Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. IV. Responses after spectacle-induced adaptation.
The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000 degrees /s(2) to 150 degrees /s was studied in six squirrel monkeys following adaptation with x2.2 magnifying and x0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20 degrees /s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, G(A), of a step of acceleration (3,000 degrees /s(2) to 150 degrees /s) increased from preadaptation values of 1.05 +/- 0.08 to 1.96 +/- 0.16, while the gain during the velocity plateau, G(V), only increased from 0.93 +/- 0.04 to 1.36 +/- 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of G(A) decreased to 0.61 +/- 0.08, and the value of G(V) decreased to 0.59 +/- 0.09 for the 3,000 degrees /s(2) steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model of the VOR containing linear and nonlinear pathways that describe the normal behavior and adaptive processes. Adaptation for the linear pathway is described by a transfer function that shows the dependence of adaptation on the frequency of the head movement. The adaptive process for the nonlinear pathway is a gain enhancement element that provides for the accentuated gain with rising head velocity and the increased cubic component of the responses to steps of acceleration. While this model is substantially different from earlier models of VOR adaptation, it accounts for the data in the present experiments and also predicts the findings observed in the earlier studies.


Determination of methotrexate in biological fluids and a parenteral injection using terbium-sensitized method.
A new sensitive, simple and rapid method for determination of methotrexate (MTX) was developed based on quenching effects of MTX on the fluorescence intensity of Tb(3+)-1,10-phenanthroline complex. The fluorescence intensity was measured with excitation wavelength of 300 nm and emission wavelength of 545 nm and the quenched fluorescence intensity is proportional to the concentration of MTX in Tris-HCl buffer solution with a pH of 7.0. The effects of pH, time, order of addition of the reagents, temperature and the concentrations of Tb(3+), buffer and 1,10-phenanthroline were investigated and optimized. The obtained linear range for the determination of MTX was 0.02-10 μg/mL. The detection limits (signal: noise = 3) was 0.015 μg/mL and the relative standard deviation for replicated determinations of 1 μg/mL of MTX was 1.9%. The proposed method is a simple, practical and relatively free from interference effects and was successfully applied to assess MTX in urine, serum and samples of an injection solution.


Career choices for pathology: national surveys of graduates of 1974-2002 from UK medical schools.
In the past 10 years there has been increasing concern about recruitment of junior doctors into pathology, particularly histopathology, in the UK. In this study, we report on career choices for pathology, derived from postal questionnaire surveys of all qualifiers from all UK medical schools in nine qualification years since 1974. 74% (24,623/33,417) and 73% (20,709/28,468) of doctors responded at 1 and 3 years after qualification. The percentage of doctors choosing pathology 1 year after qualification has fallen sharply in recent years: between 1974 and 1983 it was 4.5% (95% confidence interval 4.1-4.9%) and between 1993 and 2002 it was 2.3% (CI 2.0-2.5%). 57% of doctors who chose pathology 1 year after qualification were still working in pathology at year 10. Hours and conditions of work, the doctor's personal assessment of their aptitudes, and their experience of the subject as a student influenced long-term career choices for pathology. Recruitment of UK graduates into the pathology specialties must increase to meet demand in the new and expanding subspecialties. This depends on developing innovative ways of raising the profile of pathology to medical students and junior hospital doctors.


Crocetin restores diabetic endothelial progenitor cell dysfunction by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways.
Endothelial progenitor cell (EPC) dysfunction underlies a critical risk factor in diabetic vascular complications due to function defect in restoring endothelium injury. Crocetin has attracted increasing attention in several vascular-related diseases. In present study, we aimed to explore the role of crocetin in diabetic EPC dysfunction. EPCs were isolated from bone marrow in diabetic mice and identified using the fluorescence staining and flow cytometry. After exposure to various doses of crocetin, cell viability was detected by MTT assy. Then, colony formation, lactate dehydrogenase (LDH) release, cell apoptosis and caspase-3 activity were assessed. The underlying mechanism was also investigated by western blotting. EPCs from diabetic mice exhibited dysfunction under hyperglycemia condition. Interestingly, crocetin treatment alleviated the impairment in diabetic EPC proliferation and colony formation. Simultaneously, the increases in LDH release, cell apoptosis and caspase-3 activity were also restrained following crocetin stimulation. Additionally, EPC migration response to SDF-1 was also impaired under diabetic condition, which was partly restored by crocetin. Mechanism analysis manifested that administration with crocetin repaired the damage in the activation of PI3K/AKT-eNOS pathway and NO production, but attenuated ROS elevation in diabetic EPCs. Importantly, preconditioning with antagonist of LY294002 (for PI3K/AKT) or NG-monomethyl-l-arginine (for eNOS) antagonized the beneficial effect of crocetin on diabetic EPC dysfunction. These data corroborated that crocetin could restore the dysfunction of diabetic EPCs by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways. Therefore, this research supports a potential promising therapeutic aspect for diabetic patients.


"It depends how one understands it:" a qualitative study on differential uptake of oral cholera vaccine in three compounds in Lusaka, Zambia.
The Zambian Ministry of Health implemented a reactive one-dose Oral Cholera Vaccine (OCV) campaign in April 2016 in three Lusaka compounds, followed by a pre-emptive second-round in December. Understanding uptake of this first-ever two-dose OCV campaign is critical to design effective OCV campaigns and for delivery of oral vaccines in the country and the region. We conducted 12 Focus Group Discussions (FGDs) with men and women who self-reported taking no OCV doses and six with those self-reporting taking both doses. Simple descriptive analysis was conducted on socio-demographic and cholera-related data collected using a short questionnaire. We analyzed transcribed FGDs using the framework of dose, gender and geographic location. No differences were found by gender and location. All participants thought cholera to be severe and the reactive OCV campaign as relevant if efficacious. Most reported not receiving information on OCV side-effects and duration of protection. Those who took both doses listed more risk factors (including 'wind') and felt personally susceptible to cholera and protected by OCV. Some described OCV side-effects, mostly diarrhoea, vomiting and dizziness, as the expulsion of causative agents. Those who did not take OCV felt protected by their good personal hygiene practices or, thought of themselves and OCV as powerless against the multiple causes of cholera including poor living conditions, water, wind, and curse. Most of those who did not take OCV feared side-effects reported by others. Some interpreted side-effects as 'western' malevolence. Though > 80% discussants reported not knowing duration of protection, some who did not vaccinate, suggested that rather than rely on OCV which could lose potency, collective action should be taken to change the physical and economic environment to prevent cholera. Due to incomplete information, individual decision-making was complex, rooted in theories of disease causation, perceived susceptibility, circulating narratives, colonial past, and observable outcomes of vaccination. To increase coverage, future OCV campaigns may benefit from better communication on eligibility and susceptibility, expected side effects, mechanism of action, and duration of protection. Governmental improvements in the physical and economic environment may increase confidence in OCV and other public health interventions among residents in Lusaka compounds.


Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.
Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.


ACR Appropriateness Criteria: single brain metastasis.
Single brain metastasis represents a common neurologic complication of cancer. Given the number of treatment options that are available for patients with brain metastasis and the strong opinions that are associated with each option, appropriate treatment for these patients has become controversial. Prognostic factors such as recursive partitioning analysis and graded prognostic assessment can help guide treatment decisions. Surgery, whole brain radiation therapy (WBRT), stereotactic radiosurgery or combination of these treatments can be considered based on a number of factors. Despite Class I evidence suggestive of best therapy, the treatment recommendation is quite varied among physicians as demonstrated by the American College of Radiology's Appropriateness Panel on single brain metastasis. Given the potential concerns of the neurocognitive effects of WBRT, the use of SRS alone or SRS to a resection cavity has gained support. Since aggressive local therapy is beneficial for survival, local control and quality of life, the use of these various treatment modalities needs to be carefully investigated given the growing number of long-term survivors. Enrollment of patients onto clinical trials is important to advance our understanding of brain metastasis.


Combined atherogenic effects of celiac disease and type 1 diabetes mellitus.
Previous studies have shown a high cardiovascular risk in patients with autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Conversely, few data are available about patients with celiac disease (CD). The aim of our study was to assess carotid intima-media thickness (c-IMT), in patients with T1DM, CD or both (T1DM+CD) as compared with age- and sex-matched healthy individuals (H). We enrolled 120 patients, 30 with T1DM, 30 with CD, 30 with T1DM+CD and 30 H. Clinical, metabolic and anthropometric data were collected. All T1DM patients were on insulin while all CD patients were on a gluten-free diet. c-IMT was evaluated by high frequency linear digital ultrasound. c-IMT was significantly greater in patients with T1DM+CD than in patients with T1DM or CD (P<0.001 for both), while no difference was found between T1DM and CD. Moreover, c-IMT was greater in CD than in H (P<0.001). Glycemic control and disease duration were similar between T1DM+CD and T1DM. Lipid and anthropometric parameters were similar among groups. Furthermore, in a pooled multivariate analysis, only age and disease type were significantly correlated with c-IMT (P<0.001 for both). Our study demonstrates that celiac patients have greater c-IMT as compared with healthy individuals. Thus, non-invasive monitoring of c-IMT in CD might be useful in preventing cardiovascular disease. Moreover, patients with T1DM+CD show more severe subclinical atherosclerosis as compared with those presenting T1DM or CD only, suggesting that the association of these autoimmune diseases might accelerate the atherosclerotic process.


Molecular mechanisms in cognitive frailty: potential therapeutic targets for oxygen-ozone treatment.
In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and metabolic alterations, mitochondria dysfunctions and slowdown in regenerative processes and immune system, with a complex and multifactorial aetiology. Although several treatments are available, challenges regarding the efficacy and the costs persist. Here, we proposed an alternative non-pharmacological, non-side-effect, low cost therapy based on anti-inflammation, antioxidant, regenerative and anti-pathogens properties of ozone, through the activation of several molecular mechanisms (Nrf2-ARE, NF-κB, NFAT, AP-1, HIFα). We highlighted how these specific processes could be implicated in cognitive frailty to identify putative therapeutic targets for its treatment. The oxigen-ozone (O2-O3) therapy has never been tested for cognitive frailty. This work provides thus wide scientific background to build a consistent rationale for testing for the first time this therapy, that could modulate the immune, inflammatory, oxidant, metabolic, endocrine, microbiota and regenerative processes impaired in cognitive frailty. Although insights are needed, the O2-O3 therapy could represent a faster, easier, inexpensive monodomain intervention working in absence of side effects for cognitive frailty.


Partial regeneration of beta-cells in the islets of Langerhans by Nymphayol a sterol isolated from Nymphaea stellata (Willd.) flowers.
Reduction of the beta-cell mass is critical in the pathogenesis of diabetes mellitus. The discovery of agents which induce regeneration of pancreatic beta-cells would be useful to develop new therapeutic approaches to treat diabetes. The present study was aimed at identifying a new agent for the control of diabetes through regeneration of pancreatic beta cells and insulin secretory potential. Nymphaea stellata flower chloroform extract (NSFCExt) showed significant plasma glucose lowering effect. Further NSFCExt was utilized to isolate and identify the lead compound based on bioassay guided fractionation; we found Nymphayol (25,26-dinorcholest-5-en-3beta-ol) a new crystal [space group P2(1) (No. 4), a=9.618(5), b=7.518(5), c=37.491(5)]. It was purified by repeat column. The structure was determined on the basis of X-ray crystallography and spectral data. Oral administration of Nymphayol for 45 days significantly (p<0.05) lowered the blood glucose level and more importantly it effectively increased the insulin content in diabetic rats. In addition, Nymphayol increased the number of beta cell mass enormously. Islet-like cell clusters in the islets of Langerhans were clearly observed based on histochemical and immunohistochemical study.


Methodological Issues Surrounding the Use of Baseline Health-Related Quality of Life Data to Inform Trial-Based Economic Evaluations of Interventions Within Emergency and Critical Care Settings: A Systematic Literature Review.
Trial-based cost-utility analyses require health-related quality of life data that generate utility values in order to express health outcomes in terms of quality-adjusted life years (QALYs). Assessments of baseline health-related quality of life are problematic where trial participants are incapacitated or critically ill at the time of randomisation. This review aims to identify and critique methods for handling non-availability of baseline health-related quality of life data in trial-based cost-utility analyses within emergency and critical illness settings. A systematic literature review was conducted, following PRISMA guidelines, to identify trial-based cost-utility analyses of interventions within emergency and critical care settings. Databases searched included the National Institute for Health Research (NIHR) Journals Library (1991-July 2016), Cochrane Library (all years); National Health Service (NHS) Economic Evaluation Database (all years) and Ovid MEDLINE/Embase (without time restriction). Strategies employed to handle non-availability of baseline health-related quality of life data in final QALY estimations were identified and critiqued. A total of 4224 published reports were screened, 19 of which met the study inclusion criteria (mean trial size 1670): 14 (74 %) from the UK, four (21%) from other European countries and one (5%) from India. Twelve studies (63%) were based in emergency departments and seven (37%) in intensive care units. Only one study was able to elicit patient-reported health-related quality of life at baseline. To overcome the lack of baseline data when estimating QALYs, eight studies (42%) assigned a fixed utility weight corresponding to either death, an unconscious health state or a country-specific norm to patients at baseline, four (21%) ignored baseline utilities, three (16%) applied values from another study, one (5%) generated utility values via retrospective recall and one (5%) elicited utilities from experts. A preliminary exploration of these methods shows that incremental QALY estimation is unlikely to be biased if balanced trial allocation is achieved and subsequent collection of health-related quality of life data occurs at the earliest possible opportunity following commencement of treatment, followed by an adequate number of follow-up assessments. Trial-based cost-utility analyses within emergency and critical illness settings have applied different methods for QALY estimation, employing disparate assumptions about the health-related quality of life of patients at baseline. Where baseline measurement is not practical, measurement at the earliest opportunity following commencement of treatment should minimise bias in QALY estimation.


A comparison of the hand hygiene knowledge, beliefs and practices of Italian nursing and medical students.
This paper reports a study examining the hand hygiene knowledge, beliefs and practices of Italian nursing and medical students with the aim of informing undergraduate curricula. In comparison with registered nurses, physician status is a risk factor for non-compliance with hand hygiene guidelines. Little research has been conducted to determine if differences between the professions in relation to hand hygiene are apparent at the undergraduate level. Cross-disciplinary studies that may provide an insight into this topic are lacking. A questionnaire was administered to a convenience sample of 117 nursing and 119 medical students in a large university in Rome, Italy, to determine their hand hygiene knowledge, beliefs and practices. The data were collected in 2007-2008. Nursing students' hand hygiene knowledge (F = 9·03(1,230); P = 0·003), percentage compliance (Z = 6·197; P < 0·001) and self-reported hand hygiene practices (F = 34·54(1,230); P < 0·001) were significantly higher than that of medical students. There were no statistically significant differences between hand hygiene beliefs. Mean scores on the knowledge questions were low for both groups, reflecting primarily a knowledge deficit in relation to the use of alcohol-based hand rubs to decontaminate hands in the healthcare setting. Statistically significant disciplinary differences in hand hygiene knowledge and self-reported practices were apparent among undergraduate Italian healthcare students. Further research is needed to determine the causative factors. The overall low scores on the knowledge items indicate that these students require further education on hand hygiene, particularly in relation to the use of alcohol-based hand rubs.


Association of Central Arterial Stiffness and Pressure Pulsatility with Mild Cognitive Impairment and Dementia: The Atherosclerosis Risk in Communities Study-Neurocognitive Study (ARIC-NCS).
The association of central arterial stiffness and pressure pulsatility with mild cognitive impairment (MCI) and dementia is not well characterized in the population-based setting. The aim of this study was to quantify the cross-sectional association of arterial stiffness and pressure pulsatility with MCI and dementia among 4,461 older white and black adults from the population-based Atherosclerosis Risk in Communities Study-Neurocognitive Study. We used race-stratified multinomial logistic regression to evaluate associations of percentile cut points of carotid-femoral pulse wave velocity, central systolic blood pressure, central pulse pressure, and pulse pressure amplification with MCI and dementia versus no cognitive impairment. Among whites, those with carotid-femoral pulse wave velocity or central systolic blood pressure ≥75th percentile had a higher prevalence of MCI compared to participants <75th percentile (conditional odds ratio (OR); 95% confidence interval (CI): 1.27 (1.02, 1.56) and 1.28 (1.04, 1.57), respectively) and those with central pulse pressure ≥75th percentile had a higher prevalence of MCI (OR 1.27 (95% CI: 1.03, 1.58)) and dementia (OR 1.76 (95% CI: 1.06, 2.92) compared to participants <75th percentile. Also among whites, those with pulse pressure amplification ≤25th percentile had a higher prevalence of dementia compared to participants >25th percentile (OR 1.65; (95% CI: 1.01, 2.70). Weaker associations were seen among black participants. Higher arterial stiffness and pulsatility were associated with MCI and dementia in white participants. Longitudinal characterization of the observed associations is warranted to assess whether arterial stiffness and pressure pulsatility predict MCI and dementia among older adults.


The clinical learning portfolio: a practice development experience in gerontological nursing.
Assessment of clinical practice in post registration programmes can require a different focus to capture the essence of learning at a higher level. There are differences of opinion in the literature on the potential use of the portfolio as an assessment method. The aims of this paper are to describe the use of a portfolio of evidence-based practice and reflection to assess clinical learning in a Higher Diploma in Gerontological Nursing Programme and to present the findings of a pilot evaluation of this assessment. The evaluation was conducted by postal questionnaire distributed to the first cohort of students following graduation from the programme in 2002. Arising from this exploration of the student experience, it appears that the use of a portfolio in addition to formative assessment, can promote a link between theory and the advancement of gerontological nursing practice.


Breath hydrogen test for detecting lactose malabsorption in infants and children. Prevalence of lactose malabsorption in Japanese children and adults.
The breath hydrogen test (BHT) was adapted for use in young infants and children. The diagnostic criterion of sugar malabsorption in the BHT was determined by oral administration of 0.5 g/kg of unabsorbable sugar (lactulose) to 21 healthy infants and children. A maximum increase in breath hydrogen less than 0.05 ml/min per m2 was observed in all subjects. A good correlation between results by the BHT and by the ordinary lactose tolerance test was obtained after oral administration of 2 g/kg lactose to 21 healthy infants and children, 2 congenital lactase-deficient infants, and 7 adults. Using this test, 80 healthy Japanese infants and children (aged between one month and 15 years) and 18 adults were examined for lactose malabsorption after a dose of 1 g/kg lactose. All infants and children under 2-years old absorbed lactose completely. The incidence of lactose malabsorption was 30% in 3-year, 36% in 4-year, 58% in 5-year, and 86% in 6-year-old children, 85% in schoolchildren, and 89% in adults. Thus the incidence of lactase deficiency gradually increases with age from 3 years, and about 90% of all normal Japanese adults are lactase-deficient.


Patchiness in a microhabitat chip affects evolutionary dynamics of bacterial cooperation.
Localized interactions are predicted to favour the evolution of cooperation amongst individuals within a population. One important factor that can localize interactions is habitat patchiness. We hypothesize that habitats with greater patchiness (greater edge-to-area ratio) can facilitate the maintenance of cooperation. This outcome is believed to be particularly relevant in pathogenic microbes that can inhabit patchy habitats such as the human respiratory tract. To test this hypothesis in a simple but spatially controlled setting, we designed a transparent microhabitat chip (MHC) with multiple patchiness treatments at the 100 micron scale. The MHC is a closed system that sustains bacterial replication and survival for up to 18 hours, and allows spatial patterns and eco-evolutionary dynamics to be observed undisturbed. Using the opportunistic pathogen Pseudomonas aeruginosa, we tracked the growth of wild-type cooperators, which produce the public good pyoverdin, in competition with mutant defectors or cheaters that use, but do not produce, pyoverdin. We found that while defectors on average outperformed cooperators in all habitats, habitat patchiness significantly alleviated the ecological pressure against cooperation due to defection, leading to coexistence. Our results confirmed that habitat-level spatial heterogeneity can be important for cooperation. The MHC enables novel experiments, allows multiple parameters to be precisely varied and studied simultaneously, and will help uncover dynamical features of spatial ecology and the evolution of pathogens.


Fetal health status prediction based on maternal clinical history using machine learning techniques.
Congenital anomalies are seen at 1-3% of the population, probabilities of which are tried to be found out primarily through double, triple and quad tests during pregnancy. Also, ultrasonographical evaluations of fetuses enhance detecting and defining these abnormalities. About 60-70% of the anomalies can be diagnosed via ultrasonography, while the remaining 30-40% can be diagnosed after childbirth. Medical diagnosis and prediction is a topic that is closely related with e-Health and machine learning. e-Health applications are critically important especially for the patients unable to see a doctor or any health professional. Our objective is to help clinicians and families to better predict fetal congenital anomalies besides the traditional pregnancy tests using machine learning techniques and e-Health applications. In this work, we developed a prediction system with assistive e-Health applications which both the pregnant women and practitioners can make use of. A performance comparison (considering Accuracy, F1-Score, AUC measures) was made between 9 binary classification models (Averaged Perceptron, Boosted Decision Tree, Bayes Point Machine, Decision Forest, Decision Jungle, Locally-Deep Support Vector Machine, Logistic Regression, Neural Network, Support Vector Machine) which were trained with the clinical dataset of 96 pregnant women and used to process data to predict fetal anomaly status based on the maternal and clinical data. The dataset was obtained through maternal questionnaire and detailed evaluations of 3 clinicians from RadyoEmar radiodiagnostics center in Istanbul, Turkey. Our e-Health applications are used to get pregnant women's health status and clinical history parameters as inputs, recommend them physical activities to perform during pregnancy, and inform the practitioners and finally the patients about possible risks of fetal anomalies as the output. In this paper, the highest accuracy of prediction was displayed as 89.5% during the development tests with Decision Forest model. In real life testing with 16 users, the performance was 87.5%. This estimate is sufficient to give an idea of fetal health before the patient visits the physician. The proposed work aims to provide assistive services to pregnant women and clinicians via an online system consisting of a mobile side for the patients, a web application side for their clinicians and a prediction system. In addition, we showed the impact of certain clinical data parameters of pregnant on the fetal health status, statistically correlated the parameters with the existence of fetal anomalies and showed guidelines for future researches.


Treatment of infected non-unions with segmental defects with a rail fixation system.
We conducted this study to evaluate the use of rail fixation system in infected gap non-union of femur and tibia as an alternative to the established Ilizarov circular fixator technique. Prospective study. The study was done in the Department of Orthopaedic surgery in a medical school and level I trauma center to which the authors are/were affiliated. Between June 2010 and June 2015, 40 patients with infected gap non-union of femur and tibia were treated with the rail fixation system. Patients who were willing to undergo surgery and participate in the post-operative rehabilitation were included in the study. After radical debridement, the system was applied and corticotomy done. For closure of bone gap, acute docking and distraction was done in 18 cases and segmental bone transport in 22 cases. Early mobilization of patient was done along with aggressive physiotherapy. Bone and functional results were calculated according to ASAMI scoring system, and complications were classified according to Paley classification. The mean follow-up period was 22.56 months (range 8-44). Bone union with eradication of infection was achieved in all but 1 case (97.5%). Bone results were excellent in 57.5%, good 40%, fair 0% and poor in 2.5% cases, while functional result was excellent in 32.5%, good 65%, fair 0% and poor in 2.5% cases. The rail fixation system is an excellent alternative method to treat infected gap non-union of femur and tibia. It is simple, easy to use and patient-friendly.


Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication.
Dictyostelium discoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced the genomes of Dictyostelium fasciculatum (DF) and Polysphondylium pallidum (PP), which represent the early diverging groups 1 and 2, respectively. In contrast to DD, PP and DF have conventional telomere organization and strongly reduced numbers of transposable elements. The number of protein-coding genes is similar between species, but only half of them comprise an identifiable set of orthologous genes. In general, genes involved in primary metabolism, cytoskeletal functions and signal transduction are conserved, while genes involved in secondary metabolism, export, and signal perception underwent large differential gene family expansions. This most likely signifies involvement of the conserved set in core cell and developmental mechanisms, and of the diverged set in niche- and species-specific adaptations for defense and food, mate, and kin selection. Phylogenetic dating using a concatenated data set and extensive loss of synteny indicate that DF, PP, and DD split from their last common ancestor at least 0.6 billion years ago.


Usefulness of transjugular intrahepatic portosystemic shunt in the management of bleeding ectopic varices in cirrhotic patients.
To evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the control of bleeding from ectopic varices. From 1995 to 2004, 24 cirrhotic patients, bleeding from ectopic varices, mean age 54.5 years (range 15-76 years), were treated by TIPS. The etiology of cirrhosis was alcoholic in 13 patients and nonalcoholic in 11 patients. The location of the varices was duodenal (n = 5), stomal (n = 8), ileocolic (n = 6), anorectal (n = 3), umbilical (n = 1), and peritoneal (n = 1). TIPS controlled the bleeding in all patients and induced a decrease in the portacaval gradient from 19.7 +/- 5.4 to 6.4 +/- 3.1 mmHg. Postoperative complications included self-limited intra-abdominal bleeding (n = 2), self-limited hemobilia (n = 1), acute thrombosis of the shunt (n = 1), and bile leak treated by a covered stent (n = 1). Median follow-up was 592 days (range 28-2482 days). Rebleeding occurred in 6 patients. In 2 cases rebleeding was observed despite a post-TIPS portacaval gradient lower than 12 mmHg and was controlled by variceal embolization; 1 patient underwent surgical portacaval shunt and never rebled; in 3 patients rebleeding was related to TIPS stenosis and treated with shunt dilatation with addition of a new stent. The cumulative rate of rebleeding was 23% and 31% at 1 and 2 years, respectively. One- and 2-year survival rates were 80% and 76%, respectively. The present series demonstrates that bleeding from ectopic varices, a challenging clinical problem, can be managed safely by TIPS placement with low rebleeding and good survival rates.


Extraordinarily rapid speciation in a marine fish.
Divergent selection may initiate ecological speciation extremely rapidly. How often and at what pace ecological speciation proceeds to yield strong reproductive isolation is more uncertain. Here, we document a case of extraordinarily rapid speciation associated with ecological selection in the postglacial Baltic Sea. European flounders (Platichthys flesus) in the Baltic exhibit two contrasting reproductive behaviors: pelagic and demersal spawning. Demersal spawning enables flounders to thrive in the low salinity of the Northern Baltic, where eggs cannot achieve neutral buoyancy. We show that demersal and pelagic flounders are a species pair arising from a recent event of speciation. Despite having a parapatric distribution with extensive overlap, the two species are reciprocally monophyletic and show strongly bimodal genotypic clustering and no evidence of contemporary migration, suggesting strong reproductive isolation. Divergence across the genome is weak but shows strong signatures of selection, a pattern suggestive of a recent ecological speciation event. We propose that spawning behavior in Baltic flounders is the trait under ecologically based selection causing reproductive isolation, directly implicating a process of ecological speciation. We evaluated different possible evolutionary scenarios under the approximate Bayesian computation framework and estimate that the speciation process started in allopatry ∼2,400 generations ago, following the colonization of the Baltic by the demersal lineage. This is faster than most known cases of ecological speciation and represents the most rapid event of speciation ever reported for any marine vertebrate.


Electrochemical behavior of titanium in artificial saliva: influence of pH.
Titanium is the most common material chosen for dental implants because it is highly corrosion resistant because it constantly reforms a protective passive film layer. The formation and composition of the passive film layer is dependent on the environmental conditions. If the stable oxide layer is damaged, the titanium surface underneath can corrode. The purpose of this study was to determine if basic corrosion of commercially pure titanium (CpTi) alloy in artificial saliva was affected by pH and to understand the corrosion kinetics/mechanisms of CpTi as a function of pH. In this study, titanium alloy discs were subjected to corrosion tests. Before the tests, all samples were cleaned and polished using standard metallographic preparation methods. Artificial saliva was used as the testing medium. The following pH values were tested: 3.0, 4.5, 6.0, 6.5, 7.5, and 9.0. Different pH values were achieved by adding lactic acid (acidic) or NaOH (basic) in appropriate amounts. Potentiodynamic curves indicated behavior change at each pH. In addition, the corrosion current density value determined from the potentiodynamic curve exhibited the poorest corrosion resistance for pH 7.5. The Nyquist plot (from the electrochemical impedance spectroscopy results) indicated that pH 7.5 had the poorest resistance. Scanning electron microscopy images indicated that pH levels of 6.5, 7.5, and 9.0 had considerable surface corrosion. The results showed that the media's pH significantly influenced the corrosion behavior of CpTi. The poor corrosion behavior at the neutral pHs invites some concerns and highlights the need for further study.


Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel.
Bladder cancer is potentially curable in the majority of cases; however, the prognosis for patients with advanced disease at presentation remains poor. Current noninvasive tests such as cytology lack sufficient sensitivity to detect low-grade, low-stage tumors. Silencing of tumor suppressor genes, such as p16(INK4a), VHL, and the mismatch repair gene hMLH1, has established promoter hypermethylation as a common mechanism for tumor suppressor inactivation in human cancers. It is also a promising new target for molecular detection in bodily fluids including urine, a readily accessible fluid known to contain bladder cancer cells. Methylation-specific PCR (MSP) can determine the presence or absence of methylation of a gene locus at a sensitivity level of up to 1 methylated allele in 1000 unmethylated alleles, appropriate for identifying cancer cell DNA in a bodily fluid. We first determined the frequency of hypermethylation of the Rb tumor suppressor gene by bisulfite sequencing and of the p16(INK4a), p14(ARF), APC, and RASSF1A tumor suppressor genes by MSP in 45 bladder cancers. We then designed a panel optimal for diagnostic coverage composed of the APC, RASSF1A, and p14(ARF) tumor suppressor genes. This panel was tested for detection of hypermethylation in matched sediment DNA from urine specimens obtained before surgery from the same 45 bladder cancer patients (2 Tis, 16 Ta, 10 T1, and 17 T2-4) as well as normal and benign control DNAs. Hypermethylation of at least one of three suppressor genes (APC, RASSF1A, and p14(ARF)) was found in all 45 tumor DNAs (100% diagnostic coverage). We detected gene hypermethylation in the matched urine DNA from 39 of 45 patients (87% sensitivity), including 16 cases that had negative cytology. No hypermethylation of APC, RASSF1A, or p14(ARF) was observed in normal transitional cell DNAs or in urine DNAs from normal healthy individuals and patients with inflammatory urinary disease (cystitis). Furthermore, an unmethylated gene in the tumor DNA was always found to be unmethylated in the matched urine DNA (100% specificity). Promoter hypermethylation of tumor suppressor genes is common in bladder cancer and was found in all grades and stages of tumors examined. Hypermethylation was detected in the urine DNA from 39 of 45 (87%) patients, including cases of early-stage disease amenable to cure. MSP may enhance early detection of bladder cancer using a noninvasive urine test.


Enzymatically crosslinked gelatin-laminin hydrogels for applications in neuromuscular tissue engineering.
We report a water-soluble and non-toxic method to incorporate additional extracellular matrix proteins into gelatin hydrogels, while obviating the use of chemical crosslinkers such as glutaraldehyde. Gelatin hydrogels were fabricated using a range of gelatin concentrations (4%-10%) that corresponded to elastic moduli of approximately 1 kPa-25 kPa, respectively, a substrate stiffness relevant for multiple cell types. Microbial transglutaminase was then used to enzymatically crosslink a layer of laminin on top of gelatin hydrogels, resulting in 2-component gelatin-laminin hydrogels. Human induced pluripotent stem cell derived spinal spheroids readily adhered and rapidly extended axons on GEL-LN hydrogels. Axons displayed a more mature morphology and superior electrophysiological properties on GEL-LN hydrogels compared to the controls. Schwann cells on GEL-LN hydrogels adhered and proliferated normally, displayed a healthy morphology, and maintained the expression of Schwann cell specific markers. Lastly, skeletal muscle cells on GEL-LN hydrogels achieved long-term culture for up to 28 days without delamination, while expressing higher levels of terminal genes including myosin heavy chain, MyoD, MuSK, and M-cadherin suggesting enhanced maturation potential and myotube formation compared to the controls. Future studies will employ the superior culture outcomes of this hybrid substrate for engineering functional neuromuscular junctions and related organ on a chip applications.


Neuronal diversity in GABAergic long-range projections from the hippocampus.
The formation and recall of sensory, motor, and cognitive representations require coordinated fast communication among multiple cortical areas. Interareal projections are mainly mediated by glutamatergic pyramidal cell projections; only few long-range GABAergic connections have been reported. Using in vivo recording and labeling of single cells and retrograde axonal tracing, we demonstrate novel long-range GABAergic projection neurons in the rat hippocampus: (1) somatostatin- and predominantly mGluR1alpha-positive neurons in stratum oriens project to the subiculum, other cortical areas, and the medial septum; (2) neurons in stratum oriens, including somatostatin-negative ones; and (3) trilaminar cells project to the subiculum and/or other cortical areas but not the septum. These three populations strongly increase their firing during sharp wave-associated ripple oscillations, communicating this network state to the septotemporal system. Finally, a large population of somatostatin-negative GABAergic cells in stratum radiatum project to the molecular layers of the subiculum, presubiculum, retrosplenial cortex, and indusium griseum and fire rhythmically at high rates during theta oscillations but do not increase their firing during ripples. The GABAergic projection axons have a larger diameter and thicker myelin sheet than those of CA1 pyramidal cells. Therefore, rhythmic IPSCs are likely to precede the arrival of excitation in cortical areas (e.g., subiculum) that receive both glutamatergic and GABAergic projections from the CA1 area. Other areas, including the retrosplenial cortex, receive only rhythmic GABAergic CA1 input. We conclude that direct GABAergic projections from the hippocampus to other cortical areas and the septum contribute to coordinating oscillatory timing across structures.


Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI).
Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video-processing algorithm, Eulerian video magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here, we strive to improve aMRI by incorporating a phase-based motion amplification algorithm. Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output. Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient. Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion and may reveal subtle physiological variations of the brain as a result of pathology using processing of the fundamental harmonic or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.


Common carotid intima-media thickness measurement. A method to improve accuracy and precision.
High-resolution ultrasonographic imaging is a noninvasive method that allows estimation of the thickness of the intima-media complex in human carotid arteries. The determination of intima-media thickness involves several steps, each of which may introduce an error that influences the reproducibility of the method. In the present study, apart from the general reproducibility of the determination of intima-media thickness, the error introduced by each step was evaluated. B-mode scans were performed on 14 randomly selected patients. The common carotid arteries were examined in anterior, lateral, and posterior planes, with a standard methodology and by a new method, making use of external reference points. The error in general reproducibility in determination of the subject's mean intima-media thickness was 5.9%. This parameter was also evaluated in a paired manner after dividing the whole artery into sectors; with this protocol, the percent error in general reproducibility was 15%. The main source of variability in the evaluation of common carotid intima-media thickness was found to lie in the operator's subjectivity in the choice of the carotid sector to be processed (percent error, 10.27%). A method was therefore designed that used external reference points, resulting in reduction of this error by 38.2%. While the mean intima-media thickness might be considered a reproducible parameter to evaluate differences between populations exposed to diverse risk factors, evolutional or therapy-induced changes in the individual may be better monitored on defined carotid sectors. This may be achieved with a high reproducibility by use of the proposed method based on external reference points.


Malignant tumors associated with nevus sebaceous: therapeutic consequences.
Nevus sebaceous has been considered a relatively infrequent and unimportant congenital hamartoma for plastic surgeons unless the lesions are so big that they require a demanding defect closure. As the dignity of such tumors is primarily benign and the malformed sebaceous glands are localized abnormally high in the dermis, the temptation is appealing not to excise these tumors any more but to eradicate them by laser beam therapy. Yet a nevus sebaceous not only affects sebaceous glands but includes various other malformations of the affected skin and its appendages. In addition, different malignant tumors may occur in nevus sebaceous, even in children and young adults. We encountered 4 such malignant tumors of 18 nevi sebaceous operated on from 1989 to 1997. All nevi had been unsuspicious macroscopically. In three patients, one of them only 15 years old, an associated basal cell carcinoma was found. In the fourth patient there was a mixture of three additional tumors, a cystadenoma, a keratoacanthoma, and a basal cell carcinoma, besides the sebaceous malformations. These findings have two consequences: first, to continue surgical treatment of nevus sebaceous instead of dermabrasion or dermablation and to have the specimen examined histologically and, second, to excise such tumors as early in childhood as possible.


An automated phylogenetic tree-based small subunit rRNA taxonomy and alignment pipeline (STAP).
Comparative analysis of small-subunit ribosomal RNA (ss-rRNA) gene sequences forms the basis for much of what we know about the phylogenetic diversity of both cultured and uncultured microorganisms. As sequencing costs continue to decline and throughput increases, sequences of ss-rRNA genes are being obtained at an ever-increasing rate. This increasing flow of data has opened many new windows into microbial diversity and evolution, and at the same time has created significant methodological challenges. Those processes which commonly require time-consuming human intervention, such as the preparation of multiple sequence alignments, simply cannot keep up with the flood of incoming data. Fully automated methods of analysis are needed. Notably, existing automated methods avoid one or more steps that, though computationally costly or difficult, we consider to be important. In particular, we regard both the building of multiple sequence alignments and the performance of high quality phylogenetic analysis to be necessary. We describe here our fully-automated ss-rRNA taxonomy and alignment pipeline (STAP). It generates both high-quality multiple sequence alignments and phylogenetic trees, and thus can be used for multiple purposes including phylogenetically-based taxonomic assignments and analysis of species diversity in environmental samples. The pipeline combines publicly-available packages (PHYML, BLASTN and CLUSTALW) with our automatic alignment, masking, and tree-parsing programs. Most importantly, this automated process yields results comparable to those achievable by manual analysis, yet offers speed and capacity that are unattainable by manual efforts.


Comparison of two leukocyte extraction methods for cytomegalovirus antigenemia assay.
We carried out a prospective, parallel, and blind study on 113 blood samples from immunocompromised patients in order to compare two leukocyte extraction methods (6% dextran sedimentation and Polymorphprep separation) for cytomegalovirus (CMV) antigenemia assay. CMV was detected in 38 samples by antigenemia assay (34 by dextran sedimentation and 35 by Polymorphprep separation). No differences either in the number of positive specimens (P = 1) or in the mean CMV-positive cell counts (P = 0.41) were observed between the two leukocyte extraction methods. In conclusion, the two methods performed equally well for this assay.


Bilateral activation of the prefrontal cortex after strategic semantic cognitive training.
The prefrontal cortex (PFC) has been implicated in the ability to apply semantic organizational strategies during verbal encoding and episodic learning. However, there has been no direct evidence demonstrating which specific areas in the PFC are engaged after cognitive training using semantic organizational strategies in healthy adult human subjects. In this study, we investigated the effects of semantic strategic training on brain activity and changes in behavioral performance, after cognitive training, using functional MRI (fMRI). There was a significant activation in bilateral dorsolateral prefrontal (DLPF) and orbitofrontal (OFC) areas after cognitive training. These results demonstrate the engagement of bilateral DLPF and OFC cortex during strategic memory processes, particularly when mobilization and effort of effective use of strategies are required. The functional adaptations observed here may also shed light on some of the processes underlying recovery with cognitive rehabilitation in patient populations with brain injury.


Carboxyfluorescein diacetate succinimidyl ester and the virgin lymphocyte: a marriage made in heaven.
Carboxyfluorescein diacetate succinimidyl ester (CFSE) labelling of naïve lymphocyte populations provides unique insights into the immune response. The clonal nature of immune responses, necessitating clonal expansion to achieve a sufficiently large number of Ag-reactive effector cells, combined with the dependence of lymphocyte differentiation on cell division, underlie the usefulness of CFSE in understanding the factors that regulate responses both in vitro and in vivo. We have combined CFSE labelling with Ag receptor transgenic models, using seven channel flow cytometry to track the correlation between cell division and a number of other parameters, such as surface expression of activation markers, cytokine receptors and homing receptors, cytokine production, cytotoxic activity and indicators of apoptosis. Our data have allowed us to classify and understand immune responses in novel ways, suggesting many further avenues of enquiry and indicating previously unrecognized relationships between cell division and eventual cell fate.


Expression of genes in the canine pre-implantation uterus and embryo: implications for an active role of the embryo before and during invasion.
The aim of the present study was to assess genes expressed in maternal uterine tissue and pre-implantation embryos which are presumably involved in maternal recognition and establishment of canine pregnancy. For this purpose, 10 pregnant bitches were ovariohysterectomized between days 10 and 12 after mating. Four non-pregnant bitches served as controls. Early pregnancy was verified by flushing the uterine horns with PBS solution. The collected embryos (n = 60) were stored deep-frozen (-80 degrees C). Uterine tissue was excised, snaps frozen in liquid nitrogen and homogenized using TRI Reagent. All embryos from one litter were thawed together and also homogenized in TRI Reagent. RT-PCR was performed to prove mRNA expression of progesterone receptor, key enzymes of the prostaglandin synthesis pathway, selected growth factors, cytokines, immune cell receptors, major histocompatibility complex (MHC) and matrix-metalloproteinases (MMP). Only pregnant uteri revealed the presence of mRNA for interferon (IFN)-gamma, IL-4 and CD-8, which resembles the milieu in humans and other mammalians. Similarly, in day 10 embryos, mRNA for transforming growth factor-beta, insulin-like growth factor-1,-2, hepatocyte growth factor, leukaemia inhibitor factor, tumour necrosis factor-alpha, interleukin-1beta,-6,-8, cyclooxygenase-2, CD4(+) cells, and MMP-2 and -9 were detected, but not MHC-I or -II. We therefore suppose that the canine embryo, like its human counterpart, actively initiates measures to prevent attacks from the maternal immune system to prepare its own adhesion, nidation, growth and further development.


Relationship between functional residual capacity, respiratory compliance, and oxygenation in patients ventilated after cardiac surgery.
Measurement of functional residual capacity (FRC) is now possible at bedside, during mechanical ventilation. To determine the relationship of measured absolute and relative predicted FRC values to oxygenation and respiratory-system compliance, and to identify variables that influence FRC in ventilated patients after cardiac surgery. We retrospectively analyzed data from 99 patients ventilated after cardiac surgery. Each patient underwent an alveolar recruitment maneuver and was then ventilated with a positive end-expiratory pressure of 10 cm H2O and a tidal volume of 6-8 mL/kg predicted body weight. We measured quasi-static 2-point compliance of the respiratory system, FRC (with the oxygen-wash-out method), PaO2, and fraction of inspired oxygen (F(I)O2). We indexed the FRC values to predicted FRC reference values from sitting and supine healthy volunteers. Correlation analyses revealed no meaningful association between FRC and PaO2/F(I)O2 (r2 0.20, P < .001). There was a moderate association between absolute FRC and respiratory-system compliance (r2 0.50, P < .001). Indexing the absolute measured FRC values to the predicted FRC values did not improve the correlation. We conducted multiple linear regression analyses of height, weight, age, sex, presence of mild chronic obstructive pulmonary disease, minute volume, and peak inspiratory pressure during ventilation, and revealed weight, minute volume, and peak inspiratory pressure (r2 = 0.65) as independent covariates of FRC. Indexing the measured FRC values to the predicted supine and sitting FRC values does not improve the association between PaO2/F(I)O2 and respiratory-system compliance. In mechanically ventilated patients after cardiac surgery, FRC is influenced more by the ventilator settings than by physiologic variables (as in spontaneously breathing persons).


Recommendations of the Alzheimer's disease-related dementias conference.
The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer disease includes not only Alzheimer disease (AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease-related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD. By design, the product was up to 8 prioritized research recommendations in each topic area including estimated timelines from when work on a recommendation is started to completion or to full implementation of an ongoing activity, and recognition of shared research themes across recommendations. These included increased education and training of both researchers and health care professionals, addressing health disparities, fundamental neurobiology research, advanced diagnostics, collaborative biosample repositories, and a focus on developing effective interventions to prevent or treat ADRD by the year 2025 as targeted by the National Plan.


Effect of ocular shape and vascular geometry on retinal hemodynamics: a computational model.
A computational model for retinal hemodynamics accounting for ocular curvature is presented. The model combines (i) a hierarchical Darcy model for the flow through small arterioles, capillaries and small venules in the retinal tissue, where blood vessels of different size are comprised in different hierarchical levels of a porous medium; and (ii) a one-dimensional network model for the blood flow through retinal arterioles and venules of larger size. The non-planar ocular shape is included by (i) defining the hierarchical Darcy flow model on a two-dimensional curved surface embedded in the three-dimensional space; and (ii) mapping the simplified one-dimensional network model onto the curved surface. The model is solved numerically using a finite element method in which spatial domain and hierarchical levels are discretized separately. For the finite element method, we use an exterior calculus-based implementation which permits an easier treatment of non-planar domains. Numerical solutions are verified against suitably constructed analytical solutions. Numerical experiments are performed to investigate how retinal hemodynamics is influenced by the ocular shape (sphere, oblate spheroid, prolate spheroid and barrel are compared) and vascular architecture (four vascular arcs and a branching vascular tree are compared). The model predictions show that changes in ocular shape induce non-uniform alterations of blood pressure and velocity in the retina. In particular, we found that (i) the temporal region is affected the least by changes in ocular shape, and (ii) the barrel shape departs the most from the hemispherical reference geometry in terms of associated pressure and velocity distributions in the retinal microvasculature. These results support the clinical hypothesis that alterations in ocular shape, such as those occurring in myopic eyes, might be associated with pathological alterations in retinal hemodynamics.


Hydrodynamics from statistical mechanics: combined dynamical-NEMD and conditional sampling to relax an interface between two immiscible liquids.
We present a method to study hydrodynamic phenomena from atomistic simulations. In statistical mechanics, these fields are computed as the ensemble average over the time dependent probability density function corresponding to the time evolution of an initial conditional probability density function consistent with some initial conditions. These initial conditions typically consist in constraints on some macroscopic fields, e.g. the density field. We show how these processes can be studied by combining the dynamical approach to non-equilibrium molecular dynamics with the restrained simulation approach. As an illustration of our method, we study the relaxation to the equilibrium of an interface between two immiscible liquids. We show that, at a variance with the local time average method, the standard atomistic approach used in this field, our method is able to produce (macroscopic) fields satisfying the symmetry conditions of the problem.


Torticollis, facial asymmetry and plagiocephaly in normal newborns.
To evaluate the incidence and characteristics of torticollis, plagiocephaly and facial asymmetry in normal newborn infants. 102 healthy newborn infants were examined prospectively during their birth hospitalisation for torticollis with neck range of motion (ROM) assessment and for facial, mandibular and cranial asymmetry by photographic analysis. 73% of newborns had one or more asymmetry: torticollis (16%), asymmetry of the mandible (13%), facial asymmetry (42%) and asymmetry of the head (61%). Torticollis was associated with maternal report of the fetus being "stuck" in one intrauterine position for more than 6 weeks before delivery. Moderate facial asymmetry was associated with a longer second stage of labour, forceps delivery, a bigger baby and birth trauma. Moderate cranial and mandibular asymmetries were associated with birth trauma. More than one significant asymmetry was found in 10% of newborns. Asymmetries of the head and neck are very common in normal newborns, and sixteen (16%) of 102 study newborns were found to have torticollis. Such newborns, especially if they sleep supine, are thought to be at risk of developing deformational posterior plagiocephaly. Identification of affected infants may allow early implementation of positioning recommendations or physical therapy to prevent the secondary craniofacial deformations that are part of an increasingly common phenomenon.


Scattering of linearly polarized microwave radiation from a dielectric target including the interaction between target elements.
The theory for finding the internal field within a dielectric helix when the radiation has a wavelength larger than the diameter of the helical wire is presented. Intensities are calculated and compared to an experiment and to the theoretical results of an earlier paper that does not include the self-interaction effect. The internal field is defined in terms of a polarization matrix that is assumed to be constant across any cross section of the helix. It is found that target self-iteractions have a significant effect on the internal field. It is also noted that this effect for the far field intensities, although significant and generally a better fit to the data, is not profoundly different. That is, the effects of a more appropriately constructed internal field are less important than the geometry effect in the far field.


Absolute depth-dose-rate measurements for an 192Ir HDR brachytherapy source in water using MOSFET detectors.
Reported MOSFET measurements concern mostly external radiotherapy and in vivo dosimetry. In this paper, we apply the technique for absolute dosimetry in the context of HDR brachytherapy using an 192Ir source. Measured radial dose rate distributions in water for different planes perpendicular to the source axis are presented and special attention is paid to the calibration of the R and K type detectors, and to the determination of appropriate correction factors for the sensitivity variation with the increase of the threshold voltage and the energy dependence. The experimental results are compared with Monte Carlo simulated dose rate distributions. The experimental results show a good agreement with the Monte Carlo simulations: the discrepancy between experimental and Monte Carlo results being within 5% for 82% of the points and within 10% for 95% of the points. Moreover, all points except two are found to lie within the experimental uncertainties, confirming thereby the quality of the results obtained.


A therapeutic approach for wound healing by using essential oils of cupressus and juniperus species growing in Turkey.
Juniperus and Cupressus genera are mainly used as diuretic, stimulant, and antiseptic, for common cold and wound healing in Turkish folk medicine. In the present study, essential oils obtained from cones of Cupressus and berries of Juniperus were evaluated for their wound healing and anti-inflammatory effects. In vivo wound healing activity was evaluated by linear incision and circular excision experimental wound models, assessment of hydroxyproline content, and subsequently histopathological analysis. The healing potential was comparatively assessed with a reference ointment Madecassol. Additionally acetic-acid-induced capillary permeability test was used for the oils' anti-inflammatory activity. The essential oils of J. oxycedrus subsp. oxycedrus and J. phoenicea demonstrated the highest activities, while the rest of the species did not show any significant wound healing effect. The experimental study revealed that J. oxycedrus subsp. oxycedrus and J. phoenicea display remarkable wound healing and anti-inflammatory activities, which support the folkloric use of the plants.


Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.
Oxidative stress with reactive oxygen species generation is a key weapon in the arsenal of the immune system for fighting invading pathogens and initiating tissue repair. If excessive or unresolved, however, immune-related oxidative stress can initiate further increasing levels of oxidative stress that cause organ damage and dysfunction. Targeting oxidative stress in various diseases therapeutically has proven more problematic than first anticipated given the complexities and perversity of both the underlying disease and the immune response. However, growing evidence suggests that the endocannabinoid system, which includes the CB₁ and CB₂ G-protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development. This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.


Analysis of an outbreak of puerperal Fever due to group a streptococci by random amplified polymorphic DNA fingerprinting.
Streptococcus pyogenes is the cause of the classical childbed fever and can occur in both sporadic and epidemic form. Once an outbreak is identified on a maternity ward it is not only necessary to place the patients in strict isolation but also identify to the source of the infection. Fast reliable typing methods can aid in infection control. An outbreak of puerperal fever due to S. pyogenes was analyzed by random amplified polymorphic DNA (RAPD) analysis. Identical fingerprint patterns were found in isolates of 3 patients, the throat and infected finger of the delivering obstetrician, 2 of the physician's family members, and from the cervix of a woman who was examined by the physician 7 months after the outbreak. The outbreak was stopped after antimicrobial treatment of the physician and his family members. RAPD typing appeared to be a fast and reliable tool for epidemiological studies of S. pyogenes and is probably more efficient in strain differentiation than classical M and T serotyping.


Force-induced on-rate switching and modulation by mutations in gain-of-function von Willebrand diseases.
Mutations in the ultralong vascular protein von Willebrand factor (VWF) cause the common human bleeding disorder, von Willebrand disease (VWD). The A1 domain in VWF binds to glycoprotein Ibα (GPIbα) on platelets, in a reaction triggered, in part, by alterations in flow during bleeding. Gain-of-function mutations in A1 and GPIbα in VWD suggest conformational regulation. We report that force application switches A1 and/or GPIbα to a second state with faster on-rate, providing a mechanism for activating VWF binding to platelets. Switching occurs near 10 pN, a force that also induces a state of the receptor-ligand complex with slower off-rate. Force greatly increases the effects of VWD mutations, explaining pathophysiology. Conversion of single molecule kon (s(-1)) to bulk phase kon (s(-1)M(-1)) and the kon and koff values extrapolated to zero force for the low-force pathways show remarkably good agreement with bulk-phase measurements.


Transcutaneous bilirubinometry in Pakistani newborns: a preliminary report.
Neonatal hyperbilirubinemia is a frequently encountered problem in the neonatal period and carries a potential risk of encephalopathy. Early detection and quantification is important, and transcutaneous bilirubinometry (TcB) has been recommended as a non-invasive method for rapid screening. We prospectively compared the efficacy of TcB in 65 normal Pakistani jaundiced newborns undergoing simultaneous serum bilirubin measurements. Although the correlation between the two methods was significant (r = 0.66, P less than 0.01), the scatter was wide and the specificity only 53%. Although the technique offers the potential for non-invasive early screening of neonatal hyperbilirubinemia, it requires further validation in a larger study in our population.


We're all in this together, but for different reasons: Social values and social actions that affect COVID-19 preventative behaviors.
We examined how personal values, beliefs and concerns about COVID-19, and socio-demographics, relate to two important COVID-19 preventative behaviors: willingness to get vaccinated for COVID-19 and social distancing, in 1413 Australian adults. As expected, social focus values influenced the extent of compliance with these preventative behaviors, even when controlling for beliefs and concerns about COVID-19 and socio-demographics. We also examined the persuasiveness of four different value-expressive messages promoting social distancing, in a subsample of 737 Australian adults. We found that the message expressing self-transcendence values was ranked most persuasive by 77% of respondents. However, as hypothesized, personal values were related to message persuasiveness. As the importance ascribed to social focus values increased, the likelihood that the self-transcendence message was ranked as most persuasive increased. In contrast, the likelihood that the openness to change message was ranked as most persuasive increased for those who ascribed lesser importance to social focus values. Our findings can help the framing of government messaging around preventative behaviors, including maintaining social distancing in vaccinated populations who may still spread the disease, and preventing COVID-19 spread by or to vaccine refusers.


