The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens.
At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens. This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries. The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments. This study was registered on 24 August 2017 at clincaltrials.gov (Registration number: NCT03259269).


Efficacy of pentoxifylline in the treatment of pruritic papular eruption of HIV-infected persons.
Pruritic papular eruption (PPE) of HIV/AIDS is a common manifestation of HIV infection. Unfortunately, treatments for the unremitting pruritus have yielded only partial relief. Our purpose was to assess the clinical efficacy of pentoxifylline in the treatment of pruritus in HIV-infected patients with PPE while measuring its effects on HIV viral load and levels of serum triglycerides, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-4. Eleven of the 12 patients with PPE and HIV infection placed on a regimen of oral pentoxifylline completed the 8-week study. The degree of pruritus both before and after therapy was measured by means of a patient-reported visual analog scale (0 = none and 10 = worst experienced). A global assessment of the number and size of PPE lesions was performed by the investigator, and serum TNF-alpha, IL-4, and triglyceride levels, as well as HIV viral load, were measured. The average degree of pruritus was significantly reduced (p = 0.0009) from 6.5 at baseline examination to 3.6 at the end of the study. Ten of 11 patients experienced a reduction in their pruritus, ranging from 22.6% to 87.3%. The global assessment of PPE lesions decreased from baseline in most patients and increased slightly in one patient. Serum TNF-alpha was detectable in one patient at baseline, but was undetectable at the end of the study period. Similarly, the two patients who had detectable serum IL-4 at baseline had undetectable serum IL-4 levels at the end of the study. Triglyceride levels in six patients decreased an average of 23.9% by week 8. Although when compared with baseline values, HIV viral loads in seven patients decreased, one patient had no change, and three patients had an increase in their viral load at the end of the study, the magnitude of the changes were of little clinical importance. Pentoxifylline is a safe and efficacious treatment of pruritus in HIV-infected patients with PPE. Future controlled studies are needed to confirm the effectiveness of this treatment.


Luxation injuries in primary teeth: a retrospective study in children assisted at an emergency service.
The purpose of this study was to analyze luxation injuries in children between the ages of 0 and 5 years treated at an emergency service department. A total of 1,703 records, corresponding to a period of 10 years at the Emergency Center of the Baby Clinic at Londrina State University, Brazil, were analyzed. The age, gender, etiologic factors, type of injury, injured teeth, treatment and time interval between injury and treatment were determined for each patient. Of the examined records, 409 patients met the study criteria and included a total of 679 injured teeth. Statistical analyses were carried out using the chi-square test with the level of significance set at 5%. Trauma incidence was higher in boys (57.0%) and in children less than two years of age (40.3%). Falling while walking or running was the most predominant etiologic factor (37.7%), and the most prevalent type of injury was subluxation (32.6%). Luxation injuries decreased with increasing age (p = 0.045). Treatment usually occurred within the first 1-15 days and was significantly associated with the type of trauma (p = 0.041). "Monitor only" was the treatment most frequently observed (74.0%). In conclusion, more luxation injuries were found in younger children, predominantly in boys. Falls resulting from walking or running were the etiologic factor most observed, with subluxation as the most common type of trauma. Treatment usually occurred within the first 15 days after the injury. Despite the severity of these injuries, "monitor only" was the eligible treatment.


Suicide and Emo youth subculture--a case analysis.
Depression and suicide present a serious health problem especially for teenagers as they are increasingly diagnosed with mood disorders of different severity, possibly leading to suicidal activity. Reported here is a misfortunate young girl who committed suicide by jumping from high altitude. She left a suicide note which, together with her behavior in the death-preceding period, pointed to her apparently belonging to an Emo subculture. Although few and scarce, most existing articles and reports on Emo subculture found that its members like to focus on negative things, dark premonitions and deprivation of enjoyment, like self harm and suicide but no scientific information are available about the characteristics, trends and possible suicidal tendencies of children and adolescents who belong to this subgroup. It is for the future researches to answer whether this type of behavior and music preference are causal factors for increased suicidal vulnerability, or personal characteristics and anamnesis, upbringing and mental health status are actual sources of the problem.


Interactive segmentation for geographic atrophy in retinal fundus images.
Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12-21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of pathological images still remains an unsolved problem. In this paper we leverage the watershed transform and generalized non-linear gradient operators for interactive segmentation and present an intuitive and simple approach for geographic atrophy segmentation. We compare our approach with the state of the art random walker [5] algorithm for interactive segmentation using ROC statistics. Quantitative evaluation experiments on 100 FAF images show a mean sensitivity/specificity of 98.3/97.7% for our approach and a mean sensitivity/specificity of 88.2/96.6% for the random walker algorithm.


Comparative FISH-Mapping of MC1R, ASIP, and TYRP1 in New and Old World Camelids and Association Analysis With Coat Color Phenotypes in the Dromedary (Camelus dromedarius).
Melanocortin 1 receptor (MC1R), the agouti signaling protein (ASIP), and tyrosinase related protein 1 (TYRP1) are among the major regulators of pigmentation in mammals. Recently, MC1R and ASIP sequence variants were associated with white and black/dark brown coat colors, respectively, in the dromedary. Here we confirmed this association by independent sequencing and mutation discovery of MC1R and ASIP coding regions and by TaqMan genotyping in 188 dromedaries from Saudi Arabia and United States, including 38 black, 53 white, and 97 beige/brown/red animals. We showed that heterozygosity for a missense mutation c.901C > T in MC1R is sufficient for the white coat color suggesting a possible dominant negative effect. Likewise, we confirmed that the majority of black dromedaries were homozygous for a frameshift mutation in ASIP exon 2, except for 4 animals, which were heterozygous. In search for additional mutations underlying the black color, we identified another frameshift mutation in ASIP exon 4 and 6 new variants in MC1R including a significantly associated SNP in 3'UTR. In pursuit of sequence variants that may modify dromedary wild-type color from dark-reddish brown to light beige, we identified 4 SNPs and one insertion in TYRP1 non-coding regions. However, none of these were associated with variations in wild-type colors. Finally, the three genes were cytogenetically mapped in New World (alpaca) and Old World (dromedary and Bactrian camel) camelids. The MC1R was assigned to chr21, ASIP to chr19 and TYRP1 to chr4 in all 3 species confirming extensive conservation of camelid karyotypes. Notably, while the locations of ASIP and TYRP1 were in agreement with human-camelid comparative map, mapping MC1R identified a new evolutionary conserved synteny segment between camelid chromosome 21 and HSA16. The findings contribute to coat color genomics and the development of molecular tests in camelids and toward the chromosome level reference assemblies of camelid genomes.


NPY Impairs Cell Viability and Mitochondrial Membrane Potential Through Ca2+ and p38 Signaling Pathways in Neonatal Rat Cardiomyocytes.
NPY is involved in stress cardiomyopathy. However, the associated mechanism for NPY-induced stress cardiomyopathy remains unclear. In this study, we aimed to explore potential cell signaling pathways that are related to NPY-mediated cell viability in neonatal rat cardiomyocytes. We found that NPY induced cell viability suppression in cultured cardiomyocytes in a dose-dependent manner. After NPY treatment, expression of CaN and p-CAMKII increased significantly, and phosphorylation of p38 but not ERK and JNK was changed. Moreover, NPY treatment significantly increased PGC-1α (the key factor of mitochondrial biogenesis and energy metabolism) expression but decreased mitochondrial membrane potential in cultured cardiomyocytes. More importantly, the blockage of CaN, CAMKII, and p38 signaling pathways by their inhibitors could rescue the reduced cell viability and mitochondrial membrane potential in NPY-treated cardiomyocytes. Collectively, our data demonstrated that NPY mediated cell viability and mitochondrial membrane potential in cardiomyocytes through CaN, CAMKII, and p38 signaling pathways.


Natural Time Analysis of Seismicity within the Mexican Flat Slab before the M7.1 Earthquake on 19 September 2017.
One of the most important subduction zones in the world is located in the Mexican Pacific Coast, where the Cocos plate inserts beneath the North American plate. One part of it is located in the Mexican Pacific Coast, where the Cocos plate inserts beneath the North American plate with different dip angles, showing important seismicity. Under the central Mexican area, such a dip angle becomes practically horizontal and such an area is known as flat slab. An earthquake of magnitude M7.1 occurred on 19 September 2017, the epicenter of which was located in this flat slab. It caused important human and material losses of urban communities including a large area of Mexico City. The seismicity recorded in the flat slab region is analyzed here in natural time from 1995 until the occurrence of this M7.1 earthquake in 2017 by studying the entropy change under time reversal and the variability β of the order parameter of seismicity as well as characterize the risk of an impending earthquake by applying the nowcasting method. The entropy change ΔS under time reversal minimizes on 21 June 2017 that is almost one week after the observation of such a minimum in the Chiapas region where a magnitude M8.2 earthquake took place on 7 September 2017 being Mexico's largest quake in more than a century. A minimum of β was also observed during the period February-March 2017. Moreover, we show that, after the minimum of ΔS, the order parameter of seismicity starts diminishing, thus approaching gradually the critical value 0.070 around the end of August and the beginning of September 2017, which signals that a strong earthquake is anticipated shortly in the flat slab.


Coupling and innervation patterns of interstitial cells of Cajal in the deep muscular plexus of the guinea-pig.
Interstitial cells in the deep muscular plexus (ICC-DMP) are thought to be essential for neurotransmission in the circular muscle. There is evidence for gap junctions within the ICC-DMP network and between ICC-DMP and muscle cells; however, there is no evidence for functional coupling via these gap junctions. In addition, the innervation of individual ICC-DMP has not been studied. We investigated these questions by injecting the dye Lucifer yellow into ICC-DMP of guinea-pig ileum. Nerves were labelled immunohistochemically for protein gene product 9.5. Cells were imaged by confocal microscopy. Most (79%) of the dye-injected ICC-DMP were coupled to one to five other ICC-DMP, and 86% of them were coupled to one to five circular muscle cells. Octanol effectively blocked all coupling. Incubation in pH 6.8-7.0 reduced ICC-ICC coupling to 49% and ICC-muscle coupling to 32%. In contrast, pH 7.8-7.9 increased ICC-ICC and ICC-muscle coupling to 100%. Most ICC somata (95%) and processes (60%) were in close proximity with both nerve fibres and smooth muscle cells. These results provide direct evidence for functional coupling within the ICC-DMP network, and between this network and cells of the outer circular muscle layer and showed that coupling can be affected by pH.


Cytokine modulation of T-lymphocyte activation by intestinal smooth muscle cells.
Interleukin 1beta (IL-beta) and tumor necrosis factor alpha (TNF-alpha) are present in the neuromuscular layers during intestinal inflammation and directly affect intestinal smooth muscle function. We investigated whether IL-1beta and TNF-alpha modulate T-cell activation by murine intestinal smooth muscle cells (ISMCs). alpha- and gamma- actin expression in ISMCs was confirmed using reverse-transcription polymerase chain reaction (RT-PCR). ISMCs were analyzed for class II major histocompatibility complex (MHC), intercellular adhesion molecule 1 (ICAM-1), and B7 before and after exposure to interferon gamma (IFN-gamma; 100 or 1000 U/ mL) in the presence or absence of IL-1beta (10 ng/mL) or TNF-alpha (5 ng/mL) for 72 hours. T-cell proliferation on cytokine-pretreated ISMCs was measured in the absence or presence of anti-B7 antibodies. In a dose-dependent fashion, IFN-gamma-pretreated ISMCs expressed MHC class II, ICAM-1, and B7-2, and stimulated T-cell proliferation. Pretreatment of ISMCs with IL-1beta and IFN-gamma reduced MHC class II and ICAM-1 expression and inhibited T-cell proliferation. When added with 100 U/mL IFN-gamma, TNF-alpha enhanced MHC class II and ICAM-1 expression on ISMCs and T-cell proliferation. However, TNF-alpha and 1000 U/mL IFN-gamma significantly decreased MHC class II expression and T-cell proliferation. Anti-B7-2 monoclonal antibody but not anti-B7-1 inhibited T-cell proliferative responses by >50%. Because IL-1beta, TNF-alpha, and T cells are present in the intestinal muscle layers during inflammation, these cytokines may serve to modulate the activation of T cells in this site.


Thermoresponsive hydrogel with embedded magnetic nanoparticles for the implementation of shrinkable medical microrobots and for targeting and drug delivery applications.
The paper describes the choice of a thermoresponsive material for the implementation of untethered medical microrobots and other microdevices. These entities can be propelled at a specific location in the body using a Magnetic Resonance Imaging (MRI) system while being actuated for various functions such as the release of drugs by a volume change induced by hyperthermia of nanoparticles embedded in the hydrogel. This paper presents some preliminary results showing that poly(N-isopropylacrylamide) (PNIPA) might be an interesting choice, because of the important volume decrease when temperature is increased of some degrees. Using PNIPA based microparticles could be an interesting choice because, according to our results, volume changes are more important when the volume is smaller, and shrinking rate is higher when there are nanoparticles embedded in the hydrogel.


Diversity and distribution of cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae.
Non-toxigenic non-O1, non-O139 Vibrio cholerae strains isolated from both environmental and clinical settings carry a suite of virulence factors aside from cholera toxin. Among V. cholerae strains isolated from coastal waters of southern California, this includes cholix toxin, an ADP-ribosylating factor that is capable of halting protein synthesis in eukaryotic cells. The prevalence of the gene encoding cholix toxin, chxA, was assessed among a collection of 155 diverse V. cholerae strains originating from both clinical and environmental settings in Bangladesh and Mexico and other countries around the globe. The chxA gene was present in 47% of 83 non-O1, non-O139 strains and 16% of 72 O1/O139 strains screened as part of this study. A total of 86 chxA gene sequences were obtained, and phylogenetic analysis revealed that they fall into two distinct clades. These two clades were also observed in the phylogenies of several housekeeping genes, suggesting that the divergence observed in chxA extends to other regions of the V. cholerae genome, and most likely has arisen from vertical descent rather than horizontal transfer. Our results clearly indicate that ChxA is a major toxin of V. cholerae with a worldwide distribution that is preferentially associated with non-pandemic strains.


Early Psoriatic Arthritis Versus Early Seronegative Rheumatoid Arthritis: Role of Dermoscopy Combined with Ultrasonography for Differential Diagnosis.
Exclusion of psoriatic skin/nail lesions is important in differentiating early seronegative rheumatoid arthritis (ERA) from early polyarticular psoriatic arthritis (EPsA) and such manifestations may go unnoticed in atypical or minimally expressed cases. The aim of this study is to assess the usefulness of integrated rheumatological-dermatological evaluation in highlighting dermatological lesions missed on rheumatological examination and to investigate the role of ultrasonography (US) and dermoscopy in improving the recognition of subclinical psoriatic findings. Patients with a new diagnosis of seropositive or seronegative ERA and EPsA with prevalent hands involvement were recruited. All were reassessed for the presence of psoriatic lesions during an integrated rheumatological-dermatological clinical evaluation and underwent hands US and proximal nailfold dermoscopy. Seventy-three consecutive subjects were included in the study: 25 with seropositive ERA, 23 with seronegative ERA, and 25 with EPsA. One-fourth of the subjects initially diagnosed as seronegative ERA presented cutaneous or nail psoriasis on integrated rheumatological-dermatological evaluation, thereby being reclassified as EPsA. The presence of at least 1 extrasynovial feature on hand US and dotted vessels on proximal nailfold dermoscopy was significantly associated with EPsA, with a sensitivity of 68.0% and 96.0% and a specificity of 88.1% and 83.3% for US and dermoscopy, respectively. When used together, specificity for PsA diagnosis raised to 90.5%. Integrated rheumatological-dermatological clinical evaluation may be helpful in identifying patients with EPsA misclassified as seronegative ERA. Additionally, US and dermoscopy may be used as supportive tools in identifying subclinical psoriatic features, which may come in handy in distinguishing EPsA from ERA.


Statistical process control charts for attribute data involving very large sample sizes: a review of problems and solutions.
The use of statistical process control (SPC) charts in healthcare is increasing. The primary purpose of SPC is to distinguish between common-cause variation which is attributable to the underlying process, and special-cause variation which is extrinsic to the underlying process. This is important because improvement under common-cause variation requires action on the process, whereas special-cause variation merits an investigation to first find the cause. Nonetheless, when dealing with attribute or count data (eg, number of emergency admissions) involving very large sample sizes, traditional SPC charts often produce tight control limits with most of the data points appearing outside the control limits. This can give a false impression of common and special-cause variation, and potentially misguide the user into taking the wrong actions. Given the growing availability of large datasets from routinely collected databases in healthcare, there is a need to present a review of this problem (which arises because traditional attribute charts only consider within-subgroup variation) and its solutions (which consider within and between-subgroup variation), which involve the use of the well-established measurements chart and the more recently developed attribute charts based on Laney's innovative approach. We close by making some suggestions for practice.


Health risks from exposure to untreated wastewater used for irrigation in the Mezquital Valley, Mexico: A 25-year update.
Wastewater reuse for agriculture is common worldwide; wastewater treatment, however, is rare in many countries, leading to high potential for exposure to harmful pathogens. Mexico City, one of the largest producers of untreated wastewater for agricultural use worldwide, was the site of key epidemiologic studies conducted in the 1990s. We both reviewed the literature on and conducted a cross-sectional study of diarrheal risk and wastewater contamination to provide an updated assessment of health risks and to inform an upcoming update of the 2006 WHO guidelines on wastewater reuse. We surveyed communities in the Mezquital Valley that use wastewater for irrigation and communities that use well water to compare the prevalence of self-reported diarrheal disease in children under five years old. Wastewater, well water, household environmental samples, and stool samples were collected and analyzed. Communities exposed to wastewater had a higher one-week prevalence of diarrhea (10%) compared to unexposed communities (5%). This association remained in an adjusted modified Poisson regression model (PR = 2.31, 95% CI 1.00, 5.31), but not when limited to households engaged in agriculture. Water quality indicators document differences between irrigation water from the two community groups. These results are in agreement with 25 population studies identified by our review that were conducted since or not included in the 2006 WHO guidelines and show consistent negative impacts of wastewater exposure on health. While overall diarrheal prevalence has declined when compared to studies conducted over 25 years ago in the same region, the association of diarrheal disease and wastewater exposure has remained and possibly increased. With rising urbanization worldwide, attention to these risks and wastewater treatment is becoming increasingly important.


Serum Biomarkers Associated with Malnutrition and Nutritional Risk in Elderly Primary Care Patients: A Cross-sectional Study from Bosnia and Herzegovina.
The aim of the study was to determine the ability of ferritin, haemoglobin, albumin and total cholesterol to identify nutritional risk and malnutrition among elderly primary care patients. The cross-sectional study included 446 elderly adults over 65 years of age from four areas of Bosnia and Herzegovina. In addition to anthropometric, functional, cognitive and biochemical indicators, nutritional status was evaluated using 24-hour recall of meals, the Mini Nutritional Assessment (MNA), and Seniors in the Community: Risk Evaluation for Eating and Nutrition, Version II (SCREEN II). Malnourished/at-risk study respondents had lower mean levels of haemoglobin (P=0.001) and total cholesterol (P<0.001), compared to those with normal nutritional status. Albumin levels significantly differed regarding nutritional status (P=0.004), but not nutritional risk level (P=0.521). Significant differences in serum ferritin levels were not found between malnourished and normally nourished study respondents (P=0.779) Determinants of albumin level were eating more than three meals a day (P<0.001), fewer than two portions of fruit and vegetables a day (P=0.024), drinking one glass of wine (P<0.001) and reporting functional independence (P=0.011). The AUC curves for serum ferritin, albumin and total cholesterol levels in men and women, as well as for haemoglobin levels in women, were poor to fair (AUC<0.800). Although ferritin, haemoglobin, albumin and total cholesterol may be useful biomarkers of nutritional status, their accuracy in diagnosing malnutrition and nutritional risk among elderly primary health care patients is limited.


Prolactin and growth hormone response in induced hypoglycaemia in obese patients.
Obesity represents a metabolic abnormality which brings a disordered hormone response during functional pituitary tests. Twenty obese patients were investigated and growth hormone and prolactin response during the insulin tolerance test were determined and the result was compared to an adequate control group consisting of 10 healthy nonobese patients. Two types of prolactin response were obtained--one normal and one decreased, unlike the growth hormone response which was constantly decreased. The authors discuss the hypothesis according to which the defect of endocrine hypothalamus might be an etiological factor of obesity.


[Markers of endocrine system and inflammation as prognostic risk factors of vascular complications of type 2 diabetes mellitus].
The high risk of cardiovascular complications in patients with type 2 diabetes mellitus is a key problem in modern medicine. In this review, the basic risk factors of vascular complications in diabetes mellitus are described and their prognostic value analysed. Special attention is paid to the evaluation of the role of adipose tissue hormone adiponectin. The anti-inflammatory properties of adiponectin suggest its protective action against atherosclerosis and cardiovascular complications. In this article, we review a number of studies on the relationship between adiponectin and the main cardiovascular risk factors in patients with type 2 diabetes mellitus.


Diagnosis and treatment of osteoporosis before and after admission to long-term care institutions.
Bisphosphonate treatment rates were examined before and after admission to long-term residential care. Bisphosphonate treatment rates were low (16%) pre-admission but doubled after long-term residential care admission (30%). Men were very undertreated for osteoporosis, while a history of falls with injury was not associated with treatment. To determine the rates and independent correlates of bisphosphonate treatment in elderly residents before and after admission to long-term care (LTC) institutions. Information was collected from records of 421 residents of four LTC institutions in Edmonton, Alberta, Canada. Osteoporosis-related diagnoses, treatments, and risk factors including falls in LTC and any adulthood fractures were abstracted. Osteoporosis was defined by physician diagnosis or documented fractures of the hip, spine, or upper extremity. Multivariable analyses were undertaken to determine factors independently associated with bisphosphonate treatment. Mean age was 84 ± 8 years and 290 (70%) were female. Overall, 142 (34%) had previous fractures, 170 (41%) had physician-diagnosed osteoporosis, and 227 (54%) residents met the study's clinical definition of osteoporosis. Of those with osteoporosis, 44 (19%) were men. Before admission, 36 (16%) patients with osteoporosis were treated with bisphosphonates; after admission another 31 (14%) were started on bisphosphonates by LTC physicians. Women were far more likely than men to start bisphosphonate treatment [30 (97%) women vs. 1 (3%) man, adjusted odds ratio (aOR) = 9.20 (95% confidence intervals 1.2,70.5)]. Falls with injury were common [72/227 (31%)] but not associated with bisphosphonate treatment (adjusted p value > 0.5). Rates of pre-admission bisphosphonate treatment were low, but did double after LTC admission. Women were almost ten times more likely to start bisphosphonate treatment than men, although one fifth of those with documented osteoporosis were men. Although falls cause most fractures, a history of falls with injury was not associated with bisphosphonate treatment. Our findings suggest that targeting men and residents with falls for treatment with bisphosphonates might be warranted.


Long-term treatment with ivabradine over 12months in patients with chronic heart failure in clinical practice: Effect on symptoms, quality of life and hospitalizations.
Ivabradine is indicated to control heart rate in otherwise optimally treated patients with chronic heart failure (CHF) and reduced ejection fraction. However, data on its effectiveness outside clinical trials and longer-term effects are scarce. We performed a prospective cohort study involving 249 German resident cardiologists and analyzed the 1-year effectiveness and safety of ivabradine used in CHF outpatients. Data on symptoms, quality of life, and hospitalizations were collected. In total, 767 CHF patients were enrolled to receive ivabradine twice daily, of whom 684 (90%) were still on ivabradine at study end (mean treatment duration 11.2months). The cohort was representative of CHF patients seen in clinical practice in terms of age, risk factor profile, and comorbidities. Concomitant beta-blocker therapy was prescribed in 497 patients (65%). After one year, compared to baseline, heart rate in ivabradine-treated patients was 16bpm lower. This reduction was associated with a significant improvement in NYHA class, and less frequent signs of decompensation (36% to 8%). The proportion of hospitalized patients within 1year decreased from 23% before treatment, to 5% with ivabradine therapy. These improvements in clinical status were accompanied by a reduction in BNP and an increase in LVEF (+5.1% at 1year). Quality of life was significantly improved in all measured dimensions. Adverse drug reactions were noted in 26 patients (3%), and were in line with the known safety profile of ivabradine. Ivabradine was effective and well-tolerated in CHF patients seen in clinical practice throughout 1year of treatment.


Video gaming and working memory: a large-scale cross-sectional correlative study.
Studies have indicated that video gaming is positively associated with cognitive performance in select cognitive domains, but the magnitudes of these associations have been called into question, as they have frequently been based on extreme groups analyses that have compared video gamers with non-gamers. When including the whole range of participants, and not just extreme cases, these effects were observed to reduce markedly (Unsworth et al., 2015). To further study this issue, we compared the associations between video gaming and aspects of working memory (WM) performance in an extreme groups design to those of a design that includes the full range of participants in a large adult sample (n = 503). WM was measured with three composite scores (verbal WM, visuospatial WM, n-back). The extreme groups analyses showed that video gamers performed better than non-gamers on all three WM measures, while the whole sample analyses indicated weak positive associations between the time spent playing video games and visuospatial WM and n-back performance. Thus, study design modulated the effects, but two of the three associations between WM and video gaming were consistent across both analysis techniques. A separate study confirmed that our questionnaire-based estimate of gaming hours was reliable when compared with one-week diaries of videogame playing. While the present cross-sectional results preclude causal inferences, possible mechanisms of WM - videogame playing associations and future research directions are discussed. Overall, our results indicate that cognition - videogame playing relationships, albeit weak, are not solely due to recently discussed methodological artefacts concerning the particular analytical approach and survey reliability.


Lessons learned for surveillance strategies for trachoma elimination as a public health problem, from the evaluation of approaches utilised by Guinea worm and onchocerciasis programmes: A literature review.
A number of neglected tropical diseases are targeted for elimination or eradication. An effective surveillance system is critical to determine if these goals have been achieved and maintained. Trachoma has two related but morphologically different presentations that are monitored for elimination, the active infectious form of trachoma and trachomatous trichiasis (TT), the progression of the disease. There are a number of lessons learnt from the Guinea worm surveillance system that are particularly compatible for TT surveillance and the onchocerciasis surveillance system which can provide insights for surveillance of the infectious form of trachoma. A literature search of peer-reviewed published papers and grey literature was conducted using PUBMED and Google Scholar for articles relating to dracunculiasis or Guinea worm, onchocerciasis and trachoma, along with surveillance or elimination or eradication. The abstracts of relevant papers were read and inclusion was determined based on specified inclusion and exclusion criteria. The credibility and bias of relevant papers were also critically assessed using published criteria. A total of 41 papers were identified that were eligible for inclusion into the review. The Guinea worm programme is designed around a surveillance-containment strategy and combines both active and passive surveillance approaches, with a focus on village-based surveillance and reporting. Although rumour reporting and a monetary incentive for the identification of confirmed Guinea worm cases have been reported as successful for identifying previously unknown transmission there is little unbiased evidence to support this conclusion. More rigorous evidence through a randomised controlled trial, influenced by motivational factors identified through formative research, would be necessary in order to consider applicability for TT case finding in an elimination setting. The onchocerciasis surveillance strategy focuses on active surveillance through sentinel surveillance of villages and breeding sites. It relies on an entomological component, monitoring infectivity rates of black flies and an epidemiological component, tracking exposure to infection in humans. Challenges have included the introduction of relatively complex diagnostics that are not readily available in onchocerciasis endemic countries and target thresholds, which are practically unattainable with current diagnostic tests. Although there is utility in monitoring for infection and serological markers in trachoma surveillance, it is important that adequate considerations are made to ensure evidence-based and achievable guidelines for their utility are put in place. The experiences of both the Guinea worm and onchocerciasis surveillance strategies have very useful lessons for trachoma surveillance, pre- and post-validation. The use of a monetary reward for identification of TT cases and further exploration into the use of infection and serological indicators particularly in a post-validation setting to assist in identifying recrudescence would be of particular relevance. The next step would be a real-world evaluation of their relative applicability for trachoma surveillance.


Bone marrow-derived nonreactive astrocytes in the mouse brain after permanent middle cerebral artery occlusion.
We studied the effect of permanent unilateral middle cerebral artery occlusion (PMCAO) on the generation of bone marrow (BM)-derived astrocytes in female mice previously transplanted with enhanced green fluorescent protein-expressing BM from male donors. In addition to an untreated PMCAO group, one group of mice also received intracerebral infusion of transforming growth factor-alpha, resulting in a decrease in the size of the infarct. Two months after PMCAO, we found a specific type of astrocyte of BM origin in the side of the injury, near the lesion. These astrocytes did not express glial fibrillary acidic protein (GFAP) by conventional fluorescence immunostaining; however, GFAP was easily detectable by tyramide signal amplification. These cells also expressed S100β, confirming their astrocytic character. Unlike the endogenous reactive astrocytes, these BM-derived astrocytes did not proliferate during the first week of ischemia and did not contribute to the glial scar formation. Transforming growth factor-alpha infusion increased the number of BM-derived astrocytes, without affecting their distribution. Interestingly, exclusively by tyramide signal amplification staining, we found that endogenous astrocytes displaying an identical morphology were also present in control mouse and human brains. Our data demonstrate that a subpopulation of nonreactive astrocytes expressing low levels of GFAP can originate from transplanted BM in the ischemic brain. We believe that these cells represent a subpopulation of astrocytes earlier considered to be GFAP negative. The high number of astrocytes with identical morphology and chemical character in control brains suggest that these type of astrocytes may have important functional role in the central nervous system that calls for further studies.


Association of -174G/C interleukin/6 gene polymorphism with the risk of chronic lymphocytic, chronic myelogenous and acute myelogenous leukemias in Turkish patients.
The purpose of this study was to evaluate the relationship between -174G/C interleukin-6 (IL-6) gene promoter polymorphism and susceptibility to chronic lymphocytic (CLL), chronic myelogenous (CML) and acute myelogenous leukemia (AML) in Turkish patients. The frequencies of -174G/C polymorphism were studied in 23 unrelated CLL, 25 CML and 17 AML patients and 30 healthy individuals. Single nucleotide polymorphisms (SNPs) were genotyped by the PCR-RFLP method. A higher prevalence of the C allele was found in CLL, CML and AML patients. However, there were no statistically significant differences regarding either the genotype or the allelic frequencies of the -174G/C polymorphism between CLL, CML and AML cases. These results indicate that C allele is associated with risk of CLL, CML and AML susceptibility in Turkish patients.


HIV and other viruses in surgery: a continued occupational risk.
Hepatitis viruses and HIV represent known and suspected occupational risks to surgeons. A better understanding of these diseases will allow surgeons to provide better and more compassionate care for their patients. It is essential that surgeons view blood as a toxic substance in the operating room. Reducing potential risks can be achieved best by improvement of operating room barriers, modification of techniques used in operations, and a prompt response when blood contact or exposure occurs. Mandatory or socially imposed voluntary testing for HIV testing for patients and physicians (1) is unnecessary; (2) is expensive; and (3) continues the socio-political debate about this disease. It is time for HIV to be treated like a disease and not a social pariah. To do otherwise will result in denial of care for patients and will result in yet another adversarial issue to be interposed between surgeons and patients.


Allopathic Medicine Practitioners' perspectives on facilitating disclosure of traditional medicine use in Gauteng, South Africa: a qualitative study.
Traditional medicine (TM) plays a key role in maintaining health in many societies. Given the requirement for TM disclosure, Allopathic Medicine Practitioners (AMPs) must encourage open communication with patients to persuade those who use TM to disclose. Addressing patient non-disclosure of TM requires this dialogue to be facilitated. We sought to understand and describe how South African AMPs facilitate disclosure of TM use during a consultation with patients who use both TM and allopathic medicine (AM) and how it influences the patients' willingness to disclose TM use. This qualitative exploratory descriptive study on AMPs at Gauteng district public hospitals in South Africa was conducted between 2021 and 2022. Non-probability purposive sampling was employed to select a sample of 14 AMPs. Individual participants were encouraged to share their unique experiences and interpretations of the phenomenon concerning TM use disclosure. The raw transcribed textual data were processed using ATLAS.ti, and inductive content analysis was undertaken following the coding of the content to identify categories. The data revealed four major categories: 'providing a suitable atmosphere for disclosure,' 'encouraging patients to disclose TM usage to AMPs,' 'patient autonomy,' and 'AMP training'. During a consultation with patients who use both TM and AM, participants expressed their experiences and perceptions of TM nondisclosure. They also discussed several methods for encouraging patients to disclose their TM usage, particularly when TM is used concurrently with AM. This study expands on previously reported findings by describing how South African AMPs facilitate the disclosure of TM use during consultation. Many AMPs struggle to initiate TM conversations with their patients which results in non-disclosure. This study revealed that integrating TM into AM training programmes, promoting cross-practice, and creating a safe environment is necessary for the development and application of the most appropriate approaches that would assist in facilitating disclosure.


Data Sharing in Distributed Architectures - Concept and Implementation in HiGHmed.
Medical routine data has the potential to benefit research. However, transferring this data into a research context is difficult. For this reason Medical Data Integration Centers are being established in German university hospitals to consolidate data from primary information systems in a single location. But, small data-sets from one organization can be insufficient to answer a research question adequately. In order to obtain larger data-sets, attempts to merge and provide data-sets across institutional boundaries are made. Therefore, this paper proposes a possible process that can extract, merge, pseudonymize and provide distributed data-sets from several organizations conforming to privacy regulations. This process is executed according to the open standard BPMN 2.0, the underlying process data model is based on HL7 FHIR R4. The proposed solution is currently being deployed at eight university hospitals and one Trusted Third Party in the HiGHmed consortium.


Increased peak flow variability in children with asymptomatic hyperresponsiveness.
The relevance of increased methacholine airway responsiveness detected in children with no current or past symptoms of asthma is not known. We wished to determine whether the presence of airway hyperresponsiveness in asymptomatic children is also associated with abnormal variability of peak expiratory flow (PEF). In 12 asymptomatic children with methacholine hyperresponsiveness, we examined the diurnal variation of peak expiratory flow (PEF) and response to inhaled bronchodilator. Twelve asthmatic children with a comparable range of methacholine hyperresponsiveness, and 12 normal children without methacholine responsiveness, were used as positive and negative controls. The children were aged 11 (range 9-14) yrs. The mean diurnal variation of PEF in those children with asymptomatic hyperresponsiveness was increased at 9.3%, to a degree comparable to the symptomatic asthmatic children (10.7%), and greater than the normal children (5.7%). Methacholine stimulated airway constriction was associated with symptoms in subjects from each group, indicating that the children were capable of perceiving airway constriction. We conclude that asymptomatic children with methacholine airway hyperresponsiveness have other evidence of mild variable airflow obstruction with increased diurnal PEF variability, and can perceive airflow limitation. The lack of symptoms in the children with airway hyperresponsiveness could be due to an insufficient stimulus to cause symptomatic obstruction, or the absence of eosinophilic airway inflammation, which may be a requirement for the development of symptomatic airway hyperresponsiveness.


Meta-analysis reveals responses of coccolithophores and diatoms to warming.
A meta-analysis was conducted to explore the effects of warming on the physiological processes of coccolithophores and diatoms by synthesizing a large number of published literatures. A total of 154 studies consisting 301 experiments were synthesized in this study. Under a projected temperature increase of 3-5 °C by IPCC AR6 at the end of this century, our results suggest that the growth and photosynthetic rate of coccolithophores were significantly enhanced by the rising temperature, while the calcification of coccolithophores was only slightly promoted. Warming also had significantly positive effects on the growth but not photosynthesis of diatoms. In comparison, the effect size of warming on the growth rate of coccolithophores was larger than that of diatoms. However, there was no significant effect of warming on either the ratio of particulate inorganic carbon to particulate organic carbon (PIC:POC) of coccolithophores or the ratio of biogenic silica to carbon (BSi:C) of diatoms. Furthermore, the results reveal latitudinal and size-specific patterns of the effect sizes of warming. For diatoms, the effects of warming on growth were more prominent in high latitudes, specifically for the Southern Hemisphere species. In addition, the effect size of warming on the small-sized diatoms was larger than that of the large-sized diatoms. For coccolithophores, the growth of the Southern Hemisphere temperate strains was significantly promoted by warming. Overall, the results based on the meta-analysis indicate that the projected warming of the end of this century will be more favor to the growth of coccolithophores than that of diatoms, thus potentially affect the competitive advantages of coccolithophores over diatoms; while the mid-to high latitude species/strains of both coccolithophores and diatoms will benefit more than their counterparts in the lower latitudes. Therefore, this study offers novel insights into predicting both the inter- and intra-group competitive advantages of diatoms and coccolithophores under the future warming climate change scenario.


Molecular diversity in gene-encoded, cationic antimicrobial polypeptides.
Gene-encoded, ribosomally synthesised antimicrobial peptides (AMPs) are an ancient and pervasive component of the innate defence mechanisms used by multicellular organisms to control the natural flora and combat pathogens. Bacteria also produce such AMPs to maintain ecological niches free of rival strains. Several hundred different peptides have been characterised to date, and they show a marked degree of variability in both sequence and structure, having evolved to act against distinct microbial targets in different physiological contexts. Many of these peptides appear to function via a selective, but not receptor-mediated, permeabilisation of microbial membranes, while others interact with specific membrane associated or intracellular targets. This review presents a broad survey of different amp structural classes, emphasising both their molecular diversity and underlying similarities. The mode of action of these peptides and potential for biomedical and other application is also briefly discussed.


Unintentional injuries among older adults in northern Sweden--a one-year population-based study.
To study the epidemiology of unintentional injuries in a population of 21,000 Swedish older adults (65+) and to compare the injury incidence with similar data collected two decades earlier. This is a retrospective epidemiologic cross-sectional study based on a 1-year data set of all the 1753 registered injury events from a well-defined population. The injury rate per 1000 individuals was three times higher in the 85+ age group than in the 65-74 age group. The rate was also higher in women than in men aged 75 and older. Fractures, especially on lower and upper extremities, were the most common injuries. Falls in residential care facilities caused the most serious injuries. In transport areas, pedestrian falls and bicyclist crashes were much more common than car crashes. Of the 1753 people injured, 42% were treated as inpatients for a total of 11,569 days; 86% of these days were caused by injury events in the home (57%) or in residential care facilities (29%). Our 65+ age group occupied 69% of all hospital bed-days for trauma in all ages (0-102 years). Over the last two decades, the injury and fracture rate per 1000 individuals has increased by 40-50%, especially in the older age groups. During this time, the nursing strategy for older adults has changed in Sweden. As a result, more people live in their homes nowadays. This increase is distressing especially when we consider the current knowledge of preventive measures. The high number and proportion (>2/3) of inpatient trauma days for these age groups are a heavy burden for the medical sector. These facts call for more effective preventive measures, especially in the home and in residential care facilities, to minimize the negative health effects and the rising health costs.


Treatment of severe atopic dermatitis with a combination of subcutaneous allergen immunotherapy and cyclosporin.
The clinical efficacy of subcutaneous allergen immunotherapy (SCIT) for the treatment of patients with severe atopic dermatitis (AD) using house dust mite (HDM) extract has been reported. Cyclosporin has been regarded as an effective medication for treatment of severe AD. In this study, we investigated a clinical usefulness of combined treatment with SCIT and cyclosporin in patients with severe AD. Nine patients with severe AD and hypersensitivity to HDM were treated with a combination of SCIT using HDM extract and cyclosporin for 12 months. The primary efficacy outcome was the change in the standardized clinical severity scoring system for AD (SCORAD) values, measured at 6 and 12 months, in comparison with the values at baseline. Daily dose of cyclosporin was decreased or discontinued according to the degrees of clinical improvements in individual patients. In 8 patients who completed 12 months of treatment, the SCORAD values significantly decreased from 71.5 ± 15.5 (mean ± SD) at baseline to 20.4 ± 14.6 at 6 months and 26.3 ± 13.6 at 12 months (Wilcoxon signed-rank test, p=0.01), and no significant systemic side effects were observed. Cyclosporin was discontinued in 4 of 8 patients within 8 months after starting the combined treatment. In this study, combined treatment with SCIT and cyclosporin resulted in significant clinical improvements in patients with severe AD. Further studies are needed to test the clinical usefulness of this combined treatment for patients with severe AD.


Endovascular treatment in the multimodality management of brain arteriovenous malformations: report of the Society of NeuroInterventional Surgery Standards and Guidelines Committee.
The purpose of this review is to summarize the data available for the role of angiography and embolization in the comprehensive multidisciplinary management of brain arteriovenous malformations (AVMs METHODS: We performed a structured literature review for studies examining the indications, efficacy, and outcomes for patients undergoing endovascular therapy in the context of brain AVM management. We graded the quality of the evidence. Recommendations were arrived at through a consensus conference of the authors, then with additional input from the full Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee and the SNIS Board of Directors. The multidisciplinary evaluation and treatment of brain AVMs continues to evolve. Recommendations include: (1) Digital subtraction catheter cerebral angiography (DSA)-including 2D, 3D, and reformatted cross-sectional views when appropriate-is recommended in the pre-treatment assessment of cerebral AVMs. (I, B-NR) . (2) It is recommended that endovascular embolization of cerebral arteriovenous malformations be performed in the context of a complete multidisciplinary treatment plan aiming for obliteration of the AVM and cure. (I, B-NR) . (3) Embolization of brain AVMs before surgical resection can be useful to reduce intraoperative blood loss, morbidity, and surgical complexity. (IIa, B-NR) . (4) The role of primary curative embolization of cerebral arteriovenous malformations is uncertain, particularly as compared with microsurgery and radiosurgery with or without adjunctive embolization. Further research is needed, particularly with regard to risk for AVM recurrence. (III equivocal, C-LD) . (5) Targeted embolization of high-risk features of ruptured brain AVMs may be considered to reduce the risk for recurrent hemorrhage. (IIb, C-LD) . (6) Palliative embolization may be useful to treat symptomatic AVMs in which curative therapy is otherwise not possible. (IIb, B-NR) . (7) The role of AVM embolization as an adjunct to radiosurgery is not well-established. Further research is needed. (III equivocal, C-LD) . (8) Imaging follow-up after apparent cure of brain AVMs is recommended to assess for recurrence. Although non-invasive imaging may be used for longitudinal follow-up, DSA remains the gold standard for residual or recurrent AVM detection in patients with concerning imaging and/or clinical findings. (I, C-LD) . (9) Improved national and international reporting of patients of all ages with brain AVMs, their treatments, side effects from treatment, and their long-term outcomes would enhance the ability to perform clinical trials and improve the rigor of research into this rare condition. (I, C-EO) . Although the quality of evidence is lower than for more common conditions subjected to multiple randomized controlled trials, endovascular therapy has an important role in the management of brain AVMs. Prospective studies are needed to strengthen the data supporting these recommendations.


Temsirolimus, an mTOR inhibitor for treatment of patients with advanced renal cell carcinoma.
Temsirolimus is a targeted therapy that inhibits mammalian target of rapamycin (mTOR), a central regulator of tumor cell responses to growth stimuli. Temsirolimus has a broad anticancer activity profile that impacts tumor cell growth, proliferation, and survival through its specific inhibition of mTOR. In a randomized phase III trial that enrolled previously untreated patients with advanced renal cell carcinoma (RCC) and poor prognostic features, temsirolimus significantly prolonged overall survival compared with interferon-alpha, a standard therapy (p = 0.008). Because of the results, temsirolimus was approved by the U. S. Food and Drug Administration for treatment and is considered a first-line treatment for patients with advanced RCC with poor prognostic features. Temsirolimus is administered at a flat weekly IV dose of 25 mg given over 30-60 minutes. Gastrointestinal disorders (stomatitis, anorexia, nausea, diarrhea, and vomiting), rash, fatigue, edema, infections, and dyspnea, as well as hematologic and metabolic laboratory abnormalities occur in patients receiving temsirolimus. Metabolic side effects include hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and hypophosphatemia. Most adverse reactions associated with temsirolimus can be managed medically or addressed by supportive measures. Nurses can improve patient outcomes through early recognition of side effects and prompt interventions.


Empathetic listening boosts nostalgia levels and positive emotions in autobiographical narrators.
Nostalgic memories serve to increase human resilience. Here, we hypothesized that emotional impressions on a narrator's nostalgic memory change depending on the level of empathy in the listener's response. This independent-measures study was conducted in 120 healthy Japanese undergraduates (66 women, 54 men, M age 20.3 ± 1.9 years). Nostalgia was induced using a medley of Japanese pop songs from the years 2006-2010. Thirty minutes later each participant was randomly allocated to be interviewed by an experimenter who applied one of three listening conditions: empathy, non-empathy, or non-response. Output measures were participant's talking time, nostalgia ratings, and positive and negative emotion ratings. Data were analyzed by analysis of variance followed by a multiple comparisons test. Empathy group participants had a significantly longer talking time than non-empathy or non-response participants, higher nostalgia scores than non-response participants, and higher positive emotion scores than non-empathy and non-response participants, but lower negative emotion scores than non-reponse participants. Participants were then divided into a less nostalgia-prone and a more nostalgia-prone group using the Southampton Nostalgia Rating Scale and the data were reanalyzed for each experimental condition. The results showed that a person more prone to nostalgia felt more nostalgic and more positive toward their autobiographical memory than those who are less nostalgia-prone. The present findings have implications for human interaction in everyday life and in therapeutic settings.


The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly.
This study aimed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males, and to further understand the potential neurophysiological mechanisms mediating the changes. The study assessed forty-eight healthy elderly males randomly assigned to exercise (n = 24) or control (n = 24) groups. The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm, as well as growth hormone (GH), insulin-like growth factor-1 (IGF-1), and homocysteine levels at baseline and after either a 12 month intervention of resistance exercise training or control period. The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months. The exercise group exhibited improved reaction times (RTs), sustained P3a and P3b amplitudes, increased levels of serum IGF-1, and decreased levels of serum homocysteine. The changes in IGF-1 levels were significantly correlated with the changes in RT and P3b amplitude of the oddball condition in the exercise group. In conclusion, significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly. These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals, possibly mediated by IGF-1.


[New antiviral agents in the treatment of chronic hepatitis B and C].
Interferon (IFN) is the drug universally used in the treatment of B and C chronic hepatitis. Due to its low efficacy, 40% in the treatment of chronic hepatitis B and 10-20% in the treatment of chronic hepatitis C, and to its adverse events, in some cases severe, new antiviric molecules are being investigated. Lamivudin, famciclovir and the association of ribavirin and IFN are the more relevant and will be clinically accepted in an immediate future. It is also probable that rigid indications for hepatic transplantation in patients with liver cirrhosis by B virus change in the next years due to the use of these new antiviric drugs before and after transplantation. In this revision we analyze the current situation of these new therapies. However, most information come from pilot studies, and multicentric randomized studies are needed to establish firm conclusions about the role that these new therapies are going to play in the treatment of viral chronic hepatitis.


[Non-Hodgkin's lymphoma of the stomach. A case report].
Clinical supervision diffuse large B-cell lymphoma of the stomach at the patient of young age is presented. Difficulties of the differential diagnostics of lymphom have been caused by macroscopical polyphormism. With the purpose of verification of disease are used the chromoendoscopy and immunohistochemical research.


Predicting Adverse Drug-Drug Interactions with Neural Embedding of Semantic Predications
The identification of drug-drug interactions (DDIs) is important for patient safety; yet, compared to other pharmacovigilance work, a limited amount of research has been conducted in this space. Recent work has successfully applied a method of deriving distributed vector representations from structured biomedical knowledge, known as Embedding of Semantic Predications (ESP), to the problem of predicting individual drug side effects. In the current paper we extend this work by applying ESP to the problem of predicting polypharmacy side-effects for particular drug combinations, building on a recent reconceptualization of this problem as a network of drug nodes connected by side effect edges. We evaluate ESP embeddings derived from the resulting graph on a side-effect prediction task against a previously reported graph convolutional neural network approach, using the same data and evaluation methods. We demonstrate that ESP models perform better, while being faster to train, more re-usable, and significantly simpler.


'I told him I'm gonna get it': intimate partner birth control communication among homeless young women.
Homeless youth have disproportionately high rates of unintended pregnancy and STIs. Enhancing communication between sexual partners can improve sexual health outcomes, yet little is known about this topic among homeless youth; therefore, this study aimed to examine how homeless youth communicate with their partners about birth control. In-depth semi-structured interviews regarding intimate partner birth control communication were conducted with 10 homeless young women aged 14-22 years following their completion of a comprehensive sexual health program (Wahine Talk). We transcribed the interviews verbatim and used a structured, inductive analytic approach to identify themes. Analysis identified three themes: Getting the Conversation Started, Conversation Content, and Impact of Conversation. Birth control conversations were prompted by programme participation, birth control side effects, and family members' interest in homeless youth becoming pregnant. Barriers to communication included fear and mistimed conversations (e.g. during the initiation of sex). Homeless young people shared simultaneous desires to delay pregnancy and concerns about side effects of birth control use. Discussions about birth control with their partners may demonstrably improve homeless youth's intimate relationships and family planning efforts. Providers can support homeless young women by helping them plan conversation timing and addressing fear, including the risk of violence.


Mature bone marrow erythroid burst-forming units do not require T cells for induction of erythropoietin-dependent differentiation.
Cell-cell interactions between mature T cells and peripheral blood null cells induce erythropoietin-stimulated differentiation of peripheral blood-derived erythroid progenitors. By the use of complement-fixing cytolytic murine hybridoma and antibody uniquely reactive with mature T lymphocytes, this dependence of immature peripheral blood erythroid burst-forming unit (BFU-E) differentiation upon mature T cells or a T cell conditioned medium is confirmed. By using the same antibody, it is demonstrated that the differentiation of mature bone marrow BFU-E does not require either mature T cells or lymphocyte mitogenic factor. These findings do not preclude the presence in the bone marrow of other cells, perhaps even immature T cells, that influence erythropoietin-dependent erythroid differentiation of mature marrow BFU-E.


Cell plasticity in epithelial homeostasis and tumorigenesis.
The adult organism is characterized by remarkable plasticity, which enables efficient regeneration and restoration of homeostasis after damage. When aberrantly activated, this plasticity contributes to tumour initiation and progression. Here we review recent advances in this field with a focus on cell fate changes and the epithelial-mesenchymal transition-two distinct, yet closely related, forms of plasticity with fundamental roles in homeostasis and cancer.


Inactivation of batrachotoxin-modified Na+ channels in GH3 cells. Characterization and pharmacological modification.
Batrachotoxin (BTX)-modified Na+ currents were characterized in GH3 cells with a reversed Na+ gradient under whole-cell voltage clamp conditions. BTX shifts the threshold of Na+ channel activation by approximately 40 mV in the hyperpolarizing direction and nearly eliminates the declining phase of Na+ currents at all voltages, suggesting that Na+ channel inactivation is removed. Paradoxically, the steady-state inactivation (h infinity) of BTX-modified Na+ channels as determined by a two-pulse protocol shows that inactivation is still present and occurs maximally near -70 mV. About 45% of BTX-modified Na+ channels are inactivated at this voltage. The development of inactivation follows a sum of two exponential functions with tau d(fast) = 10 ms and tau d(slow) = 125 ms at -70 mV. Recovery from inactivation can be achieved after hyperpolarizing the membrane to voltages more negative than -120 mV. The time course of recovery is best described by a sum of two exponentials with tau r(fast) = 6.0 ms and tau r(slow) = 240 ms at -170 mV. After reaching a minimum at -70 mV, the h infinity curve of BTX-modified Na+ channels turns upward to reach a constant plateau value of approximately 0.9 at voltages above 0 mV. Evidently, the inactivated, BTX-modified Na+ channels can be forced open at more positive potentials. The reopening kinetics of the inactivated channels follows a single exponential with a time constant of 160 ms at +50 mV. Both chloramine-T (at 0.5 mM) and alpha-scorpion toxin (at 200 nM) diminish the inactivation of BTX-modified Na+ channels. In contrast, benzocaine at 1 mM drastically enhances the inactivation of BTX-modified Na+ channels. The h infinity curve reaches minimum of less than 0.1 at -70 mV, indicating that benzocaine binds preferentially with inactivated, BTX-modified Na+ channels. Together, these results imply that BTX-modified Na+ channels are governed by an inactivation process.


Distinct roles of second and third intracellular loops of human endothelin receptors in the selective activation of G alpha s/G alpha i.
Endothelin-1 (ET-1) stimulated cAMP formation in Chinese hamster ovary cells stably expressing human wild-type ET(A) (CHO/hET(A) cells) and inhibited the formation in cells expressing human wild-type ETB (CHO/hETB cells), suggesting a selective coupling of hET(A) and hETB with G alpha s and G alpha i, respectively. To find out the receptor domain(s) that determined the selective coupling, a series of chimeric receptors between hET(A) and hETB were expressed on CHO cells and the effect of ET-1 on cAMP formation in each cell line was tested. hET(A) with the replacement of the second and/or third intracellular loop (ICLII and/or III) to the corresponding region(s) of hETB failed to transmit the stimulatory effect of ET-1. hETB with the replacement of ICLIII to the corresponding region of hET(A) failed to transmit the inhibitory effect of ET-1. A chimeric receptor with ICLII of hETB and with ICLIII of hET(A) failed to transmit either effect. These results indicated the roles of ICLII and III of hETR as major determinants of the selective coupling of hET(A)/hETB with G alpha s/G alpha i, respectively.


Does Metabolic Rate Increase Linearly with Running Speed in all Distance Runners?
Running economy (oxygen uptake or metabolic rate for running at a submaximal speed) is one of the key determinants of distance running performance. Previous studies reported linear relationships between oxygen uptake or metabolic rate and speed, and an invariant cost of transport across speed. We quantified oxygen uptake, metabolic rate, and cost of transport in 10 average and 10 sub-elite runners. We increased treadmill speed by 0.45 m · s -1 from 1.78 m · s -1 (day 1) and 2.01 m · s -1 (day 2) during each subsequent 4-min stage until reaching a speed that elicited a rating of perceived exertion of 15. Average runners' oxygen uptake and metabolic rate vs. speed relationships were best described by linear fits. In contrast, the sub-elite runners' relationships were best described by increasing curvilinear fits. For the sub-elites, oxygen cost of transport and energy cost of transport increased by 12.8% and 9.6%, respectively, from 3.58 to 5.14 m · s -1 . Our results indicate that it is not possible to accurately predict metabolic rates at race pace for sub-elite competitive runners from data collected at moderate submaximal running speeds (2.68-3.58 m · s -1 ). To do so, metabolic rate should be measured at speeds that approach competitive race pace and curvilinear fits should be used for extrapolation to race pace.


Determining the effect of long-term dexamethasone and prednisolone treatment on sugammadex
Background/aim: We aimed to investigate the effect of long-term use of dexamethasone and prednisolone on the reversal effect of sugammadex. Materials and methods: TTwenty-four male Wistar albino rats were divided into three groups. Dexamethasone (600 µg/kg) was given to group D, prednisolone (10 mg/kg) was given to group P, and an equivalent volume of saline per day was administered intraperitoneally to group S for 14 days, respectively. The left hemidiaphragm with attached phrenic nerve was maintained in Krebs solution. Sugammadex (30 µmol/L) was applied while rocuronium (10 µmol/L) was present in an organ bath and a single twitch was obtained. The right hemidiaphragm was used for both adult ( ε-subunit) and fetal nicotinic acetylcholine receptor (AChR) ( ε-subunit) determination using polymerase chain reaction. Results: All animals lost weight, except group S. The mean baseline single-twitch tension was lower in both group D (14.4 ± 1.7 g) and group P (12.68 ± 0.05 g) than group S (16.8 ± 0.5 g) (P < 0.001). When sugammadex was added to the organ bath while rocuronium was present, the single twitch was measured to be lower in both group D (11.7 ± 0.7 g) and group P (11.5 ± 0.78 g) than group S (16.5 ± 0.24 g) (P < 0.001). Ɣ-AChR expression was higher in both dexamethasone and prednisolone than in saline. Conclusion: Long-term medication with dexamethasone and prednisolone caused muscle weakness, resistance to neuromuscular blockers, and upregulation of immature Ɣ-AChR and reduced the neuromuscular reversal effect of sugammadex.


Combined clinical and ultrasound criteria could accurately predict the Y chromosome in primary amenorrhea patient.
This study aimed to assess the combined clinical and ultrasound criteria as a diagnostic tool for screening the Y chromosome related to primary amenorrhea. This cross-sectional study involving 59 subjects was taken from medical records at the Reproductive Immunoendocrinology Polyclinic of Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. The medical records of subjects were then cross-checked with karyotyping analysis results. Sensitivity, specificity, and predictive values were analyzed to assess the criteria. Two subjects were presented with a Y chromosome, and one without a Y chromosome was misclassified into another group. After analysis, we found that combined clinical and ultrasound criteria could predict the Y chromosome related to primary amenorrhea with 95.9% accuracy, with sensitivity and specificity of 80% and 97.96%, respectively. Combined clinical and ultrasound criteria (introduced as Kanadi Sumapraja Criteria) could be used as a diagnostic tool for screening a Y chromosome related to primary amenorrhea.


Mutations affecting iron transport in Escherichia coli.
A mutant of Escherichia coli K-12 unable to form an essential component of the enterochelin-dependent iron transport system has been isolated. This strain carries a mutation in a gene designated fep, mapping close to two genes, entA and entD, concerned with enterochelin synthesis. Strain AN102, which carries the fep(-) allele, accumulates large quantities of enterochelin and gives a growth response to sodium citrate. The cytochrome b(1) and total iron content, and the measurement of the uptake of (55)Fe(3+), indicate an impairment of the enterochelin-dependent iron transport system. The growth response to sodium citrate is related to the presence, in strain AN102, of an inducible citrate-dependent iron transport system.


