Towards a systematic use of effect biomarkers in population and occupational biomonitoring.
Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.


Single channel currents activated by gamma-aminobutyric acid, muscimol, and (-)-pentobarbital in cultured mouse spinal neurons.
The patch electrode technique was used to record single channel current pulses in tissue-cultured mouse spinal cord neurons. In agreement with earlier noise studies, channels activated by gamma-aminobutyric acid (GABA), muscimol, and (-)-pentobarbital were found to have equal unit conductances. The kinetics of channel closing were studied by analyzing the distributions of open state lifetimes. Channels activated by (-)-pentobarbital and muscimol had longer mean open times than channels activated by GABA. As a result, the kinetics of (-)-pentobarbital- and muscimol-activated channels could be studied in greater detail. Most observed open state lifetime distributions were not exponential but contained an excess of short duration events. A sum of two exponential functions gave a much better fit than a single exponential function to most observed open state lifetime distributions. A critical comparison of noise analysis with single channel recording shows that the fast process responsible for the rapid closures would be very difficult to detect in a noise experiment. The channel noise is dominated by the slower process, and as a result, the relaxation time of the slower kinetic component derived from single channel studies is close to the mean open state lifetime derived from noise measurements. The observation of a faster process points toward either an additional population of channels or a scheme for the channel closing transition which is not a simple first order process.


Tales of diversity: Genomic and morphological characteristics of forty-six Arthrobacter phages.
The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.


Gastric secretion--from Pavlov's nervism to Popielski's histamine as direct secretagogue of oxyntic glands.
Gastric acid and pepsin secretions result from the interplay of neurohormonal factors with stimulatory and inhibitory actions on oxyntic glands. At the turn of XIX century, the notion of nervism or entire neural control of digestive functions, developed by Pavlov prevailed. However, in the second part of XX century, hormonal control has been thought to play a major role in the mechanism of gastric secretion, especially gastrin, which was isolated and synthesized in 1964 by Gregory. Polish traces in gastroenterological history started with the discovery of histamine, a non-nervous and non-gastrin compound in oxyntic mucosa by L. Popielski in 1916, who found that this amine is the most potent and direct stimulant of gastric acid secretion. This histamine concept was supported by leading American gastroenterologists such as A.C. Ivy, championed later by C.F. Code, and clinically applied for testing gastric secretion by K. Kowalewski. Recently, it received a strong support from pharmacological research when J. Black designed H(2)-receptors antagonists, which were first discovered by M.I. Grossman and S.J. Konturek to inhibit not only histamine-, but also meal- and vagally-induced gastric acid secretion, thus reinforcing the notion of the crucial significance of histamine in the control of gastric secretion as the final common chemostimulator. In conclusion, Polish traces appear to be substantial in gastric history due: 1) to discovery by Popielski that histamine is a major, direct stimulus of gastric secretion; 2) to clinical application of this agent by Kowalewski in testing maximal gastric secretory activity; and 3) to clinical use of histamine H(2)-antagonists in control of gastric acid secretion and treatment of peptic ulcers.


[Epilepsies and language disorders].
To study the effects of the epilepsies, the seizures and electroencephalographic discharges on the cognitive function of the child, specifically his language. We consider the relationship between developmental dysphasia and epilepsy, bearing in mind that this association may occur fortuitously, as a consequence of the same cause or taking the epilepsy to be responsible for the language disorder, as seizures or continuously (epileptic aphasia). We assess the relation between developmental aphasia and seizure aphasia in the epilepsies, especially the syndrome of acquired epileptic aphasia of Laundau-Kleffner (LKS). Based on the findings in the literature and a personal series of nine cases, we studied their general characteristics, clinical heterogeneity, associated clinical signs and EEG changes (present in all patients); coexistence of convulsive seizures (67-90%); aetiopathogenic findings invoked but not currently conclusive; negative neuroimaging findings apart from some SPECT and PET data; differential diagnosis; clinical course and prognosis difficult to predict. The pharmacological and/or surgical treatment, complemented by logopedics and psychopedagogics (good results in < or = 50% of the cases), the unpredictable course of LKS has to be assessed cautiously. No direct relation can be confirmed between epilepsy and language disorders, although a relationship may be found in some cases. The hypothesis that LKS, continuous spike-and-wave during slow sleep and partial benign atypical epilepsy are the severe, moderate and mild forms of the same epileptic syndrome is generally accepted. This appears during a phase of maturation in which the brain is particularly vulnerable, and is characterized by continuous spike-and-wave complexes during slow sleep, which lead to cognitive and behaviour disorders.


[Roland Morris disability questionnaire - adaptation and validation for the Portuguese speaking patients with back pain].
The objective of the current study was to adapt and validate the Roland Morris disability questionnaire (RMDQ) to the Portuguese patients because there are no European Portuguese psychometric instruments to evaluate patients suffering from low back pain. After translation and back translation the Portuguese version of the RMDQ was tested in 112 patients with low back pain (30 males and 82 females) to analyse psychometric characteristics. Analysis of measures obtained points to high levels of internal consistency (Cronbach's alpha: 0.81) and temporal stability (test-retest: r = 0.86). External validity was assessed by association with numerical pain rating scale (END), Schöber test (TS) and fingertip floor measurement (GFA). The results revealed a large correlation between the RMDQ and END (r = 0.73) and a medium correlation with TS and GFA (in this order, r = -0,52 and r = 0,42). The psychometric analysis showed that the RMDQ gives reliable measures for the disability of patients with back pain and was successfully adapted and validated to the European Portuguese patients.


Switching the in-plane easy axis by ion implantation in rare earth based magnetic films.
Ar(+) ions have been implanted into Laves phase epitaxial thin films of YFe(2) and DyFe(2). Magneto-optical Kerr effect and vibrating sample magnetometry experiments show that the easy and hard axes of magnetization in both materials rotate through an in-plane angle of 90°, whilst the strength of the magnetic anisotropy remains unaltered. This is supported by OOMMF computational modelling. Atomic force microscopy confirms that the film roughness is not affected by implanted ions. X-ray diffraction data show that the lattice parameter expands upon ion implantation, corresponding to a release of strain throughout the entire film following implantation with a critical fluence of 10(17) Ar(+) ions cm(-2). The anisotropy of the films is linked to the strain and from these data it is concluded that the source of anisotropy alters from one where magnetoelastic and magnetocrystalline effects compete to one which is governed solely by magnetocrystalline effects. The ability to locally tune the source of magnetic anisotropy without affecting the film surface and without inducing or eliminating anisotropy could be important in the fabrication of high density magnetic data storage media, spintronic devices and magneto-optical materials.


Hippocampal sclerosis in advanced age: clinical and pathological features.
Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.


Teachers' reporting of suspected child abuse and neglect: behaviour and determinants.
By reporting suspected child abuse and neglect, teachers can make an important contribution to the early detection and prevention of abuse. However, teachers are sometimes reluctant to report their suspicions. This study investigated the determinants of teachers' reporting behaviour using concepts from the Integrated Change Model. Self-report data were collected from 296 teachers employed in 15 Australian schools. Compared to their colleagues, teachers who had never suspected child abuse or neglect (non-detectors, N=57, 19%) were more likely to have a lower confidence in their skills for recognising the signs of abuse, a higher degree of perceived social support regarding reporting, less years teaching experience and lower academic qualifications. Among those who had suspected cases of child abuse or neglect (N=239, 81%), teachers who always reported their suspicions (consistent reporters, 82%) were more likely to have firm action plans about reporting and detecting signs of CAN than teachers who did not always report their suspicions (inconsistent reporters, 18%). While only a small proportion of the variance in detection and reporting status was explained, the results illustrate the utility of health promotion theory and methods for improving our understanding of these behaviours.


Relation of Exercise Capacity to Risk of Development of Diabetes in Patients on Statin Therapy (the Henry Ford Exercise Testing Project).
High exercise capacity (EC) has been associated with a lower risk of incident diabetes, whereas statin therapy has been associated with a higher risk. We sought to investigate whether the association between EC and diabetes risk is modified by statin therapy. This retrospective cohort study included 47,337 patients without diabetes or coronary artery disease at baseline (age 53 ± 13 years, 48% women, 66% white) who underwent clinical treadmill stress testing within the Henry Ford Health System from January 1, 1991, to May 31, 2009. The patients were stratified by baseline statin use and estimated peak METs achieved during exercise testing. Hazard ratios for incident diabetes were calculated using Cox proportional hazards models adjusted for demographic characteristics, co-morbidities, pertinent medications, and stress test indication. We observed 6,921 new diabetes cases (14.6%) over a median follow-up period of 5.1 years (interquartile interval of 2.6 to 8.2 years). Compared with the statin group, the no-statin group achieved higher mean METs (8.9 ± 2.7 vs 9.6 ± 3.0, respectively; p <0.001). After adjustment for covariates, a higher EC was associated with a lower risk of incident diabetes, irrespective of statin use (p-interaction = 0.15). Each 1-MET increment was associated with an 8%, 8%, and 6% relative risk reduction in the total cohort, the no-statin, and the statin groups, respectively (95% confidence interval, 0.91 to 0.93, 0.91 to 0.93, and 0.91 to 0.96, respectively; p <0.001 for all). We conclude that a higher EC is associated with a lower risk of incident diabetes regardless of statin use.


[Gamma-glytamiltransferase activity and cardiovascular diseases (ischemic heart disease and cerebral stroke)].
To investigate association between gamma-glytamiltransferase levels and the development of CVD. The data were taken from materials of the epidemiological study " Determinants of cardiovascular disease in Eastern Europe " , the HAPPIE project. We investigated representative samples from non-organized population of men and women 45 - 69 years old living in Novosibirsk - 9361 subjects (4275 men and 5086 women). The program of study included: questionnaire of previous CVD, smoking status and alcohol consumption; two blood pressure measurements; anthropometry, biochemical analysis (gamma-glytamiltransferase, total cholesterol, HDL cholesterol, and triglycerides) and rest ECG. Among all subjects we distinguished three groups: first - patients with diagnosed ischemic heart disease (angina pectoris or myocardial infarction) and without previous cerebral stroke; second - patients with previous cerebral stroke (without ischemic heart disease); third - patients without previous ischemic heart disease and cerebral stroke (control group). We revealed reliable data on sex-dependent difference of gamma-glytamiltransferase activity: men have higher gamma-glytamiltransferase activity compared with women in all age groups. Subjects who didn t take alcoholic drinks during the last year have noticeably lower gamma-glytamiltransferase level than those who took alcoholic drinks during that period. Gamma-glytamiltransferase activity was higher both in men and women in group with ischemic heart disease, than in control group. We did not reveal difference in gamma-glytamiltransferase activity between groups with cerebral stroke and control group. The similar patterns were revealed in subjects who didn't take alcoholic drinks during the last year.


Returning to work after liver transplant: experiencing the roadblocks.
Liver transplant has been the treatment of choice for people with end-stage liver disease since the mid-1980s. The theme of returning to work after liver transplantation emerged from the data of a phenomenological study examining the lived experience of people with liver transplants. Thirteen liver recipients were interviewed using a semistructured approach. Only one of the first nine participants was able to return to work after the transplant; therefore, the last four participants were purposely chosen because they had been able to return to work. The possibility of losing health insurance benefits and disability benefits prevented many participants from working. Those able to return to work had professional careers that afforded them flexibility in their work schedule. Some implications for health professionals lie in the area of healthcare and health insurance policy change. Avenues for health insurance reform could be explored in an effort to empower the transplant recipient.


Review article: epidemiology of IBS and other bowel disorders of gut-brain interaction (DGBI).
The disorders of gut-brain interactions (DGBI) are a spectrum of gastrointestinal (GI) disorders that involve the entire GI tract and are usually categorised into four major anatomic GI regions, oesophageal, gastroduodenal, bowel and anorectal. Irritable bowel syndrome (IBS), a bowel DGBI, is one of the most researched DGBI and has been the subject of copious epidemiological studies. Prevalence rates are based on diagnostic criteria. In the case of IBS, there are three central obstacles to attaining a clear picture of prevalence: the absence of biomarkers, the multitude of diagnostic criteria used over the years, and the heterogeneous nature of the methodology used in epidemiologic surveys. When the results of multiple studies, conducted over a long period of time, using different diagnostic criteria and different research methodology, and involving different study populations are pooled to determine a single summary prevalence rate it is difficult to interpret the results and to determine their reliability and significance. This pitfall is insufficiently recognised and unfortunate because prevalence rates are important for understanding the burden of disease, for allocating healthcare and research resources, and for incentivising and prioritising new treatments. The aims of the present paper are to highlight our knowledge and understanding of IBS epidemiology within the context of other DGBI, and to present strategies to improve epidemiological research, especially in advance of the new Rome V criteria, to be published in 2026.


An isokinetic method for inducing a localised fatigue effect in the plantarflexors and dorsiflexors of the ankle.
To examine the effects of dysfunction of specific musculature of the shank a reliable and valid protocol can be used to induce a localised fatigue effect. A localised dynamometry based protocol was developed to illicit a fatigue effect in either plantar flexors or dorsiflexors. An isokinetic protocol allowing for movement through the full range of motion, set at an angular velocity of 45°s(-1), was used to allow fatigue to be developed. Fatigue was established when three consecutive torque measures dropped below 50% of the average three peak contractions. Bouts of activity were based on a ratio of 40 contractions interspaced with a 30s rest. Results suggest that the protocol elicited a fatigue effect in the prime movers of either plantar flexion or dorsiflexion, supported through the analysis of power spectral density and amplitude shift of surface electromyography measures. The protocol demonstrated sound reliability with Interclass Correlation scores for all measures ranging from 0.441-0.962. The protocol is a valid and repeatable process for establishing muscular weakness in the working muscles of either plantar or dorsi flexion, as observed in the fatigued state. This can allow further examination of the effects of a localised muscular weakness on daily living tasks.


Earth observation satellite data-based assessment of wetland dynamics in the Kashmir Himalaya.
Earth observation (EO) technology offers enormous opportunities to assess the magnitude and patterns of spatial variability in wetlands over time. This study aims to assess the spatial and temporal changes in the wetlands of the Kashmir valley using multiple remote sensing satellite data products, Geographic Information System (GIS), and field observations. Moreover, role of major factors operating at different time scales including regional geology, climate, and human activities in driving the wetland change is presented. The dynamics of the wetlands are illustrated in the occurrence, seasonality, and recurrence of surface water, land cover transitions and loss patterns particularly for the period from 1984 to 2021. Constituting about 3% (495 Km2) of the total area, substantial and variable patterns of seasonal and annual changes are exhibited by the wetlands. The main transitions of the water surface reveal that 2% of the area has changed from permanent to seasonal; 8% is lost; 15% is new seasonal; 0.12% is permanently lost; and 0.3% is new permanent. About 22% of the area reveals increase in the intensity of water surface occurrence, whereas 44% shows no change, and 34% exhibits decrease. Bathymetric analysis suggests that the average depth of the wetlands ranges between 0.6 and 16.6 m. In general, alpine wetlands are relatively deeper and mostly static in their structure whereas those in the floodplain are shallow, fragmented, and showing signs of depletion during the assessment period. The results of this assessment will inform the policy on conservation and sustainability of wetlands in the Kashmir Himalaya.


Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan.
Although both psilocybin and dextromethorphan (DXM) produce psychedelic-like subjective effects, rates of non-medical use of psilocybin are consistently greater than DXM. New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher rates of non-medical use. Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. High doses of both drugs produced similar time courses and increases in participant ratings of peak overall drug effect strength. Nine subjective effect domains are proposed to be related to the reinforcing effects of psilocybin: liking, visual effects, positive mood, insight, positive social effects, increased awareness of beauty (both visual and music), awe/amazement, meaningfulness, and mystical experience. For most ratings, (1) psilocybin and DXM both produced effects significantly greater than placebo; (2) psilocybin showed dose-related increases; 3, DXM was never significantly higher than psilocybin; (4) the two highest psilocybin doses were significantly greater than DXM. These differences were consistent with two measures of desire to take the drug condition again. This analysis provides new information about domains of psilocybin subjective effects proposed to be related to its reinforcing effects (alternatively described as the "motivation" to use). Observed differences on these domains between psilocybin and DXM are consistent with the relative rates of non-medical use of psilocybin and DXM.


Drosophila telomeres: the non-telomerase alternative.
In most eukaryotes, telomeres are composed of simple repetitive sequences renewable by telomerase. By contrast, Drosophila telomeres comprise arrays of non-LTR retrotransposons HeT-A, TART, and TAHRE belonging to three different families. However, closer inspection reveals that the two quite different telomere systems share quite a few components and regulatory circuits. Here we present the current knowledge on Drosophila telomeres and discuss the possible mechanisms of telomere length control.


Efficient Path Planing for Articulated Vehicles in Cluttered Environments.
Motion planning and control for articulated logistic vehicles such as tugger trains is a challenging problem in service robotics. The case of tugger trains presents particular difficulties due to the kinematic complexity of these multiarticulated vehicles. Sampling-based motion planners offer a motion planning solution that can take into account the kinematics and dynamics of the vehicle. However, their planning times scale poorly for high dimensional systems, such as these articulated vehicles moving in a big map. To improve the efficiency of the sampling-based motion planners, some approaches combine these methods with discrete search techniques. The goal is to direct the sampling phase with heuristics provided by a faster, precociously ran, discrete search planner. However, sometimes these heuristics can mislead the search towards unfeasible solutions, because the discrete search planners do not take into account the kinematic and dynamic restrictions of the vehicle. In this paper we present a solution adapted for articulated logistic vehicles that uses a kinodynamic discrete planning to bias the sampling-based algorithm. The whole system has been applied in two different towing tractors (a tricycle and a quadricycle) with two different trailers (simple trailer and synchronized shaft trailer).


Consumer mobility predicts impacts of herbivory across an environmental stress gradient.
Environmental stress impedes predation and herbivory by limiting the ability of animals to search for and consume prey. We tested the contingency of this relationship on consumer traits and specifically hypothesized that herbivore mobility relative to the return time of limiting environmental stress would predict consumer effects. We examined how wave-induced water motion affects marine communities via herbivory by highly mobile (fish) vs. slow-moving (pencil urchin) consumers at two wave-sheltered and two wave-exposed rocky subtidal locations in the Galapagos Islands. The exposed locations experienced 99th percentile flow speeds that were 2-5 times greater than sheltered locations, with mean flow speeds >33 cm/s vs. <16 cm/s, 2-7 times higher standing macroalgal cover and 2-3 times lower cover of crustose coralline algae than the sheltered locations. As predicted by the environmental stress hypothesis (ESH), there was a negative relationship between mean flow speed and urchin abundance and herbivory rates on Ulva spp. algal feeding assays. In contrast, the biomass of surgeonfishes (Acanthuridae) and parrotfishes (Labridae: Scarinae) was positively correlated with mean flow speed. Ulva assays were consumed at equal rates by fish at exposed and sheltered locations, indicating continued herbivory even when flow speeds surpassed maximum reported swimming speeds at a rate of 1-2 times per minute. Modeled variation in fish species richness revealed minimal effects of diversity on herbivory rates at flow speeds <40 cm/s, when all species were capable of foraging, and above 120 cm/s, when no species could forage, while increasing diversity maximized herbivory rates at flow speeds of 40-120 cm/s. Two-month herbivore exclusion experiments during warm and cool seasons revealed that macroalgal biomass was positively correlated with flow speed. Fish limited macroalgal development by 65-91% at one exposed location but not the second and by 70% at the two sheltered locations. In contrast, pencil urchins did not affect algal communities at either exposed location, but reduced macroalgae by 87% relative to controls at both sheltered locations. We propose an extension of the ESH that is contingent upon mobility to explain species-specific changes in feeding rates and consumer effects on benthic communities across environmental gradients.


Nuclear receptors and inflammation control: molecular mechanisms and pathophysiological relevance.
Tissue inflammation is a tightly regulated process that normally serves to recruit the immune system to sites of infection and injury and to facilitate tissue repair processes. When an inflammatory state is excessive or prolonged, local and systemic damage to host tissues can result in loss of normal physiological functions. Here, we briefly review recent studies that advance our understanding of signaling pathways involved in initiation of inflammatory responses at the level of transcription and counterregulation of these pathways by selected members of the nuclear receptor superfamily. Studies of the intersection of nuclear receptors and inflammation have revealed mechanisms of positive and negative transcriptional control that may provide new targets for pharmacological intervention in chronic diseases, such as atherosclerosis.


[HFR aequilibrium can be an answer to malnutrition and hypotension in dialisys: case report].
The interdialytic hypotension is still the most frequent complication during the hemodialysis. A-HFR has dynamic profiles of ultrafiltration and conductivity of the dialysate that ensure a better refilling and reduce compliance during the dialysis treatment, furthermore reduce the amino acid loss and has a lower inflammatory effect. In our Center, we wanted to analyze the impact of this kind of dialysis on intradialytic tolerance and nutritional status in two malnourished patients with encouraging data on the use of AHFR in malnutrition and disequilibrium syndromes.


Comparing peak and submaximal cardiorespiratory responses during field walking tests with incremental cycle ergometry in COPD.
Field and laboratory-based tests are used to measure exercise capacity in people with COPD. A comparison of the cardiorespiratory responses to field tests, referenced to a laboratory test, is needed to appreciate the relative physiological demands. We sought to compare peak and submaximal cardiorespiratory responses to the 6-min walk test, incremental shuttle walk test and endurance shuttle walk test with a ramp cycle ergometer test (CET) in patients with COPD. Twenty-four participants (FEV(1) 50 ± 14%; 66.5 ± 7.7 years; 15 men) completed four sessions, separated by ≥24 h. During an individual session, participants completed either two 6-min walk tests, incremental shuttle walk tests, endurance shuttle walk tests using standardized protocols, or a single CET, wearing a portable gas analysis unit (Cosmed K4b(2)) which included measures of heart rate and arterial oxygen saturation (SpO(2)). Between tests, no difference was observed in the peak rate of oxygen uptake (F(3,69) = 1.2; P = 0.31), end-test heart rate (F(2,50) = 0.6; P = 0.58) or tidal volume (F(3,69) = 1.5; P = 0.21). Compared with all walking tests, the CET elicited a higher peak rate of carbon dioxide output (1173 ± 350 mL/min; F(3,62) = 4.8; P = 0.006), minute ventilation (48 ± 17 L/min; F(3,69) = 10.2; P < 0.001) and a higher end-test SpO(2) (95 ± 4%; F(3,63) = 24.9; P < 0.001). In patients with moderate COPD, field walking tests elicited a similar peak rate of oxygen uptake and heart rate as a CET, demonstrating that both self- and externally paced walking tests progress to high intensities.


Prevalence of varicose veins in an Italian elderly population.
The prevalence of varicose veins (VV) in the elderly population of the Campania Region, in Southern Italy, was estimated. A random sample of the people aged more than 65 years was drawn by means of a stratified multistage sampling design warranting that observed percentages were direct estimates of population percentages. The investigation covered 1319 subjects, 560 (42.5%) men and 759 (57.5%) women, their ages ranging from 66 to 96 years with an average value of 74.2 years, who were interviewed and visited by trained physicians. VV were defined as any reticular or truncal visible varicosities of the lower limbs, and investigated symptoms were heaviness, pain, nightly cramps, edema, eczema, hyperpigmentation, and ulceration. Some variables were studied as risk factors: age, sex, lifetime occupation, smoking, alcohol, hypertension, diabetes, and obesity; previous treatment and use of elastic stockings were also studied. Statistical associations were evaluated by Chi-square test, a two-tailed P value of 0.05 being assumed as significance level. In total, 391 (29.6%) subjects were reported to be affected by VV, but the clinical examination was positive in only 362 (27.4%) with a good correspondence between answers and clinical findings. Prevalence was greatly affected by sex, the percentage being two times higher in women (35.2%) than in men (17%). VV developed after a pregnancy in 40.5% of women, but a high percentage of women (38.2%) also reported menopause as a time starting point. No significant association between reported risk factors and VV was found among men, whereas obesity was strongly related to VV in women. One or more symptoms were reported in 92.1% of persons affected by VV, but no previous therapy was reported by 58.9% of subjects. Only 16.9% of patients used elastic stockings with a significant difference between men (7.4%) and women (20.2%).


Subcellular localization and speciation of nickel in hyperaccumulator and non-accumulator Thlaspi species.
The ability of Thlaspi goesingense Hálácsy to hyperaccumulate Ni appears to be governed by its extraordinary degree of Ni tolerance. However, the physiological basis of this tolerance mechanism is unknown. We have investigated the role of vacuolar compartmentalization and chelation in this Ni tolerance. A direct comparison of Ni contents of vacuoles from leaves of T. goesingense and from the non-tolerant non-accumulator Thlaspi arvense L. showed that the hyperaccumulator accumulates approximately 2-fold more Ni in the vacuole than the non-accumulator under Ni exposure conditions that were non-toxic to both species. Using x-ray absorption spectroscopy we have been able to determine the likely identity of the compounds involved in chelating Ni within the leaf tissues of the hyperaccumulator and non-accumulator. This revealed that the majority of leaf Ni in the hyperaccumulator was associated with the cell wall, with the remaining Ni being associated with citrate and His, which we interpret as being localized primarily in the vacuolar and cytoplasm, respectively. This distribution of Ni was remarkably similar to that obtained by cell fractionation, supporting the hypothesis that in the hyperaccumulator, intracellular Ni is predominantly localized in the vacuole as a Ni-organic acid complex.


Protective effects of passiflora incarnata on ovarian ischemia/reperfusion damage in rats with ovarian torsion.
This study aimed to investigate whether Passiflora Incarnata (PI) has a protective effect against ischemia-reperfu-sion (IR)-induced oxidative and inflammatory ovarian damage. The effects of PI on ovarian ischemia-reperfusion injury were investigated in female Wistar albino rats. The animals were randomly divided into three groups: Group 1 (sham), Group 2 (IR), and Group 3 (IR+PI). The mean levels of Malondialdehyde (MDA), Myeloperoxidase (MPO), and Total Oxidant Status (TOS) were higher in the IR group (p=0.025, p<0.001, and p=0.016, respectively). The Total Antioxidant Status (TAS) levels were lower in the IR group (p=0.005). Immunostaining revealed significant differences across the groups for Tumor necrosis factor-alpha (TNF-α): 13.84%, 49.51%, and 22.51% for Groups 1, 2, and 3, respectively (p<0.01). Bax: 10.53%, 46.74%, and 26.46% for Groups 1, 2, and 3, respectively (p<0.01). Annexin V: 12.24%, 44.86%, and 23.28% for Groups 1, 2, and 3, respectively (p<0.01). The mean scores for hemorrhage, inflammation, follicular degeneration, and congestion showed significant variations among the groups, all registering p<0.001. Passiflora Incarnata exhibited antioxidant, anti-inflammatory, and anti-apoptotic properties, promoting cell survival, histologically protecting ovarian tissue, and ameliorating IR injury by reducing oxidative stress.


[Clinical and laboratory efficacy of the novel difluoroquinolone Sparflo (sparfloxacin) in therapy of skin and soft tissue infections].
Results of clinical trial of new difluoroquinolone--Sparflo (sparfloxacin, Dr. Reddy's Laboratories Ltd) are presented. Sparfloxacin was used in the treatment of 24 patients at the Department of Wounds and Wounds infections (11 patients) and at the Department of burn wounds (13 patients) of the A.V. Vishnevsky Institute of Surgery. After the treatment with sparfloxacin pathogen eradication was stated in 18 patients, eradication with superinfection--in 13 patients, persistence--in 3 patients. Thus bacteriological efficacy amounted to 87.5 per cent. Pharmacokinetic data demonstrates long-term sparfloxacin circulation in the organism of patients with burns--elimination half-life amounted to 20 hours. Overall after the sparfloxacin use the favourable clinical effect was stated in 100 per cent patients--18 patients (75%) had clinical cure and 6 (25%)--clinical improvement. The drug tolerance was good. It is concluded that clinical and laboratory investigation demonstrated high efficacy of sparfloxacin (Sparflo, Dr. Reddy's Laboratories Ltd) in the treatment of patients with skin and tissue wounds of different localization and genesis, complicated with infections.


Effect of resident physician education regarding selective chemoprophylaxis for the prevention of early onset group B streptococcal sepsis: an outcome study.
The aim of this study was to evaluate the effect of a voluntary protocol for selective intrapartum chemoprophylaxis on the incidence of early onset group B streptococcal sepsis (GBS EOS). Cases of GBS EOS were defined as a positive GBS culture from a normally sterile fluid obtained during the first 7 days of life. All cases of GBS EOS at an urban, university-affiliated community hospital were reviewed during 2 time periods. The 2-year period before instituting a resident education program to promote selective chemoprophylaxis (1988-89) was retrospectively reviewed; the 2-year period after the education program was introduced (1990-91) was prospectively recorded. The outcome measure was the incidence of GBS EOS. The rate of GBS EOS was 7/14,335 deliveries (0.05%) before and 9/13,999 (0.064%) after the introduction of the education program (observed difference between proportions 0.016%, 95% confidence interval [CI] for the difference between the proportions -0.071% to 0.04%, P = not significant [NS]). The rate of GBS EOS in preterm infants was 5/1,331 (0.376%) before and 3/1,297 (0.23%) afterward (observed difference between proportions 0.14%, 95% CI -0.28% to 0.56%, P = NS). The incidence of GBS EOS did not decrease during the latter period due to failure of antepartum cultures to predict intrapartum GBS colonization (2 cases); non-compliance with voluntary recommendations to administer chemoprophylaxis (2 cases); failure of chemoprophylaxis or therapy for intraamniotic infection to prevent neonatal infection (3 cases); and occurrence of GBS EOS in infants without risk factors (2 cases). An education program for resident physicians regarding chemoprophylaxis for GBS EOS did not significantly reduce the absolute incidence of disease. Alternative strategies are needed that redress the causes of failure inherent in the current guidelines. Some cases of GBS EOS are not preventable because the parturient does not have risk factors that indicate chemoprophylaxis.


[Molecular biological characteristics of cancer].
The review presents the main and additional features that distinguish tumor cells from normal tissue cells. They include sustained proliferative signaling, evasion from growth suppressors, resisting cell death, enabling replicative immortality, angiogenesis induction, and invasion and metastasis activation. Basis for the formation of these features is provided by tumor genome instability. Tumors are complex tissues that consist of different cell types interacting with each other as well as with normal cells. An important characteristic of tumor cells is the ability to interact with the tumor microenvironment and the formation of tumor stroma.


Helix-length compensation studies reveal the adaptability of the VS ribozyme architecture.
Compensatory mutations in RNA are generally regarded as those that maintain base pairing, and their identification forms the basis of phylogenetic predictions of RNA secondary structure. However, other types of compensatory mutations can provide higher-order structural and evolutionary information. Here, we present a helix-length compensation study for investigating structure-function relationships in RNA. The approach is demonstrated for stem-loop I and stem-loop V of the Neurospora VS ribozyme, which form a kissing-loop interaction important for substrate recognition. To rapidly characterize the substrate specificity (k(cat)/K(M)) of several substrate/ribozyme pairs, a procedure was established for simultaneous kinetic characterization of multiple substrates. Several active substrate/ribozyme pairs were identified, indicating the presence of limited substrate promiscuity for stem Ib variants and helix-length compensation between stems Ib and V. 3D models of the I/V interaction were generated that are compatible with the kinetic data. These models further illustrate the adaptability of the VS ribozyme architecture for substrate cleavage and provide global structural information on the I/V kissing-loop interaction. By exploring higher-order compensatory mutations in RNA our approach brings a deeper understanding of the adaptability of RNA structure, while opening new avenues for RNA research.


vhcub: Virus-host codon usage co-adaptation analysis.
Viruses show noticeable evolution to adapt and reproduce within their hosts. Theoretically, patterns and factors that affect the codon usage of viruses should reflect evolutionary changes that allow them to optimize their codon usage to their hosts. Some software tools can analyze the codon usage of organisms; however, their performance has room for improvement, as these tools do not focus on examining the codon usage co-adaptation between viruses and their hosts. This paper describes the vhcub R package, which is a crucial tool used to analyze the co-adaptation of codon usage between a virus and its host, with several implementations of indices and plots. The tool is available from: https://cran.r-project.org/web/packages/vhcub/.


The traditional kampo medicine tokishakuyakusan increases ocular blood flow in healthy subjects.
The aim of this study was to examine the effects of oral administration of kampo medical formulas on ocular blood flow (OBF). A crossover protocol was used to randomly administer five grams of yokukansan, tokishakuyakusan (TSS), keishibukuryogan, or hachimijiogan to 13 healthy blinded subjects (mean age: 37.3 ± 12.3 years). The mean blur rate, a quantitative OBF index obtained with laser speckle flowgraphy, was measured at the optic nerve head before and 30 minutes after administration. Blood pressure (BP) and intraocular pressure (IOP) were also recorded. No significant changes were observed in mean BP or IOP after the administration of any of the kampo medical formulas. There was a significant increase in OBF 30 minutes after administration of TSS (100% to 103.6 ± 6.9%, P < 0.01). Next, TSS was administered to 19 healthy subjects (mean age: 32.0 ± 11.0 years) and OBF was measured before and 15, 30, 45, and 60 minutes after administration. Plain water was used as a control. OBF increased significantly after TSS administration compared to control (P < 0.01) and also increased from 30 to 60 minutes after administration compared to baseline (P < 0.05). These results suggest that TSS can increase OBF without affecting BP or IOP in healthy subjects.


Occupational cognitive stimulation, socioeconomic status, and cognitive functioning in young adulthood.
Occupational characteristics are associated with late-life cognition. However, little is known about the association between occupational factors and cognition in early adulthood, especially when controlling for early life socioeconomic status (SES) and cognition in childhood. Importantly, sex may shape the impact of occupational characteristics that provide cognitive stimulation given that education, occupational status, and workplace experiences differ by sex. Using data on 12,129 participants ages 24-32 from the U.S.-based National Longitudinal Study of Adolescent to Adult Health, we investigated the association between four factors of occupational cognitive stimulation (repetition, freedom, analytic skills, and social interaction) and young-adult episodic and working memory independent of childhood and young-adult SES, using linear regression. We adjusted for confounding due to sex, race/ethnicity, age, childhood cognition, and education. We further investigated effect measure modification of this association by sex in stratified regression models. Overall, 1-unit increases in both occupational analytic skills and social interaction were significantly associated with 0.101 (95%CI: 0.28, 0.173) and 0.096 (95%CI: 0.032, 0.160) SD higher memory, respectively. However, when sex-stratified, among men, a 1-unit increase on the social interaction scale was associated with 0.16 (95%CI: 0.05, 0.27) SD higher memory, while there was no association among women. Our results indicate that even in adulthood, activities that stimulate the mind can contribute to improved cognitive function, and the most beneficial forms of occupational stimulation are those that use analytic skills and involve social interaction (particularly among young men).


Global motion compensation for compressing holographic videos.
Large high-resolution digital holographic displays may become feasible in the near future, and they will need considerable amounts of data. Handling this bandwidth is particularly challenging for dynamic content operating at video rates. Conventional motion compensation algorithms from classical video coders are ineffective on holograms because, in contrast to natural imagery, each pixel contains partial information from the whole scene. We propose an accurate motion compensation model predicting how hologram content changes with respect to 3D rigid-body motion that arises in natural scenes. Using diffraction theory, we derive tractable closed form expressions for transforming 2D complex-valued holographic video frames. Our experiments use computer generated hologram videos with known ground truth motion. We integrated the proposed motion compensation model into the HEVC codec. We report Bjøntegaard delta-PSNR ratio gains of 8 dB over standard HEVC.


Information processing in social insect networks.
Investigating local-scale interactions within a network makes it possible to test hypotheses about the mechanisms of global network connectivity and to ask whether there are general rules underlying network function across systems. Here we use motif analysis to determine whether the interactions within social insect colonies resemble the patterns exhibited by other animal associations or if they exhibit characteristics of biological regulatory systems. Colonies exhibit a predominance of feed-forward interaction motifs, in contrast to the densely interconnected clique patterns that characterize human interaction and animal social networks. The regulatory motif signature supports the hypothesis that social insect colonies are shaped by selection for network patterns that integrate colony functionality at the group rather than individual level, and demonstrates the utility of this approach for analysis of selection effects on complex systems across biological levels of organization.


