°C for 1h. Blood plasma was separated by centrifugation and the levels of ATP and uric acid were measured 10 min after the addition of ibogaine using standard kits. The activity of copper-zinc superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were measured in erythrocytes after incubation period. The stability of SOD1 activity was further tested through in vitro incubation with H2O2 and scanning of its electrophoretic profiles. Membrane fluidity was determined using an electron paramagnetic resonance spin-labelling method. Results showed that ibogaine treatment of erythrocytes in vitro increased ATP concentration in the blood plasma without changes in neither erythrocytes membrane fluidity nor uric acid concentration. Ibogaine also increased SOD1 activity in erythrocytes at both doses applied here. Treatment with 20 μM also elevated GR activity after in vitro incubation at 37°C. Electrophoretic profiles revealed that incubation with ibogaine mitigates H2O2 mediated suppression of SOD1 activity. Some of the effects of ibogaine seem to be mediated through its influence on energy metabolism, redox active processes and the effects of discrete fluctuations of individual reactive oxygen species on different levels of enzyme activities. Overall, ibogaine acts as a pro-antioxidant by increasing activity of antioxidative enzymes and as an adaptagene in oxidative distress.


United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU).
There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as 'strong' and plenary voting revealed 'strong agreement' for 99 (98%) recommendations. The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research.


Physical activity, television viewing time, and retinal vascular caliber.
to examine the associations of physical activity and television (TV) viewing time with retinal vascular caliber in Australian adults. a total of 2024 adults aged 25 yr or older without known diabetes in the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab, 1999-2000), a population-based cross-sectional study, were evaluated. Retinal vascular calibers (both arteriolar and venular calibers) were measured from digital retinal photographs using a computer-assisted method and were summarized into central retinal artery and vein equivalents. Self-reported physical activity time and TV viewing time were obtained using interviewer-administered questionnaires. for physical activity, no statistically significant multivariate relationships emerged for men or for women. After adjusting for confounders (age, sex, education, cigarette smoking, diet quality, waist circumference, systolic blood pressure, plasma glucose levels, serum fibrinogen, serum triglyceride, and physical activity time), men who watched TV for at least 2 h·d had a venular caliber that was 4.71 microm (95% confidence interval = 1.37-8.04 microm, P = 0.006) wider compared with those watching <2 h·d of TV. No significant association with venular caliber was noted in women. these findings provide the first evidence of an association between TV viewing time (a common, leisure time sedentary behavior) and retinal microcirculation. Further research is needed to examine these associations in different populations and by using more comprehensive physical activity and sedentary behavior measures.


Which method is successful in closure of acute oroantral communication? A retrospective study.
This study's purpose is to retrospectively evaluate the success of surgical methods used in treating Oroantral Communication (OAC). This study was designed as a retrospective cohort study on patients who developed OAC after surgery maxillary posterior region. The records of patients previously treated with OAC were scanned through the hospital registry software. A data set was created by recording patients' age, gender, systemic disease, etiological reasons, and surgical methods. The primary predictor variable was the surgical method used to treat OAC. Other variables were age, gender, systemic disease and etiological reasons. The primary outcome was oroantral fistula development after the first surgical intervention. The patients who were positive in clinical examination and Valsalva test on control days were considered unsuccessful. One-way analysis of variance and Kruskal-Wallis tests were used for quantitative variables in more than two groups. Pearson chi-square test was used to compare categorical data. This retrospective cohort study was completed with 605 patients who met the study criteria among 95,883 patients who underwent surgery in the maxillary posterior region. The incidence of OAC was 0.63%. The patients consisted of 238 female and 367 male patients. The mean age was 41.06±14.48 years. Buccal flap and Buccal Fat Pad methods were used most frequently in the treatment. While treatment was completed with the first surgical intervention in 592 (97.85%) patients, OAF developed in 13 (2.15%) patients. No statistically significant relation existed between surgical technique and OAF development (p>0.005). The success rate of the Buccal Flap method was 98.7%, and the Buccal Fat Pad method was 95.8%. The results of this study showed that noninvasive methods in openings smaller than 5 mm and surgical treatment methods in openings larger than 5 mm have a high success rate with the limitations of present study.


Comparison of 61 sequenced Escherichia coli genomes.
Escherichia coli is an important component of the biosphere and is an ideal model for studies of processes involved in bacterial genome evolution. Sixty-one publically available E. coli and Shigella spp. sequenced genomes are compared, using basic methods to produce phylogenetic and proteomics trees, and to identify the pan- and core genomes of this set of sequenced strains. A hierarchical clustering of variable genes allowed clear separation of the strains into clusters, including known pathotypes; clinically relevant serotypes can also be resolved in this way. In contrast, when in silico MLST was performed, many of the various strains appear jumbled and less well resolved. The predicted pan-genome comprises 15,741 gene families, and only 993 (6%) of the families are represented in every genome, comprising the core genome. The variable or 'accessory' genes thus make up more than 90% of the pan-genome and about 80% of a typical genome; some of these variable genes tend to be co-localized on genomic islands. The diversity within the species E. coli, and the overlap in gene content between this and related species, suggests a continuum rather than sharp species borders in this group of Enterobacteriaceae.


Classification of meningiomas-advances and controversies.
Meningiomas are the most frequent primary central nervous system (CNS) tumors. Although approximately 80% of the tumors are slow growing and benign, some subtypes are associated with a less favorable outcome. An adequate classification system aims at providing a tool for estimating recurrence and overall survival of meningioma patients. The 2016 version of the World Health Organization (WHO) classification for CNS tumors constitutes a hallmark for neuropathological tumor classification since genetic alterations and histopathology are combined for a final diagnosis. Although this mainly applies to neuroepithelial tumors in meningioma research and classification the connection of histomorphological features and genetic profiles becomes more and more evident. Here we report on advances and controversies of meningioma classification in the 2016 edition of the WHO classification of CNS tumors. Furthermore we provide an outlook how a future meningioma classification system might look like.


Impact of smoking and smoking cessation on outcomes in bladder cancer patients treated with radical cystectomy.
Cigarette smoking is the best-established risk factor for urothelial carcinoma development. To elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). We retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr). RC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy. Logistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality. There was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p=0.004) and cancer-specific mortality (p=0.016) in univariable analyses and with disease recurrence in multivariable analysis (p=0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p<0.001), LN metastasis (p=0.002), disease recurrence (p<0.001), cancer-specific mortality (p=0.001), and overall mortality (p=0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p<0.001), cancer-specific mortality (HR: 0.42; p<0.001), and overall mortality (HR: 0.69; p=0.012) in multivariable analyses. The study is limited by its retrospective nature. Smoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis.