Did changes in drug reimbursement after the medicare modernization act affect chemotherapy prescribing?
The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs). We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA. The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non-small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre- versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post- versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post- versus pre-MMA. Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns.


Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.
Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.


Long-segment substernal jejunal esophageal replacement with internal mammary vascular augmentation.
We describe a technique that uses the internal mammary vessels to enhance long-segment jejunal graft blood supply in addition to an intact distal mesenteric vascular arcade. We believe that this technique, called vascular augmentation, improves jejunal graft perfusion and decreases ischemic complications.


Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease.
Non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, we synthesized a molecular combination of glutathione (GSH) and ibuprofen (IBU) via an amide bond and investigated its potential for targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation are related to AD. Evaluation of its physicochemical and in-vitro antioxidant properties indicated that compound 1 exhibits good stability toward human plasma enzymatic activity, and, like GSH, displays in-vitro free radical scavenging activity in a time and concentration-dependent manner. The new compound was also assessed by infusion in a rat model for Alzheimer's disease for its potential to antagonize the deleterious structural and cognitive effects of β-amyloid(1-40). In behavioral tests of long-term spatial memory, animals treated with codrug 1 performed significantly better than those treated with β-amyloid (Aβ) peptide. Histochemical findings confirmed the behavioral data, revealing that Aβ protein was less expressed in cerebral cortex treated with 1 than that treated with IBU. Taken together, the present findings suggest that conjugate 1 treatment may protect against the oxidative stress generated by reactive oxygen species (ROS) and the cognitive dysfunction induced by intracerebroventricular (i.c.v.) infusion of Aβ(1-40) in rats, and thus that codrug 1 could prove useful as a tool for controlling AD induced cerebral amyloid deposits and behavioral deterioration.


Dietary amylose-amylopectin starch content affects glucose and lipid metabolism in adipocytes of normal and diabetic rats.
The aim of this study was to evaluate the effects of the chronic consumption of two starches, characterized by different glycemic indices and amylose-amylopectin content, on glucose metabolism in rat epididymal adipocytes. The two chosen starches were from mung bean (32% amylose) and cornstarch (0.5% amylose). The alpha-amylase digestibility was higher for the waxy cornstarch than that of the mung bean starch (60 +/- 4 vs. 45 +/- 3%, mean +/- SEM, respectively). The glycemic index of the waxy cornstarch diet (575 g starch /kg diet) was higher than that of the mung bean starch diet (107 +/- 7 vs. 67 +/- 5%, P < 0.01) when measured in vivo in two groups of normal rats (n = 9). In a subsequent study, normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats (18 per group) consumed a diet containing 575 g starch/kg diet as either waxy cornstarch or mung bean starch. After 3 wk, food intake, epididymal fat pad weights, and plasma glucose, insulin and triglyceride concentrations did not differ between diet groups. Adipocyte diameter was smaller in rats that consumed mung bean starch compared with those that consumed the waxy cornstarch diet (P < 0.01). The mung bean diet increased maximal insulin-stimulated 14C-glucose oxidation (% of basal values, P < 0. 05). In contrast, incorporation of 14C-glucose into total lipids was significantly lower in rats that consumed the mung bean diet (P < 0. 05). We conclude that in both normal and diabetic rats, the chronic replacement of a high glycemic index starch by a low glycemic index one in a mixed diet increases insulin-stimulated glucose oxidation, decreases glucose incorporation into total lipids and decreases epididymal adipocyte diameter. Thus, the type of starch mixed into the diet has important metabolic consequences at the cellular level in both normal and diabetic rats.


Chemotherapy and target therapy in the management of adult high- grade gliomas.
Adult high grade gliomas (HGG) are the most frequent and fatal primary central nervous system (CNS) tumors. Despite recent advances in the knowledge of the pathology and the molecular features of this neoplasm, its prognosis remains poor. In the last years temozolomide (TMZ) has dramatically changed the life expectancy of these patients: the association of this drug with radiotherapy (RT), followed by TMZ alone, is the current standard of care. However, malignant gliomas often remain resistant to chemotherapy (CHT). Therefore, preclinical and clinical research efforts have been directed on identifying and understanding the different mechanisms of chemo-resistance operating in this subset of tumors,in order to develop effective strategies to overcome resistance. Moreover, the evidence of alterations in signal transduction pathways underlying tumor progression, has increased the number of trials investigating molecular target agents, such as anti-epidermal growth factor receptor (EGFR) and anti- vascular endothelial growth factor (VEGF) signaling. The purpose of this review is to point out the current standard of treatment and to explore new available target therapies in HGG.


A randomised, multi-centre, prospective, double blind pilot-study to evaluate safety and efficacy of the non-absorbable Optilene Mesh Elastic versus the partly absorbable Ultrapro Mesh for incisional hernia repair.
Randomised controlled trials with a long term follow-up (3 to 10 years) have demonstrated that mesh repair is superior to suture closure of incisional hernia with lower recurrence rates (5 to 20% versus 20 to 63%). Yet, the ideal size and material of the mesh are not defined. So far, there are few prospective studies that evaluate the influence of the mesh texture on patient's satisfaction, recurrence and complication rate. The aim of this study is to evaluate, if a non-absorbable mesh (Optilene Mesh Elastic) will result in better health outcomes compared to a partly absorbable mesh (Ultrapro Mesh). In this prospective, randomised, double blind study, eighty patients with incisional hernia after a midline laparotomy will be included. Primary objective of this study is to investigate differences in the physical functioning score from the SF-36 questionnaire 21 days after mesh insertion. Secondary objectives include the evaluation of the patients' daily activity, pain, wound complication and other surgical complications (hematomas, seromas), and safety within six months after intervention. This study investigates mainly from the patient perspective differences between meshes for treatment of incisional hernias. Whether partly absorbable meshes improve quality of life better than non-absorbable meshes is unclear and therefore, this trial will generate further evidence for a better treatment of patients. NCT00646334.


Can ACTH therapy improve the long-term outcome of drug-resistant frontal lobe epilepsy?
Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long-term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add-on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6-week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short-term follow-up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure-free at the end of ACTH treatment maintained an excellent outcome, remaining seizure-free at the end of follow-up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double-blind prospective studies are required to confirm our initial findings.


Evidence of oxygen vacancy-mediated ultrahigh SERS sensitivity of Niobium pentoxide nanoparticles through defect engineering: theoretical and experimental studies.
Oxygen vacancy engineering in metal oxide-based semiconductors has emerged as an important area of research for sensing applications, such as Surface-enhanced Raman scattering (SERS), gas sensing, etc. It has the potential to replace high-cost and unstable noble metal-based substrates in the near future. However, improving the SERS enhancement factor in semiconductor-based substrates remains a challenge. In the present study, we demonstrate that oxygen vacancy engineering in Niobium pentoxide (Nb2O5) enables ultrahigh SERS sensitivity. Oxygen vacancies were induced and manipulated in the Nb2O5 nanoparticles via a facile high-energy ball milling method and post-growth oxygen annealing. A high enhancement factor (EF) of 5.15 × 107 was obtained for the Methylene Blue (MeB) molecule on the oxygen-deficient substrate with the lowest detection limit of 10-8 M, which is 2 orders of magnitude lower than the pristine substrate. Through a careful analysis of the experimental data and theoretical calculations, we investigated the underlying mechanism behind the high EF in SERS and showed that the SERS performance is directly proportional to the oxygen vacancy concentration in the Nb2O5 nanoparticles. Density functional theory (DFT) calculation suggests a strong coupling of the vibronic states and an increased charge transfer (CT) efficiency in the Nb2O5-MeB complex mediated through the vacancy-induced trap states in the defective Nb2O5 structure. Finite element method (FEM)-based simulations revealed a field enhancement factor of ∼4.17 × 102 that contributed to the SERS EF, while the remaining is contributed to the oxygen vacancy-mediated charge transfer, i.e., a factor of ∼1.23 × 105 is due to the high CT efficiency, the highest among the reported values. We believe that these findings offer valuable insights into the fabrication of defect-tailored cost-effective semiconductor-based SERS substrates for ensuing applications, such as trace dye detection.


Soluble gp130, an antagonist of IL-6 transsignaling, is elevated in uveitis aqueous humor.
To determine the concentrations of soluble gp130, a natural antagonist of IL-6 transsignaling, in the serum and aqueous humor (AqH) of patients with uveitis. Serum was obtained from the peripheral blood of patients with active uveitis and healthy control subjects. AqH samples were collected from patients with active uveitis and those without uveitis who were undergoing routine cataract surgery. Samples were centrifuged and the cell-free supernatant frozen at -80 degrees C. Concentrations of sgp130, sIL-6R, and IL-6 were determined by a sandwich ELISA or multiplex bead immunoassay, using standard curves of known concentrations of recombinant cytokines. Serum concentrations of sgp130 were not significantly different between control individuals and patients with active anterior uveitis, regardless of the degree of intraocular inflammation cells. By contrast, the concentration of sgp130 in AqH was very low in patients with no or little inflammation, but increased significantly with disease severity. The greatest elevations of AqH sgp130 were found in patients with the highest cellular activity. Simultaneous measurement of IL-6, sIL-6R, and sgp130 revealed a high degree of correlation between the levels of these molecules, especially for sIL-6R and sgp130. Soluble gp130 is increased in the AqH of patients with active uveitis. It is likely that sgp130 partially inhibits the process of IL-6 transsignaling during inflammation. However, the concentration found is still far below that in serum, suggesting that increasing the level of sgp130 further may assist in reducing the inflammatory changes induced by IL-6 transsignaling.


[Tumor volume as a predictive factor in a group of children with poor-prognosis Hodgkin's lymphoma ].
The aim of this study is an attempt to highlight in the group of patients with a poor prognosis the cohort of patients who need to be planned escalation of doses of cytostatics and transplantation of donor cells. The analysis includes data on 126 patients with Hodgkin's lymphoma at the age from 2 to 18 years (mean age 11 years). All children were treated by risk adapted programs (DAL-HD-like and SPbLH-05). Into the group with a favorable prognosis there were stratified 58 patients (46%), with an intermediate prognosis--50 (39.7%) and with a poor prognosis--18 patients (14.3%). Isolation of patients with relative volume of tumor lesion exceeding 345cm3/m2 requires an intensification of treatment program and an introduction of risk adapted therapy with planning of high-dose treatment.


The infrared spectrum of NN···CO+ trapped in solid neon.
Codeposition of a Ne:N(2):CO = 200:1:1 mixture at 4.3 K with a beam of very pure neon atoms excited to their energy levels between 16.6 and 16.85 eV leads to stabilization in the resulting solid of sufficient NNCO(+) for detection of its NN- and CO-stretching vibration fundamentals. Detailed isotopic substitution studies and density functional calculations for the various isotopologues support the identification of NNCO(+) and permit estimation of the positions of two of its low-frequency fundamentals. A sufficient concentration of NOCN is also stabilized in the neon matrix for detection of its NO-stretching vibrational fundamental.


A Systematic Review and Network Meta-Analysis of Regorafenib and TAS-102 in Refractory Metastatic Colorectal Cancer.
Regorafenib at different dosing strategies and TAS-102 are treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these different strategies. We searched different databases for randomized controlled trials evaluating TAS-102 or regorafenib in patients with refractory mCRC who failed prior oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White's multivariate meta-regression to pool evidence from direct and indirect comparisons. Six trials at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to best-supportive care (BSC) in terms of PFS (Rego 160: hazard ratio [HR], 0.4; 95% confidence ratio [CI], 0.26-0.63; TAS-102: HR, 0.46 CI, 0.40-0.52) and OS (Rego 160: HR, 0.67; CI, 0.48-0.93; TAS-102: HR, 0.67; CI, 0.57-0.80). Network analysis showed no statistically difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR, 0.44; CI, 0.23-0.84) and PFS (HR, 0.37; CI, 0.21-0.66). Rego 80+ was associated with statistically nonsignificant improvement in OS and PFS compared with TAS-102 and Rego 160. Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. Regorafenib at a dose of 160 mg and TAS-102 appear to have similar efficacy in patients with refractory metastatic colorectal cancer. Regorafenib with a dose escalation strategy is superior to best-supportive care. Given its tolerability and the observed trend in survival benefit compared with regorafenib 160, dose escalation strategy of regorafenib (80+) may be the preferred option in this setting.


Long COVID and Wavering Incidence of Pulmonary Embolism: A Systematic Review.
Pulmonary embolism (PE) is a serious medical condition that can occur as a result of venous thromboembolism (VTE). COVID-19, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), can potentially lead to PE due to the formation of blood clots in the lungs. This study aims to collate and report trends of PE in patients with long COVID (4-12 weeks since infection) and post-COVID-19 syndrome (>12 weeks since infection). The study adhered to PRISMA Statement 2020 guidelines, and a systematic search was conducted in four databases. In total, nine observational studies were included with a total patient count of 45,825,187. The incidence of PE with long COVID/post-COVID-19 syndrome was seen among 31,885 individuals out of 44,967,887 participants. The incidence rate of PE was observed as 0.07%, given that the studies included matched controls. While we cannot state with certainty that COVID-19 infection in itself leads to higher risks of PE at a later time, this study emphasizes the need for optimized care and longitudinal studies during the COVID-19 era to account for deviations from the norm.


Inactivation of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on common surfaces by disinfectants.
This experimental laboratory-based study evaluated two disinfectants' efficacy against replication-competent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on three surfaces. Disinfectants were effictive at eliminating the presence, viability, and subsequent replication of SARS-CoV-2 on all surfaces. Although SARS-CoV-2 likely spreads primarily via airborne transmission, layered mitigation should include high-touch surface disinfection.


Analysis of leukotriene B4 metabolism in human promyelocytic HL-60 cells.
We previously reported that human alveolar macrophages rapidly metabolize the chemotactic active lipid mediator leukotriene B4 (LTB4) into the dihydro-LTB4 by reduction of one of the conjugated double bonds. We herein report that human HL-60 cells (a myeloid precursor which can be differentiated into granulocyte- as well as monocyte-like cells by dimethyl sulphoxide or phorbol myristate acetate) express a highly active LTB4 reductase in the undifferentiated state. Differentiation by dimethyl sulphoxide (1.3%) along the granulocyte lineage, as confirmed by light microscopy, conversion of NitroBlue Tetrazolium into formazan, failed to induce a substantial capacity for omega-oxidation of LTB4; this reaction is exclusively found in mature granulocytes. Studies with the cell homogenate of undifferentiated HL-60 cells indicated that the activity of the enzyme depends on the presence of NADPH, Ca2+ and Mg2+, with a pH optimum of 7.5 at 37 degrees C. The enzyme was not released into the supernatant after stimulation of HL-60 cells with phorbol myristate acetate (100 ng) or Ca2+ ionophore (7.5 microM). Subcellular fractionation revealed evidence that the LTB4 reductase is located within the membrane fraction. Purification of the enzyme by gel filtration and gel electrophoresis suggests an apparent molecular mass of 40 kDa.


Valorization of dragon fruit waste to value-added bioproducts and formulations: A review.
Owing to the increasing worldwide population explosion, managing waste generated from the food sector has become a cross-cutting issue globally, leading to environmental, economic, and social issues. Circular economy-inspired waste valorization approaches have been increasing steadily, generating new business opportunities developing valuable bioproducts using food waste, especially fruit wastes, that may have several applications in energy-food-pharma sectors. Dragon fruit waste is one such waste resource, which is rich in several value-added chemicals and oils, and can be a renewable resource to produce several value-added compounds of potential applications in different industries. Pretreatment and extraction processes in biorefineries are important strategies for recovering value-added biomolecules. There are different methods of valorization, including green extractions and biological conversion approaches. However, microbe-based conversion is one of the advanced technologies for valorizing dragon fruit waste into bioethanol, bioactive products, pharmaceuticals, and other valued products by reusing or recycling them. This state-of-the-art review briefly overviews the dragon fruit waste management strategies and advanced eco-friendly and cost-effective valorization technologies. Furthermore, various applications of different valuable bioactive components obtained from dragon fruit waste have been critically discussed concerning various industrial sectors. Several industrial sectors, such as food, pharmaceuticals, and biofuels, have been critically reviewed in detail.


Genome-wide comparison and identification of myosin gene family in Arabidopsis thaliana and Helianthus annuus.
Myosins are essential components of organelle trafficking in all the eukaryotic cells. Myosin driven movement plays a vital role in the development of pollen tubes, root hairs and root tips of flowering plants. The present research characterized the myosin genes in Arabidopsis thaliana and Helianthus annuus by using different computational tools. We discovered a total of 50 myosin genes and their splice variants in both pant species. Phylogenetic analysis indicated that myosin genes were divided into four subclasses. Chromosomal location revealed that myosin genes were located on all five chromosomes in A. thaliana, whereas they were present on nine chromosomes in H. annuus. Conserved motifs showed that conserved regions were closely similar within subgroups. Gene structure analysis showed that Atmyosin2.2 and Atmyosin2.3 had the highest number of introns/exons. Gene ontology analysis indicated that myosin genes were involved in vesicle transport along actin filament and cytoskeleton trafficking. Expression analysis showed that expression of myosin genes was higher during the flowering stage as compared to the seedling and budding stages. Tissue specific expression indicated that HanMYOSIN11.2, HanMYOSIN16.2 were highly expressed in stamen, whereas HanMYOSIN 2.2, HanMYOSIN 12.1 and HanMYOSIN 17.1 showed higher expression in nectary. This study enhance our understanding the function of myosins in plant development, and forms the basis for future research about the comparative genomics of plant myosin in other crop plants.


[Topical problems of treatment of acute renal failure in crush syndrome].
The paper analyzes some experience in treating 203 victims with crush syndrome (CS). The victims' status is determined by the force and time of compression, the degree and magnitude of destructive muscular changes, accompanying by lesions and occurring complications. Varying renal dysfunction was revealed in 97 (47.8%) patients, 55 (27%) patients developed mild and severe acute renal failure (ARF) and 38 (18.7%) patients had mild AFR. Renal dysfunction was not detected in 106 (52.2%) patients. The development of severe AFR in CS is a marker of the severity of injury, the body's response to injury and shock; it dictates the tactics of intensive therapy using extracorporeal techniques of detoxification and active or delayed surgical removal of necrotic muscles, which permits prevention of prolonged severe endotoxication and pyoseptic and vital complications. Two-three-week persistent unremoved foci of muscle necrosis and endotoxicosis exhaust the body's adaptive mechanisms, cause severe dysfunction of other organs and systems, promote delayed renal function recovery and ARF resolution.


Exile and the undestroyable perpetuity of stigmatizations--some critical (medical) anthropological reflections.
The writing of this paper has been stimulated by the observable widening dichotomy between present pluralist discourses of multiculturalism, which claim the future of mutual understanding and harmony vs. the true prevalence of a dramatically growing discordance in human relations world-wide. Given the experience of working in the long-term exile fieldwork, as well as coming from a geographically interesting and highly media-presented country, ones capacity to rethink and self-detect the modes of treating alterity seems to grow together with the imposed self-reflexivity. It remains to be seen whether the decades in which many have been on the receiving end of approaches that address the Other--the perceptual fields of "race" vs. race and visible vs. non-visible ethnicity's, etc.--will yield an output of constructive scientist voices. The potential dialogue could bring us closer to apprehending the simplistic nature of multicultural discourses, as well as expose better the reasons why they yield such slow results. Namely, we need deeper levels of understanding, and although the psychoanalytic approaches to these issues have been often discarded as reductionist, only they can orientate us, after making us painfully aware that prejudice and tolerance can present themselves side by side, and are not solely dependent on the processes of our becoming more conscious and knowledgeable citizens. The many scientists that equally engage in stereotyping, testify this claim. Thus, this is an insider's meta-narrative that joins the list of present approaches that firstly engage in tracing one's own stigmatization processes rather than solely deconstructing others.


Prevalence of sports supplements consumption and its association with food choices among female elite football players.
The present study aimed to 1) investigate the consumption of Sports Supplements (SSs) among female elite football players, 2) evaluate the influence of age on SS consumption, and 3) determine the relationship between the consumption of SSs and dietary choices among elite football players. A total of 126 female football players of Primera Iberdrola and Reto Iberdrola who participated in this descriptive, observational, and cross-sectional study completed a self-administered questionnaire on SSs and the Athletes' Food Choices Questionnaire. Overall, 84.1% of participants consumed supplements, mainly for improved sports performance (68.3%) and health (34.1%). The main sources of purchase were the Internet (34.9%) and specialized shops (23.8%), and players were commonly advised by a dietitian-nutritionist to use SSs (56.3%). The SSs most often consumed included whey protein (30.2%), sports drinks (28.6%), creatine monohydrate (28.6%), sports bars (27.8%), and caffeine (27.8%). Older players consumed more supplements at the time of data compilation. Players predominantly acquired these supplements by using the Internet and reported benefits from their use (all P ≤ 0.036). Additionally, players who consumed SSs conveyed more concern about their food choices. A high prevalence of female football players consumed SSs, particularly SSs supported by robust scientific evidence. Older players had higher supplement consumption rates. The use of SSs was related to food choices through nutritional characteristics of foods, knowledge about health and nutrition, weight control with the help of food, and the performance benefits players could acquire.


CD44 regulates dendrite morphogenesis through Src tyrosine kinase-dependent positioning of the Golgi.
The acquisition of proper dendrite morphology is a crucial aspect of neuronal development towards the formation of a functional network. The role of the extracellular matrix and its cellular receptors in this process has remained enigmatic. We report that the CD44 adhesion molecule, the main hyaluronan receptor, is localized in dendrites and plays a crucial inhibitory role in dendritic tree arborization in vitro and in vivo. This novel function is exerted by the activation of Src tyrosine kinase, leading to the alteration of Golgi morphology. The mechanism operates during normal brain development, but its inhibition might have a protective influence on dendritic trees under toxic conditions, during which the silencing of CD44 expression prevents dendritic shortening induced by glutamate exposure. Overall, our results indicate a novel role for CD44 as an essential regulator of dendritic arbor complexity in both health and disease.


Comparison of in vitro and in vivo release characteristics of sustained release ofloxacin microspheres.
The sustained release nature of ofloxacin microspheres--to eradicate bacterial biofilm associated with chronic infections from sensitive strains of bacteria--was determined both in vitro and in vivo. Ofloxacin microspheres were prepared by emulsion solvent evaporation procedure using poly(glycolic acid-co-dl-lactic acid) (PLGA) as the biodegradable polymer. The microspheres were characterized by scanning electron microscopy, in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were highly spherical with a very smooth surface. Approximately 45% of the drug was released from microspheres in sizes of 125-250 microns and 250-425 microns in 2 days compared with approximately 22% from microspheres of size range 37-125 microns indicating that surface area of the microspheres did not control the kinetics of in vitro release. However, about 96% of the drug was released from the three different size ranges in 35 days. The in vitro release profile of microspheres of size range 125-250 microns is not significantly different from microspheres in sizes of 250-425 microns. The peak plasma level of ofloxacin in animals that received the drug suspension occurred within 2 hr and was higher than that of the microspheres that occurred by the end of the second day. The plasma of animals that received the free drug was depleted of ofloxacin by the end of the first day, but the drug was sustained above 0.5 microgram/mL in the plasma of animals that received the microspheres for about 3 weeks. The results suggest that biodegradable ofloxacin microspheres can be prepared that release the antibiotic in vivo for about 3 weeks. This should provide a means for continuous treatment of chronic infections in which bacterial biofilm can occur.


Genetic K-means algorithm.
In this paper, we propose a novel hybrid genetic algorithm (GA) that finds a globally optimal partition of a given data into a specified number of clusters. GA's used earlier in clustering employ either an expensive crossover operator to generate valid child chromosomes from parent chromosomes or a costly fitness function or both. To circumvent these expensive operations, we hybridize GA with a classical gradient descent algorithm used in clustering, viz. K-means algorithm. Hence, the name genetic K-means algorithm (GKA). We define K-means operator, one-step of K-means algorithm, and use it in GKA as a search operator instead of crossover. We also define a biased mutation operator specific to clustering called distance-based-mutation. Using finite Markov chain theory, we prove that the GKA converges to the global optimum. It is observed in the simulations that GKA converges to the best known optimum corresponding to the given data in concurrence with the convergence result. It is also observed that GKA searches faster than some of the other evolutionary algorithms used for clustering.


Comparison of the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) with a short-form five-item version (ALSAQ-5) in a longitudinal survey.
To compare results on the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) with those gained on the short-form five-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) in a longitudinal study. Postal survey. Copies of the ALSAQ-40 which incorporates the five items of the ALSAQ-5, were completed on two occasions. Respondents were also asked to indicate how much change they had experienced since baseline on each of the five domains of the questionnaire. The database of all patient members of the Motor Neurone Disease Association for England, Wales and Northern Ireland. Nine hundred and twenty-seven patient members returned questionnaires at baseline, and 764 completed questionnaires at both baseline and follow-up. Results on the five dimensions of the ALSAQ-40 and ALSAQ-5 were found to be highly correlated, and 95% confidence intervals on mean scores were found to overlap for each dimension. The instruments both provide a similar picture of change in terms of their responsiveness. For example, effect sizes were calculated for patients who claimed their health had deteriorated a little since baseline, and gave almost identical results (e.g. for the Physical functioning domain effect sizes of 0.12 and 0.11 were found on the long and short measures respectively). Results suggests that the ALSAQ-5 provides similar results to the ALSAQ-40 yet with considerable economy. In instances where a very brief health status measure is required then the ALSAQ-5 may be the instrument of choice.


Inducible expression of the human interferon beta 1 gene linked to a bovine papilloma virus DNA vector and maintained extrachromosomally in mouse cells.
A 1.6-kilobase DNA segment of the genomic human interferon beta 1 (IF-beta 1) gene was inserted into each of two possible orientations at the single HindIII site of a recombinant plasmid pBPV69T, consisting of the 69% transforming region of the bovine papilloma virus type 1 (BPV-1) and a modified SalI-SalI fragment of plasmid pBR322. After cleavage of the pBR322 sequences from this recombinant, BPV69T-IF-beta 1 hybrid DNAs were transfected onto C127 mouse cells by the standard calcium precipitation technique. Mouse cells transformed by this hybrid DNA produced low levels of human IF-beta 1 constitutively and responded to induction with either inactivated Newcastle disease virus or polyriboinosinic acid-polyribocytidylic acid. The BPV69T-IF-beta 1 hybrid DNA was nonintegrated in the transformed mouse cells but had acquired DNA sequences as a result of the transfection. Accurate transcripts of the IF-beta 1 mRNA were detected in cells only after induction. When the IF-beta 1 gene was oriented in the plasmid in the same direction of transcription as the BPV-1 genome, transcription was promoted from within the BPV-1 sequences. These results indicate that the regulatory sequences responsible for the inducible expression of the human IF-beta 1 gene are present in the 1.6-kilobase genomic segment and that these sequences can function in a free extrachromosomal state linked to BPV-1 sequences.


Increasing late stage colorectal cancer and rectal cancer mortality demonstrates the need for screening: a population based study in Ireland, 1994-2010.
This paper describes trends in colorectal cancer incidence, survival and mortality from 1994 to 2010 in Ireland prior to the introduction of population-based screening. We examined incidence (National Cancer Registry Ireland (NCRI) and mortality (Central Statistics Office) from 1994 to 2010. Age standardised rates (ASR) for incidence and mortality have been calculated, weighted by the European standard population. Annual percentage change was calculated in addition to testing for linear trends in treatment and case fraction of early and late stage disease. Relative survival was calculated considering deaths from all causes. The colorectal cancer ASR was 63.7 per 100,000 in males and 38.7 per 100,000 in females in 2010. There was little change in the ASR over time in either sex, or when colon and rectal cancers were considered separately; however the number of incident cancers increased significantly during 1994-2010 (1752 to 2298). The case fractions of late stage (III/IV) colon and rectal cancers rose significantly over time. One and 5 year relative survival improved for both sexes between the periods 1994-2008. Colorectal cancer mortality ASRs decreased annually from 1994-2009 by 1.8% (95% CI -2.2, -1.4). Rectal cancer mortality ASRs rose annually by 2.4% (95% CI 1.1, 3.6) and 2.8% (95% CI 1.2, 4.4) in males and females respectively. Increases in late-stage disease and rectal cancer mortality demonstrate an urgent need for colorectal cancer screening. However, the narrow age range at which screening is initially being rolled-out in Ireland means that the full potential for reductions in late-stage cancers and incidence and mortality are unlikely to be achieved. While it is possible that the observed increase in rectal cancer mortality may be partly an artefact of cause of death misclassification, it could also be explained by variations in treatment and adherence to best practice guidelines; further investigation is warranted.


Length of the distal esophageal sphincter and competency of the cardia.
Pressure and abdominal length of the distal esophageal sphincter are important factors in maintaining competency of the cardia against challenges of intraabdominal pressure. Some patients with normal distal esophageal sphincter pressure and position may have reflux which could be due to the inability of the cardia to overcome challenges of intragastric pressure. Three experimental studies and one clinical study were designed to evaluate this problem. The results showed that the resistance to flow through the cardia is related to the integrated effect of distal esophageal sphincter pressure and length; the ratio of distal esophageal sphincter to intragastric pressure necessary to maintain competency is inversely related to the length of sphincter present; gastric dilatation has an adverse effect on the degree of competency achieved by a given distal esophageal sphincter length; and patients with an overall distal esophageal sphincter length of 2 cm or less measured at rest in the fasting state are subject to reflux caused by gastric dilatation, increased intragastric pressure independent of intraabdominal pressure, or both.


The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis.
Naturally occurring feline infectious peritonitis (FIP) is usually fatal, giving the impression that immunity to the FIP virus (FIPV) is extremely poor. This impression may be incorrect, because not all cats experimentally exposed to FIPV develop FIP. There is also a belief that the incidence of FIP may be affected by a number of host, virus, and environmental cofactors. However, the contribution of these cofactors to immunity and disease incidence has not been determined. The present study followed 111 random-bred specific pathogen free (SPF) cats that were obtained from a single research breeding colony and experimentally infected with FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Forty of the 111 (36%) cats survived their initial challenge exposure to a Type I cat-passaged field strains of FIPV. Six of these 40 survivors succumbed to FIP to a second or third challenge exposure, suggesting that immunity was not always sustained. Exposure to non-FIP-inducing feline coronaviruses prior to challenge with virulent FIPV did not significantly affect FIP incidence but did accelerate the disease course in some cats. There were no significant differences in FIP incidence between males and females, but resistance increased significantly between 6 months and 1 or more years of age. Genetic testing was done on 107 of the 111 infected cats. Multidimensional scaling (MDS) segregated the 107 cats into three distinct families based primarily on a common sire(s), and resistant and susceptible cats were equally distributed within each family. Genome-wide association studies (GWAS) on 73 cats that died of FIP after one or more exposures (cases) and 34 cats that survived (controls) demonstrated four significant associations after 100k permutations. When these same cats were analyzed using a sib-pair transmission test, three of the four associations were confirmed although not with genome-wide significance. GWAS was then done on three different age groups of cases to take into account age-related resistance, and different associations were observed. The only common and strong association identified between the various GWAS case configurations was for the 34.7-45.8Mb region of chromosome A3. No obvious candidate genes were present in this region.


Conducting non-commercial international clinical trials: the ICR-CTSU experience.
Academic clinical trials play a fundamental role in the development of new treatments, the repurposing of existing treatments and in addressing areas of unmet clinical need. With cancer treatments increasingly targeted at molecular subtypes, and with priority placed on developing new treatments for rare tumour types, the need for international trial participation to access sufficient patient numbers for successful trial conduct is growing. However, lack of harmonisation of international legal, ethical and financial systems can make this challenging and the cost and effort of conducting trials internationally can be considered prohibitive, particularly where the sample size is comparatively small. The Institute of Cancer Research - Clinical Trials and Statistics Unit (ICR-CTSU) is a UK-based academic clinical trials unit that specialises in the design, conduct and analysis of clinical trials of cancer treatments with an expanding portfolio of trials in molecular subtypes of breast and urological cancers and in other rare cancer types. Implementing appropriate mechanisms to enable international participation has therefore been imperative. In this article, we explain how we have approached the challenges involved and describe examples of successful international trial conduct, achieved through robust collaborations with academic and industry partners. Conducting academic trials internationally is challenging but can and should be achieved through appropriate governance mechanisms and strong collaborations.


The overall agreement of proposed definitions of mucopurulent cervicitis in women at high risk of Chlamydia infection.
The overall agreement between different criteria for cervicitis in women infected with Chlamydia trachomatis and/or Mycoplasma genitalium, and in women who tested negative was examined. Women attending a clinic for sexually transmitted diseases were enrolled because of sexual partners' suspected chlamydia infection. M. genitalium was tested in a sample of first-catch urine and an endocervical specimen, whereas specimens from four different sites were used for detection of C. trachomatis. Signs of friability and purulent endocervical discharge were documented at gynaecological examination. Specimens for microscopy were taken from the endocervix and urethra as well as the vaginal discharge, and bacterial vaginosis was examined for. The criteria being evaluated included cervical friability and/or pus; polymorphonuclear leukocytes (PMNL)/epithelium cell ratio in the vaginal discharge; and more than 30 PMNL per high-power field in the endocervical smear. The overall agreement of the indicators of cervicitis in women infected with C. trachomatis and/or M. genitalium was 40.5% (15/37), and for those women with negative tests 35.3% (12/34). The criteria for cervicitis require further evaluation, including study of a control group of women at low risk of having a sexually transmitted infection.


Constitutive activation of the mTOR signaling pathway within the normal glomerulus.
Agents that target the activity of the mammalian target of rapamycin (mTOR) kinase in humans are associated with proteinuria. However, the mechanisms underlying mTOR activity and signaling within the kidney are poorly understood. In this study, we developed a sensitive immunofluorescence technique for the evaluation of activated pmTOR and its associated signals in situ. While we find that pmTOR is rarely expressed in normal non-renal tissues, we consistently find intense expression in glomeruli within normal mouse and human kidneys. Using double staining, we find that the expression of pmTOR co-localizes with nephrin in podocytes and expression appears minimal within other cell types in the glomerulus. In addition, we found that pmTOR was expressed on occasional renal tubular cells within mouse and human kidney specimens. We also evaluated mTOR signaling in magnetic bead-isolated glomeruli from normal mice and, by Western blot analysis, we confirmed function of the pathway in glomerular cells vs. interstitial cells. Furthermore, we found that the activity of the pathway as well as the expression of VEGF, a target of mTOR-induced signaling, were reduced within glomeruli of mice following treatment with rapamycin. Collectively, these findings demonstrate that the mTOR signaling pathway is constitutively hyperactive within podocytes. We suggest that pmTOR signaling functions to regulate glomerular homeostasis in part via the inducible expression of VEGF.


Heat shock protein A12A encodes a novel prosurvival pathway during ischaemic stroke.
Heat shock protein A12A (HSPA12A) is a newly discovered member of the Hsp70 family. The biological characteristics and functional roles of HSPA12A are poorly understood. This study investigated the effects of HSPA12A on ischaemic stroke in mice. Ischaemic stroke was induced by left middle cerebral artery occlusion for 1 h followed by blood reperfusion. We observed that HSPA12A was highly expressed in brain neurons, and neuronal HSPA12A expression was downregulated by ischaemic stroke and stroke-associated risk factors (aging, obesity and hyperglycaemia). To investigate the functional requirement of HSPA12A in protecting ischaemic brain injury, HSPA12A knockout mice (Hspa12a-/-) were generated. Hspa12a-/- mice exhibited an enlarged infarct volume and aggravated neurological deficits compared to their wild-type (WT) littermates after stroke. These aggravations in Hspa12a-/- mice were accompanied by more apoptosis and severer hippocampal morphological abnormalities in ischaemic hemispheres. Long-term examination revealed impaired motor function recovery and neurogenesis in stroke-affected Hspa12a-/- mice compared to stroke-affected WT controls. Significant reduced activation of GSK-3β/mTOR/p70S6K signalling was also observed in ischaemic hemispheres of Hspa12a-/- mice compared to WT controls. Administration with lithium (non-selective GSK-3β inhibitor) activated GSK-3β/mTOR/p70S6K signalling in stroke-affected Hspa12a-/- mice. Notably, lithium administration attenuated the HSPA12A deficiency-induced aggravation in infarct size, neurological deficits and neuronal death in Hspa12a-/- mice after stroke. Altogether, the findings suggest that HSPA12A expression encodes a critical novel prosurvival pathway during ischaemic stroke. We identified HSPA12A as a novel neuroprotective target for stroke patients.


Molecular Epidemiology of Hepatitis B Virus in Turkish Cypriot.
There is an increased demand for molecular and epidemiological information regarding Hepatitis B Virus (HBV) infection as the disease severity depends on these specifications. We have aimed to analyze nucleos(t)ide analogues (NA) resistance and typical HBsAg escape mutations with the dispersion of HBV genotype/subgenotype/HBsAg serotypes on overlapping pol/S gene regions in the Turkish population. Samples were collected in Northern Cyprus. Reverse transcriptase (rt) region between 80-250 amino acids were amplified. Typical HBsAg escape mutations were determined as HBIg escape (6.48%), vaccine escape (8.34%), HBsAg misdiagnosis (9.25%), and immune escape mutations (8.34%). NAs resistances were determined as primary (2.78%), partial (2.78%), and compensatory mutations (26.85%) in overlapping pol/S gene region. The study patients were predominantly infected with HBV genotype D/D1 (98%). However, the predominant HBsAg serotype was ayw2 (99%). The most common NA resistance mutation was rtQ215H/P/S (16.67%), however, for S gene the misdiagnosis mutations were observed most frequently (9.25%). We can conclude that HBV D/D1 is the dominant strain and ayw2 is the dominant serotype in the Turkish Cypriot. Cyprus is an island located in the Eastern Mediterranean region, and it is, therefore, a key location for human trafficking and immigration; as a result of this reputation, it is necessary to analyze HBV phylogenetically for local dynamics, and our results indicate that treatment naïve population is prone to these pol/S gene mutations. However, if HBV strains were also analyzed among Greek Cypriots too, this would enable a complete island survey. With this work, we believe that we have enlightened this subject for further research. There is an increased demand for molecular and epidemiological information regarding Hepatitis B Virus (HBV) infection as the disease severity depends on these specifications. We have aimed to analyze nucleos(t)ide analogues (NA) resistance and typical HBsAg escape mutations with the dispersion of HBV genotype/subgenotype/HBsAg serotypes on overlapping pol/S gene regions in the Turkish population. Samples were collected in Northern Cyprus. Reverse transcriptase (rt) region between 80–250 amino acids were amplified. Typical HBsAg escape mutations were determined as HBIg escape (6.48%), vaccine escape (8.34%), HBsAg misdiagnosis (9.25%), and immune escape mutations (8.34%). NAs resistances were determined as primary (2.78%), partial (2.78%), and compensatory mutations (26.85%) in overlapping pol/S gene region. The study patients were predominantly infected with HBV genotype D/D1 (98%). However, the predominant HBsAg serotype was ayw2 (99%). The most common NA resistance mutation was rtQ215H/P/S (16.67%), however, for S gene the misdiagnosis mutations were observed most frequently (9.25%). We can conclude that HBV D/D1 is the dominant strain and ayw2 is the dominant serotype in the Turkish Cypriot. Cyprus is an island located in the Eastern Mediterranean region, and it is, therefore, a key location for human trafficking and immigration; as a result of this reputation, it is necessary to analyze HBV phylogenetically for local dynamics, and our results indicate that treatment naïve population is prone to these pol/S gene mutations. However, if HBV strains were also analyzed among Greek Cypriots too, this would enable a complete island survey. With this work, we believe that we have enlightened this subject for further research.


Cellular Processes in Human Ovarian Follicles Are Regulated by Expression Profile of New Gene Markers-Clinical Approach.
In the growing ovarian follicle, the maturing oocyte is accompanied by cumulus (CCs) and granulosa (GCs) cells. Currently, there remain many unanswered questions about the epithelial origin of these cells. Global and targeted gene transcript levels were assessed on 1, 7, 15, 30 days of culture for CCs and GCs. Detailed analysis of the genes belonging to epithelial cell-associated ontological groups allowed us to assess a total of 168 genes expressed in CCs (97 genes) and GCs (71 genes) during long-term in vitro culture. Expression changes of the analyzed genes allowed the identification of the group of genes: TGFBR3, PTGS2, PRKX, AHI1, and IL11, whose expression decreased the most and the group of ANXA3, DKK1, CCND1, STC1, CAV1, and SFRP4 genes, whose expression significantly increased. These genes' expression indicates CCs and GCs epithelialization processes and their epithelial origin. Expression change analysis of genes involved in epithelization processes in GCs and CCs during their in vitro culture made it possible to describe the most significantly altered of the 11 genes. Detailed analysis of gene expression in these two cell populations at different time intervals confirms their ovarian surface epithelial origin. Furthermore, some gene expression profiles appear to have tumorigenic properties, suggesting that granulosa cells may play a role in cancerogenesis.


Comparison of different phenotypic and genotypic methods for the detection of methicillin-resistant Staphylococcus aureus.
Staphylococcus aureus is known as a powerful pathogen that causes various infections. Emergence of methicillin-resistant S. aureus (MSRA) is responsible for nosocomial and community-acquired infections worldwide. The present study aimed to evaluate the performance and ability of eight different phenotypic and genotypic methods for the detection of MSRA. A total of 186 S. aureus isolates were defined as methicillin-susceptible S. aureus (MSSA; 95) and MSRA (91) using polymerase chain reaction (PCR) as the gold standard. Susceptibility to methicillin was investigated using oxacillin, methicillin, cefotetan, cefoxitin, and cefmetazole disks, by oxacillin Adata Tab and strips. For all S. aureus isolates minimal inhibitory concentrations of oxacillin were determined using the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines. Among the diagnostic methods studied, broth microdilution and the cefoxitin disk had the highest specificity (98.9 and 94.7%), sensitivity (100 and 98.9%), and concordance with PCR results (98.9 and 93.6%). The cefotetan and cefmetazole disks had the lowest concordance with PCR results. Our results suggest that microdilution and cefoxitin disk methods have high sensitivities compared with other methods for detection of MSRA. The cefoxitin disk method may be preferred in clinical laboratories because it is easy to perform and does not require special equipment.


Discovery and development of purine-scaffold Hsp90 inhibitors.
Hsp90 allows cancer cells to tolerate the many components of dysregulated pathways in a transformation-specific manner by interacting with several client substrates, such as kinases, hormone receptors and transcription factors that are directly involved in driving multistep malignancy, and also with mutated oncogenic proteins required for the transformed phenotype. This distinctive broad involvement in maintaining the transformed phenotype has suggested Hsp90 as an important target in cancer therapy. Discovery of pharmacological agents that selectively inhibit its function have aided in probing the biological functions of Hsp90 at the molecular level and in validating it as a novel target for anticancer drug action. Two natural product derivatives, 17-allylamino-17-desmethoxy-geldanamycin (17AAG) and 17-dimethylaminoethylamino-17-desmethoxy-geldanamycin (17DMAG) have further entered clinical trials, proving that Hsp90 may be modulated pharmacologically without causing target related toxicities in humans. In spite of their usefulness as proof-of-principle compounds, the clinical use of these two agents has been encumbered with some limitations due to their structural characteristics and also to less than optimal pharmacological profiles. Thus, the identification of Hsp90 inhibitors with improved structural characteristics and better pharmacological profiles is a major focus of interest in the field. One such emerging class is the purine-scaffold series. This review intends to inform the reader on efforts ranging from the discovery to their clinical translation.


Comparison of the rates of motility of Salmonella with those of other enteric bacteria.
Comparison of the rates of motility through a semisolid medium of 16 common Salmonella sp., 14 Escherichia coli serotypes, 4 Arizona strains, 2 Escherichia freundii (Citrobacter) isolates, 2 Proteus sp., and 2 Pseudomonas sp. revealed the following. (i) Very closely related bacteria could demonstrate markedly different rates of progression. (ii) All of the salmonellae tested advanced faster than the Proteus and Pseudomonas test cultures but some Salmonella sp., notably S. choleraesuis and S. typhi, progressed relatively slowly compared to many other test cultures. (iii) The mean rate of motility for the fastest 14 Salmonella sp. (1.49 cm/hr) was not statistically greater than the mean value for the 14 E. coli serotypes (1.31 cm/hr) at the 1% level of significance. Selective motility procedures may not be a reliable means of isolating all Salmonella sp. from materials contaminated with other bacteria.


Muscle Strength Is a Poor Screening Test for Predicting Lower Extremity Injuries in Professional Male Soccer Players: A 2-Year Prospective Cohort Study.
Lower extremity muscle strength tests are commonly used to screen for injury risk in professional soccer. However, there is limited evidence on the ability of such tests in predicting future injuries. To examine the association between hip and thigh muscle strength and the risk of lower extremity injuries in professional male soccer players. Case-control study; Level of evidence, 3. Professional male soccer players from 14 teams in Qatar underwent a comprehensive strength assessment at the beginning of the 2013/2014 and 2014/2015 seasons. Testing consisted of concentric and eccentric quadriceps and hamstring isokinetic peak torques, eccentric hip adduction and abduction forces, and bilateral isometric adductor force (squeeze test at 45°). Time-loss injuries and exposure in training and matches were registered prospectively by club medical staff throughout each season. Univariate and multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% CIs. In total, 369 players completed all strength tests and had registered injury and exposure data. Of these, 206 players (55.8%) suffered 538 lower extremity injuries during the 2 seasons; acute muscle injuries were the most frequent. Of the 20 strength measures examined, greater quadriceps concentric peak torque at 300 deg/s (HR, 1.005 [95% CI, 1.00-1.01]; P = .037) was the only strength measure identified as significantly associated with a risk of lower extremity injuries in multivariate analysis. Greater quadriceps concentric peak torque at 60 deg/s (HR, 1.004 [95% CI, 1.00-1.01]; P = .026) was associated with the risk of overuse injuries, and greater bilateral adductor strength adjusted for body weight (HR, 0.75 [95% CI, 0.57-0.97; P = .032) was associated with a lower risk for any knee injury. Receiver operating characteristic curve analyses indicated poor predictive ability of the significant strength variables (area under the curve, 0.45-0.56). There was a weak association with the risk of lower extremity injuries for 2 strength variables: greater quadriceps concentric muscle strength at (1) high and (2) low speeds. These associations were too small to identify an "at-risk" player. Therefore, strength testing, as performed in the present study, cannot be recommended as a screening test to predict injuries in professional male soccer.


A comparison of results obtained between two methods of detecting the existence of circadian rhythmicity in cell division: an autoradiographical and a biochemical approach.
In the course of a study of circadian rhythmicity in the number of cells in the S-phase of the cell cycle in mouse kidney, a comparison was made between 2 methods of estimation of DNA synthetic activity. One of the methods used was an autoradiographical analysis of the tritiated thymidine labelling index; the other was a biochemical assay of the DNA content of the tissues coupled with liquid scintillation counting, to obtain an estimate of the incorporation of tritiated thymidine, expressed as dpm per microgram of DNA. The correlation between individual estimates of DNA-synthetic activity, using the 2 methods was highly significant, as was the correlation between the 2 data sets with respect to time of zeniths. There was a suggestion that the biochemical assay procedure may be the more sensitive indicator of circadian rhythmicity in relatively homogeneous tissues with low proliferative rates. Estimated over a 3-da period, the time of maximal DNA synthetic activity lay between the hours of 22.00 and 02.00. The nadir of the curve was less well defined and occurred between 02.00 and 14.00 hours. The autoradiographical study took 5 weeks to complete exclusive of histological and autoradiographic preparation. The biochemical assay was completed in 4 days.


The aortic valve with two leaflets--a study in 2,000 autopsies.
Our study is based on the examination of 2,000 aortic valves obtained from fresh cadavers (1,499 males, 501 females) at the Institute of Forensic Medicine in Rio de Janeiro. We discovered 13 valves having two leaflets, giving a prevalence of 0.65%, much lower than generally reported in the literature. All 13 valves were from males, 10 from whites, three from mulattos, and none from blacks. Special attention was given to the raphe and the leaflets, the calcification of which can lead to stenosis. The only valves with normal texture and flexibility were two obtained from children less than one year old. All the other valves were thickened, and five of them had some degree of calcification. Six valves were judged to be functioning normally, while 7 valves were abnormal, 5 being stenotic and two showing evidence of insufficiency. The insufficiency in one was due to endocarditis, but in the other was due to redundancy of the leaflets. The only other cardiac anomaly discovered in these 13 cases was one patient with aortic coarctation. Bifoliate aortic valve, therefore, is probably the most common cardiac anomaly, although its prevalence as discovered in Brazil is lower than that reported in the literature. It affects mainly white males. After the fourth decade of life, most valves present some thickening, with stenosis being the most common complication. As is well recognised, infective endocarditis and aortic insufficiency are the other frequent complications. It is in general, nonetheless, an isolated anomaly.


Effects of Diode Laser Debonding of Ceramic Brackets on Enamel Surface and Pulpal Temperature.
Debonding of ceramic brackets due to their high bond strength and low fracture toughness is one of the most challenging complications of orthodontic clinicians. Application of lasers might be effective in the debonding of ceramic brackets as they reduce bond strength of resins and, therefore, can eliminate the risk of enamel damage. However, the thermal effects of laser radiation on dental tissue can cause undesirable results. The aim of this study is to evaluate the enamel surface characteristics and pulpal temperature changes of teeth after debonding of ceramic brackets with or without laser light. Thirty polycrystalline brackets were bonded to 30 intact extracted premolars, and later debonded conventionally or through a diode laser (2.5 W, 980 nm). The laser was applied for 10 seconds with sweeping movement. After debonding, the adhesive remnant index (ARI), the lengths and frequency of enamel cracks were compared among the groups. The increase in intrapulpal temperature was also measured. The collected data were analyzed by Chi-squared test and paired t-test using Statistical Package for Social Sciences (SPSS) software. There was no case of enamel fracture in none of the groups. Laser debonding caused a significant decrease in the frequency and lengths of enamel cracks, compared to conventional debonding. In laser debonding group, the increase in intrapulpal temperature (1.46°C) was significantly below the benchmark of 5.5°C for all the specimens. No significant difference was observed in ARI scores among the groups. Laser-assisted debonding of ceramic brackets could reduce the risk of enamel damage, without causing thermal damage to the pulp. However, some increases in the length and frequency of enamel cracks should be expected with all debonding methods.


Recurrence and survival after resection of adenocarcinoma of the gastric cardia. Rotterdam Esophageal Tumor Study Group.
In a retrospective study, the results after resection of carcinoma of the gastric cardia in the era without neoadjuvant therapy or extended lymph node dissection were evaluated. All 184 patients who underwent resection between January 1983 and December 1993 were included. Recurrence of disease, survival and prognostic factors were determined. The overall cumulative 5-year recurrence rate was 71% and the survival rate 23%. Multivariate analysis identified locoregional lymph node and distant metastases as the crucial prognosticators of recurrence of disease and survival. These results were similar to those from a previous study concerning our patients operated during the years 1983-88. The prognosis of a resected cardiacarcinoma has remained unchanged in our hands over the past 10 years. These results stress the importance of exploring new ways, such as the use of new diagnostic tools, to optimize preoperative patient selection and more aggressive treatment regimens to improve final outcome.


A multivariate approach for assessing leaf photo-assimilation performance using the IPL index.
The detection of leaf functionality is of pivotal importance for plant scientists from both theoretical and practical point of view. Leaves are the sources of dry matter and food, and they sequester CO2 as well. Under the perspective of climate change and primary resource scarcity (i.e. water, fertilizers and soil), assessing leaf photo-assimilation in a rapid but comprehensive way can be helpful for understanding plant behavior under different environmental conditions and for managing the agricultural practices properly. Several approaches have been proposed for this goal, however, some of them resulted very efficient but little reliable. On the other hand, the high reliability and exhaustive information of some models used for estimating net photosynthesis are at the expense of time and ease of measurement. The present study employs a multivariate statistical approach to assess a model aiming at estimating leaf photo-assimilation performance, using few and easy-to-measure variables. The model, parameterized for apple and pear and subjected to internal and external cross validation, involves chlorophyll fluorescence, carboxylative activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo), air and leaf temperature. Results prove that this is a fair-predictive model allowing reliable variable assessment. The dependent variable, called IPL index, was found strongly and linearly correlated to net photosynthesis. IPL and the model behind it seem to be (1) reliable, (2) easy and fast to measure and (3) usable in vivo and in the field for such cases where high amount of data is required (e.g. precision agriculture and phenotyping studies).


Phase I study of neoadjuvant chemoradiotherapy consisting of S-1 and cisplatin for patients with resectable advanced gastric cancer (KOGC-01).
The prognosis for advanced gastric cancer is poor, with surgery as the only treatment for resectable advanced gastric cancer. Therefore, treatment options that might improve the prognosis are needed. To that end, neoadjuvant chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated. The chemotherapy schedule included one cycle repeated after 6 weeks. S-1 was administered orally every day on days 1-21 and CDDP was infused on days 1, 8 and 15. Radiation therapy was started concurrently with chemotherapy and repeated daily on days 1-5, 8-12, 15-19, and 22-26. A total of 10 patients were recruited. The first four patients were entered into level 1 (CDDP, 20 mg/m²). The next six patients were entered into level 0 (15 mg/m²), because of dose-limiting toxicity (delaying the second course of chemotherapy in two patients) that had been observed at level 1. The maximum tolerated dose (MTD) of CDDP was 20 mg/m². Seven patients underwent surgery and all had an R0 (no residual tumor) resection without surgical complications. Neoadjuvant chemoradiotherapy with S-1 and CDDP may cause surgery to be delayed, but shows promise for resectable advanced gastric cancer.


Chemotherapy of Schistosomiasis present and past.
The primary objective of chemotherapy is to cure individual patient by eradication of the infection. This eradication leads to cessation of egg deposition which is the main pathogenic agent for the patient and community. The present generation of antischistosomal drugs provides physicians and public health practitioners with flexible, well tolerated, convenient, highly efficient tools for control of schistosomal morbidity in human, in contrast old generation of antischistosomal drugs were not so.


Assessing Disaster Preparedness Among Select Children's Summer Camps in the United States and Canada.
Children's summer camps are at risk for multiple pediatric casualties during a disaster. The degree to which summer camps have instituted disaster preparedness is unknown. We assessed disaster preparedness among selected camps nationally for a range of disasters. We partnered with a national, web-based electronic health records system to send camp leadership of 315 camp organizations a 14-question online survey of disaster preparedness. One response from each camp was selected in the following order of importance: owner, director, physician, nurse, medical technician, office staff, and other. The results were analyzed using descriptive statistics. A total of 181 camps responses were received, 169 of which were complete. Camp types were overnight (60%), day (21%), special/medical needs (14%), and other (5%). Survey respondents were directors (52%), nurses (14%), office staff (10%), physicians (5%), owners (5%), emergency medical technicians (2%), and other (12%). Almost 18% of camps were located >20 mi from a major medical center, and 36% were >5 mi from police/fire departments. Many camps were missing emergency supplies: car/booster seats for evacuation (68%), shelter (35%), vehicles for evacuation (26%), quarantine isolation areas (21%), or emergency supplies of extra water (20%) or food (17%). Plans were unavailable for the following: power outages (23%); lockdowns (15%); illness outbreaks (15%); tornadoes (11%); evacuation for fire, flood, or chemical spill (9%); and other severe weather (8%). Many camps did not have online emergency plans (53%), plans for children with special/medical needs (38%), methods to rapidly communicate information to parents (25%), or methods to identify children for evacuation/reunification with parents (40%). Respondents reported that staff participation in disaster drills varied for weather (58%), evacuations (46%), and lockdowns (36%). The majority (75%) of respondents had not collaborated with medical organizations for planning. A substantial proportion of camps were missing critical components of disaster planning. Future interventions must focus on developing summer camp-specific disaster plans, increasing partnerships, and reassessing national disaster plans to include summer camp settings.


Reprogramming Prostate Cancer Cells into Induced Pluripotent Stem Cells: a Promising Model of Prostate Cancer Stem Cell Research.
Prostate cancer stem cells (PrCSCs) are responsible for the development of castration-resistant disease and are associated with poor outcomes; however, the origin of PrCSCs is still not known due to the lack of a suitable model. In the current study, the human prostate cancer cell line 22RV1 was used to generate induced pluripotent stem cells (iPSCs) via the exogenous expression of four classic transcription factors (OCT-4, SOX2, KLF4, and C-MYC). The iPSCs were analyzed by phase contrast microscopy, real-time polymerase chain reaction, immunofluorescence, alkaline phosphatase (AP) activity, and examined for karyotype and embryoid body and teratoma formation. The analyses demonstrated that the prostate cancer cells were successfully reprogrammed into iPSCs by characteristic human embryonic stem cell morphology, cell marker expression, AP activity, embryoid body, and pluripotency capability in generating all three embryonic germ layers. These results may provide a convenient and accessible model for studying the origin of PrCSCs and the process by which progenitor cells are transformed into PrCSCs.