Closed-loop control of renal perfusion pressure in physiological experiments.
This paper presents the design, experimental modeling, and control of a pump-driven renal perfusion pressure (RPP)-regulatory system to implement precise and relatively fast RPP regulation in rats. The mechatronic system is a simple, low-cost, and reliable device to automate the RPP regulation process based on flow-mediated occlusion. Hence, the regulated signal is the RPP measured in the left femoral artery of the rat, and the manipulated variable is the voltage applied to a dc motor that controls the occlusion of the aorta. The control system is implemented in a PC through the LabView software, and a data acquisition board NI USB-6210. A simple first-order linear system is proposed to approximate the dynamics in the experiment. The parameters of the model are chosen to minimize the error between the predicted and experimental output averaged from eight input/output datasets at different RPP operating conditions. A closed-loop servocontrol system based on a pole-placement PD controller plus dead-zone compensation was proposed for this purpose. First, the feedback structure was validated in simulation by considering parameter uncertainty, and constant and time-varying references. Several experimental tests were also conducted to validate in real time the closed-loop performance for stepwise and fast switching references, and the results show the effectiveness of the proposed automatic system to regulate the RPP in the rat, in a precise, accurate (mean error less than 2 mmHg) and relatively fast mode (10-15 s of response time).


Best practices in interprofessional education and training in surgery: experiences from American College of Surgeons-Accredited Education Institutes.
Interprofessional education (IPE) in health care describes a process for training that places health care learners from different professional disciplines into an environment or situation in which shared or linked educational goals are pursued. IPE represents a new way of thinking about education as a value proposition directed at high-quality interprofessional patient care and as such is an innovative strategy endorsed in statements by the Institute of Medicine and the World Health Organization. The requirements of the American College of Surgeons-accredited Education Institutes (ACS-AEIs) for Comprehensive (Level I) accreditation state that education and training activities at the accredited institutes (simulation centers) must be multidisciplinary in nature. Until recently, concepts of shared interprofessional educational goals and facilitation of interdisciplinary colearning have not been addressed explicitly by the Consortium of ACS-AEIs. In March 2012, the ACS Education Division convened a forum on IPE at the Annual Meeting of the Consortium of ACS-accredited Education Institutes in Chicago, IL. Five different ACS-AEI perspectives on IPE and training were presented, covering (1) simulation-based crisis resource management training for operating room teams, (2) the use of multidisciplinary simulation at an academic medical center-based simulation facility, (3) the development of a collaborative IPE curriculum between nursing and medical schools at a major university, (4) the development of a simulation-based interprofessional obstetrics educational program at a university medical center, and (5) the development of an interprofessional macrosystem simulation program in conjunction with opening a new hospital facility. We describe these experiences and present them as best practices in simulation-based IPE in surgery. These IPE experiences in the ACS-AEIs reflect varied and robust approaches to integrated interdisciplinary teaching and learning. Demands and directives to increase these types of educational activities in the near future will have to be met with a wider range of offerings and greater specific knowledge and expertise within the ACS-AEI Consortium.


Radiographic characteristics of lower-extremity bowing in children.
Lower-extremity bowing is common in infants and children and can result from a variety of conditions. At radiography, developmental bowing shows varus angulation centered at the knee, "metaphyseal beaking," thickening of the medial tibial cortices, and tilted ankle joints. Tibia vara (Blount disease) demonstrates genu varum and depression of the proximal tibia medially. Congenital bowing manifests as posteromedial bowing with cortical thickening along the concavity of the curvature and, in some cases, diaphyseal broadening. In rickets, radiographic changes occur primarily at sites of rapid growth and are predominantly metaphyseal, with widening of the zone of provisional calcification. Achondroplasia is characterized by shortening and thickening of the long bones with metaphyseal flaring and cupping. In neurofibromatosis, there may be anterolateral bowing of the tibia, and there is often focal narrowing and intramedullary sclerosis or cystic change at the apex of the angulation. The tibia is typically involved at the junction of the middle and distal thirds. Osteogenesis imperfecta demonstrates bowing from softening due to osteoporosis and multiple fractures and typically involves the entire skeleton. In camptomelic dysplasia, lower-extremity bowing is associated with a short trunk, short limbs, and deficiencies in pelvic bone development. Recognition of these pathologic conditions is important for differentiating those that will resolve spontaneously from those that require surgery or other treatment.


Self-purification of marine environments for heavy metals: a study on removal of lead(II) and copper(II) by cuttlebone.
The aim of this study was to determine adsorption properties of cuttlebone, cuttlefish bone as dead biomass, for lead(II) and copper(II) from aqueous solutions. Adsorption kinetic, isotherm and effect of pH (in the range of 2.0-7.0) were investigated in a single component batch system at room temperature (25 ± 1 °C). The heavy metal adsorption by cuttlebone was relatively rapid and reached equilibrium in 120 min in all the cases. The pseudo-second order rate equation described the adsorption kinetic of both the ions. The adsorption capacities of Pb2+ and Cu2+ were constantly increased by pH and the optimum condition of pH was determined to be 7.0. The Freundlich model was better fitted than other models with the isotherm data, indicating sorption of the metal ions in a heterogeneous surface. According to the Langmuir model, the maximum adsorption capacities of cuttlebone for Pb2+ and Cu2+ were determined to be 45.9 and 39.9 mg/g, respectively. The results indicated cuttlebone as a promising adsorbent for Pb2+ and Cu2+, which presents a high capacity of self-purification in marine environments and also can be used for removal of the metal ions from water and wastewater.


Sparse Density Estimation on the Multinomial Manifold.
A new sparse kernel density estimator is introduced based on the minimum integrated square error criterion for the finite mixture model. Since the constraint on the mixing coefficients of the finite mixture model is on the multinomial manifold, we use the well-known Riemannian trust-region (RTR) algorithm for solving this problem. The first- and second-order Riemannian geometry of the multinomial manifold are derived and utilized in the RTR algorithm. Numerical examples are employed to demonstrate that the proposed approach is effective in constructing sparse kernel density estimators with an accuracy competitive with those of existing kernel density estimators.


Double-tailored nonimaging reflector optics for maximum-performance solar concentration.
A nonimaging strategy that tailors two mirror contours for concentration near the étendue limit is explored, prompted by solar applications where a sizable gap between the optic and absorber is required. Subtle limitations of this simultaneous multiple surface method approach are derived, rooted in the manner in which phase space boundaries can be tailored according to the edge-ray principle. The fundamental categories of double-tailored reflective optics are identified, only a minority of which can pragmatically offer maximum concentration at high collection efficiency. Illustrative examples confirm that acceptance half-angles as large as 30 mrad can be realized at a flux concentration of approximately 1000.


Penetration Depth in Nanoparticles Incorporated Radiofrequency Hyperthermia into the Tissue: Comprehensive Study with Histology and Pathology Observations.
In present study, the effective penetration of radiofrequency (RF) induced gold decorated iron oxide nanoparticles (GS@IONPs) hyperthermia was investigated. The effective penetration depth of RF also the damage potency of hyperthermia was evaluated during histopathology observations which were done on the chicken breast tissue and hepatocellular carcinoma (HCC) models. The thermal damages are well- documented in our previous cellular study which was engaged with potency of RF hyperthermia in Epithelial adenocarcinoma (MCF-7) and fibroblast (L-929) cells deaths [1]. In recent work, PEGylated iron oxide nanoparticles (IONPs) were used as base platform for gold magnetic nanoparticles (GS@IONPs) formation. The 144.00015 MHz, 180W RF generator was applied for stimulating the nanoparticles. The chicken breast tissue and the hepatocellular tumor model was considered in the experimental section. In histology studies, the structural changes also the effective penetration depth of RF induced nanoparticles was observed through microscopic monitoring of the tissue slices in histology observations (Gazi medical school). The highest damage level was seen in 8.0 µm tissue slices where lower damages were seen in depth of 1.0 cm and more inside tissue. The histology observations clarified the effective penetration depth of RF waves and irreversible damages in the 2.0 cm inside the tissue.


The impact of pregnancy on the individual and military organization: a postpartum active duty survey.
Using a postpartum survey, comparing singles to married, we sought to expand existing information on pregnancy occurring among active duty service women. The study instrument was a 59-question survey distributed in the initial 24 hours postpartum and collected prior to discharge. The majority affirmed that pregnancy had not changed career plans. Singles did not consider their commands supportive during pregnancy, (p=.04). Eighty-two percent of pregnancies among singles were unplanned, (p=.006). The majority of single pregnancies occurred while assigned to operational units, (p=.004); and during their first enlistment, (p<.001). Three-quarters of all singles required Women Infants and Children (WIC) financial support, (p<.001); and fewer fathers were, or planned to be involved, (p<.001). Unplanned pregnancy, contraceptive failure, and pregnancy complications highlight areas of organizational and individual concern warranting further study among active duty.


Angiogenesis and progression in human melanoma.
In tumor growth, angiogenesis, the process of new-formation of blood vessels from pre-existing ones, is uncontrolled and unlimited in time. The vascular phase is characterized by the new-formation of vascular channels that enhances tumor cell proliferation, local invasion and hematogenous metastasis. Human malignant melanoma is a highly metastatic tumor with poor prognosis, and high resistance to treatment. Parallel with progression, melanoma acquires a rich vascular network, whereas an increasing number of tumor cells express the laminin receptor, which enables their adhesion to the vascular wall, favouring tumor cell extravasation and metastases. Melanoma neovascularization has been correlated with poor prognosis, overall survival, ulceration and increased rate of relapse. Secretion of various angiogenic cytokines, i.e. VEGF-A, FGF-2, PGF-1 and -2, IL-8, and TGF-1 by melanoma cells promote the angiogenic switch and has been correlated to transition from the radial to the vertical growth phase, and to the metastatic phase. Moreover, melanoma cells overexpress alphavbeta3, alphavbeta5, alpha2beta1 and alpha5beta1 integrins and release, together with stromal cells, higher amount of metalloproteases that increasing their invasive potential and angiogenesis. Basing on these observations, different molecular targets of antiangiogenic molecules has be recognized and various antiangiogenic agents are currently in preclinical and clinical trials for melanoma.


Bacteriological and clinical studies of sulbenicillin.
A new semi-synthetic penicillin, sulbenicillin, was evaluated with regard to clinical effect on infections caused by Pseudomonas aeruginosa and other bacteria, serum concentrations obtained after intravenous administration and antibacterial spectrum, in comparison with the closely related antibiotic carbenicillin. The antibacterial spectra of sulbenicillin and carbenicillin were similar but the MIC values were lower for sulbenicillin against most of the bacterial strains tested. The serum concentrations obtained after administration of 5 g sulbenicillin were significantly higher than those obtained after 5 g carbenicillin although no significant differences in serum half-lives were observed. The clinical effect of sulbenicillin--alone or alternating with carbenicillin--on pseudomonas infections with varying localisation was found to be good in 11 and fair in 3 of 16 treated patients. Two treatment failures were cases of chronic wound infection. In addition to the pseudomonas infections, 9 of the patients also had concurrent infections with other bacteria, e.g. pencillinase-producing staphylococci and Klebsiella, and in all these cases bacterial growth was eliminated during therapy. No serious side effects were observed during sulbenicillin treatment but some of the patients developed massive growth of fungi in the urine, which disappeared after the treatment was stopped.


[Study of Interaction between Fluorinated Coating Glass and the Medicines].
The adsorption of active pharmaceutical ingredients on the surface of medical devices such as polyvinl chloride, ethylene-vinyl acetate copolymer and glass often prevent the acuurate dose of drug. At dispensing of pharmaceuticals, mètre glass (MG) has been widely used for dispensing syrup. When measuring the viscous syrup, it often takes long time to dispense the accurate volume due to their adhesiveness on the glass surface. In this study, we investigate the adhesion of various syrups to MG made with uncoated glass or glass with a strongly hydrophobic silicone or fluorinated coating in terms of the following formulation parameters: viscosity, surface tension, contact angle, and surface free energy. The contact angles for syrups on the coated glass surfaces were significantly higher than those on the uncoated glass surface. In addition, the relationship between surface tension and contact angle was examined. We found that the contact angle was independent of surface tension for the uncoated glass, while it increased with increasing surface tension for the coated glasses. These results can be explained as follows: the silicone or fluorinated coatings inhibit the hydrogen bonding that usually takes place between water and silanol and siloxane groups at glass surfaces. The coatings reduced the surface free energy and increased the hydrophobicity of the glass, reduced its wettability by the syrups, and thus reduced the adhesion loss for the syrups. It was considered that as for the hydrophobic action, properties of matter of sample influence the coated device by coating in order that it is reinforced.


A rarely seen diffuse parenchymal lung disease: diffuse pulmonary meningotheliomatosis.
Pulmonary meningothelial-like nodules (MLNs) are usually detected incidentally during pathologic evaluation of resected pulmonary parenchymal specimens and autopsies. These nodules are generally asymptomatic and most often single. Diffuse pulmonary involvement by MLNs is less frequently described. MLNs are benign lesions and have been associated with neoplastic and non-neoplastic pulmonary conditions and occasionally with extrapulmonary diseases. We report a case of a female patient presenting with multiple and bilateral pulmonary nodules diagnosed with "diffuse pulmonary meningotheliomatosis" by video-assisted thoracoscopic surgery (VATS). Diffuse pulmonary meningotheliomatosis should be included in the differential diagnosis of diffuse bilateral lung nodules in the radiologic studies.


Telomere dysfunction promotes metastasis in a TERC null mouse model of head and neck cancer.
Squamous cell carcinoma arises from highly proliferative basal layer epithelial cells, which normally divide for a short time before detaching from the basement membrane and undergoing terminal differentiation. Basal layer cells in stratified epithelia express the reverse transcriptase known as telomerase. Most human cells do not express telomerase and therefore are subject to loss of telomeric DNA with age due to the inability of lagging strand synthesis to completely replicate chromosomal ends. Late generation telomerase deficient mice exhibit signs of premature aging including reduced function of proliferating cellular compartments. We examined development of squamous cell carcinoma in a telomerase deficient murine background with long and short telomeres. G1 Terc-/- mice (long telomeres) had fewer lymph node metastases, which correlated with increased numbers of apoptotic cells in these tumors compared with wild-type mice. However, G5 Terc-/- mice with short telomeres had increased metastatic tumor burden similar to wild type mice. This increased metastasis correlated with genomic instability and aneuploidy in tumor cells from G5 Terc-/- mice. A number of similarities with human SCC were noted in the mouse model, and dramatic differences in global gene expression profiles were shown between primary and metastatic tumors. We concluded that telomere shortening promotes metastatic tumor development in a Terc null mouse model of head and neck cancer.


[Comparative hemodynamic characteristics of Soviet-made mechanical heart valve prostheses in the mitral position].
The article deals with hemodynamic evaluation of Soviet-made, and heart valve prostheses in late-term periods after operation for mitral valve replacement. Fourty-six patients were examined: a ball prosthesis was implanted in 21 patients (1st group), as disk prosthesis--in 15 patients (2nd group) and a prosthesis--in 10 patients (3rd group). A good clinical result of the operation was achieved in all patients, they were referred to functional class I and II. Catheterization of the left and right parts of the heart, left ventriculography, and test with dosed physical exertion were carried out. Loading was continued till cardiac output increased approximately by 60 per cent in 6 patients of the 1st group, 12 patients of the second group, and in all 10 patients of the 3rd group. The study showed that the prostheses do not yield to foreign models of heart valves in hemodynamic characteristics and cause a lower stenosing effect than the prostheses do. No essential differences were detected between the prostheses.


Rapid hydrogel-based phage susceptibility test for pathogenic bacteria.
Phage therapy is one alternative to cure infections caused by antibiotic resistant bacteria. Due to the narrow host range of phages, hundreds to thousands of phages are required to cover the diversity of bacterial pathogens. In personalized phage therapy, fast selection of the phages for individual patients is essential for successful therapy. The aims of this study were to set up a rapid hydrogel-based liquid phage susceptibility assay (PST) for the selection of phages for therapeutic use and to establish a "ready-to-screen" plate concept, where phages are readily stored in hydrogel as small droplets in microtiter plate wells. We first tested four commercially available hydrogels (GrowDex, Askina, Purilon, and Intrasite) for their suitability as phage matrices in PSTs with four phages, two of which infecting Escherichia coli and two Staphylococcus aureus. Of these four hydrogels, GrowDex was the best matrix for PST, as it did not inhibit bacterial growth, released phages quickly when mixed with bacterial culture, and maintained phage viability well. We then optimized the assay for both optical density and microscopy readers using GrowDex as matrix with 23 bacterial strains representing 10 different species and 23 phages possessing different morphologies and genome sizes. When the bacterial growth was monitored by microscopy reader, the PST was executed in just 3 hours, and there was no need for overnight culturing bacterial cells prior to the assay, whereas using optical density reader, bacteria had to be pre-cultured overnight, and the assay time was five hours. Finally, we evaluated the effect of three different chemical stabilizers (trehalose, hyaluronic acid, and gelatin) in a six-month stability assay with six model phages. These phages assay behaved very differently in respect to the chemical stabilizers, and there was not a single stabilizer suitable for all phages. However, when gelatin (0.01%) or hyaluronic acid (0.2 mg/ml) was used as stabilizer, all tested phages were still considered as positives in PST after a six-month storage in 1 ml volume. In "ready-to-screen" plates, the differences in phage stabilities were even more profound, varying from two to six months for the most and least stable phages, respectively.


Pharmacokinetics and clinical predictors of surfactant redosing in respiratory distress syndrome.
Limited data are available on predictors for surfactant retreatment in preterm infants with respiratory distress syndrome (RDS). To study the pharmacokinetics of exogenous surfactant and the clinical parameters associated with surfactant redosing. Exogenous surfactant pharmacokinetics was studied in 125 preterm infants (birth weight 997 ± 432 g; gestational age 28.0 ± 2.6 weeks) with moderate to severe RDS requiring mechanical ventilation. Clinical and respiratory parameters were recorded hourly, and surfactant disaturated-phosphatidylcholine (DSPC) half-life, pool size, and endogenous synthesis were calculated by stable isotope tracing of surfactant DSPC isolated from serial tracheal aspirates. Univariate and multiple logistic regression were used to study the effects of clinical and surfactant kinetic variables on the need for redosing. Fifty-three infants (42.4%) received one dose, 51 (40.8%) two doses, and 21 (16.8%) three doses. Median (interquartile range, IQR) DSPC half-life was 21 (13-39), 11 (7-17), and 10 (7-16) h after the first, second, and third dose, respectively (p = 0.07). Univariate analysis showed a significantly shorter DSPC half-life in infants requiring more surfactant doses. On logistic analysis, risk of redosing was higher with lower birth weight, worse radiological score, shorter DSPC half-life, and surfactant dose of 100 mg/kg, whilst it was lower with elective high-frequency ventilation at time of intubation, instead of conventional ventilation. When optimizing surfactant replacement therapy and its cost-benefit ratio, pharmacokinetics and clinical variables associated with need of redosing should be taken into account.


