Identification of Salmonella serotypes isolated from cantaloupe and chile pepper production systems in Mexico by PCR-restriction fragment length polymorphism.
A study was conducted in 2006 to determine the prevalence of Salmonella on three cantaloupe farms in Matamoros, Coahuila, Mexico, and on one farm that cultivates chile peppers var. Bell in Culiacán, Sinaloa, Mexico. Samples from cantaloupe farms consisted of cantaloupe rinses, irrigation water, water from furrows in the field, and workers' hands. Samples from the chile pepper farm consisted of rinses of chile peppers obtained at the field, pepper rinses obtained at the packing house, and irrigation water from the field. A total of 55 samples were obtained from both production systems. Twelve and 10 samples from the cantaloupe and chile pepper production systems, respectively, tested positive for Salmonella according to a traditional culture method. The difference between the proportion of Salmonella-positive samples from the cantaloupe production system (12 of 28 = 0.43) and the chile pepper production system (10 of 27 = 0.37) was not statistically significant (P > 0.05). A PCR-restriction fragment length polymorphism (RFLP) method based on the fliC gene was used to determine the serotype of the isolates. Salmonella Typhimurium was the only serotype found associated with the cantaloupe production system, whereas both Salmonella Typhimurium and Enteritidis serotypes were found associated with the chile pepper production system. Results showed that 91% (20 of 22) and 9% (2 of 22) of the isolates from both agricultural systems matched with the Salmonella Typhimurium and Salmonella Enteritidis reference strain restriction profiles, respectively. This study demonstrates the utility of the PCR-RFLP technique for determining the serotypes of Salmonella isolates obtained from cantaloupe and chile pepper production systems.


Pharmacological inhibition of TRalpha1 receptor potentiates the thyroxine effect on body weight reduction in rats: potential therapeutic implications in controlling body weight.
It has been previously reported that thyroid hormone receptor alpha1 (TRalpha1) is involved in the regulation of food intake and heart rhythm. Herein, we show that pharmacological inhibition of TRalpha1 by dronedarone, an amiodarone like compound (shown to antagonize thyroid hormone binding to TRalpha1), prevented the thyroid hormone induced increase in food intake and heart rate acceleration in rats. This resulted in a marked reduction in body weight. It is likely that thyroid analogs may prove potential therapeutic agents for controlling body weight.


Nocturnal enuresis.
Nocturnal enuresis is a treatable condition. It is defined as functional urinary incontinence during sleep beyond the age (arbitrarily taken to be) of 6 years old at which control should be established. Although it is a physically benign condition, it is unfortunately associated with emotional-behavioural disturbances and developmental delays. Diagnosis is usually straight-forward, and based mainly on history and physical examination. Often, only a microscopic examination of urine is required to exclude urinary tract infection. Treatment begins with a baseline recording of the frequency of enuresis. This is incorporated into motivational therapy which consists of counselling, enhancement of self-responsibility and self-efficacy with positive reinforcement for success. Failing which, enuretic alarm provides the single most effective mode of treatment. However, it suffers from poor compliance. Medication is usually used on an as-needed basis because most relapse after cessation of treatment. Imipramine is the most well-studied and commonly used medication but suffers from potential toxicity. Desmopressin, on the other hand, has few adverse side-effects and is just as effective as imipramine. Its main drawback is its cost.


Relationship between traditional games and the intensity of emotions experienced by participants.
The aims of this study were to analyze the intensity of emotions (positive, negative, or ambiguous) produced when players took part in traditional games with a different social structure and to examine the explanations given by those participants for these emotional experiences. Participants (N = 556) were recruited from 4 Spanish universities. After taking part in each of the games, they were asked to complete the Games and Emotions Questionnaire to indicate the intensity of their emotional experiences and to explain what, in their view, had led to the strongest emotion felt. The application of a mixed-methods approach identified statistically significant differences in relation to 3 variables. These were (a) the type of emotion, (b) motor domain, and (c) type of result (win, loss, and noncompetitive). The intensity of positive emotions was higher in cooperative games and lower in individual games. Comments referring to negative emotions were more frequent as the social structure of games became more complex (minimal presence of individual games and predominance of cooperation-opposition games). Winning was associated with the highest intensity ratings of positive and ambiguous emotions, whereas being defeated produced the highest values for negative emotions. The intensity ratings for negative emotions were lower in noncompetitive games than in games where players lost. The results confirm that traditional games can play a key role in relation to the emotional facets of physical education.


Role of proton pump inhibitor on esophageal carcinogenesis and pancreatic acinar cell metaplasia development: an experimental in vivo study.
Chronic gastro-duodenal reflux in the esophagus is a major risk for intestinal metaplasia and Barrett's adenocarcinoma. A role for chronic use of proton pump inhibitor (PPI) in the increased incidence of esophageal adenocarcinoma in Western countries has been previously suggested. The aim of this work was to study the effect of chronic administration of omeprazole (a proton pump inhibitor) per os in a model of reflux induced esophageal carcinogenesis. One week after esophago-gastro-jejunostomy, 115 Sprague-Dawley rats were randomized to receive 10 mg/Kg per day of omeprazole or placebo, 5 days per week. The esophago-gastric specimens were collected 28 ± 2 weeks after randomization and analyzed in a blinded fashion. Mortality and esophageal metaplasia rates did not differ between the two groups (p = 0.99 for mortality, p = 0.36 for intestinal metaplasia and p = 0.66 for multi-layered epithelium). Gastric pancreatic acinar cell metaplasia (PACM) was more frequently observed in PPI-treated rats (p = 0.003). Severe ulcer lesions significantly prevailed in the placebo group (p = 0.03). Locally invasive esophageal epithelial neoplasia were observed in 23/39 PPI-treated versus 14/42 placebo-animals (p = 0.03). In conclusion, chronic omeprazole treatment improved the healing of esophageal ulcerative lesions. Locally invasive neoplastic lesions and PACM prevailed among PPI-treated animals. However, neither an effect on the overall mortality nor on the incidence of pre-neoplastic lesions was observed in this work.


Experimental Models of Endotheliopathy: Impact of Shock Severity.
Hemorrhagic shock (HS) followed by resuscitation is often associated with sympathoadrenal activation (SAA) and endothelial damage (ED). We aimed to evaluate the impact of HS alone on the magnitude of SAA and consecutive ED, and to characterize potential targets for a standardized and reproducible model of HS-induced endotheliopathy in rats. Rats were subjected either to a volume-controlled HS (40% of total blood volume: v-HS group) or to a laboratory-guided HS (l-HS) targeting base deficit (BD) more than 5.5 mmol/L and/or lactate more than 2.2 mmol/L using a pressure-controlled volume loss. At the end of shock, mean arterial pressure was significantly higher in the v-HS than the l-HS group (36 ± 5.6 vs. 30 ± 3.0 mmHg; P < 0.01). Base deficit and lactate were higher in l-HS than the v-HS group (BD: 9.5 ± 2.5 vs. 3.0 ± 1.0 mmol/L; P < 0.001; lactate: 4.1 ± 1.3 vs. 1.6 ± 0.6 mmol/L; P < 0.001). sVEGFR-1 and syndecan-1 were approximately 50% higher in the l-HS than the v-HS group (% changes vs. baseline: 160 ± 10 vs. 116 ± 36; P < 0.01; 170 ± 37 vs. 113 ± 27; P < 0.001). Adrenaline was 2-fold higher in l-HS than the v-HS group (1964 ± 961% vs. 855 ± 451%; P < 0.02, respectively). Moreover, linear regression analysis revealed an independent association of shock severity BD with syndecan-1 (rho = 0.55, P = 0.0005), sVEGFR1 (rho = 0.25, P < 0.05), and adrenaline (rho = 0.31, P = 0.021). Our findings indicate that ED has already occurred during HS without reperfusion; intensity is strongly related to the severity of HS and consecutive SAA; and severity may appropriately be targeted and standardized in a HS model controlled by biological endpoints such as BD and/or lactate.


The Role of Thyroid Function in Alzheimer's Disease.
The thyroid gland is crucial for the regulation of metabolism, growth, and development of various tissues, organs, systems, including the central nervous system. Recent studies have implicated the role of thyroid dysfunction in the etiology of Alzheimer's disease (AD), while AD leads to a significant increase in the prevalence of thyroid dysfunction. In this review, we have analyzed the role of thyroid function in the pathophysiology of AD as well as its biomarkers. The present review aims to provide encouraging targets for early screening of AD risk factors and intervention strategies.


Contact Mode Atomic Force Microscopy as a Rapid Technique for Morphological Observation and Bacterial Cell Damage Analysis.
Electron microscopy is one of the tools required to characterize cellular structures. However, the procedure is complicated and expensive due to the sample preparation for observation. Atomic force microscopy (AFM) is a very useful characterization technique due to its high resolution in three dimensions and because of the absence of any requirement for vacuum and sample conductivity. AFM can image a wide variety of samples with different topographies and different types of materials. AFM provides high-resolution 3D topography information from the angstrom level to the micron scale. Unlike traditional microscopy, AFM uses a probe to generate an image of the surface topography of a sample. In this protocol, the use of this type of microscopy is suggested for the morphological and cell damage characterization of bacteria fixed on a support. Strains of Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Pseudomonas hunanensis (isolated from garlic bulb samples) were used. In this work, bacterial cells were grown in specific culture media. To observe cell damage, Staphylococcus aureus and Escherichia coli were incubated with different concentrations of nanoparticles (NPs). A drop of bacterial suspension was fixed on a glass support, and images were taken with AFM at different scales. The images obtained showed the morphological characteristics of the bacteria. Further, employing AFM, it was possible to observe the damage to the cellular structure caused by the effect of NPs. Based on the images obtained, contact AFM can be used to characterize the morphology of bacterial cells fixed on a support. AFM is also a suitable tool for the investigation of the effects of NPs on bacteria. Compared to electron microscopy, AFM is an inexpensive and easy-to-use technique.


Prediction of postoperative cardiopulmonary function in patients undergoing pneumonectomy.
This paper addresses itself to the question of whether it is possible to calculate the postoperative values for cardiopulmonary function before surgery, Data of 29 patients were analyzed before and 6 months after pneumonectomy: whole body plethysmography, ergometry, blood gas analysis, right heart catheterization, and quantified perfusion scan of the lung. Using a simple formula, the postoperative value was calculated preoperatively and compared with the value actually measured 6 months postoperatively. The results showed a fairly good correlation for lung volumes, especially FEV1 (r = 0.66; P < 0.001), but no good predictability for the pulmonary hemodynamics (e.g., Pap = 38.6 +/- 9.8 mmHg preoperatively calculated vs. 29.9 +/- 6.3 mmHg postoperatively measured). These results and the predominant prognostic value of FEV1 are the basis of a suggested flow sheet for preoperative evaluation of patients undergoing pneumonectomy.


Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice.
For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.


Relationship between cerebral oxygenation, cardiac output, and blood pressure during transitional period in extremely low gestational age neonates.
To describe the relationship between cerebral oxygenation, cardiac output, arterial blood pressure (BP), and cerebral blood flow velocity in extremely low gestational age neonates (ELGANs) during transition. This study comprises secondary analyses from a prospective observational study conducted at a tertiary Neonatal Intensive Care Unit. Recruited ELGANs underwent cerebral saturation (CrSO2) monitoring and serial echocardiography during 72 h from birth. Correlative analyses of CrSO2 and cerebral fractional tissue oxygen extraction (CFTOE) with left (LVO) and right ventricular output (RVO), superior vena cava (SVC) flow, middle cerebral artery blood flow mean velocity (MCA.MV), systolic (SBP), diastolic (DBP), and mean (MBP) BP were conducted. Fifty ELGANs with median (range) gestational age of 25.9 (23.1-27.9) weeks were recruited. Echocardiography was performed sequentially at a median (range) age 5.0 (3.8-6.6), 17.3 (15.4-19.4), 31.0 (27.0-34.1), and 53.7 (49.3-58.3) hours. RVO, LVO, CrSO2, and SBP increased over time but no changes in MBP, DBP, CFTOE, MCA.MV or SVC flow were noted. A weak correlation was identified between CrSO2 and SBP (r2 = 0.11, p = 0.047) and MBP (r2 = 0.12, p = 0.04) at 17.3 (15.4-19.4) hours. No correlation of either CrSO2 or CFTOE with any measures of blood flow was identified. There is a weak correlation between measures of cardiac output, BP, and MCA.MV with both CrSO2 and CFTOE in ELGANs during transition. Whether this finding suggests intact cerebral autoregulation requires prospective evaluation in a cohort of sick ELGANs.


[Cross-forearm replantation in bilateral amputation].
We report the case of a 27-year-old patient who sustained a traumatic amputation of his 4 limbs. For the right upper limb, the site of amputation was at the level of the upper third of the forearm. For the left upper limb, the site of amputation was at the level of the Cower third of the forearm. In both cases, the loss of soft tissue was so extensive that hand replantation was impossible in the initial position. In such an unusual case, replantation of the right hand to the left side was attempted in this young patient. Osteosynthesis of the radius to the ulna in supination was performed, and arteries, veins, nerves and tendons were repaired. The other segments of amputated limbs were debrided and cleaned. Within a year, protective sensibility was restored in the replanted hand, but intrinsic muscles were paralysed. Secondarily, transfer of thumb opposition and capsulorrhaphy at the level of the metacarpophalangeal joints of long fingers were performed in order to provide a useful key-grip between the three first fingers.


A Noise Reduction Method for Dual-Mass Micro-Electromechanical Gyroscopes Based on Sample Entropy Empirical Mode Decomposition and Time-Frequency Peak Filtering.
The different noise components in a dual-mass micro-electromechanical system (MEMS) gyroscope structure is analyzed in this paper, including mechanical-thermal noise (MTN), electronic-thermal noise (ETN), flicker noise (FN) and Coriolis signal in-phase noise (IPN). The structure equivalent electronic model is established, and an improved white Gaussian noise reduction method for dual-mass MEMS gyroscopes is proposed which is based on sample entropy empirical mode decomposition (SEEMD) and time-frequency peak filtering (TFPF). There is a contradiction in TFPS, i.e., selecting a short window length may lead to good preservation of signal amplitude but bad random noise reduction, whereas selecting a long window length may lead to serious attenuation of the signal amplitude but effective random noise reduction. In order to achieve a good tradeoff between valid signal amplitude preservation and random noise reduction, SEEMD is adopted to improve TFPF. Firstly, the original signal is decomposed into intrinsic mode functions (IMFs) by EMD, and the SE of each IMF is calculated in order to classify the numerous IMFs into three different components; then short window TFPF is employed for low frequency component of IMFs, and long window TFPF is employed for high frequency component of IMFs, and the noise component of IMFs is wiped off directly; at last the final signal is obtained after reconstruction. Rotation experimental and temperature experimental are carried out to verify the proposed SEEMD-TFPF algorithm, the verification and comparison results show that the de-noising performance of SEEMD-TFPF is better than that achievable with the traditional wavelet, Kalman filter and fixed window length TFPF methods.


The effects of body weight on serum cholesterol, serum triglycerides, serum urate and systolic blood pressure.
The effects of body weight and age on serum cholesterol, serum triglycerides, serum urate and systolic blood pressure were examined in 600 male and 400 female blood donors aged 20 to 49 years. In the men significant correlations with body mass index were found for all four variables in each decade. In the women below 40 only the correlation with blood pressure was significant. In the fifth decade the correlations resembled those in the men, save for triglycerides. After adjusting for weight, age had no independent influence on the prevalence of hypertriglyceridaemia or hypertension in either sex. In men the effect of body weight on the prevalence of hypercholesterolaemia was age dependent. Age influenced hyperuricaemia independently of weight. In women only serum cholesterol was affected by age after allowing for weight. There was marked clustering of high values of the four variables in the heavier men and women and this increased with age. The leanest men and women were remarkably free of high values.


The Milwaukee brace in paralytic scoliosis.
The Milwaukee brace possesses excellent passive properties in addition to the well known dynamic action, and is of definite value in the bracing of paralytic curves in children in whom a fusion should be de-delayed. This application is a temporary but at the same time a long term expedient to allow spine growth prior to surgery.


Haplotypes of human leukocyte antigens among patients with nasopharyngeal cancer in Greece.
The concept that the major histocompatibility complex (MHC) plays an important role in the pathogenesis of nasopharyngeal cancer (NPC) in several ethnic groups has gained increased attention during the last 15 years. Earlier studies have suggested that an increased risk of NPC is associated with specific phenotypes of human leukocyte antigens (HLA). The present study was performed to examine the association of HLA specificities and haplotypes with NPC in a Greek population. In a genotypical study of 53 patients, a significant association between the haplotype HLA-B5DR11 and NPC was found, mainly in patients > 45 years. Also, the above haplotype was significantly associated with longer disease-free interval. HLA-B5 and HLA-B5DR11 were more often seen among patients with squamous cell histology than among those with the undifferentiated type. These results suggest that MHC loci are probably implicated in the pathogenesis and outcome of NPC in Greek patients.


The mechanism of the nephridial apparatus of Paramecium multimicronucleatum. I. Expulsion of water from the vesicle.
Recent analysis of the mechanism of the nephridial apparatus of Paramecium multimicronucleatum by high-speed cinematography (300 fps at x 250) confirms the observations by electron microscopy (Schneider, 1960) that once the pore is opened, the vesicle is invaginated by adjacent cytoplasm and is emptied by collapsing under pressure from that cytoplasm, aided perhaps by pressure of the fibrils which anchor the ampullae to the excretory canal. There is no indication of active contraction of the vesicle or its membrane. There is no permanent pore to the vesicle. The vesicle is closed by a sealing of the ruptured membrane where it is in contact with the pellicular excretory canal. At onset of expulsion of vesicular fluid the membrane across the basal opening of the excretory canal is ripped along one semicircular portion of the excretory pore and is driven up against the opposite wall as a flap while the water rushes out. A constriction of the vesicular and cell membranes at the base of the excretory canal reseals the opening.


Transfer free energies and average static accessibilities for ribonuclease A in guanidinium hydrochloride and urea solutions.
Isopiestic vapor pressure measurements have been used to obtain free energies of transfer of ribonuclease A from dilute buffer to solutions of either urea or guanidine hydrochloride (GdnHCl) over a wide cosolute concentration range. The free energies of transfer vary monotonically from 0 to -8 kcal/mol in 8 M urea and to -18 kcal/mol in 6 M GdnHCl. These values are not large in relation to free energies of transfer of constituent groups of the protein from water to cosolute solutions of the same concentration. The assumption is made that the magnitude of the free energy of transfer of the protein is governed by the average static accessibility of the constituent groups to the solution. The free energies of transfer to different cosolute concentrations of a hypothetical 100% accessible ribonuclease A were determined using literature values of the free energies of transfer of constituent groups and the amino acid composition. The ratio of the experimentally determined free energy of transfer to the free energy of transfer of the 100% accessible protein gave 11% accessible surface area for the native protein in 1 M GdnHCl or 2 M urea. Additional considerations led to a value of 36% for the accessible surface area of the denatured protein in 6 M GdnHCl or 8 M urea.


Economics and public health at CDC.
Economics is the study of decisions--the incentives that lead to them and the consequences that result from them--as they relate to present and future production, distribution, and consumption of goods and services when resources are limited and have alternative uses. At CDC, economics is used to systematically identify, measure, value, and compare the costs and consequences of alternative prevention strategies. Costs and consequences in public health can be measured in various ways, including incidence or prevalence of disease; numbers of adverse events; utility measures, such as quality-adjusted life years; and monetary values. Because it deals with behavior, economics is not really about money at all. Money is just a convenient way to measure incentives and consequences.


Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells.
Lichens, which represent symbiotic associations of fungi and algae, are potential sources of numerous natural products. Physciosporin (PHY) is a potent secondary metabolite found in lichens and was recently reported to inhibit the motility of lung cancer cells via novel mechanisms. The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells. PHY was isolated from lichen extract by preparative TLC. The effect of PHY on cell viability, motility and tumourigenicity was elucidated by MTT assay, hoechst staining, flow cytometric analysis, transwell invasion and migration assay, soft agar colony formation assay, Western blotting, qRT-PCR and PCR array in vitro as well as tumorigenicity study in vivo. PHY decreased the viability of various CRC cell lines (Caco2, CT26, DLD1, HCT116 and SW620). Moreover, PHY elicited cytotoxic effects by inducing apoptosis at toxic concentrations. At non-toxic concentrations, PHY dose-dependently suppressed the invasion, migration and colony formation of CRC cells. PHY inhibited the motility of CRC cells by suppressing epithelial-mesenchymal transition and downregulating actin-based motility markers. In addition, PHY downregulated β-catenin and its downstream target genes cyclin-D1 and c-Myc. Moreover, PHY modulated KAI1 C-terminal-interacting tetraspanin and KAI1 expression, and downregulated the downstream transcription factors c-jun and c-fos. Finally, PHY administration showed considerable bioavailability and effectively decreased the growth of CRC xenografts in mice without causing toxicity. PHY suppresses the growth and motility of CRC cells via novel mechanisms.


Nursing in Israel.
Nurses in Israel struggle with many of the same problems faced by nurses in other parts of the world, such as increased use of technology, overwhelming amounts of information, and demands for high quality of services to larger numbers of people within tighter budgets. In addition to the aging of the general population, the country has welcomed large numbers of immigrants. The nation's expenditures for healthcare and nursing education have, at times, had to take a back seat to the government's efforts to house new immigrants, to relocate groups, and to defend the nation against politically motivated violence and attacks. All of this is in the context of regional conflicts and international debates.


Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.
Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual.


Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection.
The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy.


"Gesundheit!" sneezing, common colds, allergies, and Staphylococcus aureus dispersion.
Staphylococcus aureus is among the most important pathogens in today's hospital setting. The effects of sneezing on the airborne dispersal of S. aureus and other bacteria were assessed in 11 healthy nasal S. aureus carriers with experimentally induced rhinovirus colds. Airborne dispersal was studied by volumetric air sampling in 2 chamber sessions with and without histamine-induced sneezing. After 2 days of preexposure measurements, volunteers were inoculated with a rhinovirus and monitored for 14 days. Daily quantitative nasal- and skin-culture samples for bacteria and nasal-culture samples for rhinovirus were obtained, cold symptoms were assessed, and volunteer activities were recorded during sessions. All participants developed a cold. Sneezing caused a 4.7-fold increase in the airborne dispersal of S. aureus, a 1.4-fold increase in coagulase-negative staphylococci (CoNS), and a 3.9-fold increase in other bacteria (P < .001). An additional 2.83 colony forming units (cfu) of S. aureus/m3/min, 3.24 cfu of CoNS/m3/min, and 474.61 cfu of other bacteria/m3/min were released per sneeze. Rhinovirus exposure did not change the frequency of sneezing or airborne dispersal. Having respiratory allergies increased the spread of S. aureus by 3.8-fold during sneezing sessions (P < .001). Nasal S. aureus carriers disperse a significant amount of S. aureus into the air by sneezing. Experimental colds do not alter bacterial dispersal, but respiratory allergies multiply the effect of dispersing S. aureus.


Effect of curcumin on intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats.
This study was designed to investigate the protective effects of curcumin against colchicine-induced cognitive impairment and oxidative stress in rats. Male Wistar rats (weighing 150-200 g) received colchicine intracerebroventricularly (15 microg per rat), and cognitive dysfunctions were evaluated by the Morris water maze and the plus maze performance task and supported by biochemical tests. Central administration of colchicine caused memory deficit in both the Morris water maze and the elevated plus maze task paradigm tasks. Chronic treatment with curcumin (5-50 mg/kg, p.o.) twice daily for a period of 25 days beginning 4 days prior to colchicine injection significantly improved the colchicine-induced cognitive impairment. Biochemically, chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the decreased reduced glutathione level and acetylcholinesterase activity, and attenuated the raised colchicine-induced elevated nitrite levels. The results of the present study indicate that curcumin has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.


A parametric study of cognitive defusion and the believability and discomfort of negative self-relevant thoughts.
A previous time-series study showed that rapidly repeating a single-word version of a negative self-referential thought reduced the discomfort and the believability associated with that thought. The present parametric study examined whether durations of word repetition were differentially effective in altering the discomfort and believability of negative self-referential thought. In two studies, both discomfort and believability varied systematically with the duration of word repetition. The effects of rapid repetition on emotional discomfort bottomed out after 3 s to 10 s of rapid repetition, whereas the effects on believability did so after 20 s to 30 s of repetition. This study lends support to the cognitive defusion interpretation of the effect of word repetition, suggesting that emotional discomfort and believability may be distinctive functional aspects of cognitive events.


3D imaging techniques for improved colonoscopy.
Colonoscopy screening with a conventional 2D colonoscope is known to reduce mortality due to colorectal cancer by half. Unfortunately, the protective value of this procedure is limited by missed lesions. To improve the sensitivity of colonoscopy to precancerous lesions, 3D imaging techniques could be used to highlight their characteristic morphology. While 3D imaging has proved beneficial for laparoscopic procedures, more research is needed to assess how it will improve applications of flexible endoscopy. In this editorial, we discuss the possible uses of 3D technologies in colonoscopy and factors that have hindered the translation of 3D imaging to flexible endoscopy. Emerging 3D imaging technologies for flexible endoscopy have the potential to improve sensitivity, lesion resection, training and automated lesion detection. To maximize the likelihood of clinical adoption, these technologies should require minimal hardware modification while maintaining the robustness and quality of regular 2D imaging.


A SAED and HREM study of structural defects in brownmillerite, LaBa(x)Sr(1-x)CuGaOy related oxides.
The synthesis and microstructural characterization, by means of selected area electron diffraction (SAED) and high resolution electron microscopy (HREM), of the solid solution LaBa(x)Sr(1-x)CuGaO5 (0.1 < or = 5 x < or = 0.9) is reported. Although an average brownmillerite Ima2 structure is proposed for the whole compositional range, SAED and HREM clearly show that structural defects appear as barium content increases.


Diagnostic validation of smart wearable device embedded with single-lead electrocardiogram for arrhythmia detection.
To validate a single-lead electrocardiogram algorithm for identifying atrial fibrillation, atrial premature beats, ventricular premature beats, and sinus rhythm. A total of 656 subjects aged 19 to 94 years were enrolled. Participants were simultaneously tested with a wristwatch (Huawei Watch GT2 Pro, Huawei Technologies Co., Ltd, Shenzhen, China) and a 12-lead electrocardiogram for 3 minutes. A total of 1926 electrocardiogram signals from 628 subjects (282 men and 346 women) aged 19 to 94 years (median 64 years) were analyzed using an algorithm. The numbers of subjects with atrial fibrillation, atrial premature beats, ventricular premature beats, and sinus rhythm were 129, 141, 107, and 251, respectively, and together they had a total of 1926 electrocardiogram signals. For the three-class classification system, the recall, precision, and F1 score were 97.6%, 96.5%, 97.0% for sinus rhythm; 96.7%, 96.9%, 96.8% for atrial fibrillation; and 92.8%, 94.2%, 93.5% for ectopic beats, respectively. The macro-F1 score of the three-class classification system was 95.8%. For the four-class classification system, the recall, precision, and F1 score were 97.6%, 96.5%, 97.0% for sinus rhythm; 96.7%, 96.9%, 96.8% for atrial fibrillation; 90.5%, 89.4%, 89.9% for atrial premature beats; and 86.1%, 89.6%, 87.8% for ventricular premature beats, respectively. The macro-F1 score of the four-class classification system was 92.9%. The single-lead electrocardiogram algorithm embedded into smart wearables demonstrated good performance in detecting atrial fibrillation, atrial/ventricular premature beats, and sinus rhythm, and thus would facilitate atrial fibrillation screening and management.


Systematic Analysis of Gene Expression in Lung Adenocarcinoma and Squamous Cell Carcinoma with a Case Study of FAM83A and FAM83B.
In our previous study, we constructed a Lung Cancer Explorer (LCE) database housing lung cancer-specific expression data and clinical data from over 6700 patients in 56 studies. Using this dataset of the largest collection of lung cancer gene expression along with our meta-analysis method, we systematically interrogated the association between gene expression and overall survival as well as the expression difference between tumor and normal (adjacent non-malignant tissue) samples in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQCC). A case study for FAM83A and FAM83B was performed as a demonstration for hypothesis testing with our database. We showed that the reproducibility of results across studies varied by histological subtype and analysis type. Genes and pathways unique or common to the two histological subtypes were identified and the results were integrated into LCE to facilitate user exploration. In our case study, we verified the findings from a previous study on FAM83A and FAM83B in non-small cell lung cancer. This study used gene expression data from a large cohort of patients to explore the molecular differences between lung ADC and SQCC.


A Shearless Microfluidic Device Detects a Role in Mechanosensitivity for AWCON Neuron in Caenorhabditis elegans.
AWC olfactory neurons are fundamental for chemotaxis toward volatile attractants in Caenorhabditis elegans. Here, it is shown that AWCON responds not only to chemicals but also to mechanical stimuli caused by fluid flow changes in a microfluidic device. The dynamics of calcium events are correlated with the stimulus amplitude. It is further shown that the mechanosensitivity of AWCON neurons has an intrinsic nature rather than a synaptic origin, and the calcium transient response is mediated by TAX-4 cGMP-gated cation channel, suggesting the involvement of one or more "odorant" receptors in AWCON mechano-transduction. In many cases, the responses show plateau properties resembling bistable calcium dynamics where neurons can switch from one stable state to the other. To investigate the unprecedentedly observed mechanosensitivity of AWCON neurons, a novel microfluidic device is designed to minimize the fluid shear flow in the arena hosting the nematodes. Animals in this device show reduced neuronal activation of AWCON neurons. The results observed indicate that the tangential component of the mechanical stress is the main contributor to the mechanosensitivity of AWCON . Furthermore, the microfluidic platform, integrating shearless perfusion and calcium imaging, provides a novel and more controlled solution for in vivo analysis both in micro-organisms and cultured cells.


Early feasibility testing and engineering development of the transapical approach for the HeartWare MVAD ventricular assist system.
Implantation of ventricular assist devices (VADs) for the treatment of end-stage heart failure (HF) falls decidedly short of clinical demand, which exceeds 100,000 HF patients per year. Ventricular assist device implantation often requires major surgical intervention with associated risk of adverse events and long recovery periods. To address these limitations, HeartWare, Inc. has developed a platform of miniature ventricular devices with progressively reduced surgical invasiveness and innovative patient peripherals. One surgical implant concept is a transapical version of the miniaturized left ventricular assist device (MVAD). The HeartWare MVAD Pump is a small, continuous-flow, full-support device that has a displacement volume of 22 ml. A new cannula configuration has been developed for transapical implantation, where the outflow cannula is positioned across the aortic valve. The two primary objectives for this feasibility study were to evaluate anatomic fit and surgical approach and efficacy of the transapical MVAD configuration. Anatomic fit and surgical approach were demonstrated using human cadavers (n = 4). Efficacy was demonstrated in acute (n = 2) and chronic (n = 1) bovine model experiments and assessed by improvements in hemodynamics, biocompatibility, flow dynamics, and histopathology. Potential advantages of the MVAD Pump include flow support in the same direction as the native ventricle, elimination of cardiopulmonary bypass, and minimally invasive implantation.


Phase-shifting lateral shearing interferometry using wedge-plate and interferometric grating.
A simple and robust method for introducing a phase-shifting test procedure in a wedge-plate shearing interferometer is proposed. The output of the wedge-plate lateral shearing interferometer (LSI) is superposed onto a sinusoidal grating, forming a moiré pattern. The in-plane translation of grating perpendicular to the grating lines is used for introducing a known amount of phase shifts in the interferometer. Direct measurement of phase using a four-step phase-shifting method is undertaken. The applicability of this devised phase-shifting wedge-plate LSI has been successfully tested for setting the collimation position of optical beams. Good accuracy and precision are achieved.


[Complete occlusion of the capsulorhexis incision by anterior capsule shrinkage].
The capsulorhexis technique has become established as procedure of choice for anterior capsular opening in cataract surgery. With the spread of the method even relatively rare complications are gaining in importance. In a patient with cataract and multifocal chorioretinitis, phacoemulsification with implantation of a one-piece PMMA posterior chamber IOL through a capsulorhexis opening was performed without complications. Within a period of 3 months, shrinking of the anterior capsule led to complete occlusion of the anterior aperture. To our knowledge, no comparably severe finding has been reported. The anterior capsule was successfully opened by by means of Nd:YAG laser capsulotomy. However, improvement in visual acuity was limited by cystoid macular edema due to the basic condition. No relations with other systemic or eye diseases have yet been demonstrated. As another case report describes a similar--though less severe--combination of progressive constriction of the anterior capsule and inflammatory eye disease, the opening of the anterior capsule in such cases should be sufficiently large. If anterior capsular shrinkage has developed, Nd:YAG-laser capsulotomy is a low-risk method of therapy.


Does postponing minimum retirement age improve healthy behaviors before retirement? Evidence from middle-aged Italian workers.
By increasing the residual working horizon of employed individuals, pension reforms that rise minimum retirement age can affect individual investment in health-promoting behaviors before retirement. Using the expected increase in minimum retirement age induced by a 2004 Italian pension reform and a difference-in-differences research design, we show that middle-aged Italian males affected by the reform reacted to the longer working horizon by increasing regular exercise, with positive consequences for obesity and self-reported satisfaction with health.


[Pyeloureteral stenting using nitinol stents].
To test the effectiveness of nitinol stents in restoring patency of pyeloureteral segment (PUS). Endoureteral nitinol stents were used in 54 patients. The indications for stenting were recurrent strictures of upper urinary tract and ureteral tumor obstruction in 34 and 20 patients, respectively. In 9 (16.6%) of them, including 4 women and 5 men aged 28-65 years, stenting was performed for extensive recurrent PUS strictures. In 8 patients extensive strictures resulted from various surgical interventions on the PUS. In 2 patients, PUS narrowing was caused by open pyelolithotomy, in 6 patients by pyeloplasty, both open (4) and laparoscopic (2). A female patient with solitary right kidney and Bourneville - Pringle disease of the PUS received two metal prostheses. In all cases, nitinol stents were adequately installed in PUS. Hematuria was observed in 1 patient. During the follow-up period of 8 to 60 months, the results of stenting were considered good in 6 (66.7%) and satisfactory in 2 (22.2%) patients. At month 10, 1 (11.1%) patient developed the stent obstruction by proliferative tissue and underwent ureteroscopy with recanalization of the nitinol stent. The patient with Bourneville - Pringle disease was found to have a stone formed in the renal pelvic end of the endoprosthesis; she underwent percutaneous nephrolithotripsy. In another patient a lower calyceal stone migrated and wedged into the proximal end of the stent. The stone was extracted using percutaneous nephroscopy. Pyeloureteral stenting is an effective method to restore patency of the PUS in patients with extensive recurrent strictures. For adequate functioning of the stents, they need to be of optimal length and correctly installed.