A review of the frequencies of Plasmodium falciparum Kelch 13 artemisinin resistance mutations in Africa.
Artemisinin resistance (AR) emerged in South East Asia 13 years ago and the identification of the resistance conferring molecular marker, Plasmodium falciparum Kelch 13 (Pfk13), 7 years ago has provided an invaluable tool for monitoring AR in malaria endemic countries. Molecular Pfk13 surveillance revealed the resistance foci in the Greater Mekong Subregion, an independent emergence in Guyana, South America, and a low frequency of mutations in Africa. The recent identification of the R561H Pfk13 AR associated mutation in Tanzania, Uganda and in Rwanda, where it has been associated with delayed parasite clearance, should be a concern for the continent. In this review, we provide a summary of Pfk13 resistance associated propeller domain mutation frequencies across Africa from 2012 to 2020, to examine how many other countries have identified these mutations. Only four African countries reported a recent identification of the M476I, P553L, R561H, P574L, C580Y and A675V Pfk13 mutations at low frequencies and with no reports of clinical treatment failure, except for Rwanda. These mutations present a threat to malaria control across the continent, since the greatest burden of malaria remains in Africa. A rise in the frequency of these mutations and their spread would reverse the gains made in the reduction of malaria over the last 20 years, given the lack of new antimalarial treatments in the event artemisinin-based combination therapies fail. The review highlights the frequency of Pfk13 propeller domain mutations across Africa, providing an up-to-date perspective of Pfk13 mutations, and appeals for an urgent and concerted effort to monitoring antimalarial resistance markers in Africa and the efficacy of antimalarials by re-establishing sentinel surveillance systems.


Purification and characterization of phosphoglycerate mutase from methanol-grown Hyphomicrobium X and Pseudomonas AM1.
Phosphoglycerate mutase has been purified from methanol-grown Hyphomicrobium X and Pseudomonas AMI by acid precipitation, heat treatment, ammonium sulphate fractionation, Sephadex G-50 gel filtration and DEAE-cellulose column chromatography. The purification attained using the Hyphomicrobium X extract was 72-fold, and using the Pseudomonas AMI extract, 140-fold. The enzyme purity, as shown by analytical polyacrylamide gel electrophoresis, was 50% from Hyphomicrobium X and 40% from Pseudomonas AMI. The enzyme activity was associated with one band. The purified preparations did not contain detectable amounts of phosphoglycerate kinase, phosphopyruvate hydratase, phosphoglycerate dehydrogenase or glycerate kinase activity. The molecular weight of the enzymic preparation was 32000 +/- 3000. The enzyme from both organisms was stable at low temperatures and, in the presence of 2,3-diphosphoglyceric acid, could withstand exposure to high temperatures. The enzyme from Pseudomonas AMI has a broad pH optimum at 7-0 to 7-6 whilst the enzyme from Hyphomicrobium X has an optimal activity at pH 7-3. The cofactor 2,3-diphosphoglyceric acid was required for maximum enzyme activity and high concentrations of 2-phosphoglyceric acid were inhibitory. The Km values for the Hyphomicrobium X enzyme were: 3-phosphoglyceric acid, 6-0 X 10(-3) M: 2-phosphoglyceric acid, 6-9 X 10(-4) M; 2,3-diphosphoglyceric acid, 8-0 X 10(-6) M; and for the Pseudomonas AMI ENzyme: 3-4 X 10(-3) M, 3-7 X 10(-4) M and 10 X 10(-6) M respectively. The equilibrium constant for the reaction was 11-3 +/- 2-5 in the direction of 2-phosphoglyceric acid to 3-phosphoglyceric acid and 0-09 +/- 0-02 in the reverse direction. The standard free energy for the reaction proceeding from 2-phosphoglyceric acid to 3-phosphoglyceric acid was -5-84 kJ mol(-1) and in the reverse direction +5-81 kJ mol(-1).


Purdue pegboard performance of disabled and normal readers: unimanual versus bimanual differences.
Differences between dyslexics and controls in the unimanual and bimanual conditions of the peg placement section of the Purdue Pegboard Test were examined. Twenty-three disabled and twenty-three normal readers were studied. The groups were carefully screened on a neuropsychological battery. The disabled readers were comprised of a relatively homogeneous language-disordered subgroup exhibiting deficits in naming. Significant Group X Condition interactions were obtained for both raw and percentile scores and indicated that disabled readers performed worse than controls in the unimanual compared to bimanual conditions. The dyslexics performed particularly poorly compared with controls on the left hand condition. The implications of these data for hypotheses which argue for left hemisphere dysfunction, as well as those which posit interhemispheric transfer deficits in reading disabled children, are discussed.


Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.
The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.


Tau proteins are abnormally expressed in olfactory epithelium of Alzheimer patients and developmentally regulated in human fetal spinal cord.
In pathological conditions, the microtubule-associated tau proteins may accumulate in neuronal perikarya or be expressed de novo in certain populations of neurons. For example, olfactory epithelium (OE) neurons in Alzheimer's disease (AD) patients express tau in their axons when these axons become dystrophic. In this study, we examined human postmortem olfactory tissue with a panel of tau antibodies that bind to epitopes located in subdomains spanning nearly the entire length of all six known isoforms of human CNS tau. In addition, the developing human spinal cord was probed with a similar panel of tau antibodies to determine whether or not fetal tau epitopes were reexpressed in the dystrophic OE neurites of AD patients. Electron microscopy was performed to examine the ultrastructure of the filaments present in these dystrophic OE neurites. We show here that all the tau epitopes examined are expressed in dystrophic OE neurites of AD patients, but that certain tau epitopes are preferentially expressed in the dystrophic neurites of AD. We also demonstrate that many of the epitopes present in the dystrophic neurites of AD are expressed early in the developing spinal cord and are later extinguished, including adult tau epitopes present in the brain. Finally, our EM studies reveal the presence within dystrophic OE neurites of approximately 10 to 15-nm-diameter filaments. These results suggest that the entire extent of multiple tau molecules is present in dystrophic OE neurites, with certain modifications of tau occurring preferentially in the dystrophic neurites of AD patients.


Trimodal evoked potentials compared with magnetic resonance imaging in the diagnosis of multiple sclerosis.
Twenty-three patients with the clinical diagnosis of possible multiple sclerosis (MS) were tested with magnetic resonance imaging (MRI) and trimodal evoked potentials. Fourteen patients showed abnormalities on both MRI scans and at least one evoked potential modality (65%). Four patients had normal MRI scans but at least one abnormality on evoked potential testing (17%). One patient had normal triple evoked potentials with an abnormal MRI result. Four patients had normal results on both MRI and triple evoked potential testing; two of these patients were later found to have immunologic abnormalities in the cerebrospinal fluid consistent with the diagnosis of MS. Combined evoked potential testing was found to have a higher sensitivity than MRI in confirming a diagnosis of MS. Three patients with the clinical diagnosis of definite MS were also tested. All these patients showed abnormalities on evoked potential testing, although one patient had a normal MRI result. Of all 26 patients who were studied, 17 showed abnormal MRI results and 21 showed at least one abnormality on evoked potential testing.


Brief evidence-based interventions for universal child health services: a restricted evidence assessment of the literature.
Universal child health services (UCHS) provide an important pragmatic platform for the delivery of universal and targeted interventions to support families and optimize child health outcomes. We aimed to identify brief, evidence-based interventions for common health and developmental problems that could be potentially implemented in UCHS. A restricted evidence assessment (REA) of electronic databases and grey literature was undertaken covering January 2006 to August 2019. Studies were eligible if (i) outcomes related to one or more of four areas: child social and emotional wellbeing (SEWB), infant sleep, home learning environment or parent mental health, (ii) a comparison group was used, (iii) universal or targeted intervention were delivered in non-tertiary settings, (iv) interventions did not last more than 4 sessions, and (v) children were aged between 2 weeks postpartum and 5 years at baseline. Seventeen studies met the eligibility criteria. Of these, three interventions could possibly be implemented at scale within UCHS platforms: (1) a universal child behavioural intervention which did not affect its primary outcome of infant sleep but improved parental mental health, (2) a universal screening programme which improved maternal mental health, and (3) a targeted child behavioural intervention which improved parent-reported infant sleep problems and parental mental health. Key lessons learnt include: (1) Interventions should impart the maximal amount of information within an initial session with future sessions reinforcing key messages, (2) Interventions should see the family as a holistic unit by considering the needs of parents with an emphasis on identification, triage and referral, and (3) Brief interventions may be more acceptable for stigmatized topics, but still entail considerable barriers that deter the most vulnerable. Delivery and evaluation of brief evidence-based interventions from a UCHS could lead to improved maternal and child health outcomes through a more responsive and equitable service. We recommend three interventions that meet our criteria of "best bet" interventions.


Two-dimensional-related catalytic materials for solar-driven conversion of COx into valuable chemical feedstocks.
The discovery of improved chemical processes for CO and CO2 hydrogenation to valuable hydrocarbon fuels and alcohols is of paramount importance for the chemical industry. Such technologies have the potential to reduce anthropogenic CO2 emissions by adding value to a waste stream, whilst also reducing our consumption of fossil fuels. Current thermal catalytic technologies available for CO and CO2 hydrogenation are demanding in terms of energy input. Various alternative technologies are now being developed for COx hydrogenation, with solar-driven processes over two-dimensional (2D) and 2D-related composite materials being particularly attractive due to the abundance of solar energy on Earth and also the high selectivity of defect-engineered 2D materials towards specific valuable products under very mild reaction conditions. This review showcases recent advances in the solar-driven COx reduction to hydrocarbons over 2D-based materials. Optimization of 2D catalyst performance demands interdisciplinary research that embraces catalyst electronic structure manipulation and morphology control, surface/interface engineering, reactor engineering and density functional theory modelling studies. Through improved understanding of the structure-performance relationships in 2D-related catalysts which is achievable through the application of modern in situ characterization techniques, practical photo/photothermal/photoelectrochemical technologies for CO and CO2 reduction to high-valuable products such as olefins could be realized in the not-too-distant future.


