Comparison of dynamic electromyographic analysis of masticatory capsules with materials of different textures.
The aim of this study was to compare the mastication electromyographic indexes of capsules used for the masticatory efficiency evaluation "ME-mastig" and of materials of different textures (gum, raisins, and peanuts). Thirty young, healthy, adult subjects, with an average age of 23.46 years old, with no symptoms of temporomandibular dysfunction (TMD), confirmed by the clinical exam, RDC/TMD, and the static test of electromyography (EMG) were chosen. Afterward, dynamic tests were performed (bilateral mastication of the compounds) to determine number of chewing cycles (CYCLES); masticatory frequency (FREQ); SMI (symmetrical masticatory index - corresponding to the value of neuromuscular coordination during mastication); and IMPACT (corresponding to impact - total electromyographic activity performed by the system during chewing). Cycle and frequency were similar. Regarding SMI and IMPACT, the raisin, the capsule, and the peanut were similar between each other, and different from the gum. Masticatory capsules and the natural foods with different textures had similar results regarding EMG indexes.


Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration.
Monocytes, macrophages, dendritic cells and microglia play critical roles in the local immune response to acute and chronic tissue injury and have been implicated in the pathogenesis of age-related macular degeneration. Defects in Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling cause enhanced accumulation of bloated subretinal microglia/macrophages in senescent mice and this phenomenon is reported to result in the acceleration of age-related retinal degeneration. The purpose of this study was to determine whether defects in CCL2-CCR2 and CX3CL1-CX3CR1 signalling pathways, alone or in combination, cause age-dependent retinal degeneration. We tested whether three chemokine knockout mouse lines, Ccl2(-/-), Cx3cr1(-/-) and Ccl2(-/-)/Cx3cr1(-/-), in comparison to age-matched C57Bl/6 control mice show differences in subretinal macrophage accumulation and loss of adjacent photoreceptor cells at 12-14 months of age. All mouse lines are derived from common parental strains and do not carry the homozygous rd8 mutation in the Crb1 gene that has been a major confounding factor in previous reports. We quantified subretinal macrophages by counting autofluorescent lesions in fundus images obtained by scanning laser ophthalmoscopy (AF-SLO) and by immunohistochemistry for Iba1 positive cells. The accumulation of subretinal macrophages was enhanced in Ccl2(-/-), but not in Cx3cr1(-/-) or Ccl2(-/-)/Cx3cr1(-/-) mice. We identified no evidence of retinal degeneration in any of these mouse lines by TUNEL staining or semithin histology. In conclusion, CCL2-CCR2 and/or CX3CL1-CX3CR1 signalling defects may differentially affect the trafficking of microglia and macrophages in the retina during ageing, but do not appear to cause age-related retinal degeneration in mice.


The evolution of HoxD-11 expression in the bird wing: insights from Alligator mississippiensis.
Comparative morphology identifies the digits of the wing of birds as 1,2 and 3, but they develop at embryological positions that become digits 2, 3 and 4 in other amniotes. A hypothesis to explain this is that a homeotic frame shift of digital identity occurred in the evolution of the bird wing, such that digits 1,2 and 3 are developing from embryological positions 2, 3 and 4. Digit 1 of the mouse is the only digit that shows no late expression of HoxD-11. This is also true for the anterior digit of the bird wing, suggesting this digit is actually a digit 1. If this is the case, we can expect closer relatives of birds to show no HoxD-11 expression only in digit 1. To test this prediction we investigate HoxD-11 expression in crocodilians, the closest living relatives of birds. Using degenerate primers we cloned a 606 nucleotide fragment of exon 1 of the alligator HoxD-11 gene and used it for whole-mount in-situ detection in alligator embryos. We found that in the pentadactyl forelimbs of alligator, as in the mouse, late expression of HoxD-11 is absent only in digit 1. The ancestral condition for amniotes is that late-phase HoxD-11 expression is absent only in digit 1. The biphalangeal morphology and lack of HoxD-11 expression of the anterior digit of the wing is like digit 1 of alligator and mouse, but its embryological position as digit 2 is derived. HoxD-11 expression in alligator is consistent with the hypothesis that both digit morphology as well as HoxD-11 expression are shifted towards posterior in the bird wing.


Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum.
Neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDDs) with a specific biomarker, aquaporin-4-immunoglobulin G (AQP4-IgG). Prior NMO/NMOSD epidemiological studies have been limited by lack of AQP4-IgG seroprevalence assessment, absence of population-based USA studies, and under-representation of blacks. To overcome these limitations, we sought to compare NMO/NMOSD seroepidemiology across 2 ethnically divergent populations. We performed a population-based comparative study of the incidence (2003-2011) and prevalence (on December 31, 2011) of NMO/NMOSD and AQP4-IgG seroincidence and seroprevalence (sera collected in 80-84% of IDD cases) among patients with IDD diagnosis in Olmsted County, Minnesota (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean]). AQP4-IgG was measured by M1 isoform fluorescence-activated cell-sorting assays. The age- and sex-adjusted incidence (7.3 vs 0.7/1,000,000 person-years [p < 0.01]) and prevalence (10 vs 3.9/100,000 [p = 0.01]) in Martinique exceeded that in Olmsted County. The AQP4-IgG age- and sex-adjusted seroincidence (6.5 vs 0.7/1,000,000 person-years [p < 0.01]) and seroprevalence (7.9 vs 3.3/100,000 [p = 0.04]) were also higher in Martinique than Olmsted County. The ethnicity-specific prevalence was similar in Martinique and Olmsted County: 11.5 and 13/100,000 in blacks, and 6.1 and 4.0/100,000 in whites, respectively. NMO/NMOSD represented a higher proportion of IDD cases in Martinique than Olmsted County (16% vs 1.4%; p < 0.01). The onset age (median = 35-37 years) and female:male distribution (5-9:1) were similar across both populations; 60% of prevalent cases were either blind in 1 eye, dependent on a gait aid, or both. This study reports the highest prevalence of NMO/NMOSD in any population (10/100,000 in Martinique), estimates it affects 16,000 to 17,000 in the USA (higher than previous predictions), and demonstrates it disproportionately affects blacks. Ann Neurol 2016;79:775-783.


Spatial frequencies or emotional effects? A systematic measure of spatial frequencies for IAPS pictures by a discrete wavelet analysis.
The influence of the emotional attributes of a visual scene on early perception processes remains a key question in contemporary affective neurosciences. The International Affective Picture System (IAPS; Lang et al., 2005) was developed to provide a set of standardized stimuli for experimental investigations of emotional processes. These stimuli have been widely used in brain activity investigations to study the influence of valence and/or arousal on visual processing. However, visual perception is strongly influenced by the physical properties of the images shown, especially their spatial frequency content, an aspect that has been unexpectedly neglected at large. In this study, we examine the complete set of IAPS with a discrete wavelet transform to highlight relations between the energy in different spatial frequencies and the emotional features of the pictures. Our results showed that these associations are weak when the complete dataset is considered, but for selected subsets of pictures, clear differences are present in both affective and spatial frequency content. The IAPS remains a powerful tool to explore emotional processing, but we strongly suggest that researchers use subsets of images that are controlled for the energy of their spatial frequencies when investigating emotional influence on visual processing.


Multiple tumor-suppressor-1 gene and esophageal-carcinoma.
The multiple tumor suppressor 1 (MTS1) gene is homozygously deleted frequently in cell lines derived from a wide variety of tumors. We investigated the deletion of the MTS1 gene in esophageal cancer cell lines and primary esophageal squamous carcinomas using the polymerase chain reaction. Sixteen and 15 of 23 esophageal cancer cell lines showed homozygous deletion of MTS1 exon 1 and exon 2, respectively, while none of 21 primary esophageal carcinomas showed the deletion. An analysis of MTS1 gene mutations was carried out by direct DNA sequencing in 8 cell lines and 21 primary carcinomas showing no homozygous deletion. In contrast to previous reports of esophageal carcinoma, there were no mutations recognized in the region sequenced. Our study suggests that the inactivation of the MTS 1 gene may play an important role in esophageal carcinoma cell lines but may be less important in primary carcinomas of the human esophagus.


[Adhesive intercellular interactions].
The process of intercellular interactions during morphogenesis, inflammation and malignant growth are considered from the point of view of possible intercellular contacts provided by cell adhesion molecules. The system analysis of different cell adhesion molecules classes? their structure and influence on functional cell activity is performed. Clinical importance of expression disturbances of cell adhesion molecules at various pathological processes is considered.


Multisensory integration in cortical regions responding to locomotion-related visual and somatomotor signals.
During real-world locomotion, in order to be able to move along a path or avoid an obstacle, continuous changes in self-motion direction (i.e. heading) are needed. Control of heading changes during locomotion requires the integration of multiple signals (i.e., visual, somatomotor, vestibular). Recent fMRI studies have shown that both somatomotor areas (human PEc [hPEc], human PE [hPE], primary somatosensory cortex [S-I]) and egomotion visual regions (cingulate sulcus visual area [CSv], posterior cingulate area [pCi], posterior insular cortex [PIC]) respond to either leg movements and egomotion-compatible visual stimulations, suggesting a role in the analysis of both visual attributes of egomotion and somatomotor signals with the aim of guiding locomotion. However, whether these regions are able to integrate egomotion-related visual signals with somatomotor inputs coming from leg movements during heading changes remains an open question. Here we used a combined approach of individual functional localizers and task-evoked activity by fMRI. In thirty subjects we first localized three egomotion areas (CSv, pCi, PIC) and three somatomotor regions (S-I, hPE, hPEc). Then, we tested their responses in a multisensory integration experiment combining visual and somatomotor signals relevant to locomotion in congruent or incongruent trials. We used an fMR-adaptation paradigm to explore the sensitivity to the repeated presentation of these bimodal stimuli in the six regions of interest. Results revealed that hPE, S-I and CSv showed an adaptation effect regardless of congruency, while PIC, pCi and hPEc showed sensitivity to congruency. PIC exhibited a preference for congruent trials compared to incongruent trials. Areas pCi and hPEc exhibited an adaptation effect only for congruent and incongruent trials, respectively. PIC, pCi and hPEc sensitivity to the congruency relationship between visual (locomotion-compatible) cues and (leg-related) somatomotor inputs suggests that these regions are involved in multisensory integration processes, likely in order to guide/adjust leg movements during heading changes.


Changes in the surface membrane during myoblast fusion.
1. During fusion of chick-embryo myoblasts in culture, the surface membrane is affected as follows. Uptake of 2-aminoisobutyrate and 2-deoxyglucose, each of which is concentrated 20-fold relative to its concentration in the medium, is unaltered; uptake of alpha-methyl glucoside and choline (15 mM), each of which equilibrates relative to its concentration in the medium, approximately doubles. An approximate doubling also occurs in iodinatable surface protein (and in total protein) and in cell surface area as judged by light-microscopy. Adenylate cyclase (in the absence or the presence of fluoride) increases by more than 2-fold. 2. It is concluded that, during myoblast fusion cells increase in size, and this is reflected in an increased rate of simple diffusion; the rate of facilitated processes such as the uptake of amino acids and sugars, on the other hand, remains unaltered, though the activity of certain enzymes is increased. These results indicate that specific changes in the function of surface membrane occur during myoblast fusion in vitro.


Saccharomyces cerevisiae expresses three functionally distinct homologues of the nramp family of metal transporters.
The baker's yeast Saccharomyces cerevisiae expresses three homologues of the Nramp family of metal transporters: Smf1p, Smf2p, and Smf3p, encoded by SMF1, SMF2, and SMF3, respectively. Here we report a comparative analysis of the yeast Smf proteins at the levels of localization, regulation, and function of the corresponding metal transporters. Smf1p and Smf2p function in cellular accumulation of manganese, and the two proteins are coregulated by manganese ions and the BSD2 gene product. Under manganese-replete conditions, Bsd2p facilitates trafficking of Smf1p and Smf2p to the vacuole, where these transport proteins are degraded. However, Smf1p and Smf2p localize to distinct cellular compartments under metal starvation: Smf1p accumulates at the cell surface, while Smf2p is restricted to intracellular vesicles. The third Nramp homologue, Smf3p, is quite distinctive. Smf3p is not regulated by Bsd2p or by manganese ions and is not degraded in the vacuole. Instead, Smf3p is down-regulated by iron through a mechanism that does not involve transcription or protein stability. Smf3p localizes to the vacuolar membrane independently of metal treatment, and yeast cells lacking Smf3p show symptoms of iron starvation. We propose that Smf3p helps to mobilize vacuolar stores of iron.


Amplifier design considerations for blood cell counter sampling probes.
Blood cell counters that operate on the Coulter principle of an electrical resistance change when a cell passes through a small sampling orifice are especially sensitive to electrical noise. The sampling probe is immersed in an electrolyte (isotonic diluent for blood cells), which in itself presents an electrochemically noisy environment. The probe, owing to its large size, acts as an antenna for environmental electrical noise up to 60 Hz. Additionally, the basic Coulter method for cell counting requires a dc potential across the sampling orifice electrodes contained within the probe. This potential produces electrolysis of the diluent and generation of gas bubbles at the electrode surfaces. Sampling (counting) time must be short (less than 30 seconds) to avoid sample heating and an intolerably high noise level as a consequence of ionic motion and gas bubble generation. The resistance change that takes place when a cell passes through the sampling orifice is only a small fraction of a percent, thus noise is a serious problem. Electric noise produces false counts and general degradation of counting function. This paper presents a discussion of a currently used method for signal acquisition and some of the problems encountered in the clinical laboratory. A novel alternative design has been implemented using integrated circuit components, which eliminates many of the problems associated with the use of small bench-type counters. Design philosophy is discussed in detail including presentation of the final circuitry developed. Performance characteristics of the signal acquisition circuitry are presented.(ABSTRACT TRUNCATED AT 250 WORDS)


The clinical and economic burden after an osteoporosis fracture in France: a nationwide population-based study.
Osteoporosis-related fragility fractures increase the risk of subsequent fractures and are associated with substantial morbidity and mortality. Emphasis should be placed on the prevention of recurrent fractures, which will decrease both the clinical burden on patients and the economic burden on the health system. Fragility fractures are associated with increased morbidity and mortality. Quantifying the clinical and economic burden of subsequent fractures following an initial osteoporosis-related fracture is a key to informing public health policies. A retrospective cohort study, using the national French health insurance claims database. Males and females ≥ 50 years, with a hospital discharge diagnosis of osteoporosis with fracture or a relevant fragility fracture (hip, vertebrae, femur, pelvis, wrist/hand, forearm, humerus/clavicle) between 2011 and 2014, were included and followed until death or end of 2016, whichever came first. Index fracture was the first qualifying hospitalization; subsequent fractures were defined as those occurring either at a different site from the index fracture or at the same site ≥ 90 days apart. Costs abstracted included hospitalization, external consultation, outpatient visits, and treatment. A total of 544,426 participants (132,148 [24.3%] males and 412,278 [75.7%] females), of whom 16,110 (12.2%) males and 73,538 (17.8%) females had at least one subsequent fracture during follow-up, were included. Incidence of subsequent fracture was highest in the first year following index fracture. During follow-up, 161,179 patients died; mortality was highest among those with a hip fracture at index (29,971 (51.6%) males and 65,254 (39.6%) females). Total mean costs per patient in the year following index fracture were highest for males and females with a hip fracture (€18,585 and €15,754, respectively). Subsequent fractures among osteoporotic participants with an initial fracture result in increased clinical mortality and high healthcare resource use. Emphasis should be placed on the prevention of recurrent fractures.


[Diet or health--the linkage between vegetarianism and anorexia nervosa].
Vegetarianism in its various forms, is widely encountered in different societies all over the world; thus, combining nutritional, social, behavioral and psychological aspects. The prevalence of vegetarianism in the western world, as well as in Israel, is dealt with in this review. The extent of vegetarianism among young patients with eating disorders is much higher than in any other age group. Anorexia nervosa patients in Israel admit to be vegetarians in 85% (mean), as compared to 65% (mean) in other western countries. The last three decades abound with nutritional messages concerning healthy life styles. Food Pyramids recommend meat avoidance as a remedy and promise for longevity. This reason for abstaining from meat has led to the adoption of vegetarian diets in grownups. All age groups have mastered the "Vegi" trend, and mostly young girls. They express feelings of disgust especially towards red meat. Despite the knowledge gained by the public about the linkage between diet and health, the proportion of patients suffering from eating disorders is rising. There seems to be a direct connection between the "Vegi" fashion of the teenagers and eating disorders which start typically in adolescence. Many surveys point to the abuse of vegetarianism as a mask for weight control. The vegetarian diet, a selective way of eating, might precede different eating disorders and increase the risk of developing anorexia nervosa.


Swimming Upstream: Creating a Culture of High-Value Care.
As health system leaders strategize the best ways to encourage the transition toward value-based health care, the underlying culture-defined as a system of shared assumptions, values, beliefs, and norms existing within an environment-continues to shape clinician practice patterns. The current prevailing medical culture contributes to overtesting, overtreatment, and health care waste. Choosing Wisely lists, appropriateness criteria, and guidelines codify best practices, but academic medicine as a whole must recognize that faculty and trainees are all largely still operating within the same cultural climate. Addressing this culture, on both local and national levels, is imperative for engaging clinicians in reforms and creating sustained changes that will deliver on the promise of better health care value. This Perspective outlines four steps for health system leaders to understand, cultivate, and maintain cultural changes toward value-based care: (1) Build the will for change through engaging frontline providers and communicating patient-centered motivations for health care value; (2) create necessary infrastructure to support value improvement efforts; (3) expose physicians to value-based payment structures; and (4) demonstrate leadership commitment and visibility to shared goals. The authors support their recommendations with concrete examples from emerging models and leaders across the country.


[Proteins sharing PNPLA domain, a new family of enzymes regulating lipid metabolism].
Genome sequencing technologies led to tremendous breakthrough in biology uncovering numerous genes unknown so far and thus opening the field of deep investigations to understand their associated biological functions. As a matter of fact, functional genomics have been progressively replacing sequence genomics with as a main objective to yield insight into cellular physiology. Recently, an emerging group of genes coding for proteins bearing a common domain termed patatin (PNPLA domain) have been discovered. Members of this new enzymatic family displaying lipase and transacylase properties appeared to have major roles in the regulation of lipid metabolism. The aim of this review is to make an overview on the latest discoveries concerning this new family of proteins and their relationship with lipid metabolism, physiology of mammals and their potential involvement in human pathology.


Calorie restriction for treatment of gestational diabetes.
Birth weights of infants of 35 gestational diabetic mothers treated with calorie restriction alone (1200-1800 kcal) were compared with those of infants of 2337 nondiabetic women, including two control groups (A and B) matched for race, body mass index, age, and parity. All women were screened for gestational diabetes with the O'Sullivan screening method, and a 3-h oral glucose tolerance test was performed on all abnormal results. Control group A mothers had a normal screen, and control group B mothers had an abnormal screen with a normal glucose tolerance test. Pregnancy weight gain was significantly less for the gestational diabetic mothers (mean +/- SD 4.6 +/- 4.9 kg) than for the general prenatal population (9.3 +/- 5.3 kg), group A control subjects (9.7 +/- 5.3 kg), and group B control subjects (9.7 +/- 5.4 kg; P less than 0.0005). No infant of a gestational diabetic mother was below the 10th percentile for weight, and birth weights were similar to those of the control groups even though weight gain after the 28th wk of gestation was only 1.7 +/- 1.6 kg. The frequency of macrosomia (birth weight greater than or equal to 4000 g) was similar among the gestational diabetic mothers (9.3%), the general prenatal population (7.4%), and group A mothers (11.6%) but significantly higher for the group B control subjects (20.9%; chi 2 = 8.57, P less than 0.005). This study demonstrated that gestational diabetic mothers who are calorie restricted have infants with normal birth weights and a frequency of macrosomia less than that of screen-positive nondiabetic women with similar macrosomic risk factors.


The effect of patient reminders on the use of screening mammography in an urban health department primary care setting.
Mammography screening continues to be under-utilized, especially among women from lower socioeconomic groups. In order to determine whether having direct access to health care services has an effect on mammography use among low income women, we conducted a randomized trial of two alternative letter reminders among 1,717 women who were enrolled at two locations of a multi-site inner city health department in Detroit. All participants were 39(1/2) years of age and older and were due for a screening mammogram at randomization. A physician-directed reminder form was placed in each of the participant's medical records at the beginning of the study. In addition participants were randomized to receive either a letter directing them to visit their primary care physician, a letter directing them to contact the clinic directly to schedule a mammogram, or no letter. Study participants were predominantly African-American, two-thirds of whom were over age 50, and who had minimal health insurance coverage. During the intervention year, mammograms were completed by 179 out of 967 study women at site one (18.5%), and 90 out of 750 study women at site two (12%). A multivariate model controlling for the simultaneous effect of age, insurance type, visit history and past mammography use, showed no significant independent effect of either type of letter reminder on mammography completion during the study year. In conclusion, letters targeted at women due for screening mammograms did not have a beneficial effect on mammography utilization above and beyond that of a physician medical record reminder.


Selection of Postacute Stroke Rehabilitation Facilities: A Survey of Discharge Planners From the Northeast Cerebrovascular Consortium (NECC) Region.
The process of determining the level of care and specific postacute care facility for stroke patients has not been adequately studied. The objective of this study was to better understand the factors that influence postacute care decisions by surveying stroke discharge planners. Requests were sent to discharge planners at 471 hospitals in the Northeast United States to complete an online survey regarding the factors impacting the selection of postacute care. Seventy-seven (16%) discharge planners completed the online survey. Respondents were mainly nurses and social workers and 73% reported ≥20 years healthcare experience. Patients and families were found to be significantly more influential than physicians (P < 0.001) and other clinicians (P = 0.04) in influencing postdischarge care. Other clinicians were significantly more influential than physicians (P < 0.001). Insurance and quality of postacute care were the factors likely to most affect the selection of postacute care facility. Insurance was also identified as the greatest barrier in the selection of level of postacute care (70%; P < 0.001) and specific postacute care facility (46%; P = 0.02). More than half reported that pressure to discharge patients quickly impacts a patients' final destination. Nonclinical factors are perceived by discharge planners to have a major influence on postacute stroke care decision making.


Automatic measurement of blood pressure: evaluation of the Copal UA-231 automatic sphygmomanometer.
The suitability of an automatic sphygmomanometer for epidemiological work was evaluated in two studies. In the first, blood pressure measurements were made alternately on the automatic machine and on a Hawksley random zero instrument on 14 volunteers on each of four consecutive days by a single medical observer. No significant difference was found between the mean diastolic pressure obtained by each instrument but the mean systolic pressure was 5 mm higher on average on the automatic machine. In the second study, the effect of cuff position for the automatic instrument was examined. Differences between recommended and errant cuff positions of up to 4.5 mmHg were recorded but these did not reach statistical significance. These studies indicate that if used carefully this automatic instrument is suitable for survey and experimental use.


Sall1 and Sall4 cooperatively interact with Myocd and SRF to promote cardiomyocyte proliferation by regulating CDK and cyclin genes.
Sall1 and Sall4 (Sall1/4), zinc-finger transcription factors, are expressed in the progenitors of the second heart field (SHF) and in cardiomyocytes during the early stages of mouse development. To understand the function of Sall1/4 in heart development, we generated heart-specific Sall1/4 functionally inhibited mice by forced expression of the truncated form of Sall4 (ΔSall4) in the heart. The ΔSall4-overexpression mice exhibited a hypoplastic right ventricle and outflow tract, both of which were derived from the SHF, and a thinner ventricular wall. We found that the numbers of proliferative SHF progenitors and cardiomyocytes were reduced in ΔSall4-overexpression mice. RNA-sequencing data showed that Sall1/4 act upstream of the cyclin-dependent kinase (CDK) and cyclin genes, and of key transcription factor genes for the development of compact cardiomyocytes, including myocardin (Myocd) and serum response factor (Srf). In addition, ChIP-sequencing and co-immunoprecipitation analyses revealed that Sall4 and Myocd form a transcriptional complex with SRF, and directly bind to the upstream regulatory regions of the CDK and cyclin genes (Cdk1 and Ccnb1). These results suggest that Sall1/4 are critical for the proliferation of cardiac cells via regulation of CDK and cyclin genes that interact with Myocd and SRF.


[Conversion from peridural to transdermal opiate analgesia in abdominal tumor pain syndrome].
In a 32 years old patient with advanced gastric cancer epidural analgesia with local anaesthetic and morphine via a thoracic epidural catheter was required because of intractable pain and intolerable side effects of intravenous morphine. In spite of good efficacy it was decided to remove the catheter because of technical problems and the risk of infection during chemotherapy. Analgesic therapy proceeded to non-invasive transdermal fentanyl, using an intravenous fentanyl pca-pump during transition. The equipotent daily dose ratio of epidural morphine to transdermal fentanyl was calculated as 2.25:1.


Minimal Clinically Important Difference for Safe and Simple Novel Acute Ischemic Stroke Therapies.
Determining the minimal clinically important difference (MCID) is essential for evaluating novel therapies. For acute ischemic stroke, expert surveys have yielded MCIDs that are substantially higher than the MCIDs observed in actual expert behavior in guideline writing and clinical practice, potentially because of anchoring bias. We administered a structured, internet-based survey to a cross-section of academic stroke neurologists in the United States. Survey responses assessed demographic and clinical experience, and expert judgment of the MCID of the absolute increase needed in the proportion of patients achieving functional independence at 3 months to consider a novel, safe neuroprotective agent as clinically worthwhile. To mitigate anchoring bias, the survey response framework used a base 1000 rather than base 100 patient framework. Survey responses were received from 122 of 333 academic stroke neurologists, there were 23% women, 72.8% had ≥6 years of practice experience, and neurovascular disease accounted for more than half of practice time in >70%. Responder-nonresponder and continuum of resistance tests indicated that responders were representative of the full expert population. Among respondents, the median MCID was 1.3% (interquartile range, 0.8% to >2%). Stroke expert responses to MCID surveys are affected by anchoring and centrality bias. When survey design takes these into account, the expert-derived MCID for a safe acute ischemic stroke treatment is 1.1% to 1.5%, in accord with actual physician behavior in guideline writing and clinical practice. This revised MCID value can guide clinical trial design and grant-funding and regulatory agency decisions.


Promotion effects of flavonoids on browning induced by enzymatic oxidation of tyrosinase: structure-activity relationship.
Tyrosinase, widely distributed in nature, is a copper-containing polyphenol oxidase involved in the formation of melanin. Flavonoids are most often considered as tyrosinase inhibitors but have also been confirmed to be tyrosinase substrates. Four structure-related flavonoids including flavones (apigenin and luteolin) and flavonols (kaempferol and quercetin) are found to promote not inhibit browning induced by tyrosinase catalyzed oxidation both in model systems and in mushrooms under aerobic conditions. A comparison with enzymatic oxidation and autooxidation of flavonoids alone has helped to clarify why flavonoids function as a substrate rather than an inhibitor. Flavonoids almost do not affect the kinetics of melanin formation from enzymatic oxidation of l-dopa in excess. In addition, a new brown complex formed during the reaction of flavonoid quinone and dopaquinone is suggested to enhance the browning effects by competing with isomerization and autooxidation. Structure-activity relationships of the four flavonoids in melanin formation leading to browning induced by autooxidation and enzymatic oxidation confirm the enzymatic nature of the browning.


Dentists' restorative decision-making and implications for an 'amalgamless' profession. Part 5: knowledge factors.
A phase-down of amalgam in Australia is possible given the Australian Government intends to ratify the Minamata Convention. There is little research as to the influence of a dentist's knowledge on decision-making, which may be of use when determining the impact of any change. An online survey relating to aspects of and attitudes to use of direct restorative materials was distributed to all dentists who were members of the Australian Dental Association or Members or Fellows of the Royal Australasian College of Dental Surgeons. There were 408 respondents. Fifty-eight per cent agreed that there was consistency in undergraduate teaching. Fifty-two per cent stated that there was a difference between undergraduate teaching and the 'real world'. Postgraduate education was ranked the most important influence on decision-making. Ninety-six per cent stated that knowledge of the evidence base is important and 89% believed that they practised evidence-based dentistry. Dental schools need to maintain teachers' and students' understanding of the evolving technology of direct restorative materials. There is a perceived disconnect between undergraduate teaching and the 'real' world. The evidence base is viewed as confusing, contradictory and not readily understandable. The creation of clinical guidelines would be useful.