Short-term administration of progesterone and estradiol independently alter carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women.
The individual effects of estrogen and progesterone on baroreflex function remain poorly understood. We sought to determine how estradiol (E2) and progesterone (P4) independently alter the carotid-cardiac and carotid-vasomotor baroreflexes in young women by using a hormone suppression and exogenous add-back design. Thirty-two young women were divided into two groups and studied under three conditions: 1) after 4 days of endogenous hormone suppression with a gonadotropin releasing hormone antagonist (control condition), 2) after continued suppression and 3 to 4 days of supplementation with either 200 mg/day oral progesterone (N = 16) or 0.1 to 0.2 mg/day transdermal 17β-estradiol (N = 16), and 3) after continued suppression and 3 to 4 days of supplementation with both hormones. Changes in heart rate (HR), mean arterial pressure (MAP), and femoral vascular conductance (FVC) were measured in response to 5 s of +50 mmHg external neck pressure to unload the carotid baroreceptors. Significant hormone effects on the change in HR, MAP, and FVC from baseline at the onset of neck pressure were determined using mixed model covariate analyses accounting for P4 and E2 plasma concentrations. Neither P4 (P = 0.95) nor E2 (P = 0.95) affected the HR response to neck pressure. Higher P4 concentrations were associated with an attenuated fall in FVC (P = 0.01), whereas higher E2 concentrations were associated with an augmented fall in FVC (P = 0.02). Higher E2 was also associated with an augmented rise in MAP (P = 0.01). We conclude that progesterone blunts whereas estradiol enhances carotid-vasomotor baroreflex sensitivity, perhaps explaining why no differences in sympathetic baroreflex sensitivity are commonly reported between low and high combined hormone phases of the menstrual cycle.


Preoperative left ventricular function in degenerative mitral valve disease.
The aim of the study is to determine the impact of the underlying etiology (Barlow's disease or fibroelastic deficiency) on left ventricular function in patients with degenerative mitral valve disease and severe mitral regurgitation. We studied 233 patients (mean age: 53.8 ± 12.9) undergoing surgery for severe mitral regurgitation due to degenerative mitral valve disease at Almazov Federal Heart Centre between 2009 and 2011. Pathologic diagnoses for valvular tissue specimens were provided by an experienced pathologist. Preoperative strain and strain rate were determined using speckle tracking (Vivid 7 Dimension, EchoPAC'08). Barlow's disease was identified by the pathologist in 60 patients (25.8%), and fibroelastic deficiency in 173 patients (74.2%). There were no significant differences between groups in preoperative mitral regurgitation volume (70.5 ± 9.6 vs. 71.6 ± 8.5 ml, P = 0.40), and in global systolic (ejection fraction: 52.7 ± 6.6 vs. 52.0 ± 7.4%, P = 0.53) and diastolic (E/e': 12.2 ± 3.9 vs. 12.8 ± 4.2, P = 0.35) left ventricular function. Despite the lack of difference in ejection fraction and diastolic tissue Doppler parameters, in patients with Barlow's disease in comparison with fibroelastic deficiency a significant decrease of the left ventricular longitudinal systolic strain (-13.5 ± 2.2 vs. -15.6 ± 2.3%, P = 0.00001) and early diastolic strain rate (1.04 ± 0.20 vs. 1.14 ± 0.18 s, P = 0.0004) were detected. Patients with severe mitral regurgitation due to Barlow's disease have a lower preoperative left ventricular systolic function than those with fibroelastic deficiency, which may affect their postoperative prognosis.


Transaortic cryoablation of uncommon atrioventricular nodal reentrant tachycardia after Senning and Rastelli operations.
A 36-years-old woman with a congenital corrected transposition of the great arteries, who underwent Senning and Rastelli operations, was admitted with a symptomatic supraventricular tachycardia. During an electrophysiological study, uncommon atrioventricular (AV) nodal reentrant tachycardia was induced. The coronary veins and coronary sinus did not connect to the systemic venous atrium. The His bundle electrogram (HBE) was recorded at the anterior septum of the mitral valve via the aorta. The target of ablation was the site of the earliest atrial activation during the tachycardia, 5 mm posterior to the AV node, and a successful cryoablation was performed using a transaortic approach. Both the antegrade and retrograde conduction of the slow AV nodal pathway was eliminated.


Small cell lung cancer: have we made any progress over the last 25 years?
Twenty-five years ago, small cell lung cancer was widely considered to be the next cancer added to the list of "curable cancers." This article attempts to summarize the progress made toward that goal since then. Clinical trials have provided landmarks in the therapy of limited-stage small cell lung cancer (LS-SCLC). These are: (a) the proof that thoracic radiation therapy adds to systemic chemotherapy, (b) the superiority of twice-daily radiation therapy over daily fractionation, and (c) the need for prophylactic central nervous system radiation (prophylactic cranial irradiation). Each of these innovations adds about 5%-10% to the overall survival rate. In extensive-stage disease, irinotecan plus cisplatin may be a possible alternative to the "standard" etoposide-cisplatin chemotherapy doublet, but there has been little progress otherwise. It is imperative that, whenever possible, patients be given the opportunity to participate in future clinical trials so that the survival for these patients can continue to improve.


Dissecting gene expression at the blood-brain barrier.
The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published data sets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier data sets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published data sets, combined with forthcoming genomic and proteomic blood-brain barrier data sets, will continue to fuel the molecular genetic revolution of.


Au 4f spin-orbit coupling effects in supported gold nanoparticles.
Using X-ray photoelectron spectroscopy we examine the Au 4f spin-orbit components in Au 4f spectra of nanosized Au particles on a TiO2 support. In general, the peak ratios of the Au 4f7/2 and 4f5/2 excitations are found to deviate from the statistical ratio of 4 : 3 and their linewidths (FWHM) are not equal. We reveal that both the FWHM and the Au 4f7/2-to-4f5/2 peak ratios increase appreciably as the Au atomic concentration on the surface of the TiO2 support and the size of Au nanoparticles decrease. On the contrary, the Au 4f spin-orbit splitting remains essentially unchanged. Our findings are discussed in terms of alterations in the electronic band structure.


Intra- and Inter-Rater Reliability of the Modified Tuck Jump Assessment.
The Tuck Jump Assessment (TJA) is a clinician-friendly screening tool that was designed to support practitioners with identification of neuromuscular deficits associated with anterior cruciate ligament injury. This study aimed to evaluate the inter- and intra-rater reliability of the modified scoring (0 to 2) TJA to add an additional range of objectivity for each criterion. A total of 24 elite youth volleyball athletes (12 males and 12 females) were included in this study. Each participant's recorded performance of the TJA was scored independently by two raters across ten criteria using the modified scale. The two raters then scored the same videos one week later. Another investigator who was blind to the identity of the raters analyzed the scores from both raters for each participant. Kappa coefficient (k) and percentage of exact agreement (PEA) for both intra- and inter-rater reliability were analyzed for each item. Intraclass correlation coefficients (ICC) were calculated to determine intra- and inter-rater reliability of the modified TJA total score. Intra- and inter-rater k was good to excellent for most items (0.65-0.91). Average PEA between the two raters and two sessions ranged from 83.3 to 100% in all scored items. The ICC for the total score was excellent in both inter- and inter-rater correlations (0.94-0.96). This research demonstrated that the modified version of the TJA predominantly shows good to excellent intra- and inter-rater reliability in all analyzed criteria.


Late response to allergen is associated with increased concentrations of tumor necrosis factor-alpha and IL-5 in induced sputum.
Bronchial antigen challenge of sensitized atopic patients with asthma results in an early fall in FEV1, followed in a proportion of patients by a late (4 to 24 hours) fall. The late response is accompanied by an increase in bronchial reactivity, which is widely believed to reflect local influx and degranulation of inflammatory cells, particularly eosinophils, in association with elevated local secretion of cytokines. We hypothesized that the development of a late-phase bronchoconstrictor response and airway eosinophilia after allergen challenge of sensitized atopic patients with asthma is associated with elevated induced sputum concentrations of the eosinophil-active cytokines IL-5 and granulocyte-macrophage colony-stimulating factor and the proinflammatory cytokine tumor necrosis factor-alpha. We counted inflammatory leukocytes and measured cytokine concentrations in induced sputum at baseline and 24 hours after inhalational allergen challenge of 15 atopic patients with asthma who had previously demonstrated a late response. We observed significant increases in the numbers of eosinophils and the concentrations of their granule products, eosinophil cationic protein and eosinophil peroxidase. In contrast, the numbers of neutrophils and concentrations of two of their products, myeloperoxidase and human neutrophil lipocalin, did not significantly change. The numbers of sputum eosinophils correlated with the maximal late-phase fall in FEV1. Concentrations of IL-5 and tumor necrosis factor-alpha, but not granulocyte-macrophage colony-stimulating factor, were significantly elevated after allergen challenge. We conclude that the relatively noninvasive technique of induced sputum production can be used to monitor the effect of bronchial provocation on cytokine concentrations in asthma.


Herbal drugs and natural bioactive products as potential therapeutics: A review on pro-cognitives and brain boosters perspectives.
Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an individual. 'Memory' can be defined in various ways but in an overall view, memory is the retention of the information that the brain grasps. Different factors are responsible for the disbalance in the brain's hippocampus region and the acetylcholine level, which masters the memory and cognitive functions. Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and natural products that could act as memory enhancers and how they can be potentially utilized in the near future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in biological activity of the same herb and emphasize the requirement for a higher standardization in cultivation methods and plant processing. The demand for further studies evaluating the interactions of herbal drugs is mentioned.