Predicting 3D pose in partially overlapped X-ray images of knee prostheses using model-based Roentgen stereophotogrammetric analysis (RSA).
After total knee replacement, the model-based Roentgen stereophotogrammetric analysis (RSA) technique has been used to monitor the status of prosthetic wear, misalignment, and even failure. However, the overlap of the prosthetic outlines inevitably increases errors in the estimation of prosthetic poses due to the limited amount of available outlines. In the literature, quite a few studies have investigated the problems induced by the overlapped outlines, and manual adjustment is still the mainstream. This study proposes two methods to automate the image processing of overlapped outlines prior to the pose registration of prosthetic models. The outline-separated method defines the intersected points and segments the overlapped outlines. The feature-recognized method uses the point and line features of the remaining outlines to initiate registration. Overlap percentage is defined as the ratio of overlapped to non-overlapped outlines. The simulated images with five overlapping percentages are used to evaluate the robustness and accuracy of the proposed methods. Compared with non-overlapped images, overlapped images reduce the number of outlines available for model-based RSA calculation. The maximum and root mean square errors for a prosthetic outline are 0.35 and 0.04 mm, respectively. The mean translation and rotation errors are 0.11 mm and 0.18°, respectively. The errors of the model-based RSA results are increased when the overlap percentage is beyond about 9%. In conclusion, both outline-separated and feature-recognized methods can be seamlessly integrated to automate the calculation of rough registration. This can significantly increase the clinical practicability of the model-based RSA technique.


Methane emissions from upland forest soils and vegetation.
Most work on methane (CH(4)) emissions from natural ecosystems has focused on wetlands because they are hotspots of CH(4) production. Less attention has been directed toward upland ecosystems that cover far larger areas, but are assumed to be too dry to emit CH(4). Here we review CH(4) production and emissions in upland ecosystems, with attention to the influence of plant physiology on these processes in forests. Upland ecosystems are normally net sinks for atmospheric CH(4) because rates of CH(4) consumption exceed CH(4) production. Production of CH(4) in upland soils occurs in microsites and may be common in upland forest soils. Some forests switch from being CH(4) sinks to CH(4) sources depending on soil water content. Plant physiology influences CH(4) cycling by modifying the availability of electron donors and acceptors in forest soils. Plants are the ultimate source of organic carbon (electron donor) that microbes process into CH(4). The availability of O(2) (electron acceptor) is sensitive to changes in soil water content, and therefore, to transpiration rates. Recently, abiotic production of CH(4) from aerobic plant tissue was proposed, but has not yet been verified with independent data. If confirmed, this new source is likely to be a minor term in the global CH(4) budget, but important to quantify for purposes of greenhouse gas accounting. A variety of observations suggest that our understanding of CH(4) sources in upland systems is incomplete, particularly in tropical forests which are stronger sources then expected.


An international classification of retinopathy of prematurity. The Committee for the Classification of Retinopathy of Prematurity.
Because of modern life-support systems capable of keeping tiny premature infants alive, retinopathy of prematurity has recurred. No classification system currently available adequately describes the observations of the disease being made today. A new classification system, the work of 23 ophthalmologists from 11 countries, is presented in an attempt to meet this need. It emphasizes the location and the extent of the disease in the retina as well as its stages. The term "plus" is employed with the stage to denote progressive vascular incompetence. A computer-compatible diagram for recording the results of the examination employing the new classification system is furnished.


Biomechanical effect of mineral heterogeneity in trabecular bone.
Due to daily loading, trabecular bone is subjected to deformations (i.e., strain), which lead to stress in the bone tissue. When stress and/or strain deviate from the normal range, the remodeling process leads to adaptation of the bone architecture and its degree of mineralization to effectively withstand the sustained altered loading. As the apparent mechanical properties of bone are assumed to depend on the degree and distribution of mineralization, the goal of the present study was examine the influences of mineral heterogeneity on the biomechanical properties of trabecular bone in the human mandibular condyle. For this purpose nine right condyles from human dentate mandibles were scanned and evaluated with a microCT system. Cubic regional volumes of interest were defined, and each was transformed into two different types of finite element (FE) models, one homogeneous and one heterogeneous. In the heterogeneous models the element tissue moduli were scaled to the local degree of mineralization, which was determined using microCT. Compression and shear tests were simulated to determine the apparent elastic moduli in both model types. The incorporation of mineralization variation decreased the apparent Young's and shear moduli by maximally 21% in comparison to the homogeneous models. The heterogeneous model apparent moduli correlated significantly with bone volume fraction and degree of mineralization. It was concluded that disregarding mineral heterogeneity may lead to considerable overestimation of apparent elastic moduli in FE models.


Identification of differentially expressed genes in the brain of Sebastiscus marmoratus in response to tributyltin exposure.
Tributyltin (TBT), a ubiquitous marine environmental contaminant, has been reported to affect functioning of the central nervous system. However, the mechanism of its neurotoxicity remains unknown. In this study, an Anneal Control Primer-differential display Reverse Transcription-PCR method was employed to investigate differentially expressed genes in the brain of Sebastiscus marmoratus in response to acute TBT exposure. A total of 18 gene sequences were identified as having the potential for being differentially expressed, of which 9 could be identified with homologous database sequences. The expression profiles of 4 genes, namely cytochrome c oxidase subunit II, GRB2-associated binding protein 2, adaptor-related protein complex 2, and guanine nucleotide exchange factor p532, were analyzed in the brain using real time fluorescence quantitative PCR after treatment with 10, 100 and 1000 ng/L of TBT for 50 days. The results showed that chronic exposure to TBT induced down-regulation of these genes in a dose dependent manner. The present study provided a basis for studying the response of fish to TBT exposure and allowed the characterization of new potential neurotoxic biomarkers of TBT contamination in seawater.


Dietary modeling shows that substitution of whole-grain for refined-grain ingredients of foods commonly consumed by US children and teens can increase intake of whole grains.
Currently available whole-grain foods are not frequently consumed, and few children achieve the whole-grain intake recommendation. To investigate the influence on whole-grain consumption of substituting whole-grain for refined-grain ingredients of foods commonly consumed by children. Secondary cross-sectional analysis of publicly available food consumption data collected by the US Department of Agriculture. A nationally representative sample of US children aged 9 to 18 years (n=2,349) providing 24-hour dietary recall data in the 2003-2004 National Health and Nutrition Examination Survey. Whole-grain intake was modeled by replacing varying proportions of refined flour contained in foods such as pizza crust, pasta, breads, and other baked goods with whole-wheat flour, and by replacing a proportion of white rice with brown rice. Replacement levels were based on the acceptability of whole-grain foods tested among children in elementary schools, and ranged from 15% to 50%; the majority were ≤25%. Sample-weighted mean premodeled and postmodeled whole-grain intake, standard errors, and statistical significance of differences between demographic subgroups were determined using SUDAAN (version 9.0.3, 2007, Research Triangle Institute, Research Triangle Park, NC). Whole-grain intake increased 1.7 oz eq per day (from 0.5 to 2.2 oz eq/day). Premodeled and postmodeled whole-grain intakes were 6% and 28%, respectively, of total grain intake (7.7 oz eq/day). Major sources of postmodeled whole-grain intakes were breads/rolls (28.0%); pizza (14.2%); breakfast cereals (11.0%); rice/pasta (10.6%); quick breads such as tortillas, muffins, and waffles (10.8%); other baked goods (9.9%); and grain-based savory snacks other than popcorn (7.3%). Premodeled whole-grain intake differed by poverty level, but postmodeled whole-grain intake did not. The substitution of whole grain for a specific proportion of refined grain ingredients of commonly consumed foods increased whole-grain intake and reduced disparities between demographic subgroups of children and teens.


Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats.
The Flinders Sensitive Line of rats (FSL) has been selectively bred to have increased sensitivity to cholinergic drugs. Typically, these rats react with twice as great a hypothermic effect to muscarinic agonists such as oxotremorine, as do similarly bred Flinders Resistant Line rats (FRL). We compared the effects of three chemically different calcium channel inhibitors (diltiazem, nicardipine and verapamil) on the hypothermia induced in FRL and FSL rats by oxotremorine (0.2 mg kg-1 s.c.). Each drug was injected i.p. in a dose of 20 mumol kg-1 30 min before oxotremorine. Methylatropine (2 mg kg-1 s.c.) was administered 15 min before oxotremorine to block the peripheral effects of the agonist. The hypothermic effect of oxotremorine in FSL rats was antagonized by nicardipine and diltiazem. In contrast, verapamil failed to influence the hypothermic response in FSL rats. Verapamil significantly (P less than 0.05) augmented oxotremorine hypothermia in FRL rats. Diltiazem and nicardipine were without effect on oxotremorine-induced hypothermia in FRL rats. There were no significant changes in temperature in separate groups of FRL and FSL rats treated with calcium channel inhibitors alone.


[The assessment of the mental health of children with psychosomatic diseases].
The mental health of children and adolescents who suffered from gastrointestinal diseases due to psychosomatic causes (duodenal ulcer, chronic gastroduodenitis) was examined. Those with the diseases are a group at risk for nervous and mental disorders, and impaired psychophysical adaptation.


WASp Is Essential for Effector-to-Memory conversion and for Maintenance of CD8+T Cell Memory.
Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, micro thrombocytopenia, eczema, and a high incidence of autoimmunity and malignancy. A defect in the T cell compartment is thought to be a major cause of immunodeficiency in patients with WAS; However, whether the antigen specific T memory cell is altered has not been extensively studied. Here, we examined the expansion/contraction kinetics of CD8+ memory T cells and their maintenance in WASp-/- mice. The results showed that WAS protein (WASp) is not required for differentiation of CD8+ effector T cells; however, CD8+ T cells from WASp-/- mice were hyperactive, resulting in increased cytokine production. The number of CD8+ T memory cells decreased as mice aged, and CD8+ T cell recall responses and protective immunity were impaired. WASp-deficient CD8+ T cells in bone marrow chimeric mice underwent clonal expansion, but the resulting effector cells failed to survive and differentiate into CD8+ memory T cells. Taken together, these findings indicate that WASp plays an intrinsic role in differentiation of CD8+ memory T cells.