Venous thromboembolism following vigorous deep tissue massage.
Venous thromboembolism (VTE) is an increasing public health concern, in part because of lack of awareness among patients and physicians. Nonpenetrating trauma to the legs may be an under-recognized potential risk factor for VTE. We report a case of VTE following vigorous deep tissue massage in a previously healthy 67-year-old man with no other identifiable risk factors. The etiology, risk factors, and implications for the prevention and detection of VTE are reviewed. There are few other published reports of VTE associated with massage, but under-reporting seems likely. Vigorous massage or any equivalent trauma to the legs should be considered and evaluated as a possible risk factor for VTE, especially in older adults. Additional research is needed to clarify the risks associated with nonpenetrating trauma to the legs in older adults and other susceptible groups. Improved awareness of VTE, including its risk factors and symptoms, is an urgent priority for more effective prevention, detection, and treatment.


Pretreatment lymphocyte-monocyte ratio as a potential prognostic factor in a cohort of patients with upper tract urothelial carcinoma.
To investigate the potential prognostic impact of the lymphocyte-monocyte ratio (LMR) in a large European cohort of patients with localised upper urinary tract urothelial carcinoma (UTUC). The LMR as an indicator of systemic inflammatory response has been shown to represent a potential prognostic factor in various types of human cancers. Up to date, the prognostic significance of the LMR in UTUC has not been evaluated. Clinico-pathological data from 182 non-metastatic patients with UTUC, operated between 1990 and 2012 at a single tertiary academic centre, were evaluated retrospectively. Pretreatment LMR was assessed 1 day before surgery. Patients were categorised using an LMR cut-off value of 2.0 according to a calculation by receiver-operating curve analysis. Patients' overall survival (OS) was assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the LMR, a multivariate proportional Cox regression model was applied for OS. In multivariate analyses, age on the date of surgery (<65 vs ≥65 years, HR=2.10, 95% CI 1.22 to 3.64), pathological T-stage (pT1 vs pT2-4, HR=2.15, 95% CI 1.26 to 3.67), as well as the LMR (<2 vs ≥2, HR=0.56, 95% CI 0.35 to 0.92) were independent predictors of OS of patients with UTUC. In the cohort studied, patients with an elevated (≥2) preoperative LMR had a subsequently longer OS after radical surgery for UTUC, compared with those with a low (<2) preoperative LMR. Thus, we believe this parameter might be considered an additional prognostic factor in UTUC in the future.


Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli.
The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including beta-lactams. However, the kinetic constants of the efflux process, needed for the quantitative understanding of resistance, were not available until those accompanying the efflux of some cephalosporins were recently determined by combining efflux with the hydrolysis of drugs by the periplasmic beta-lactamase. In the present study we extended this approach to the study of a wide range of penicillins, from ampicillin and penicillin V to ureidopenicillins and isoxazolylpenicillins, by combining efflux with hydrolysis with the OXA-7 penicillinase. We found that the penicillins had a much stronger apparent affinity to AcrB and higher maximum rates of efflux than the cephalosporins. All penicillins showed strong positive cooperativity kinetics for export. The kinetic constants obtained were validated, as the MICs theoretically predicted on the basis of efflux and hydrolysis kinetics were remarkably similar to the observed MICs (except for the isoxazolylpenicillins). Surprisingly, however, the efflux kinetics of cloxacillin, for example, whose MIC decreased 512-fold in Escherichia coli upon the genetic deletion of the acrB gene, were quite similar to those of ampicillin, whose MIC decreased only 2-fold with the same treatment. Analysis of this phenomenon showed that the extensive decrease in the MIC for the acrB mutant is primarily due to the low permeation of the drug and that comparison of the MICs between the parent and the acrB strains is a very poor measure of the ability of AcrB to pump a drug out.


Impact of variability in baseline pain on the placebo response in randomized, placebo-controlled, crossover trials in peripheral neuropathic pain.
Large placebo responses often negatively affect randomized controlled trials within the pain area. Understanding different possible factors that influence the placebo response is therefore important. In this retrospective analysis, we hypothesized that a large variability in baseline pain score would predict a greater placebo response and analyzed the impact of the coefficient of variation, SD, and difference between the highest and lowest numeric rating scale (NRS) score at baseline on the placebo response. A total of 160 observations on placebo response from 3 controlled clinical trials with a crossover design were included in this study. In general, the placebo response was low with a mean reduction in pain intensity of 0.5 points (range -5 to 7) measured on a 0 to 10 point NRS, and only 15% were placebo responders as defined by more than 30% reduction in NRS pain score from baseline to the end of the placebo treatment period. We found no significant impact of baseline pain coefficient of variation, SD, or the difference between lowest and highest baseline pain score on the placebo response. Placebo response in one trial did not predict placebo response in another trial. A large placebo response was not associated with a large treatment response. In conclusion, in this retrospective data analysis, there was no impact of baseline pain variability on the placebo response in controlled clinical trials with a crossover design in patients with peripheral neuropathic pain.


Incidence and case fatality rates of first-ever stroke in a black Caribbean population: the Barbados Register of Strokes.
Estimation of stroke incidence among black populations outside the USA and the UK has been hampered by the lack of community-based studies. We aimed to document the incidence of first-ever stroke in Barbados, a Caribbean island with a population of 268,000 people. A national community-based prospective register of first-ever strokes, using multiple overlapping sources of notification, was established. During the first year, 352 patients (95.2% black) were registered, 142 males and 210 females (59.7%), with a mean age of 72.5 years (range 24 to 104; SD 14.8). Cerebral infarction (IS) occurred in 81.8%, intracerebral hemorrhage (ICH) in 11.9%, subarachnoid hemorrhage (SAH) in 2.0%, whereas 4.3% of strokes were unclassified (UC). The crude annual incidence rate for the black population was 1.40 (95% CI: 1.25,1.55) per 1000 (1.35 standardized to the European population) for all strokes, 1.20 (1.07,1.34) for IS, 0.18 (0.12,0.23) for ICH, and 0.03 (0.01,0.05) for SAH. Lacunar infarction (LACI) accounted for 50.7% of IS among the black population, whereas 15.6% and 26.8% were caused by total anterior circulation infarction (TACI) and partial anterior circulation infarction (PACI), respectively. At 7 and 28 days, respectively, case fatality rates for blacks were 13.1% and 27.8% for all strokes, 46.3% and 58.5% for ICH, 7.6% and 21.7% for IS, 32.6% and 65.1% for TACI, and 2.1% and 9.0% for LACI. Stroke incidence among the black population of Barbados is lower than among African-origin populations in the USA and UK. Lacunar infarction is the predominant stroke subtype.


Kinetics of the reactions of Cl atoms with several ethers.
The reactions of Cl with tetrahydrofuran, tetrahydropyran, and dimethyl ether have been studied as a function of temperature, pressure, and O(2) concentration. The temperature was varied from approximately 280 to 360 K, the mole fraction of O(2) ranged from zero to approximately 0.6, and the experiments were made in a bath of argon at total pressures ranging from approximately 300 to 760 Torr. The rate coefficients were measured using the relative rate method with gas chromatographic analysis. The reaction of Cl with isobutane was the reference reaction, the rate coefficients for which were calibrated against the reaction of propane with chlorine atoms as a function of temperature. The rate coefficients were unaffected by the concentration of O(2) or by variation in pressure. The rate coefficient for the reaction of Cl with isobutane increased slightly with decreasing temperature. This weak temperature dependence of the rate coefficient was in satisfactory agreement with information in the literature and is represented in Arrhenius form by k(T) = (1.02(-0.25)(+0.32)) x 10(-10) exp(99 +/- 88/T) cm(3) molecule(-1) s(-1), where the uncertainties represent two standard deviations. The rate coefficients for the reactions of Cl with the ethers did not show a statistically significant dependence on temperature. Their average values over our range of temperature are: for Cl + tetrahydrofuran, k = (2.71 +/- 0.34) x 10(-10) cm(3) molecule(-1) s(-1); for Cl + tetrahydropyran, k = (2.03 +/- 0.82) x 10(-10) cm(3) molecule(-1) s(-1); and for Cl + dimethyl ether, k = (1.73 +/- 0.22) x 10(-10) cm(3) molecule(-1) s(-1), in which the uncertainties are again two standard deviations.


Iron and hepcidin: a story of recycling and balance.
To avoid iron deficiency and overload, iron availability is tightly regulated at both the cellular and systemic levels. The liver peptide hepcidin controls iron flux to plasma from enterocytes and macrophages through degradation of the cellular iron exporter ferroportin. The hepcidin-ferroportin axis is essential to maintaining iron homeostasis. Genetic inactivation of proteins of the hepcidin-activating pathway causes iron overload of varying severity in human and mice. Hepcidin insufficiency and increased iron absorption are also characteristic of anemia due to ineffective erythropoiesis in which, despite high total body iron, hepcidin is suppressed by the high erythropoietic activity, worsening both iron overload and anemia in a vicious cycle. Hepcidin excess resulting from genetic inactivation of a hepcidin inhibitor, the transmembrane protease serine 6 (TMPRSS6) leads to a form of iron deficiency refractory to oral iron. Increased hepcidin explains the iron sequestration and iron-restricted erythropoiesis of anemia associated with chronic inflammatory diseases. In mice, deletion of TMPRSS6 in vivo has profound effects on the iron phenotype of hemochromatosis and beta-thalassemia. Hepcidin manipulation to restrict iron is a successful strategy to improve erythropoiesis in thalassemia, as shown clearly in preclinical studies targeting TMPRSS6; attempts to control anemia of chronic diseases by antagonizing the hepcidin effect are ongoing. Finally, the metabolic pathways identified from iron disorders are now being explored in other human pathologic conditions, including cancer.