Nature of Synergy between Brønsted and Lewis Acid Sites in Sn-Beta Zeolites for Polyoxymethylene Dimethyl Ethers Synthesis.
The role of Lewis and Brønsted acid sites and their potential synergy remains ambiguous for the production of polyoxymethylene dimethyl ethers (OME), which are suitable as a Diesel substitute. Here, this synergistic effect was investigated by using a series of beta polymorph A (BEA) zeolites with various degrees of Brønsted and Lewis acidity. Lewis acidity was introduced in dealuminated zeolites by Sn grafting in dichloromethane. These sites were only active in paraformaldehyde decomposition, OME growth, and acetalization. The Brønsted acid sites arising from bridging hydroxyl groups were active for all reaction steps, and notably for trioxane ring-opening and dissociation to formaldehyde (FA), which did not occur on the Lewis acid sites. Presence of both Lewis and Brønsted acid sites led to a four-fold increase in turnover frequency and a significant decrease of byproduct formation compared with the parent zeolite during OME synthesis from dimethoxymethane and trioxane. The synergistic effect between both types of acid sites is explained by FA insertion on Lewis acid sites leading to OME growth. Interaction between tetrahedral Sn and the carbonyl group of FA resulted in an activated carbonyl bond, which was likely the initial step for insertion of FA into OME.


Does the pretreatment polysomnogram predict response to cognitive therapy in depressed outpatients? A preliminary report.
Although several studies reveal that cognitive therapy effectively remediates depressive symptoms in many unipolar nonpsychotic depressed outpatients, the question as to which depressions respond to cognitive therapy remains unanswered. We hypothesized that patients with reduced rapid eye movement (REM) latency (less than or equal to 65.0 min) before treatment would be less likely than those with nonreduced REM latency (greater than 65.0 min) to respond to cognitive therapy. The rationale for this prediction was that endogenous depressions are more likely to exhibit this abnormality and also tend to respond to tricyclic antidepressant medication. Thus, we queried whether these depressions might also respond less to a psychosocial intervention. To date, 39 outpatients with nonpsychotic, unipolar major depression (by the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and Research Diagnostic Criteria) who score at least 14 on the 17-item Hamilton Rating Scale for Depression have completed this project, which is still in process. Preliminary findings do not suggest a systematic relationship between pretreatment REM latency and response to cognitive therapy. Further, these results suggest that at least some patients with biological dysregulation, as indicated by reduced REM latency, show a favorable response to an acute trial of cognitive therapy. Study limitations include a small sample of patients who exhibit extremely reduced REM latencies (less than or equal to 51.0 min) and a small number of endogenous depressions. Data collection continues.


Raman microspectroscopy of noncancerous and cancerous human breast tissues. Identification and phase transitions of linoleic and oleic acids by Raman low-temperature studies.
We present the results of Raman studies in the temperature range of 293-77 K on vibrational properties of linoleic and oleic acids and Raman microspectroscopy of human breast tissues at room temperature. Our results confirmed the significant role of unsaturated fatty acids in differentiation of noncancerous and cancerous breast tissues and the role of vibrational spectroscopy in phase transition identification. We have found that vibrational properties are very sensitive indicators to specify phases and phase transitions typical of unsaturated fatty acids at the molecular level. Using Raman spectroscopy we have identified high-temperature, middle-temperature and low-temperature phases of linoleic acid. Results obtained for linoleic acid were compared with parameters characteristic of α and γ phases of oleic acid - the parent compound of polyunsaturated fatty acids.


Effects of platelet-rich fibrin on healing of intra-bony defects treated with anorganic bovine bone mineral.
Anorganic bovine bone mineral (ABBM) is extensively used in the treatment of intra-bony defects. Platelet-rich fibrin (PRF) is a new-generation platelet concentrate with a simplified technique. Although certain studies have reported the use of PRF in the treatment of intra-bony defects, to date, none of them have evaluated its additive effects with ABBM. Therefore, a randomised, split-mouth clinical trial was conducted to compare healing of intra-bony defects treated with an ABBM-PRF combination with healing of those treated with ABBM alone. By using a split-mouth design, 15 paired intra-bony defects were randomly treated with either ABBM alone (control group) or ABBM-PRF combination (test group). Following clinical parameters and radiographical measurements were recorded at baseline and 6 months after treatment: plaque index (PI), gingival index (GI), probing depth (PD), gingival recession (GR), clinical attachment level (CAL), vertical bone loss, depth of defect and defect angle. Preoperative clinical and radiographical measurements were similar for the test and control groups. Statistically significant reductions in GI, PD, CAL, vertical bone loss, depth of intra-bony defect and widening of defect angle were detected after treatment in both groups. With respect to inter-group analysis, gain in CAL was significantly greater in the test group than in the control group, whereas no inter-group differences were observed in any other parameter. The results of this study indicate that both therapies are effective in the treatment of intra-bony defects.


Retained human tissues: a molecular genetics goldmine or modern grave robbing? A legal approach to obtaining and using stored human samples.
The widespread retention of thousands of children's organs in the UK without parental consent has met with public outrage and calls for government intervention. These issues are brought to the fore by developments in molecular genetics that allow a person's full DNA sequence to be obtained from miniscule samples. The molecular genetic testing of retained organs and human tissue can greatly benefit family members and future research, but only if proposals to alter regulation can be successfully implemented. A review of present UK regulation indicates that it is both unclear and inadequate to ensure sufficient ethical/legal safeguards to satisfy public expectations. This paper reviews the legal and ethical status of previously retained samples. It discusses whether they may be regarded as abandoned if the patient cannot be traced and then used anonymously in ethically approved research. The legal status of retained samples is discussed as regards ownership and commerciality. This raises the question of who is the next of kin to give consent if the samples are to be regarded as gifted. Present proposals risk damaging the future by too much sensitivity. Getting the balance of interests right at this juncture is vital groundwork for such beneficial medical developments.


The host-pathogen interaction during HBV infection: immunological controversies.
HBV is a hepatotropic and non-cytopathic virus that causes more than one million deaths annually from liver cirrhosis and hepatocellular carcinoma. As the virus itself is non-cytopathic, it is widely accepted that both viral control and liver pathology are mediated by the host immune system. Until recently, the focus has been on the crucial role of adaptive immune responses in controlling HBV infection, but the potential contribution of the innate system is now an important area of controversy. Unanswered questions include whether and when HBV can trigger components of innate immunity, and whether HBV can actively suppress the induction of innate immunity. We discuss the data available from animal models and human HBV infection addressing the role of innate immunity in the first part of this review. In the second part, we address the immunopathogenesis of the inflammatory events that characterize chronic hepatitis B. The mechanisms thought to be responsible for liver inflammation, namely the intrahepatic recruitment of inflammatory cells, which is orchestrated by chemokines, have been described; however, the underlying immunological triggers are much less clear. The prevailing idea is that liver inflammation results from a recovery of HBV-specific T-cells directly causing liver injury, but this scenario is supported by scanty experimental data. By contrast, recent findings raise the possibility of a contribution from innate components, such as natural killer cells.


The function of the RNA-binding protein hnRNP in cancer metastasis.
Heterogeneous ribonucleoproteins (hnRNPs) are involved in a variety of key cellular functions and are most likely involved in different steps of pre-mRNA processing. Over the past decades, the central roles of hnRNPs have been detected, which show that they are involved in RNA splicing, telomere biogenesis, DNA repair, cell signaling, and in transcription and translation. Mounting evidence suggests that they are involved in the regulation of mRNA stability and translation in many cancer types. The hnRNPs have a variety of potential roles in inhibition of apoptosis, angiogenesis, cell invasion, and epithelial-mesenchymal transition (EMT). It is thus suggested that hnRNP might be a novel and promising therapeutic target and a marker for treatment response and prognostic evaluation. The aims of this review are to survey the existing evidence and discuss the diverse functions of hnRNPs in cancer metastasis.


Bacterial interference: effects of oral antibiotics on the normal throat flora and its ability to interfere with group A streptococci.
The effects of orally administered penicillin and tetracycline on the composition of the normal throat flora and its interference with the growth of group A streptococci were evaluated by throat culture and an agar overlay technique. Tetracycline caused only a slight, transient quantitative decrease in the composition of the flora and interference activity. Penicillin caused significant quantitative and qualitative decreases in both the composition of the flora and interference activity. The diminution in interference activity persisted up to 3 weeks after therapy. The differences observed between the antibiotic regimens correlated with differences in initial susceptibility of the flora to the antibiotic used and emergence of the resistance during therapy. Results indicated that although effects of antibiotics on the composition of the flora are transient, effects on its ability to interfere with group A streptococci may persist long after therapy is discontinued. It is thus possible that penicillin therapy may enhance susceptibility of certain individuals to subsequent infection with group A streptococci.