Perioperative tobacco interventions by Chinese anesthesiologists: practices and attitudes.
The prevalence of cigarette smoking in China is high. Surgery provides an excellent opportunity for patients to quit smoking, and anesthesiologists can play an important role in tobacco control. However, little is known about the practices, knowledge, and attitudes of Chinese anesthesiologists regarding perioperative tobacco interventions. Chinese anesthesiologists were surveyed at a national meeting in 2009, with written questionnaires distributed to 800 practicing anesthesiologists. The survey response rate was 60.3%, and 10% of respondents themselves smoked cigarettes. Most (73%) of them frequently or almost always asked about smoking status; 51% advised about the health risk of tobacco use; and 60% advised patients to quit. Compared with nonsmokers, smokers were significantly less likely to advise about the health risks of smoking and quitting. A high proportion of respondents had accurate perceptions of perioperative and long-term health risks of smoking. Although most respondents agreed that advising patients to quit is the responsibility of anesthesiologists and the perioperative period is a good time to help patients quit smoking, few knew how to counsel about smoking or help patients get the help they needed to quit. Nonetheless, most of the respondents were willing to learn about perioperative interventions and spend an extra 5 min to help patients quit smoking. Given their adequate knowledge of health risks of smoking, strong perception of responsibilities, and willingness to participate in tobacco control, Chinese anesthesiologists are poised to play a significant role in tobacco control in China that could improve perioperative outcomes and promote long-term health.


Vasopressin V2 receptor expression along rat, mouse, and human renal epithelia with focus on TAL.
In renal epithelia, vasopressin influences salt and water transport, chiefly via vasopressin V(2) receptors (V(2)Rs) linked to adenylyl cyclase. A combination of vasopressin-induced effects along several distinct portions of the nephron and collecting duct system may help balance the net effects of antidiuresis in cortex and medulla. Previous studies of the intrarenal distribution of V(2)Rs have been inconclusive with respect to segment- and cell-type-related V(2)R expression. Our study therefore aimed to present a high-resolution analysis of V(2)R mRNA expression in rat, mouse, and human kidney epithelia, supplemented with immunohistochemical data. Cell types of the renal tubule were identified histochemically using specific markers. Pronounced V(2)R signal in thick ascending limb (TAL) was corroborated functionally; phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter type 2 (NKCC2) was established in cultured TAL cells from rabbit and in rats with diabetes insipidus that were treated with the V(2)R agonist desmopressin. We found solid expression of V(2)R mRNA in medullary TAL (MTAL), macula densa, connecting tubule, and cortical and medullary collecting duct and weaker expression in cortical TAL and distal convoluted tubule in all three species. Additional V(2)R immunostaining of kidneys and rabbit TAL cells confirmed our findings. In agreement with strong V(2)R expression in MTAL, kidneys from rats with diabetes insipidus and cultured TAL cells revealed sharp, selective increases in NKCC2 phosphorylation upon desmopressin treatment. Macula densa cells constitutively showed strong NKCC2 phosphorylation. Results suggest comparably significant effects of vasopressin-induced V(2)R signaling in MTAL and in connecting tubule/collecting duct principal cells across the three species. Strong V(2)R expression in macula densa may be related to tubulovascular signal transfer.


Importance of staff job satisfaction in provision of a high quality microbiology service.
The practice of quality assurance is a vital aspect of clinical laboratory work. Much effort has been rightly put in to setting up and running external quality assurance programmes, internal quality assurance and control, gaining accreditation with Clinical Pathology Accreditation (UK) Ltd (CPA) and undertaking clinical audit. The contribution that biomedical scientists can make at all levels to quality assurance is very important, because a good pathology service depends on teamwork. The attitude of each individual member of staff can therefore affect the quality the of a laboratory's output.


Vitamin D insufficiency and diabetes risks.
Diabetes is an increasing epidemic; hyperglycemia results from lack of insulin or inadequate insulin secretion following increases in insulin resistance. Huge costs are placed upon sufferers and health providers, aggravated as serious and disabling complications develop. Thus, measures to reduce the diabetic burden are public health concerns. Vitamin D, identified ≈100 years ago, promotes calcium absorption and utilization, preventing and curing rickets & osteomalacia. Calcium is necessary for insulin secretion, suggesting vitamin D may contribute to maintaining insulin secretion. Vitamin D, formed in skin in bright sunshine, is scarce in foodstuffs. Data linking hypovitaminosis D to hyperglycemia, type 2 diabetes (T2DM) and metabolic disorders increasing cardiovascular risk [metabolic 'syndrome'] has accumulated over ≈40 years. Many mechanisms are known whereby hypovitaminosis D could be causal, e.g. by increasing insulin resistance, reducing insulin secretion and increasing autoimmune or inflammatory damage to pancreatic islets. Major questions still to be answered are whether increasing vitamin D status to the maximum seen in healthy people would reduce the risk of diabetes, the severity of the disease or of its complications, including cardiovascular disease. These questions urgently require answers. If on-going/ planned RCTs confirm causality, maintenance of adequate vitamin D status at the population level by food-fortification or supplementation would be cost-effective measures likely to reduce the burden and costs of diabetes to individuals and health services. Additionally, vitamin D(2/3) supplementation is cheap but whether some non-hypercalcemia-inducing analogue may prove safer has not yet been addressed at the population level.


Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV).
The International Committee on Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. This task encompasses the classification of virus species and higher-level taxa according to the genetic and biological properties of their members; naming virus taxa; maintaining a database detailing the currently approved taxonomy; and providing the database, supporting proposals, and other virus-related information from an open-access, public web site. The ICTV web site (http://ictv.global) provides access to the current taxonomy database in online and downloadable formats, and maintains a complete history of virus taxa back to the first release in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting in 1971. This Report provides a comprehensive description of all virus taxa covering virus structure, genome structure, biology and phylogenetics. The ninth ICTV report, published in 2012, is available as an open-access online publication from the ICTV web site. The current, 10th report (http://ictv.global/report/), is being published online, and is replacing the previous hard-copy edition with a completely open access, continuously updated publication. No other database or resource exists that provides such a comprehensive, fully annotated compendium of information on virus taxa and taxonomy.


Self-assembly of ellipsoidal particles at fluid-fluid interfaces with an empirical pair potential.
Colloidal particles adsorbed at fluid-fluid interfaces interact via mechanisms that can be specific to the presence of interfaces, for instance, lateral capillary interactions induced by nonspherical particles. Capillary interactions are highly relevant for self-assembly and the formation of surface microstructures, however, these are very challenging to model due to the multibody nature of capillary interactions. This work pursues a direct comparison between our computational modelling approach and experimental results on surface microstructures formed by ellipsoidal particles. We begin by investigating the accuracy of using pairwise interactions to describe the multibody capillary interaction by contrasting exact two- and three-particle interaction energies and we find that the pairwise approximation appears reasonable for the experimentally relevant configurations studied. We then develop an empirical pair potential and use it in Monte-Carlo type simulations to efficiently model the structure formation process for relevant particle properties such as aspect ratio, contact angle and surface coverage, and succeed in reproducing our experimental observations where we spread sterically-stabilised ellipsoidal particles onto an oil-air interface at high surface coverage. At lower surface coverages, we find that the self-assembly process falls into the diffusion-limited colloid aggregation universality class.


Clinical management of the hypereosinophilic syndromes.
Hypereosinophilic syndromes (HESs) are rare disorders characterized by marked hypereosinophilia that is directly responsible for organ damage or dysfunction. Different pathogenic mechanisms have been discovered in patient subgroups leading to the characterization of myeloproliferative and lymphocytic disease variants. In the updated terminology, idiopathic HES is now restricted to patients with HES of undetermined etiology. The practical clinical approach of patients with the different HES variants is reviewed herein, focusing on specific diagnostic tools and therapeutic options. Corticosteroids, hydroxyurea and IFN-α remain the classical agents for treatment of most patients with HESs. The specific role of therapeutic compounds that have become available more recently, namely, tyrosine kinase inhibitors and IL-5 antagonists, is discussed.


Insulin-like growth factor (IGF)-I, IGF-I receptor, and IGF binding protein-3 messenger ribonucleic acids and protein in corpora lutea from prostaglandin F(2alpha)-treated gilts.
Insulin-like growth factor-I (IGF-I) is produced within the porcine corpus luteum (CL) and is thought to play an autocrine/paracrine role in CL development/function during the early luteal phase. This study examines the hypotheses that the luteolytic actions of prostaglandin F(2alpha) (PGF(2alpha)) during the early luteal phase may involve either a decrease in IGF-I or IGF receptor (IGF-IR), or an increase in IGF binding protein (IGFBP)-3, expression, any of which could interfere with the luteotropic actions of IGF-I in this tissue. Cycling gilts were treated twice daily with PGF(2alpha) (or saline) on Days 5-9 of the cycle to induce premature luteolysis. CL were collected on Days 6-9, and RNA, protein, or progesterone was extracted. By slot blot analysis, steady-state levels of IGF-I and IGFBP-3 mRNA were not different in PGF(2alpha)-treated vs. control animals; however, IGF-IR mRNA was increased in treated animals on Day 9. No changes in IGF-I content (ng/CL measured by RIA) were observed with respect to treatment. According to ligand blot analysis, the levels of IGFBP-3 increased on Day 6 and decreased on Days 8-9, while IGFBP-2 was higher on Days 6-7 and decreased on Day 9 in treated animals. IGF-IR levels, determined from Western blots, were higher on Day 7 (P < 0.05) and lower on Day 9 in PGF(2alpha)-treated animals vs. control animals (P < 0.05). In conclusion, PGF(2alpha)-induced premature luteolysis was associated with an increase in steady-state levels of IGF-IR mRNA, but it did not appear to be linked to changes in mRNA levels for IGF-I or IGFBP-3. However, since IGFBP-2 and -3 protein levels increased early in the treatment period (Days 6-7), it is possible that they may mediate the luteolytic actions of PGF(2alpha) by sequestering IGF-I and preventing its interaction with the IGF-IR.