The expression and differentiation pattern of cell antigens and adhesion molecules on the nonadherent cell population in canine long-term marrow culture: a biphasic development of myeloid and lymphoid cells.
During maturation of normal hematopoietic progenitors, there appears to be differentiation-dependent expression of adhesion receptors, which may contribute to the homing and lodging of stem progenitor cells into the marrow and for the eventual release of mature effector cells from the marrow cavity. Using a model of long-term marrow culture, we studied the expression pattern of different lineage cell antigens and cell adhesion molecules on the nonadherent cells in canine long-term marrow culture. CD4+ cells became a major proportion of both the small and large cell subsets by day 8 of culture. Small CD4+ cells, the majority of which are negative for other T-cell antigens during the first 2 weeks of culture, express low levels of CD4 (CD4lo) and coexpress granulocytic and/or monocytic markers. These CD4lo cells have progenitor potential as measured by the long-term culture-initiating cell assay and differentiate into myeloid (first wave) and lymphoid (second wave) cells. The T cells, which appear in 2-week-old long-term marrow culture, respond to Con A but not to alloantigen. At the same time, most of the large cells are CD14+, CD11b+, DLA-DR+ and CD4lo+, while granulocytes are not observed. This phenotypic pattern closely resembles that found on myelomonocytic cells developing from fetal thymic and fetal liver CD34+ precursors in a model of human fetal thymic organ culture. The cell adhesion molecules--CD44, CD18, L-selectin, CD11a-c as well as VLAalpha4, dramatically increase from the first week of long-term marrow culture, while ICAM-1 and a new beta2 cell adhesion molecule, alpha dbeta2, increased slightly from the third week on. In the large ("monocytic") cell population, alpha dbeta2 was exclusively expressed by CD4+ cells. The differentiation pattern of T-cell antigens and adhesion molecules seen in the canine long-term marrow culture appear to mimic those required for developmental interactions between leukocytes and endothelial cells; that is, an early expression of L-selectin and CD44, followed by the integrins, and later on by ICAM-1 and alpha dbeta2. Our data support the view that in a model of canine long-term marrow culture hematopoietic precursors retain their intrinsic developmental potential.


Coping with the consequences of short-term illness shocks: The role of intra-household labor substitution.
In developing countries where medical infrastructure, service delivery systems, and the markets for health insurance are underdeveloped, one important mechanism to cope with the consequences of health shocks is the intra-household substitution of labor. This paper studies the impact of short-term illness shocks on labor supply and wage earnings of prime-aged individuals using data from agricultural households in India. It also documents the compensating intra-household labor supply responses of other non-ill members of the household. We find that an illness shock reduces an individual's monthly wage earnings by 7.1% via the decline in the individual's days of employment in the labor market. Further, an illness shock to the household head causes a compensating increase in the wage labor supply of the wife. An illness shock to the wife, however, induces the household head to devote more time to domestic activities. The compensating labor supply responses are only partially able to insure the loss in total wage income of the household. Our results indicate that the gender-based specialization of labor weakens in the event of an illness shock.


Dilemmas in the management of osteoporosis.
Fragility fracture is the clinically apparent and relevant outcome in osteoporosis. Osteoporotic fragility fractures occur most commonly in the vertebrae, hip and wrist, and are associated with substantial disability, pain and reduced quality of life. It is estimated that more than 2 million women have osteoporosis in England and Wales. In the UK, there are over 300,000 fractures each year, causing severe pain and disability to individuals at an estimated annual cost to the NHS of over £1.73 billion. As a result of increased bone loss after the menopause in women, and age-related bone loss in both women and men, the prevalence of osteoporosis increases markedly with age, from 2% at 50 years to more than 25% at 80 years in women. Despite the development of a number of guidelines for the diagnosis and treatment of osteoporosis, management of the condition is not straightforward. Here we provide a reminder of some specific dilemmas facing generalists in regards to the management of osteoporosis, including diagnosis and investigation for reversible secondary causes; the effectiveness and duration of pharmacological management with oral bisphosphonates; and the role of calcium and vitamin D.


Characterization of tissue-derived macromolecules affecting transmitter synthesis in rat spinal cord neurons.
Rat spinal cord cells maintained in neuron-rich cultures were exposed to extracts of skeletal muscle or to medium conditioned by non-neuronal cells. The conditioned media enhanced neuronal acetylcholine (ACh) synthesis, choline acetyltransferase activity, and protein synthesis, and decreased gamma-aminobutyric acid (GABA) synthesis. Muscle extract prepared from newborn rats produced similar enhancements but did not depress GABA synthesis. Muscle extracts prepared from normal and denervated adult rat limbs contained relatively little activity. These results suggest that different molecular factors might mediate the effects on GABA and ACh synthesis. Gel filtration of conditioned media and muscle extracts revealed that all of these activities were confined to a macromolecular fraction with an apparent Mr of 40,000. These tissue-derived factors affecting neuronal protein and transmitter synthesis are in turn distinct from a neuronal survival-promoting factor obtained from serum (Kaufman, L. M., and J. N. Barrett (1983) Science 220: 1394-1396).


Radiology utilization in the emergency department: trends of the past 2 decades.
The objective of our study was to assess radiology utilization trends for emergency department (ED) patients from 1993 through 2012. For this retrospective study, we reviewed radiology utilization at a 793-bed quaternary care academic medical center from January 1, 1993, through December 31, 2012, during which time the number of ED patient visits increased from approximately 48,000 to 61,000, and determined the number of imaging studies by modality (radiography, sonography, CT, MRI, other) and associated relative value units (RVUs). We used linear regression to assess for trends in the number of imaging RVUs and imaging accession numbers, our primary and secondary outcomes, respectively. The total RVUs attributable to ED imaging per 1000 ED visits increased 208% from 1993 to 2007 (p < 0.0001) and then decreased 24.7% by 2012 (p = 0.0019). The total number of imaging accession numbers per 1000 ED visits increased 47.8% from 1993 until 2005 (p = 0.0003) and then decreased 26.9% by 2012 (p < 0.0001). CT RVUs per 1000 ED visits increased 493% until 2007 (p < 0.0001) and then decreased 33.4% (p < 0.0001), and MRI RVUs increased 2475% until 2008 (p < 0.0001) and then decreased 20.6% (p < 0.0032). Sonography RVUs increased 75.7% over the study period (p < 0.0001), whereas radiography RVUs decreased 28.1% (p = 0.0009). After a period of substantial increase from 1993 to 2007, volume-adjusted ED imaging RVUs declined from 2007 through 2012, largely because of the decreasing use of CT and MRI. Additional studies are needed to determine the causes of this decline, which may include quality improvement activities, advocacy for appropriateness by leadership, concerns regarding radiation exposure and cost, and health information technology interventions.


Analysis and characterization of photo-plethysmographic signal.
Qualitative assessment of the overall clinical status of the subject and characterization of complex cardiovascular dynamics from digital blood volume pulsations measured noninvasively using a photo-plethysmographic device is addressed. A novel concept is employed to detect the dominant nonsinusoidal periodicity embedded in the data series and to extract the associated periodic component. The detection and the extraction of periodic component is performed with moving window to accommodate the variations of the physiological oscillations. The covariance matrix formed by the gradually varying pattern is used as a simple measure of qualitative assessment. Further, the characterization of the underlying system in the light of nonlinear dynamical analysis is also presented. The stable subjects are shown to behave as a low-dimensional system whereas the diseased subjects exhibit comparatively high dimensional activity.


Exploring the Role of TaPLC1-2B in Heat Tolerance at Seedling and Adult Stages of Wheat through Transcriptome Analysis.
Heat stress is a major abiotic stress that can cause serious losses of a crop. Our previous work identified a gene involved in heat stress tolerance in wheat, TaPLC1-2B. To further investigate its mechanisms, in the present study, TaPLC1-2B RNAi-silenced transgenic wheat and the wild type were comparatively analyzed at both the seedling and adult stages, with or without heat stress, using transcriptome sequencing. A total of 15,549 differentially expressed genes (DEGs) were identified at the adult stage and 20,535 DEGs were detected at the seedling stage. After heat stress, an enrichment of pathways such as phytohormones and mitogen-activated protein kinase signaling was mainly found in the seedling stage, and pathways related to metabolism, glycerophospholipid metabolism, circadian rhythms, and ABC transporter were enriched in the adult stage. Auxin and abscisic acid were downregulated in the seedling stage and vice versa in the adult stage; and the MYB, WRKY, and no apical meristem gene families were downregulated in the seedling stage in response to heat stress and upregulated in the adult stage in response to heat stress. This study deepens our understanding of the mechanisms of TaPLC1-2B in regard to heat stress in wheat at the seedling and adult stages.