Update on chemoradiotherapy for head and neck cancer.
Locoregionally advanced head and neck cancer is associated with a poor prognosis despite treatment with surgery or radiation or both. In the past several years, chemotherapy has become an integral part of potentially curative therapy for head and neck cancer and has been increasingly used to achieve the goals of organ preservation and prolongation of survival. Since 1998, many randomized studies that compared concurrent chemoradiotherapy with radiotherapy alone have been published. These studies used different chemotherapy regimens, either single-agent or combination, and various radiation fractionation schemes and almost uniformly supported the superiority of chemoradiotherapy over radiotherapy alone in terms of locoregional control as well as overall survival. Given the toxicity of concurrent chemoradiotherapy, careful selection of patients is critical. Many issues remain to be addressed in future trials, including the optimal chemotherapy regimen, the use of altered fractionation radiotherapy, and the role of induction chemotherapy.


Omics for Investigating Chitosan as an Antifungal and Gene Modulator.
Chitosan is a biopolymer with a wide range of applications. The use of chitosan in clinical medicine to control infections by fungal pathogens such as Candida spp. is one of its most promising applications in view of the reduced number of antifungals available. Chitosan increases intracellular oxidative stress, then permeabilizes the plasma membrane of sensitive filamentous fungus Neurospora crassa and yeast. Transcriptomics reveals plasma membrane homeostasis and oxidative metabolism genes as key players in the response of fungi to chitosan. A lipase and a monosaccharide transporter, both inner plasma membrane proteins, and a glutathione transferase are main chitosan targets in N. crassa. Biocontrol fungi such as Pochonia chlamydosporia have a low content of polyunsaturated free fatty acids in their plasma membranes and are resistant to chitosan. Genome sequencing of P. chlamydosporia reveals a wide gene machinery to degrade and assimilate chitosan. Chitosan increases P. chlamydosporia sporulation and enhances parasitism of plant parasitic nematodes by the fungus. Omics studies allow understanding the mode of action of chitosan and help its development as an antifungal and gene modulator.


Of mice and men (and rats): phthalate-induced fetal testis endocrine disruption is species-dependent.
For over 15 years, reproductive toxicologists have explored the physiological outcomes and mechanism of fetal phthalate exposure to determine the risk posed to human male reproductive health. This review examines the fetal male reproductive system response to phthalate exposure across species including rat, mouse, and human, with emphasis on the testis. In the rat, in utero phthalate exposure causes male reproductive tract malformations, in large part, by targeting the testis and inhibiting fetal Leydig cell hormone production. Despite mouse phthalate pharmacokinetics being similar to the rat, inhibition of fetal Leydig cell hormone synthesis is not observed in the mouse. The species-specific differences in testicular response following in utero phthalate exposure and the discordant reaction of the rodent fetal testis when exposed to phthalates ex vivo versus in vivo have made determining risk to humans difficult, yet critically important. The recent use of fetal testis xenotransplants to study phthalate toxicity suggests that the human fetal testis responds like the mouse fetal testis; it appears refractory to phthalate-induced inhibition of testosterone production. Although this result is unfulfilling from the perspective of identifying environmental contributions to human reproductive maldevelopment, it has important implications for phthalate risk assessment.


Noise-Induced Network Topologies.
We analyze transport on a graph with multiple constraints and where the weight of the edges connecting the nodes is a dynamical variable. The network dynamics results from the interplay between a nonlinear function of the flow, dissipation, and Gaussian, additive noise. For a given set of parameters and finite noise amplitudes, the network self-organizes into one of several metastable configurations, according to a probability distribution that depends on the noise amplitude α. At a finite value α, we find a resonantlike behavior for which one network topology is the most probable stationary state. This specific topology maximizes the robustness and transport efficiency, it is reached with the maximal convergence rate, and it is not found by the noiseless dynamics. We argue that this behavior is a manifestation of noise-induced resonances in network self-organization. Our findings show that stochastic dynamics can boost transport on a nonlinear network and, further, suggest a change of paradigm about the role of noise in optimization algorithms.


Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study.
To determine whether aromatherapy with lavender oil is effective in the treatment of agitated behaviour in patients with severe dementia. A placebo controlled trial with blinded observer rater. A long-stay psychogeriatric ward. Fifteen patients meeting ICD-10 diagnostic criteria for severe dementia and suffering from agitated behaviour defined as a minimum score of three points on the Pittsburgh Agitation Scale (PAS). A 2% lavender oil aromatherapy stream was administered on the ward for a two hour period alternated with placebo (water) every other day for a total of ten treatment sessions. For each subject 10 total PAS scores were obtained. Five during treatment and five during placebo periods. Nine patients (60%) showed an improvement, five (33%) showed no change and one patient (7%) showed a worsening of agitated behaviour during aromatherapy compared with placebo. A comparison of the group median PAS scores during aromatherapy showed a significant improvement in agitated behaviour during aromatherapy compared with placebo (median PAS scores 3 c.f. 4; Wilcoxon Signed-Ranks test p = 0.016 (one-tailed)). Lavender oil administered in an aroma stream shows modest efficacy in the treatment of agitated behaviour in patients with severe dementia.


Growth or differentiation? Adaptive regeneration in the brittlestar Amphiura filiformis.
Amphiura filiformis is a burrowing brittlestar, which extends arms in the water column when suspension feeding. In previous studies, unexpectedly high variability was observed in regeneration rate between individuals even when experiments were performed under identical conditions. The aims of this work were to understand this variability and interpret the observed variability in terms of adaptation to sublethal predation. Our experiments on the dynamics of arm regeneration in A. filiformis revealed that the developmental program during regeneration is well adapted to its burrowing life style. We demonstrate that there is a trade-off between regeneration in length and functional recovery for feeding (differentiation index). The amount of tissue lost (length lost), which represents the quantity of tissue needed to completely regenerate an intact arm with no previous history of regeneration, determines whether the arm will invest more energy in growth and/or in differentiation, which must be a reflection of the ability to differentially regulate developmental programs during regeneration. We show that combining regeneration rate with differentiation index provides an ideal tool for the definition of a standard temporal framework for both field and laboratory studies of regeneration.


A tool to facilitate mother--infant attachment.
Although the MIST is helpful, it is still in its embryonic stage of development. It will need to be refined further by practitioners and researchers to see if it is relevant to them and to different cultures and socioeconomic groups. Research must be done to see if each researcher finds the same results and if the items are significant, or if the different gradations are just arbitrary. These are important questions to be asked. We must begin to look at tools for evaluating mother--infant interactions because, until we have a tool, significant mother--infant intervention cannot begin.


Alignment properties of a ferroelectric nematic liquid crystal on the rubbed substrates.
The orientation characteristics of FNLC-919, a new material with a ferroelectric nematic phase at room temperature, were investigated. Its alignment characteristics varied greatly depending on the relative rubbing direction on both substrates of a liquid crystal cell. In a cell where the two substrates were rubbed in the same direction, they were arranged homogeneously along the rubbing direction without domains or defects in the ferroelectric nematic phase. In a cell where the two substrates were rubbed in the anti-parallel direction, the two domains were twisted in the opposite direction. We quantitatively obtained the twisted direction and angle by matching the experimental data and calculation results using Jones matrix calculations. From the electro-optical experiment, it was confirmed that the polarization direction was opposite to the rubbing direction. In addition, the wavelength and temperature dependence of birefringence was measured for FNLC-919. In a cell where the rubbing direction between two substrates was 90°, two domains of opposite directions were observed in the nematic phase. When it becomes a ferroelectric nematic phase on cooling, the twist is determined to be only in one direction. The twist direction and angle were quantitatively obtained in the nematic and ferroelectric nematic phases. It was twisted more in the ferroelectric nematic phase than in the nematic phase.


De novo DNA methyltransferases DNMT3A and DNMT3B are essential for XIST silencing for erosion of dosage compensation in pluripotent stem cells.
Human pluripotent stem cells (hPSCs) have proven to be valuable tools for both drug discovery and the development of cell-based therapies. However, the long non-coding RNA XIST, which is essential for the establishment and maintenance of X chromosome inactivation, is repressed during culture, thereby causing erosion of dosage compensation in female hPSCs. Here, we report that the de novo DNA methyltransferases DNMT3A/3B are necessary for XIST repression in female hPSCs. We found that the deletion of both genes, but not the individual genes, inhibited XIST silencing, maintained the heterochromatin mark of H3K27me3, and did not cause global overdosage in X-linked genes. Meanwhile, DNMT3A/3B deletion after XIST repression failed to restore X chromosome inactivation. Our findings revealed that de novo DNA methyltransferases are primary factors responsible for initiating erosion of dosage compensation in female hPSCs, and XIST silencing is stably maintained in a de novo DNA-methylation-independent manner.