[Treatment of idiopathic pulmonary fibrosis].
Idiopathic pulmonary fibrosis (IPF) is a severe disease with a median survival time of only 24-36 months. It is characterized by inexorably progressive respiratory failure and by acute exacerbations that are often rapidly fatal. The standard treatment based on steroids and immunosuppressive drugs is no longer recommended Lung transplantation is the only treatment with an impact on survival but it concerns only a minority of patients and must be performed early in the disease process. Patients not eligible for transplantation should be given the opportunity to participate in clinical trials of promising new therapies. Many trials have recently been completed or are currently underway, but few results have been published. In the meantime, supportive treatment (oxygen therapy and rehabilitation), vaccination, and treatment of comorbidities (gastroesophageal reflux, sleep apnea) are recommended.


Rapid Parallel Evolution of Azole Fungicide Resistance in Australian Populations of the Wheat Pathogen Zymoseptoria tritici.
Zymoseptoria tritici is a globally distributed fungal pathogen which causes Septoria tritici blotch on wheat. Management of the disease is attempted through the deployment of resistant wheat cultivars and the application of fungicides. However, fungicide resistance is commonly observed in Z. tritici populations, and continuous monitoring is required to detect breakdowns in fungicide efficacy. We recently reported azole-resistant isolates in Australia; however, it remained unknown whether resistance was brought into the continent through gene flow or whether resistance emerged independently. To address this question, we screened 43 isolates across five Australian locations for azole sensitivity and performed whole-genome sequencing on 58 isolates from seven locations to determine the genetic basis of resistance. Population genomic analyses showed extremely strong differentiation between the Australian population recovered after azoles began to be used and both Australian populations recovered before azoles began to be used and populations on different continents. The apparent absence of recent gene flow between Australia and other continents suggests that azole fungicide resistance has evolved de novo and subsequently spread within Tasmania. Despite the isolates being distinct at the whole-genome level, we observed combinations of nonsynonymous substitutions at the CYP51 locus identical to those observed elsewhere in the world. We observed nine previously reported nonsynonymous mutations as well as isolates that carried a combination of the previously reported L50S, S188N, A379G, I381V, Y459DEL, G460DEL, and N513K substitutions. Assays for the 50% effective concentration against a subset of isolates exposed to the tebuconazole and epoxiconazole fungicides showed high levels of azole resistance. The rapid, parallel evolution of a complex CYP51 haplotype that matches a dominant European haplotype demonstrates the enormous potential for de novo resistance emergence in pathogenic fungi.IMPORTANCE Fungicides are essential to control diseases in agriculture because many crops are highly susceptible to pathogens. However, many pathogens rapidly evolve resistance to fungicides. A large body of studies have described specific mutations conferring resistance and have often made inferences about the origins of resistance based on sequencing data from the target gene alone. Here, we show the de novo acquisition of resistance to the ubiquitously used azole fungicides in genetically isolated populations of the wheat pathogen Zymoseptoria tritici in Tasmania, Australia. We confirm evidence for parallel evolution through genome-scale analyses of representative worldwide populations. The emergence of complex resistance haplotypes following a well-documented recent introduction of azoles into Australian farming practices demonstrates how rapidly chemical resistance evolves in agricultural ecosystems.


Identifying belief targets to increase bone marrow registry participation among students who have never donated blood.
New members on bone marrow registries worldwide are needed to allow sufficient diversity in the donor pool to meet patient needs. We used the theory of planned behaviour belief-basis and surveyed students who had not donated blood previously (i.e. non-donors) (N = 150) about the behavioural, normative, and control beliefs informing their intentions to join the Australian Bone Marrow Donor Registry. Key beliefs predicting non-donors' intentions included: viewing bone marrow donation as an invasion of the body (β = -.35), normative support from parents (β = .40), anticipating pain/side effects from giving blood (β = -.27), and lack of knowledge about how to register (β = -.30). Few non-donors endorsed these beliefs, suggesting they are ideal targets for change in strategies encouraging bone marrow donor registration.


Effects of chronic oral rimonabant administration on energy budgets of diet-induced obese C57BL/6 mice.
The endocannabinoids have been recognized as an important system involved in the regulation of energy balance. Rimonabant (SR141716), a selective inverse agonist of cannabinoid receptor 1 (CB1), has been shown to cause weight loss. However, its suppressive impact on food intake is transient, indicating a likely additional effect on energy expenditure. To examine the effects of rimonabant on components of energy balance, we administered rimonabant or its vehicle to diet-induced obese (DIO) C57BL/6 mice once daily for 30 days, by oral gavage. Rimonabant induced a persistent weight reduction and a significant decrease in body fatness across all depots. In addition to transiently reduced food intake, rimonabant-treated mice exhibited decreased apparent energy absorption efficiency (AEAE), reduced metabolizable energy intake (MEI), and increased daily energy expenditure (DEE) on days 4-6 of treatment. However, these effects on the energy budget had disappeared by days 22-24 of treatment. No chronic group differences in resting metabolic rate (RMR) or respiratory quotient (RQ) (P > 0.05) were detected. Rimonabant treatment significantly increased daily physical activity (PA) levels both acutely and chronically. The increase in PA was attributed to elevated activity during the light phase but not during the dark phase. Taken together, these data suggested that rimonabant caused a negative energy balance by acting on both energy intake and expenditure. In the short term, the effect included both reduced intake and elevated PA but the chronic effect was only on increased PA expenditure.


Surgical treatment of morbid obesity with reflux esophagitis.
Experience with six morbidly obese patients with symptomatic reflux esophagitis associated with hiatal hernia, the diagnoses confirmed by upper GI x-ray contrast studies and endoscopy, has been reported. Truncal vagotomy with Heineke-Mikilicz pyloroplasty and gastric bypass with Roux-en-Y gastrojejunostomy has controlled all symptoms of esophagitis and produced effective weight loss. It is suggested that if the proximal gastric pouch is no larger than 25 ml there is no need to perform truncal vagotomy and pyloroplasty.


Seeds Act as Vectors for Antibiotic Resistance Gene Dissemination in a Soil-Plant Continuum.
Though the evidence for antibiotic resistance spread via plant microbiome is mounting, studies regarding antibiotic resistome in the plant seed, a reproductive organ and important food resource, are still in their infancy. This study investigated the effects of long-term organic fertilization on seed bacterial endophytes, resistome, and their intergenerational transfer in the microcosm. A total of 99 antibiotic resistance genes (ARGs) and 26 mobile genetic elements (MGEs) were detected by high-throughput quantitative PCR. The amount of organic fertilizer applied was positively correlated to the number and relative abundance of seed-associated ARGs and MGEs. Moreover, the transmission of ARGs from the rhizosphere to the seed was mainly mediated by the shared bacteria and MGEs. Notably, the rhizosphere of progeny seedlings derived from seeds harboring abundant ARGs was found to have a higher relative abundance of ARGs. Using structural equation models, we further revealed that seed resistome and MGEs were key factors affecting the ARGs in the progeny rhizosphere, implying the seed was a potential resistome reservoir for rhizosphere soil. This study highlights the overlooked role of seed endophytes in the dissemination of resistome in the soil-plant continuum, and more attention should be paid to plant seeds as vectors of ARGs within the "One-Health" framework.


Phenformin-induced lactic acidosis in diabetic patients.
Eighteen diabetic patients with lactic acidosis (L.A.) were analyzed for possible causal factors, metabolic changes, and efficacy of treatment. An antecedent phenformin therapy was performed in fifteen cases and was associated with renal insufficiency in ten cases and liver disease in eight cases. Tissular anoxia of primary hemodynamic or respiratory origin was absent in all cases. The severe metabolic acidosis (pH m.93 +/- 0,03; HCO3-= 6 +/- 1 MM; PaCO2 = 18 +/- 2 MM. Hg) and hyperlactatemia (14.2 +/- 0.3 mM) were associated with high lactate/pyruvate ration (70 +/- 22). High alanine levels (up to 4.6 mM) were measured in some of these patients. High beta-hydroxybutrate levels were sometimes measured (up to 7.6 mM), and substantial amounts of acetoacetate were also detected in twelve cases. Glucagon level was always increased (1,050 +/- 240 pg./ml.), and insulin/glucagon ratio was low. Cortisol (49 +/- 10 mug./100 ml.) and HGH (10.8 +/- 0.6 ng./ml.) were also elevated. Increased plasma levels of phenformin were measured in five L.A. diabetic subjects (50 +/- 5 mug./ml.) by comparison with other phenformin-treated diabetic subjects. The specificity of the assay was investigated, and phenformin metabolites were characterized by thin-layer chromatography. Por the treatment of L.A., adjunction of dialysis and furosemide improved the efficacy of early and massive sodium bicarbonate infusion. It is suggested that accumulation of phenformin via renal insufficiency plays a determinant role in causing L.A. through an impairment of lactate metabolism in the liver. An accelerated epuration of the drug may be helpful in therapy of L.A. Phenformin treatment should be avoided in case of renal and/or liver insufficiency.