[Diffusion ability of lungs at advanced age].
Changes in lungs ventilation is mainly studied in the research on the features of respiratory system in ageing process. The condition of alveolar--capillary oxygen diffusion expressing the presence of central acinar lung emphysema is much less investigated. The purpose of the research was to study particularities of lung diffusion ability, which is considered to be one of the important mechanisms determining blood oxygenation in elderly. Results of the research and discussion. The dynamic of body surface changes is much less variable with age, than the dynamic of the lung diffusion ability. This is considered to be the reason of preservation of age differences of lung diffusion ability referred to 1 M2 of a body surface. There are two differences in dynamic of DLCO (diffusion lungs capacity) referred to total lungs capacity and referred to 1 M2 of a body surface. The indicator of double correlation of vital capacity of lungs (VCL) of elderly patients and Dlco makes +0.764; between intrathoracic gas volume and DLCO +0.654; between the residual volume of lungs (RV) and DLCO +0.729; between the Tiffno index and DlCO +0.654. The same parameters of young patients with COPD were 0.112; -0.245; 0.105; 0.312 correspondingly. Age related reduction of ratio of lungs diffusion ability to total lungs capacity is less prominent comparing to the ratio of DlCO body surface. The sex dependant differences of DlCO/TC smooth out in with each decade in contrast to DlCO/m2. A close correlation was revealed between DLCO and vital lungs capacity, the residual volume of lungs, intrathoracic gas volume and Tiffno indicator in elderly patients with COPD.


Microbial diversity through an oceanographic lens: refining the concept of ocean provinces through trophic-level analysis and productivity-specific length scales.
In the marine realm, microorganisms are responsible for the bulk of primary production, thereby sustaining marine life across all trophic levels. Longhurst provinces have distinct microbial fingerprints; however, little is known about how microbial diversity and primary productivity change at finer spatial scales. Here, we sampled the Atlantic Ocean from south to north (~50°S-50°N), every ~0.5° latitude. We conducted measurements of primary productivity, chlorophyll-a and relative abundance of 16S and 18S rRNA genes, alongside analyses of the physicochemical and hydrographic environment. We analysed the diversity of autotrophs, mixotrophs and heterotrophs, and noted distinct patterns among these guilds across provinces with high and low chlorophyll-a conditions. Eukaryotic autotrophs and prokaryotic heterotrophs showed a shared inter-province diversity pattern, distinct from the diversity pattern shared by mixotrophs, cyanobacteria and eukaryotic heterotrophs. Additionally, we calculated samplewise productivity-specific length scales, the potential horizontal displacement of microbial communities by surface currents to an intrinsic biological rate (here, specific primary productivity). This scale provides key context for our trophically disaggregated diversity analysis that we could relate to underlying oceanographic features. We integrate this element to provide more nuanced insights into the mosaic-like nature of microbial provincialism, linking diversity patterns to oceanographic transport through primary production.


Design of a novel, one-sided, pedal-activated wheelchair.
The present paper proposes the design of a novel, one-sided, pedal-activated wheelchair for patients with hemiplegia or hemiparesis. The design comprises a planetary hub transmission, which is embedded in the hub of the wheelchair, with drive, neutral, and reverse modes. The paper first discusses the structural characteristics and motion transmission of the wheelchair, and then presents the motion design of the hub transmission, followed by assembly and testing of the prototype. The results confirm that the proposed wheelchair and hub transmission can meet users' demands, thus improving comfort and independence.


Experimental investigation of the effect of thresholding on temporal statistics of avalanches.
Avalanchelike behavior reflected in power-law statistics is a ubiquitous property of extended systems addressed in a number of generic models. The paper presents an experimental investigation of the effect of thresholding on the statistics of durations and waiting times between avalanches using acoustic emission accompanying unstable plastic deformation. It is found that durations of acoustic events obey power-law statistical distributions robust against thresholding. The quiescent time distributions follow the Poisson law for low threshold values. Both these results corroborate the hypothesis that plastic deformation is akin to the phenomena associated with self-organized criticality (SOC), often advanced on the basis of power-law amplitude statistics. Increasing the threshold height enforces deviation from the Poisson distributions toward apparent power-law behavior. Such a thresholding effect may hinder the experimental determination of SOC-like dynamics because of the inevitable noise.


How low can you go? Chronic hypoglycemia versus normal glucose homeostasis.
Set point errors in glucose homeostasis that result in chronic, mild hyperglycemia in the setting of maturity onset diabetes of the young have been described. Similar set point errors may exist that result in chronic, asymptomatic glucopenia. A healthy 39-year-old female was referred for evaluation of chronic, persistent, and asymptomatic glucopenia that persisted over the prior several years with a record of numerous random plasma glucose concentrations between 35 and 45 mg/dL. She denied ethanol intake and family history of hypoglycemia or diabetes. She was not taking any medications known to cause hypoglycemia, and a urine sulfonylurea screen was negative. Fasting insulin and C-peptide levels were not elevated, and pancreatic imaging studies were normal. We hypothesized that this patient possessed an error in glucose metabolism that resulted in chronic, asymptomatic glucopenia. In a series of clinical studies, we demonstrated a nadir plasma glucose concentration of 35 mg/dL in the absence of symptoms during a 60-hour fast. C-peptide secretion was appropriately suppressed during symptomatic hypoglycemia with exogenous insulin infusion, and counterregulatory hormone secretion was intact during insulin-induced symptomatic hypoglycemia. Finally, the patient demonstrated an incremental increase in insulin concentration in response to minimal increases in plasma glucose during a sequential, stepped infusion of 10% dextrose. We conclude that this patient exhibits features of a set point error in glucose homeostasis that manifests as chronic, asymptomatic glucopenia. Although the mechanism for this condition remains to be elucidated, such set point errors do exist and should be considered in the differential diagnosis of chronic hypoglycemia.


Adrenergic inhibition of carbon dioxide excretion by trout red blood cells in vitro is mediated by activation of Na+/H+ exchange.
We have used a sensitive new technique to assess the mechanism(s) of adrenergic inhibition of rainbow trout (Oncorhynchus mykiss) red blood cell (RBC) carbon dioxide excretion in vitro. The effect was only apparent using blood acidified to simulate metabolic acidosis. Red blood cell CO2 excretion was inhibited in a dose-dependent manner by physiologically relevant concentrations of noradrenaline (10-1000 nmol l-1) or adrenaline (100-1000 nmol l-1). The beta-adrenoceptor antagonist propranolol abolished the inhibitory effect of adrenaline, whereas the alpha-adrenoceptor antagonist phentolamine was without effect. The action of noradrenaline on RBC CO2 excretion was mimicked by the beta-adrenoceptor agonist isoproterenol, but not by the alpha-adrenoceptor agonist phenylephrine. Therefore, adrenergic inhibition of CO2 excretion is mediated by RBC beta-adrenoceptors, presumably of the beta 1 subtype. The Na+/H+ exchange inhibitor amiloride effectively blocked adrenergic stimulation of Na+/H+ exchange (as indicated from measurements of pHe and RBC pHi) and entirely prevented the inhibition of CO2 excretion. Noradrenaline significantly reduced the rate of CO2 excretion even in the presence of the Cl-/HCO3- exchange inhibitor SITS. Therefore, adrenergic inhibition of CO2 excretion is accomplished via activation of RBC Na+/H+ exchange rather than by a direct inhibition of Cl-/HCO3- exchange. The observed relationship between CO2 excretion rates and the RBC transmembrane pH difference (pHe-pHi) and the occurrence of the inhibition only at low pHe provide further evidence of the linkage with RBC Na+/H+ exchange. We suggest that adrenergic activation of RBC Na+/H+ exchange impedes CO2 excretion by causing a rise in intracellular HCO3- levels concurrent with a reduction of intracellular PCO2. The net result is a reduced gradient for HCO3- entry into the RBC in conjunction with a diminution of the outwardly directed PCO2 gradient. Thus, the rate of formation of CO2 from the dehydration of plasma HCO3- is reduced and, in turn, a portion of this CO2 is not excreted but recycled through the red blood cell.


Arcanobacterium canis sp. nov., isolated from otitis externa of a dog, and emended description of the genus Arcanobacterium Collins et al. 1983 emend. Yassin et al. 2011.
A polyphasic taxonomic study was performed on an unidentified Arcanobacterium-like Gram-stain-positive bacterium isolated from otitis externa of a dog. Comparative 16S rRNA gene sequencing showed that the bacterium belonged to the genus Arcanobacterium and was most closely related to the type strains of Arcanobacterium haemolyticum (97.2 %), Arcanobacterium hippocoleae (96.5 %) and Arcanobacterium phocae (96.4 %). The presence of the major menaquinone MK-9(H(4)) supported the affiliation of this strain to the genus Arcanobacterium. The polar lipid profile contained the major lipids phosphatidylcholine, diphosphatidylglycerol, phosphatidylinositol mannoside and an unidentified phospholipid (PL2). Major fatty acids were C(14 : 0), C(16 : 0), C(18 : 0), C(18 : 1)ω9c and C(18 : 2)ω6,9c/anteiso-C(18 : 0) (detected as a summed feature). C(10 : 0) and C(12 : 0) were present in minor amounts. The results of physiological and biochemical testing clearly distinguished the unknown bacterium from other species of the genus Arcanobacterium. Based on these tests, it is proposed that the unknown bacterium should be classified in the novel species Arcanobacterium canis sp. nov. The type strain of Arcanobacterium canis is P6775(T) (= CCM 7958(T) = CCUG 61573(T) = CIP 110339(T)). An emended description of the genus Arcanobacterium is also provided.


Ab initio study of substituent effects in the interactions of dimethyl ether with aromatic rings.
Ab initio calculations have been used to investigate the interaction energies of dimers of dimethyl ether with benzene, hexafluorobenzene, and several monosubstituted benzenes. The potential energy curves were explored at the MP2/aug-cc-pVDZ level for two basic configurations of the dimers, one in which the oxygen atom of the dimethyl ether was pointed towards the aromatic ring and the other in which the oxygen atom was pointed away from the aromatic ring. Once the optimum intermolecular distances between the dimethyl and the aromatic ring had been determined for each of the dimers in both configurations at the MP2/aug-cc-pVDZ level, single point energy calculations were performed at the MP2/aug-cc-pVTZ level. A CCSD(T) correction term to the energy was determined and this was combined with the MP2/aug-cc-pVTZ energies to estimate the CCSD(T)/aug-cc-pVTZ interaction energies of the dimers. The estimated CCSD(T)/aug-cc-pVTZ interaction energies are predicted to be attractive for all of the dimers in both configurations and dispersion interactions are found to be a large component of the stabilization of the dimers. For the dimers with the dimethyl ether oxygen pointing towards the aromatic ring, the strengths of interaction energies are found to increase as the aromatic ring becomes more electron deficient, while for the dimers with the dimethyl ether oxygen pointing away from the aromatic ring, they increase as the aromatic ring becomes more electron rich. In both cases, the trends can be explained in terms of the electrostatic potentials of the dimethyl ether and the aromatic rings.


Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita.
Myotonia, defined as delayed relaxation of muscle after contraction, is seen in a group of genetic disorders that includes autosomal dominant myotonia congenita (Thomsen's disease) and autosomal recessive myotonia congenita (Becker's disease). Both disorders are characterized electrophysiologically by increased excitability of muscle fibers, reflected in clinical myotonia. These diseases are similar except that transient weakness is seen in patients with Becker's, but not Thomsen's disease. Becker's and Thomsen's diseases are caused by mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1). Genetic screening of a panel of 18 consecutive myotonia congenita (MC) probands for mutation in CLCN1 revealed that a novel Gln-68-Stop nonsense mutation predicts premature truncation of the chloride channel protein. Four previously reported mutations, Arg-894-stop, Arg-338-Gln, Gly-230-Glu, and del 1437-1450, were also noted in our sample set. The Arg-338-Gln and Gly-230-Glu mutations were found in patients with different phenotypes from those of previous reports. Further study of the Arg-338-Gln and Gln-230-Glu alleles may shed light on variable modes of transmission (dominant versus recessive) in different families. Physiologic study of these mutations may lead to better understanding of the pathophysiology of myotonia in these patients and of voltage-gated chloride channel structure/function relationships in skeletal muscles.


Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.
CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.


Fetal origins of perinatal morbidity and/or adult disease.
The developmental origin of health and disease hypothesis holds that events occurring during the early development of an individual and specifically during intrauterine life have profound consequences on future health. Low birth weight, a marker of intrauterine stress, has been linked to predisposition to hypertension, cardiovascular diseases, diabetes, and stroke. The compelling animal evidence and significant human epidemiologic data to support this conclusion is reviewed. In addition, we propose that early embryo manipulation and culture that occur during use of assisted reproductive technologies may represent a stressful event that could be associated with future health problems. The effects of embryo culture on early development and gene expression and methylation status is reviewed and discussed.


Allicin inhibits cell polarization, migration and division via its direct effect on microtubules.
Allicin (diallyl thiosulfinate) is a major biologically active component of garlic that is known to inhibit cell proliferation and induce apoptosis. The effects of allicin are attributed to its ability to react with thiol groups. However, the mechanism underlying the cytostatic activity of allicin, as well as the identity of the relevant subcellular targets, are not known. In the present study, we found that the effects of allicin on cell polarization, migration, and mitosis are similar to the effects of microtubule-depolymerizing drugs such as nocodazole. Moreover, treatment of cultured fibroblasts with micromolar doses of allicin results in microtubule depolymerization in cells within minutes of its application, without disrupting the actin cytoskeleton or inducing direct cytotoxic effects. Furthermore, allicin blocks the polymerization of pure tubulin in vitro in a concentration-dependent manner, suggesting that it acts directly on tubulin dimers. Sulfhydryl (SH)-reducing reagents such as 2-mercaptoethanol and dithiothreitol abolish the effect of allicin on microtubule polymerization. Thus, allicin is a potent microtubule-disrupting reagent interfering with tubulin polymerization by reaction with tubulin SH groups.


Controlled rapid sequence induction and intubation - an analysis of 1001 children.
Classic rapid sequence induction puts pediatric patients at risk of cardiorespiratory deterioration and traumatic intubation due to their reduced apnea tolerance and related shortened intubation time. A 'controlled' rapid sequence induction and intubation technique (cRSII) with gentle facemask ventilation prior to intubation may be a safer and more appropriate approach in pediatric patients. The aim of this study was to analyze the benefits and complications of cRSII in a large cohort. Retrospective cohort analysis of all patients undergoing cRSII according to a standardized institutional protocol between 2007 and 2011 in a tertiary pediatric hospital. By means of an electronic patient data management system, vital sign data were reviewed for cardiorespiratory parameters, intubation conditions, general adverse respiratory events, and general anesthesia parameters. A total of 1001 patients with cRSII were analyzed. Moderate hypoxemia (SpO2 80-89%) during cRSII occurred in 0.5% (n = 5) and severe hypoxemia (SpO2 <80%) in 0.3% of patients (n = 3). None of these patients developed bradycardia or hypotension. Overall, one single gastric regurgitation was observed (0.1%), but no pulmonary aspiration could be detected. Intubation was documented as 'difficult' in two patients with expected (0.2%) and in three patients with unexpected difficult intubation (0.3%). The further course of anesthesia as well as respiratory conditions after extubation did not reveal evidence of 'silent aspiration' during cRSII. Controlled RSII with gentle facemask ventilation prior to intubation supports stable cardiorespiratory conditions for securing the airway in children with an expected or suspected full stomach. Pulmonary aspiration does not seem to be significantly increased.


Physiological changes in red spruce seedlings during a simulated winter thaw.
We evaluated net photosynthesis, respiration, leaf conductance, xylem pressure potential (XPP) and cold hardiness in red spruce (Picea rubens Sarg.) seedlings exposed to either a continuous thaw (CT) or a daytime thaw with freezing nights (FN) for 8 days during mid-winter. Physiological differences between CT and FN seedlings were evident for all measured parameters. However, the temporal expression of treatment differences varied among parameters. When compared to FN seedlings, CT seedlings had higher rates of respiration following 24 h of treatment, and a higher net photosynthetic rate, leaf conductance and XPP after 48 h of treatment. The CT seedlings were significantly less cold tolerant than the FN seedlings following 4 days of thaw, whereas FN seedlings did not deharden over the 8 days of treatment. Examination of temporal trends among thaw-associated changes in physiology suggested that, although greater carbon exchange occurred as stomatal conductance increased, the transition from negative to positive net photosynthesis was not the result of increases in conductance, but may have been associated with thaw-induced increases in XPP. Because thaw-associated changes in gas exchange and cold hardiness were offset in time, we conclude that, if changes in these processes are physiologically linked, the linkage is indirect.


Plasmodium falciparum parasitaemia described by a new mathematical model.
A new mathematical model of Plasmodium falciparum asexual parasitaemia is formulated and fitted to 35 malaria therapy cases making a spontaneous recovery after primary inoculation. Observed and simulated case-histories are compared with respect to 9 descriptive statistics. The simulated courses of parasitaemia are more realistic than any previously published. The model uses a discrete time-step of 2 days. Its realistic behaviour was achieved by the following combination of features (i) intra-clonal antigenic variation, (ii) large variations of the variants' baseline growth rate, depending on both variant and case, (iii) innate autoregulation of the asexual parasite density, variable among cases, (iv) acquired variant-specific immunity and (v) acquired variant-transcending immunity, variable among cases. Aspects of the model's internal behaviour, concerning variant dynamics, as well as the respective contributions of the three control mechanisms (iii) - (v), are displayed. Some implications for pathogenesis and control are discussed.


Bacterial contamination of surgical suture resembles a biofilm.
Although much attention is currently directed to studying microbial biofilms on a variety of surfaces, few studies are designed to study bacterial growth on surgical suture. The purpose of this study was to compare the kinetic development of Staphylococcus aureus and Enterococcus faecalis on five surgical suture materials and to clarify factors that might influence this growth. Pure cultures of S. aureus and E. faecalis were incubated with five types of suture for four days using either tissue culture medium or a bacterial growth medium. Suture-associated bacteria were quantified daily. In selected experiments, the bacterial growth medium was supplemented with heparin, a substance known to promote S. aureus biofilm formation. The ultrastructure of S. aureus biofilm developing on braided suture was studied with scanning electron microscopy. Staphylococcus aureus and E. faecalis were recovered in greater numbers (typically p < 0.01) from braided than from monofilament suture, and the numbers of bacteria were greater (often p < 0.01) on sutures incubated in bacterial growth medium rather than tissue culture medium. Addition of heparin 1,000 U/mL to silk or braided polyglactin 910 suture incubated three days with S. aureus resulted in greater numbers of bacteria on day one but not on subsequent days. Scanning electron microscopy showed a maturing S. aureus biofilm that developed from small clusters of cells among amorphous material and fibrillar elements to larger clusters of cells that appeared covered by more consolidated extracellular material. Bacterial growth was favored on braided vs. monofilament suture, and heparin enhanced bacterial adherence after day one, but not at subsequent times. Staphylococcus aureus adhered to suture material and formed a structure consistent with a bacterial biofilm.


The association between health literacy and self-management abilities in adults aged 75 and older, and its moderators.
Low health literacy is an important predictor of poor health outcomes and well-being among older adults. A reason may be that low health literacy decreases older adults' self-management abilities. We therefore assessed the association between health literacy and self-management abilities among adults aged 75 and older, and the impact of demographic factors, socioeconomic factors, and health status on this association. We used data of 1052 older adults, gathered for a previously conducted randomized controlled trial on Embrace, an integrated elderly care model. These data pertained to health literacy, self-management abilities, demographic background, socioeconomic situation, and health status. Health literacy was measured by the validated three-item Brief Health Literacy Screening instrument. Self-management abilities were measured by the validated Self-Management Ability Scale (SMAS-30). After adjustment for confounders, self-management abilities were poorer in older adults with low health literacy (β = .34, p < .001). This was more pronounced in medium- to high-educated older adults than in low-educated older adults. Sex, age, living situation, income, presence of chronic illness, and mental health status did not moderate the association between health literacy and self-management abilities. Low health literacy is associated with poor self-management abilities in a wide range of older adults. Early recognition of low health literacy among adults of 75 years and older and interventions to improve health literacy might be very beneficial for older adults.


Changes in biologically active ultraviolet radiation reaching the Earth's surface.
Since publication of the 1998 UNEP Assessment, there has been continued rapid expansion of the literature on UV-B radiation. Many measurements have demonstrated the inverse relationship between column ozone amount and UV radiation, and in a few cases long-term increases due to ozone decreases have been identified. The quantity, quality and availability of ground-based UV measurements relevant to assessing the environmental impacts of ozone changes continue to improve. Recent studies have contributed to delineating regional and temporal differences due to aerosols, clouds, and ozone. Improvements in radiative transfer modelling capability now enable more accurate characterization of clouds, snow-cover, and topographical effects. A standardized scale for reporting UV to the public has gained wide acceptance. There has been increased use of satellite data to estimate geographic variability and trends in UV. Progress has been made in assessing the utility of satellite retrievals of UV radiation by comparison with measurements at the Earth's surface. Global climatologies of UV radiation are now available on the Internet. Anthropogenic aerosols play a more important role in attenuating UV irradiances than has been assumed previously, and this will have implications for the accuracy of UV retrievals from satellite data. Progress has been made inferring historical levels of UV radiation using measurements of ozone (from satellites or from ground-based networks) in conjunction with measurements of total solar radiation obtained from extensive meteorological networks. We cannot yet be sure whether global ozone has reached a minimum. Atmospheric chlorine concentrations are beginning to decrease. However, bromine concentrations are still increasing. While these halogen concentrations remain high, the ozone layer remains vulnerable to further depletion from events such as volcanic eruptions that inject material into the stratosphere. Interactions between global warming and ozone depletion could delay ozone recovery by several years, and this topic remains an area of intense research interest. Future changes in greenhouse gases will affect the future evolution of ozone through chemical, radiative, and dynamic processes In this highly coupled system, an evaluation of the relative importance of these processes is difficult: studies are ongoing. A reliable assessment of these effects on total column ozone is limited by uncertainties in lower stratospheric response to these changes. At several sites, changes in UV differ from those expected from ozone changes alone, possibly as a result of long-term changes in aerosols, snow cover, or clouds. This indicates a possible interaction between climate change and UV radiation. Cloud reflectance measured by satellite has shown a long-term increase at some locations, especially in the Antarctic region, but also in Central Europe, which would tend to reduce the UV radiation. Even with the expected decreases in atmospheric chlorine, it will be several years before the beginning of an ozone recovery can be unambiguously identified at individual locations. Because UV-B is more variable than ozone, any identification of its recovery would be further delayed.


Novel genome reveals susceptibility of popular gamebird, the red-legged partridge (Alectoris rufa, Phasianidae), to climate change.
We produced a high-quality de novo genome assembly of the red-legged partridge A. rufa, the first reference genome of its genus, by utilising novel 10× Chromium technology. The estimated genome size was 1.19 Gb with an overall genome heterozygosity of 0.0022; no runs of homozygosity were observed. In total, 21,589 protein coding genes were identified and assigned to 16,772 orthologs. Of these, 201 emerged as unique to Alectoris and were enriched for positive regulation of epithelial cell migration, viral genome integration and maturation. Using PSMC analysis, we inferred a major demographic decline commencing ~140,000 years ago, consistent with forest expansion and reduction of open habitats during the Eemian interglacial. Present-day populations exhibit the historically lowest genetic diversity. Besides implications for management and conservation, this genome also promises key insights into the physiology of these birds with a view to improving poultry husbandry practices.


Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.
The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.


[Methodical approaches to studying prevalence and quantitative of Campylobacter species in foodstuff].
The circuit of microbiological crop for definition Campylobacter spp. in foodstuff based on the procedure described in method FDA 2001z, with the modified set of nutrient mediums discribed. The offered method is comparable with official definition Campylobacter spp. under ISO 10272. All stages for detection, including microaerobic incubation are provided with accessible industrial manufacturing ingredients (nutrient mediums, aerotolerant additives, CO2, barrier packages). The method allows to find out Campylobacter spp. at a level 4 cells per 100 g in product and is suitable for calculation of this microorganisms in foodstuff.


Sickness certification at oncology clinics: perceived problems, support, need for education and reasons for certifying unnecessarily long sickness absences.
Physicians' work with sickness certifications is an understudied field. The aims of this study were to gain knowledge of experiences concerning the sickness certification process among physicians working at oncology clinics. In 2008, all physicians working in Sweden (n = 36 898) were sent a questionnaire concerning sick-listing practices. All respondents working at an oncology clinic (n = 428) were included in the current study. Most of the physicians had sickness certification consultations at least weekly (91.3%). More than one fifth (22.3%) reported that they worked at a clinic with a workplace policy regarding the handling of sickness certification and 61.1% reported receiving at least some support in such cases from their immediate manager. Issuing unnecessary long sickness certificates were related to experiencing delicate interactions with patients and to lack of time. To a moderate degree, further competence was requested regarding: different types of compensation in the social insurance system, responsibilities of the Social Insurance Agency and employers, and sickness insurance rules. The large majority of physicians working in oncology reported regularly having consultations involving sickness certification. Overall, they reported few problems, low level of need for more competence regarding sickness certification, and low frequency of issuing sickness absences for longer periods than necessary.


Synthesis, structure, and substitution mechanism of new Ru(II) complexes containing 1,4,7-trithiacyclononane and 1,10-phenanthroline ligands.
Two new Ru complexes containing the 1,10-phenanthroline (phen) and 1,4,7-trithiacyclononane ([9]aneS3, SCH2CH2SCH2CH2SCH2CH2) ligands of general formula [Ru(phen)(L)([9]aneS3)]2+ (L = MeCN, 3; L = pyridine (py), 4) have been prepared and thoroughly characterized. Structural characterization in the solid state has been performed by means of X-ray diffraction analyses, which show a distorted octahedral environment for a diamagnetic d6 Ru(II), as expected. 1H NMR spectroscopy provides evidence that the same structural arrangement is maintained in solution. Further spectroscopic characterization has been carried out by UV-vis spectroscopy where the higher acceptor capability of MeCN versus the py ligand is manifested in a 9-15-nm blue shift in its MLCT bands. The E1/2 redox potential of the Ru(III)/Ru(II) couple for 3 is anodically shifted with respect to its Ru-py analogue, 4, by 60 mV, which is also in agreement with a higher electron-withdrawing capacity of the former. The mechanism for the reaction Ru-py + MeCN--> Ru-MeCN + py has also been investigated at different temperatures with and without irradiation. In the absence of irradiation at 326 K, the thermal process gives kinetic constants of k2 = 1.4 x 10(-5) s(-1) (DeltaH(++) = 108 +/- 3 kJ mol(-1), DeltaS(++) = -8 +/- 9 J K(-1) mol(-1)) and k-2 = 2.9 x 10(-6) s(-1) (DeltaH(++) = 121 +/- 1 kJ mol(-1), DeltaS(++) = 18 +/- 3 J K(-1) mol(-1)). The phototriggered process is faster and consists of preequilibrium formation of an intermediate that thermally decays to the final Ru-MeCN complex with an apparent rate constant of (k1Khnu)app = 1.8 x 10(-4) s(-1) at 304 K, under the continuous irradiation experimental conditions used.


Randomized controlled trial comparing the costs of gastric cancer screening systems between serological risk-based upper gastrointestinal endoscopy and the existing barium photofluorography: gastric cancer screening labeled by serum examination in place of aged gastric cancer organized screening systems (GALAPAGOS study).
Although the risk of gastric cancer can be stratified according to Helicobacter pylori (H. pylori) IgG antibody titer and pepsinogen levels (ABC classification), a population-based gastric cancer screening system combining serological tests and endoscopy has not been introduced. This study aimed to compare the total testing cost per participant between the ABC classification method and the existing protocol. Using the minimization method with sex and age as allocation factors, 1206 participants were randomly assigned to the following two methods for a 5-year intervention: barium photofluorography as primary examination followed by detailed examination with upper gastrointestinal endoscopy (Ba-Endo) and risk-based upper gastrointestinal endoscopy by ABC classification (ABC-Endo). The primary endpoint was the total testing cost per participant over a 5-year period. The secondary endpoint was the expense required to detect one gastric cancer. The total testing cost per participant was 39,711 yen in Ba-Endo (604 participants) and 45,227 yen in ABC-Endo (602 participants), with the latter being significantly higher (p < 0.001). During the intervention period, gastric cancer was found in 11 and eight participants in Ba-Endo and ABC-Endo, respectively. The expenses required to detect one gastric cancer were 2,240,931 yen in Ba-Endo and 3,486,662 yen in ABC-Endo. The testing cost per participant turned out to be higher in the ABC-Endo group than in the Ba-Endo group. This superiority trial, based on the hypothesis that the cost of testing is lower for ABC-Endo than for Ba-Endo, was rejected.


Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms. To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response. The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes -- natural killer (NK) cells (CD3-CD16+ and CD3-CD56+) and naïve T cells (CD4+CD45RA+) -- to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue.. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes. Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3-CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms. These findings suggest that lymphocytes are modestly related to clinical outcomes over time.


Selection on stability across ecological scales.
Much of the focus in evolutionary biology has been on the adaptive differentiation among organisms. It is equally important to understand the processes that result in similarities of structure among systems. Here, we discuss examples of similarities occurring at different ecological scales, from predator-prey relations (attack rates and handling times) through communities (food-web structures) to ecosystem properties. Selection among systemic configurations or patterns that differ in their intrinsic stability should lead generally to increased representation of relatively stable structures. Such nonadaptive, but selective processes that shape ecological communities offer an enticing mechanism for generating widely observed similarities, and have sparked new interest in stability properties. This nonadaptive systemic selection operates not in opposition to, but in parallel with, adaptive evolution.


Duloxetine, a Balanced Serotonin-Norepinephrine Reuptake Inhibitor, Improves Painful Chemotherapy-Induced Peripheral Neuropathy by Inhibiting Activation of p38 MAPK and NF-κB.
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe, toxic side effect that frequently occurs in anticancer treatment and may result in discontinuation of treatment as well as a serious reduction in life quality. The CIPN incidence rate is as high as 85-90%. Unfortunately, there is currently no standard evidence-based CIPN treatment. In several clinical trials, it has been reported that duloxetine can improve CIPN pain induced by oxaliplatin (OXA) and paclitaxel (PTX); thus, The American Society of Clinical Oncology (ASCO) recommends duloxetine as the only potential treatment for CIPN. However, this guidance lacks the support of sufficient evidence. Our study shows that duloxetine markedly reduces neuropathic pain evoked by OXA or PTX. Duloxetine acts by inhibiting the activation of p38 phosphorylation, thus preventing the activation and nuclear translocation of the NF-κB transcription factor, reducing the inflammatory response and inhibiting nerve injury by regulating nerve growth factor (NGF). Furthermore, in this study, it is shown that duloxetine does not affect the antitumor activity of OXA or PTX. This study not only provides biological evidence to support the use of duloxetine as the first standard CIPN drug but will also lead to potential new targets for CIPN drug development.


Induction of emesis with apomorphine using a novel gingival administration method in dogs.
To describe a novel method of inducing emesis in the dog using gingival administration of apomorphine, compare the efficacy of inducing emesis with gingival apomorphine to conjunctival apomorphine, and describe adverse effects associated with the gingival route. Retrospective study from January 2017 to September 2018. Independent all-hours primary and secondary emergency and critical care referral center. Five hundred fifty-eight client-owned dogs. The medical records of dogs presenting for induction of emesis were searched. Dogs receiving either gingival or conjunctival apomorphine were included in the study. A short online survey was sent to clients whose dogs received gingival apomorphine. Apomorphine was administered conjunctivally in 430 (77.1%) dogs and gingivally in 128 (22.9%) dogs. There was no difference between route of administration and success of emesis (p = 0.29). A total of 14 clients responded to the survey, and diarrhea, lethargy, hyperactivity, and sedation were reported as adverse effects of gingival apomorphine administration. No clients sought veterinary attention for any of the adverse effects reported. Gingival administration of apomorphine is easy, appears to be safe, and is an effective method of inducing emesis in the dog. Gingival administration of apomorphine may be considered in cases where parenteral administration is not feasible and could replace conjunctival administration in compliant dogs.


An alternative approach identified optimal risk thresholds for treatment indication: an illustration in coronary heart disease.
Treatment thresholds based on risk predictions can be optimized by considering various health (economic) outcomes and performing marginal analyses, but this is rarely performed. We demonstrate a general approach to identify treatment thresholds optimizing individual health (economic) outcomes, illustrated for statin treatment based on 10-year coronary heart disease (CHD) risk predicted by the Framingham risk score. Creating a health economic model for a risk-based prevention strategy, risk thresholds can be evaluated on several outcomes of interest. Selecting an appropriate threshold range and decrement size for the thresholds and adapting the health economic model accordingly, outcomes can be calculated for each risk threshold. A stepwise, or marginal, comparison of clinical as well as health economic outcomes, that is, comparing outcomes using a specific threshold to outcomes of the former threshold while gradually lowering the threshold, then takes into account the balance between additional numbers of individuals treated and their outcomes (additional health effects and costs). In our illustration, using a Markov model for CHD, we evaluated risk thresholds by gradually lowering thresholds from 20% to 0%. This approach can be applied to identify optimal risk thresholds on any outcome, such as to limit complications, maximize health outcomes, or optimize cost-effectiveness. In our illustration, keeping the population-level fraction of statin-induced complications <10% resulted in thresholds of T = 6% (men) and T = 2% (women). Lowering the threshold and comparing quality-adjusted life-years (QALYs) after each 1% decrease, QALYs were gained down to T = 1% (men) and T = 0% (women). Also accounting for costs, net health benefits were favorable down to T = 3% (men) and T = 6% (women). Using a stepwise risk-based approach to threshold optimization allows for preventive strategies that optimize outcomes. Presenting this comprehensive overview of outcomes will better inform decision makers when defining a treatment threshold.


Propagation of F-actin disassembly via Myosin15-Mical interactions.
The F-actin cytoskeleton drives cellular form and function. However, how F-actin-based changes occur with spatiotemporal precision and specific directional orientation is poorly understood. Here, we identify that the unconventional class XV myosin [Myosin 15 (Myo15)] physically and functionally interacts with the F-actin disassembly enzyme Mical to spatiotemporally position cellular breakdown and reconstruction. Specifically, while unconventional myosins have been associated with transporting cargo along F-actin to spatially target cytoskeletal assembly, we now find they also target disassembly. Myo15 specifically positions this F-actin disassembly by associating with Mical and using its motor and MyTH4-FERM cargo-transporting functions to broaden Mical's distribution. Myo15's broadening of Mical's distribution also expands and directionally orients Mical-mediated F-actin disassembly and subsequent cellular remodeling, including in response to Semaphorin/Plexin cell surface activation signals. Thus, we identify a mechanism that spatiotemporally propagates F-actin disassembly while also proposing that other F-actin-trafficked-cargo is derailed by this disassembly to directionally orient rebuilding.


Evaluation of the permeability of five desensitizing agents using computerized fluid filtration.
The aim of this study was to evaluate the permeability of five desensitizing agents using computerized fluid filtration (CFF) test method. Sixty dentin discs of 500 ± 200-mm-thick were prepared from middle dentin of bovine incisors without exposed the pulp and then randomly divided into five groups (n = 12). The permeability of the discs was measured using the CFF test method before and after application of the following desensitizers: Admira Protect (Voco, Cuxhaven, Germany), Seal and Protect (Dentsply, Konstanz, Germany), Sensi Kill (DFL, Brazil), Systemp Desensitizer (Ivoclar Vivadent, Liechtenstein), BisBlock (Bisco, USA). Fluid movement measurements were made at 2-min intervals for 8 min, and a mean of the values obtained was calculated for each specimen. The results were analyzed using Kruskal-Wallis test and Wilcoxon signed ranks tests with a significance threshold of P < 0.05. There were no significant differences in permeability among desensitizing agents (P > 0.05); however dentin permeability was reduced in all groups (P < 0.05). The in vitro fluid conductance of dentin discs were reduced by treating with these five desensitizing agents.


["Non-solvent shock agglomeration"--the technology of a new alternative method for determination of ibuprofen. 6. Stability of s(+)-ibuprofen].
Due to its low melting range approx. 53 degrees C optically pure ibuprofen can be regarded as problematic in a pharmaceutic-technological sense. With regard to the non-solvent shock agglomeration method this means that the process and product temperatures must strictly be kept in the range of 10 K above the melting point of the substance. Higher temperatures can induce degradation of S(+)ibuprofen. During storage under stress conditions (31 degrees C for a period of 18 months) ibuprofen shows extreme stability independent of its optical activity. Racemic ibuprofen is inert to the influence of light; in individual cases optically pure substance containing an increased level of impurities can show slight degradation tendencies. The thermal and photo stability of ibuprofen is independent of the preparation technology. For comparison, conventional, fluid bed granulated, briquetted and from organic solvents especially recrystallised and optically active substances were investigated besides the shock agglomerated substances.


Evaluation of Anti-nociceptive and Anti-inflammatory Activities of Novel Chalcone Derivatives.
Chalcone (1,3-diarylprop-2-en-1-one) derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methylsulfonyl substitution. Compounds with substituents such as: 1) H, 2) Me, 3) F and 4) Cl at para position of the phenyl ring of (E)-3-(4-Methanesulfonylphenyl)-1-phenylprop-2 en-1-one were selected in the first group. The regioisomer compounds with 5) H, 6) Me, 7) F and 8) OMe substitutions at C-4 of phenyl ring of (E)-1-(4-Methanesulfonylphenyl)-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/ anti-nociceptive effects. The comparison of estimated ED50 of each pair of the regioisomeric compounds indicates that the relative position of SO2Me to carbonyl moiety did not affect the potency.