Generation of Induced Pluripotent Stem Cells from Turner Syndrome (45XO) Fetal Cells for Downstream Modelling of Neurological Deficits Associated with the Syndrome.
Chromosomal aneuploidies cause severe congenital malformations including central nervous system malformations and fetal death. Prenatal genetic screening is purely diagnostic and does not elucidate disease mechanism. Although cells from aneuploid fetuses are valuable biological material bearing the chromosomal aneuploidy, these cells are short lived, limiting their use for downstream research experiments. Generation of induced pluripotent stem cell (iPSC) models is an effective method of cell preparation for perpetual conservation of aneuploid traits. They are self-renewing and differentiate into specialized cells reminiscent of embryonic development. Thus, iPSCs serve as excellent tools to study early developmental events. Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome. The syndrome is characterized by infertility, short stature, endocrine, metabolic, autoimmune and cardiovascular disorders and neurocognitive defects. The following protocol describes isolation and culturing of fibroblasts from TS (45XO) fetal tissue, generation of integration free TSiPSCs through delivery of episomal reprogramming plasmids by nucleofection followed by characterization. The reprogramming TSiPSCs were initially screened by live cell alkaline phosphatase staining followed by extensive probing for pluripotency biomarkers. Selected colonies were mechanically dissected, passaged several times and stable self-renewing cells were used for further experiments. The cells expressed pluripotency transcription factors OCT4, NANOG, SOX2, cell surface markers SSEA 4 and TRA1-81 typical of pluripotent stem cells. The original 45XO karyotype was retained post reprogramming. The TSiPSCs were able to form embryoid bodies and differentiate into cells of endoderm, mesoderm and ectoderm expressing lineage specific biomarkers ((SRY BOX17), (MYOSIN VENTRICULAR HEAVY CHAINα/β), (βIII TUBULIN)). The exogenous episomal plasmids were lost spontaneously and not detected after passage 15 in cells. These TSiPSCs are a valuable cellular resource for modelling defective molecular and cellular neurodevelopment causing neurocognitive deficits associated with Turner syndrome.


Reference values for serum levels of vitamin B12 and folic acid in a population-based sample of adults between 35 and 80 years of age.
To examine folic acid and vitamin B12 status in a group of 1000 persons sampled from the community of Umeå, Sweden, and aged 35, 40, 45, 50, 55, 60, 65, 70, 75 or 80 years. Reference data for folate and age-stratified reference data for vitamin B12 are presented, together with an examination of potential confounders. All subjects participated in extensive health examinations and interviews, and laboratory blood testing was performed. A series of exclusion criteria were applied, and data from 961 subjects were analysed. Vitamin B12 levels were found to decrease with increasing age, whereas folate levels remained constant across the age span studied. None of the vitamins was found to vary with sex, education, smoking or alcohol consumption, body mass index, prescription-free vitamin supplements, level of haemoglobin, or mean cell volume of erythrocytes. Further, none of these factors was associated with the age-related decrease of vitamin B12 level. The offered reference ranges should be used only in order to rule out deficiency. For B12 levels, the age of the subject should be considered such that, for elderly people in particular, values above the medians should be considered as indicative of normal vitamin status.


Luminescent nanoparticles embedded in TiO2 microtube cavities for the activation of whispering-gallery-modes extending from the visible to the near infrared.
Luminescent nanoparticles (NPs) are deposited onto two dimensional (2D) pre-strained TiO2 nanomembranes by spin-coating. After rolling up the 2D differentially strained TiO2 nanomembranes into 3D microtube structures, the NPs are embedded within the tube windings. The embedded NPs serve as a light source for optical whispering-gallery-mode resonances under laser excitation, and therefore allow the TiO2 microtube to work as an active microcavity operating in emission mode. The spectral range of resonant modes can be tuned from the visible to the near infrared by embedding the proper NPs in the TiO2 tube wall. Rolled-up TiO2 microcavities combined with luminescent NPs could offer interesting opportunities in a variety of research fields, such as bio- and nanophotonics, optoelectronics, and optofluidics.


Socioeconomic, lifestyle and biological determinants of cervical screening coverage: Lolland-Falster Health Study, Denmark.
Cervical cancer is preventable. Screening is important for early detection. However, even in high-income countries, coverage is sub-optimal. We identified socioeconomic, lifestyle and biological determinants of cervical screening coverage. In Denmark, women aged 23-64 are free of charge personally invited to screening. All cervical cell samples are registered centrally in the Patobank. We linked data from the Lolland-Falster Health Study (LOFUS) with Patobank data. LOFUS was a population-based health survey undertaken in 2016-2020. With logistic regression, coverage defined as ≥1 cervical sample registered within a 6-year period from 2015 to 2020 was compared across levels of risk factors expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Among 13 406 women of screening aged 23-64 and invited to LOFUS, 72% had ≥1 cervical sample registered. Non-participation in LOFUS was a strong predictor of low coverage; aOR 0.32; 95% CI 0.31-0.36. Among LOFUS participants, education was a strong predictor of coverage in univariate analysis, OR 0.58; 95% CI 0.48-0.71, but this association disappeared in multi-variate analysis, aOR 0.86; 95% CI 0.66-1.10. In multi-variate analysis, predictors of low coverage were high age, living without a partner, retired, current smoker, poor self-rated health, elevated blood pressure and elevated glycated haemoglobin. Women with low cervical screening coverage had limited contact to healthcare, exemplified by non-participation in LOFUS, and pertinent health and social problems, exemplified by elevated blood pressure and glycated haemoglobin, poor self-rated health, and retirement already in screening age. Structural changes in screening are needed to reach non-screened women.


Baseline Volumetric Multiparametric MRI: Can It Be Used to Predict Survival in Patients with Unresectable Intrahepatic Cholangiocarcinoma Undergoing Transcatheter Arterial Chemoembolization?
Purpose To evaluate whether baseline MRI can help predict survival in patients with unresectable intrahepatic cholangiocarcinoma (ICCA) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. The study included 111 patients (mean age, 62 years ± 12; range, 29-86 years), with 44 men (mean age, 61 years ± 12; range, 29-81 years) and 67 women (mean age, 63 years ± 12; range, 34-86 years). Patients underwent TACE after baseline MRI, which included contrast-enhanced and diffusion-weighted imaging with apparent diffusion coefficient (ADC) mapping between 2003 and 2016. The single largest tumor was assessed independently by a radiologist for anatomic and functional (viable tumor volume, percentage viable tumor volume [100 × viable tumor volume/whole tumor volume], viable tumor burden [100 × viable tumor volume/whole liver volume], and ADC) parameters. Survival analysis was performed with Kaplan-Meier and Cox regression analysis. Results Overall survival (OS) was higher with a baseline ADC of 1415 × 10-6 mm2/sec or less compared with greater than 1415 × 10-6 mm2/sec (P = .005; 25th percentile of OS, 17 months vs 7 months, respectively), percentage viable tumor volume greater than 90% compared with 90% or less (P = .001; 25th percentile of OS, 20 months vs 7 months, respectively), and viable tumor burden greater than 6.6% compared with 6.6% or less (P = .09; 25th percentile of OS, 17 months vs 7 months, respectively). Baseline ADC greater than 1415 × 10-6 mm2/sec (hazard ratio [HR]: 2.176 [95% confidence interval: 1.217, 3.891]; P = .009) and percentage viable tumor volume greater than 90% (HR: 0.319 [95% confidence interval: 0.148, 0.685]; P = .003) were associated with OS independent of clinical confounders (age and sex). At multiparametric MRI risk stratification (with low ADC and high percentage viable tumor volume considered favorable for survival), differences in OS were noted (P = .002; 25th percentile of OS for low vs intermediate vs high risk, 22 months vs 10 months vs 7 months, respectively). Conclusion Baseline multiparametric MRI assessment including volumetric ADC, percentage viable tumor volume, and viable tumor burden can help predict mortality risk among patients with intrahepatic cholangiocarcinoma undergoing transcatheter arterial chemoembolization. © RSNA, 2018 Online supplemental material is available for this article.


Dose management in CT facility.
Computed Tomography (CT) examinations have rapidly increased in number over the last few years due to recent advances such as the spiral, multidetector-row, CT fluoroscopy and Positron Emission Tomography (PET)-CT technology. This has resulted in a large increase in collective radiation dose as reported by many international organisations. It is also stated that frequently, image quality in CT exceeds the level required for confident diagnosis. This inevitably results in patient radiation doses that are higher than actually required, as also stressed by the US Food and Drug Administration (FDA) regarding the CT exposure of paediatric and small adult patients. However, the wide range in exposure parameters reported, as well as the different CT applications reveal the difficulty in standardising CT procedures. The purpose of this paper is to review the basic CT principles, outline the recent technological advances and their impact in patient radiation dose and finally suggest methods of radiation dose optimisation.


[Consensus cerebrovascular accident].
A consensus conference on stroke was held on March 22, 1991. Subjects on which consensus was reached were: There are different kinds of cerebral haemorrhage and infarction, which can be differentiated by computerized tomography, and this can have practical consequences. At clinical examination special attention should be paid to cognitive impairment. Angiography is indicated only if carotid surgery or unusual causes are considered. CSF examination and EEG are performed only on special indications. Cardiological consultation is necessary in young patients, or if clinical signs of cardiogenic embolism are present. Coumarin derivatives are prescribed in some of these cardiac causes of stroke, to prevent recurrence. There is as yet no effective medical treatment for cerebral infarction. In lobar and cerebellar haemorrhage surgical treatment may be indicated. In the acute phase of stroke it is always important to prevent aspiration pneumonia, pulmonary embolism and decubitus, and to care for muscles and joints. Advantages and disadvantages of gastric tube and indwelling catheter should be weighed. Treatment of hypertension after the acute phase is indicated to prevent recurrent stroke. After TIA and minor stroke, aspirin is prescribed, which reduces the risk of cerebral and myocardial infarction by 30%. Carotid endarterectomy in symptomatic patients with carotid stenosis of 70% or more, reduces the number of fatal or disabling strokes by 50%, if perioperative complications are less than 4%. Rehabilitation after stroke reduces disability and improves the adaptation of both the patient and his environment. The patient should be stimulated and supported; good information, including the family, is essential. Supplying aids and taking special measures should be done on individual basis, after a period of training.(ABSTRACT TRUNCATED AT 250 WORDS)