Influence of cross-education training in postoperative hand therapy.
Early studies have shown an effect of cross-education training in normal volunteers and in patients with neuromuscular disorders. In this prospective study, I evaluated application of this principle after upper extremity surgery and immobilization. A detailed therapy program to the contralateral unoperated extremity was initiated in one half of the patients. The other half of the patients had only routine postoperative instructions for rest, elevation, and protective splinting. Range of motion and strength measurements were done preoperatively and at intervals up to three months after operation. Analysis of results shows little difference in range of motion measurements in either group. However, return of strength in the extremity operated on was significantly augmented, up to 150% of the control group, in the patients who received cross-education training. Application of this principle to rehabilitation after injury to specific functional units may increase recovery.


Myofibril orientation as a metric for characterizing heart disease.
Myocyte disarray is a hallmark of many cardiac disorders. However, the relationship between alterations in the orientation of individual myofibrils and myofilaments to disease progression has been largely underexplored. This oversight has predominantly been because of a paucity of methods for objective and quantitative analysis. Here, we introduce a novel, less-biased approach to quantify myofibrillar and myofilament orientation in cardiac muscle under near-physiological conditions and demonstrate its superiority as compared with conventional histological assessments. Using small-angle x-ray diffraction, we first investigated changes in myofibrillar orientation at increasing sarcomere lengths in permeabilized, relaxed, wild-type mouse myocardium from the left ventricle by assessing the angular spread of the 1,0 equatorial reflection (angle σ). At a sarcomere length of 1.9 μm, the angle σ was 0.23 ± 0.01 rad, decreased to 0.19 ± 0.01 rad at a sarcomere length of 2.1 μm, and further decreased to 0.15 ± 0.01 rad at a sarcomere length of 2.3 μm (p < 0.0001). Angle σ was significantly larger in R403Q, a MYH7 hypertrophic cardiomyopathy model, porcine myocardium (0.24 ± 0.01 rad) compared with wild-type myocardium (0.14 ± 0.005 rad; p < 0.0001), as well as in human heart failure tissue (0.19 ± 0.006 rad) when compared with nonfailing samples (0.17 ± 0.007 rad; p = 0.01). These data indicate that diseased myocardium suffers from greater myofibrillar disorientation compared with healthy controls. Finally, we showed that conventional, histology-based analysis of disarray can be subject to user bias and/or sampling error and lead to false positives. Our method for directly assessing myofibrillar orientation avoids the artifacts introduced by conventional histological approaches that assess myocyte orientation and only indirectly evaluate myofibrillar orientation, and provides a precise and objective metric for phenotypically characterizing myocardium. The ability to obtain excellent x-ray diffraction patterns from frozen human myocardium provides a new tool for investigating structural anomalies associated with cardiac diseases.


Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901.
Nelarabine (compound 506U78), a novel purine nucleoside, is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine (ara-G). Nelarabine is rapidly demethoxylated in blood by adenosine deaminase to ara-G. Pre-clinical and clinical studies have demonstrated the selective cytotoxicity of ara-G to T-lineage derived cells. CALGB Protocol 59901 was a Phase II study of nelarabine in patients with systemically untreated cutaneous T-cell lymphoma (CTCL) or refractory/relapsed systemic T-cell lymphoma (STCL). The objectives were to determine response rate, remission duration and safety profile associated with nelarabine given at 1.5 g m(-2) per day on days 1, 3 and 5 as an intravenous infusion every 21 days for a minimum of two cycles and to continue up to two cycles beyond CR up to a maximum of eight cycles. Nineteen patients were enrolled in the study: 11 CTCL and eight STCL patients. Grade 3 or 4 adverse events were documented in 50% and 28%, respectively. In particular, 33% of patients experienced Grade 3 or 4 neurologic toxicities. There were two partial remissions lasting 3 months and 5.5 months, respectively. Median event-free survival was 1.2 months and median overall survival was 3 months. Due to lack of efficacy and excessive toxicity, nelarabine is not recommended as monotherapy in adult patients with CTCL and STCL at this dose schedule.


A randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. The Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia.
A prospective randomized clinical trial was performed in 339 postmenopausal patients with advanced breast cancer. Two single modality treatment sequences, doxorubicin plus cyclophosphamide (AC) followed on failure by tamoxifen (TAM), and TAM followed by AC, were compared with combined modality chemo-endocrine therapy (TAM plus AC). The response rate to initial TAM (22.1%) was inferior to that for AC (45.1%), and for TAM plus AC (51.3%). However, patients randomized to the sequence TAM followed by AC showed a 42.5% overall tumor response to sequential protocol therapy, similar to the 46.9% for those randomized to AC followed by TAM. Furthermore, survival in all three arms was almost identical. Adverse prognostic factors for survival were liver metastases, short disease-free interval, poor performance status, and prior adjuvant chemotherapy. In no subgroup was significantly better survival associated with initial cytotoxic therapy. Endocrine therapy followed on failure by cytotoxics is appropriate for postmenopausal patients with advanced breast cancer.


Antimicrobial peptides in frog skin secretions.
Skin secretions from many species of anurans (frogs and toads) are a rich source of peptides with broad-spectrum antimicrobial activities that may be developed into agents with therapeutic potential, particularly for topical applications. This chapter describes the use of norepinephrine (injection or immersion) to stimulate peptide release from granular glands in the skin in procedures that do not appear to cause distress to the animals. The peptide components in the secretions are separated using reversed-phase HPLC on octadecylsilyl-silica (C(18)) columns after partial purification on Sep-Pak C(18) cartridges. Peptides with antimicrobial activity are then identified by demonstration of their abilities to inhibit growth of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria in liquid phase microtiter plate assays. Individual peptides with activity are purified to near homogeneity by further chromatography on butylsilyl-(C(4)) and diphenylmethylsilyl-silica columns and characterized structurally by automated Edman degradation and mass spectrometry.


The Effects of Home Care Provider Mix on the Care Recipient: An International, Systematic Review of Articles from 2000 to 2020.
In this systematic review, we examine the literature from 2000 to 2020 to ascertain whether we can make strong conclusions about the relative benefit of adding informal care or formal care providers to the care mix among individuals receiving care in the home, specifically focusing on care recipient outcomes. We evaluate how informal care and formal care affect (or are associated with) health care use of care recipients, health care costs of care recipients, and health outcomes of care recipients. The literature to date suggests that informal care, either alone or in concert with formal care, delivers improvements in the health and well-being of older adults receiving care. The conclusions one can draw about the effects of formal care are less clear.


The Protective Effect of Metformin Use on Early Nd:YAG Laser Capsulotomy.
To determine the effect of metformin on early Nd:YAG laser treatment for posterior capsule opacification (PCO) and to explore a molecular mechanism to explain a possible protective effect of metformin against PCO. We conducted: 1) a retrospective cohort study of patient eyes undergoing phacoemulsification at our institution; and 2) laboratory investigation of the effect of metformin on the behavior of lens epithelial cells in the context of an animal model for PCO. Population-averaged Cox proportional hazards modeling was used to estimate risk for time to Nd:YAG. For laboratory studies, expression of markers for epithelial-to-mesenchymal transition (EMT) implicated in PCO pathogenesis was measured in tissue culture and following extracapsular lens extraction in a mouse model. The rate of Nd:YAG laser capsulotomy was 13.1% among the 9798 eyes. Both metformin use and diabetes were protective factors for Nd:YAG laser capsulotomy in univariate analysis. However, in multivariable analysis with nondiabetics as the reference group, only metformin use among diabetics was significantly protective of Nd:YAG (hazard ratio: 0.68, 95% CI: 0.54-0.85, P = 0.0008), while eyes of patients with diabetes without metformin use did not significantly differ (P = 0.5026). Treatment of lens epithelial cells with metformin reduced the level of the EMT markers ⍺-SMA and pERK induced by TGF-β2. Similarly, metformin treatment reduced ⍺-SMA expression in lens epithelial cells following extracapsular lens extraction in a mouse model. The protective effect of metformin against early Nd:YAG may relate to its ability to downregulate EMT in residual lens epithelial cells that otherwise trend toward myofibroblast development and PCO.


The Effect of the Orientation Towards Analyte Flow on Electrochemical Sensor Performance and Current Fluctuations.
Analyte flow influences the performance of every gas sensor; thus, most of these sensors usually contain a diffusion barrier (layer, cover, inlet) that can prevent the negative impact of a sudden change of direction and/or the rate of analyte flow, as well as various unwanted impacts from the surrounding environment. However, several measurement techniques use the modulation of the flow rate to enhance sensor properties or to extract more information about the chemical processes that occur on a sensitive layer or a working electrode. The paper deals with the experimental study on how the analyte flow rate and the orientation of the electrochemical sensor towards the analyte flow direction influence sensor performance and current fluctuations. Experiments were carried out on a semi-planar, three-electrode topology that enabled a direct exposure of the working (sensing) electrode to the analyte without any artificial diffusion barrier. The sensor was tested within the flow rate range of 0.1-1 L/min and the orientation of the sensor towards the analyte flow direction was gradually set to the four angles 0°, 45°, 90° and 270° in the middle of the test chamber, while the sensor was also investigated in the standard position at the bottom of the chamber.


Late-onset mania associated with corticosteroids and small cell lung carcinoma.
Episodes of mania typically occur in the context of bipolar disorder, with an average age of onset of 25 years. A condition with identical symptoms, known as secondary mania, generally occurs in isolation in older adults and has an identifiable organic etiology. Here, we report a 57-year-old man who presented to the emergency department with a 3 weeks history of sudden onset mania with psychotic symptoms. He had no previous psychiatric history, and his presentation coincided with the initiation of a course of steroids. Despite the absence of physical symptoms, investigations revealed a previously undetected adrenocorticotropic hormone-releasing small cell lung carcinoma that led to his death within months. This case highlights the complexity of distinguishing primary from secondary mania when it occurs after the peak incidence period of early adulthood. Undertaking a comprehensive medical workup is generally recommended.