Social robots as depictions of social agents.
Social robots serve people as tutors, caretakers, receptionists, companions, and other social agents. People know that the robots are mechanical artifacts, yet they interact with them as if they were actual agents. How is this possible? The proposal here is that people construe social robots not as social agents per se, but as depictions of social agents. They interpret them much as they interpret ventriloquist dummies, hand puppets, virtual assistants, and other interactive depictions of people and animals. Depictions as a class consist of three physical scenes with part-by-part mappings between them: (a) a base scene (the raw physical artifact), (b) the depiction proper (the artifact construed as a depiction), and (c) the scene depicted (the scene people are to imagine). With social robots, evidence shows people form the same three scenes plus mappings: They perceive the raw machinery of a robot, construe it as a depiction of a character, and, using the depiction as a guide, engage in the pretense that they are interacting with the character depicted. With social robots, people also recognize three classes of agents - the characters depicted, the intended recipients of the depictions (those who view or interact with the robots), and the authorities responsible for the robots (the designers, makers, and owners). Construing social robots as depictions, we argue, accounts for many phenomena not covered by alternative models.


Tuberculous arthritis--unexpected extrapulmonary tuberculosis detected by FDG PET/CT.
FDG PET/CT imaging has been used in various medical fields, including neoplastic and infectious diseases, for a long time. We reported a 62-year-old man with fever, chronic cough, arthralgia of the left side of the hip, and body weight loss. Chest radiograph showed increased infiltration in both upper lungs, and the acid-fast stain of sputum was positive. Whole-body PET/CT scan revealed a lesion with intense FDG uptake in the joint of the side left of the hip. Osteoarthritis of the hip was initially impressed by an orthopedist. However, tuberculous arthritis was subsequently confirmed by deep pus culture.


Culturally Adapting an Advance Care Planning Communication Intervention With American Indian and Alaska Native People in Primary Care.
Introduction: Advance care planning (ACP) is a process in which patients, families, and providers discuss and plan for desired treatment goals. American Indian and Alaska Native people (AI/AN) have higher prevalence of many serious, life-limiting illnesses compared with the general population; yet AI/ANs use ACP considerably less than the overall population. Method: We conducted a qualitative study to culturally adapt an existing ACP intervention for AI/ANs in two primary care settings. Results: We found that it is important to incorporate patients' cultural values and priorities into ACP, determine who the patient wants involved in ACP conversations, and consider the culturally and locally relevant barriers and facilitators when developing an ACP intervention with AI/AN communities. Discussion: At the core, ACP interventions should be clear and understandable across populations and tailored to facilitate culturally appropriate and meaningful patient-provider communication. Our results and methodology of culturally adapting an intervention may be applicable to other underrepresented populations.


Rotaxane Formation of Multicyclic Polydimethylsiloxane in a Silicone Network: A Step toward Constructing "Macro-Rotaxanes" from High-Molecular-Weight Axle and Wheel Components.
Rotaxanes consisting of a high-molecular-weight axle and wheel components (macro-rotaxanes) have high structural freedom, and are attractive for soft-material applications. However, their synthesis remains underexplored. Here, we investigated macro-rotaxane formation by the topological trapping of multicyclic polydimethylsiloxanes (mc-PDMSs) in silicone networks. mc-PDMS with different numbers of cyclic units and ring sizes was synthesized by cyclopolymerization of a α,ω-norbornenyl-functionalized PDMS. Silicone networks were prepared in the presence of 10-60 wt % mc-PDMS, and the trapping efficiency of mc-PDMS was determined. In contrast to monocyclic PDMS, mc-PDMSs with more cyclic units and larger ring sizes can be quantitatively trapped in the network as macro-rotaxanes. The damping performance of a 60 wt % mc-PDMS-blended silicone network was evaluated, revealing a higher tan δ value than the bare PDMS network. Thus, macro-rotaxanes are promising as non-leaching additives for network polymers.


Maternal satisfaction with intrapartum care and associated factors among mothers who gave birth in public hospitals of the South West Shewa Zone, Ethiopia, 2022.
Maternal satisfaction with intrapartum care is a multidimensional assumption of satisfaction with self and with the physical environment of the delivery ward and quality of care. Maternal satisfaction with intrapartum care affects the selection of birthplace and helps to identify gaps between actual and intended healthcare outcomes. This study aims to assess factors that affect maternal satisfaction with intrapartum care. To assess maternal satisfaction with intrapartum care and associated factors among mothers who gave birth in public hospitals in the South-west Shewa Zone, Ethiopia, 2022. A cross-sectional study approach among 420 mothers was conducted between April 14 and June 14, 2022. Systematic random sampling was used to select mothers for face-to-face interviews every two intervals. Bivariate and multivariable logistic regression analyses were carried out. P-values of <0.25 in association with study variables were transferred to multivariable logistic regression models. An adjusted odds ratio with a 95% confidence interval was computed, and p-values of <0.05 were considered statistically significant in the multivariable model. The results of this study are presented using text, tables, and charts. Data were collected from 420 participants, and 413 mothers completed the interview, giving a response rate of 98.33%. The overall maternal satisfaction with intrapartum care was 245 (59.32%) [95% CI: 55-64]. Mothers who were considered normal during labor and delivery (AOR = 2.57 (95% CI: 1.30-5.07), had a labor duration of 12 h or less (AOR = 1.59 (95% CI: 1.03-2.44), and experienced a waiting time of <15 min (AOR = 2.06 (95% CI: 1.21-3.52) were significantly associated with maternal satisfaction with intrapartum care. More than half of mothers were satisfied with the overall intrapartum care they received. Health facility managers and healthcare providers work together to improve maternal satisfaction with intrapartum care.


A historical overview of laryngeal carcinoma and the first total laryngectomies.
Laryngeal cancer was a well known entity since antiquity and its treatment evolved through several phases. The lack of knowledge in anatomy and pathology as well as the absence of anesthesia and proper instrumentation made the treatment almost impossible. Ancient physicians were performing laryngotomy or tracheotomy in an attempt to prevent the suffocation symptoms produced by tumoral masses. In 19th century the invention of laryngoscope and the advent of pathology and anesthesiology encouraged surgeons to operate on man. In 1873 Theodor Billroth (1829-1894) performed the first laryngectomy followed by several other colleagues among which Enrico Bottini (1837-1903) and Themistocles Gluck (1853-1942). Thanks to their contribution a new era came in laryngeal cancer treatment: the conservation laryngeal surgery.


Organizational Twitter Use: Content Analysis of Tweets during Breast Cancer Awareness Month.
On an average, at least one out of eight women are at risk of falling prey to breast cancer during their lifespan. Amongst varied initiatives to spread awareness about breast cancer, the most well-known campaign is Breast Cancer Awareness Month. This article explored, through content analysis, how four different health-related organizations-Susan G. Komen, U.S. News Health, Woman's Hospital, and Breast Cancer Social Media-used their Twitter accounts to talk about varied aspects of breast cancer during the month of October, which is observed as Breast Cancer Awareness Month. All the tweets by these organizations were analyzed for the presence or absence of the theoretical parameters of the Health Belief Model (HBM). A content analysis of 2916 tweets based on the HBM revealed that the content posted by these organizations reflected the use of varied theoretical constructs of the framework. Overall, the study demonstrated that while different organizations shared valuable breast cancer-related content on Twitter, each used the social media platform in a different fashion, evident through focus on different types of HBM constructs while publishing breast cancer-related tweets.


Anopheles gambiae purine nucleoside phosphorylase: catalysis, structure, and inhibition.
The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for AgPNP at 226 s-1 for guanosine in pre-steady-state studies. 5'-Deaza-1'-aza-2'-deoxy-1'-(9-methylene)-Immucillin-H (DADMe-ImmH) is a transition-state mimic for a 2'-deoxyinosine ribocation with a fully dissociated N-ribosidic bond and is a slow-onset, tight-binding inhibitor with a dissociation constant of 3.5 pM. This is the tightest-binding inhibitor known for any PNP, with a remarkable Km/Ki* of 5.4 x 10(7), and is consistent with enzymatic transition state predictions of enhanced transition-state analogue binding in enzymes with enhanced catalytic efficiency. Deoxyguanosine is a weaker substrate than deoxyinosine, and DADMe-Immucillin-G is less tightly bound than DADMe-ImmH, with a dissociation constant of 23 pM for AgPNP as compared to 7 pM for HsPNP. The crystal structure of AgPNP was determined in complex with DADMe-ImmH and phosphate to a resolution of 2.2 A to reveal the differences in substrate and inhibitor specificity. The distance from the N1' cation to the phosphate O4 anion is shorter in the AgPNP.DADMe-ImmH.PO4 complex than in HsPNP.DADMe-ImmH.SO4, offering one explanation for the stronger inhibitory effect of DADMe-ImmH for AgPNP.


Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells.
The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs), relevant in viral pathogenesis and immune evasion. We found that dengue virus host adaptation leads to the accumulation of different species of sfRNAs in vertebrate and invertebrate cells. This process does not depend on differences in the host machinery; but it was found to be dependent on the selection of specific mutations in the viral 3'UTR. Dissecting the viral population and studying phenotypes of cloned variants, the molecular determinants for the switch in the sfRNA pattern during host change were mapped to a single RNA structure. Point mutations selected in mosquito cells were sufficient to change the pattern of sfRNAs, induce higher type I interferon responses and reduce viral fitness in human cells, explaining the rapid clearance of certain viral variants after host change. In addition, using epidemic and pre-epidemic Zika viruses, similar patterns of sfRNAs were observed in mosquito and human infected cells, but they were different from those observed during dengue virus infections, indicating that distinct selective pressures act on the 3'UTR of these closely related viruses. In summary, we present a novel mechanism by which dengue virus evolved an RNA structure that is under strong selective pressure in the two hosts, as regulator of non-coding RNA accumulation and viral fitness. This work provides new ideas about the impact of host adaptation on the variability and evolution of flavivirus 3'UTRs with possible implications in virulence and viral transmission.


The Importance of a Biopsychosocial Approach in Melanoma ResearchExperiences from a Single-center Multidisciplinary Melanoma Working Group in Middle-Europe.
The biopsychosocial model represents a very important theoretical framework developed in the 21th century. According to a body mind unity theory, it postulates that research must focus not only on biomedical but also on other aspects in order to understand complex interactions occurring on different system levels. With regard to the occurrence of melanoma, both immunologic surveillance and a lack of cancerogenic factors are crucial in the suppression of tumor development. In addition, a reduction in mental stress (employing effective strategies for coping with stress) in cases of malignant disease seems to prolong life. Focusing on these theories, examples of studies that followed an interdisciplinary, biopsychosocial approach to melanoma research conducted at one center are given to emphasize the multi-dimensional and interdisciplinary aspects of the biopsychosocial model.


[NT-proBNP as a diagnostic marker in dogs with dyspnea and in asymptomatic dogs with heart murmur].
The cardiac biomarker NT-proBNP indicates cardiac load in terms of myocardial wall stress. The objective of the study was to compare the results of NT-proBNP measurements in healthy dogs and dogs with dyspnea as well as asymptomatic dogs with heart murmur with the literature. Between April 2007 and December 2007 dogs with dyspnea of non-cardiac origin (n=11), dogs with dyspnea of cardiac origin (n=18) and asymptomatic dogs with heart murmur (n=22) were included. Twelve clinically healthy dogs served as a control group. All animals underwent cardiologic examination including echocardiography and measurement of serum NT-proBNP concentration. Serum was centrifuged and frozen within 30 minutes and was stored frozen until analysis was performed. Median NT-proBNP concentration in healthy dogs was 240 pmol/l (range 131-546 pmol/l). Dogs with dyspnea and primary respiratory disease displayed a median NT-proBNP concentration of 876 pmol/l (range 97-2614 pmol/l). In patients with dyspnea of non-cardiac origin, there was a difference in the values of NT-proBNP of dogs with and without pulmonary hypertension diagnosed by echocardiography. Dogs with dyspnea of cardiac origin displayed a median NT-proBNP concentration of 2000 pmol/l (range 137-2614 pmol/l). Low normal NT-proBNP values were only found in patients with pericardial effusion. Median NT-proBNP concentration in asymptomatic dogs with heart murmur was 698.5 pmol/l (range 121-2614 pmol/l). Considerably increased values were particularly measured in asymptomatic patients with severe congenital heart disease. NT-proBNP represents a useful additional diagnostic parameter in veterinary clinical cardiology to assess the severity of cardiac disease. Interpretation must take into consideration the clinical picture of the patient, as dogs with severe arrhythmias, sepsis and pulmonary thromboembolism may display high NT-proBNP levels without congestive heart failure. Our results indicate the following cut-off values: <500 pmol/l: no relevant cardiac load; 500-900 pmol/l: moderate cardiac load; >900 pmol/l: severe cardiac load.


Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in an animal tumor model: causal involvement of increased sensitivity of cisplatin-treated tumors to CTL-mediated killing in therapeutic synergy.
The goal of this study was to investigate the therapeutic potentials of combining chemotherapy with human papillomavirus (HPV) E7 subunit vaccines in an animal tumor model and to determine the underlying therapeutic mechanisms. Animals bearing HPV E6/E7-expressing tumors were treated intratumorally with a selected cytotoxic drug, cisplatin, twice at 1-week interval and s.c. with E7 subunit vaccines thrice at 1-week interval. Tumor chemoimmunoresponse was measured by tumor size. Ag-specific CTL activities and tumor histology were checked in mice under treatments. Apoptosis, in vivo T-cell subset depletion, adoptive CTL transfer, and tumor regression were used to determine the mechanisms for antitumor therapeutic effects. Combined therapy using cisplatin plus E7 subunit vaccines improved cure and recurrence rates of tumors and long-term antitumor immunity dramatically more than single therapy alone. In particular, both components of E7 subunit vaccines were required for induction of Ag-specific CTL as well as therapeutic synergy when combined with cisplatin. This therapeutic synergy was abrogated by depletion of CD8(+) T cells in vivo and was concomitant with histologic changes (such as heavy infiltration of lymphocytes and reduced tumor cell density). Finally, the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing was found to be responsible for therapeutic synergy. E7 subunit vaccines plus cisplatin mediate antitumor therapeutic synergy through the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing. Moreover, E7-based therapeutic vaccines have the potential to improve chemotherapy in patients with cervical cancer.


Axonal uptake of horseradish peroxidase isoenzymes during Wallerian degeneration.
Horseradish peroxidase isoenzymes were applied around crushed mouse hypoglossal nerves to study the influence of electrical charge on the uptake and ultrastructural distribution of macromolecules in axons distal to an injury. Both isoenzymes tested (Sigma type IX, cationic and type VII, anionic) were readily taken up into axons and moved in a distal direction along the nerve. Samples taken 1-3 mm below the crush showed that reaction products from both enzymes covered the inner surface of the axonal plasma membrane and were attached to organelles, particularly microtubules and neurofilaments. However, reaction product in the Schwann cell basement lamina and in the endoneurial collagen was much more dense with cationic peroxidase than with the anionic isoenzyme. Our study shows that both cationic and anionic macromolecules can move into axons distal to a nerve lesion. It can be assumed that also other agents can be taken up into axons and that 'wound substances' in this way may influence the processes by which axons are destroyed during Wallerian degeneration.


Resistance to Fluopicolide and Propamocarb and Baseline Sensitivity to Ethaboxam Among Isolates of Pseudoperonospora cubensis From the Eastern United States.
Chemical control is currently the most effective method for controlling cucurbit downy mildew (CDM) caused by Pseudoperonospora cubensis. Most commercial cucurbit cultivars, with the exception of a few new cucumber cultivars, lack adequate disease resistance. Fluopicolide and propamocarb were among the most effective fungicides against CDM in the United States between 2006 and 2009. Since then, reduced efficacy of these two fungicides under field conditions was reported starting around 2013 but occurrence of resistance to fluopicolide and propamocarb in field isolates of P. cubensis had not been established. Thirty-one isolates collected from cucurbits in the eastern United States were tested for their sensitivity to fluopicolide and propamocarb using a leaf disc assay. This same set of isolates and four additional isolates (i.e., 35 isolates) were also used to establish the baseline sensitivity of P. cubensis to ethaboxam, an ethylamino-thiazole-carboxamide fungicide, which was recently granted registration to control CDM in the United States. About 65% of the isolates tested were resistant to fluopicolide with at least one resistant isolate being present in samples collected from 12 of the 13 states in the eastern United States. About 74% of the isolates tested were sensitive to propamocarb with at least one resistant isolate being among samples collected from 8 of the 12 states in the study. The frequency of resistance to fluopicolide and propamocarb was high among isolates collected from cucumber, while the frequency was low among isolates collected from other cucurbit host types. All isolates tested were found to be sensitive to ethaboxam and EC50 values ranged from 0.18 to 3.08 mg a.i./liter with a median of 1.55 mg a.i./liter. The ratio of EC50 values for the least sensitive and the most sensitive isolate was 17.1, indicating that P. cubensis isolates were highly sensitive to ethaboxam. The most sensitive isolates to ethaboxam were collected from New York, North Carolina, and Ohio, while the least sensitive isolates were collected from Georgia, Michigan, and New Jersey. These results show that ethaboxam could be a viable addition to fungicide programs used to control CDM in the United States.


Emaciation and Sporadic Mortality in Older Laying Hens Caused by Intussusception of the Proventriculus.
Laying hens (n = 2267) ranging in age from 2 to 4 yr in a study evaluating ovarian cancer prevention were necropsied. Those that died or were culled during the 2-yr study (n = 1591) were necropsied weekly to determine the most probable cause of death or culling and cancer status. Hens surviving until the end of the study (n = 676) were euthanized and necropsied. Hens necropsied before and after a hen with proventricular intussusception served as cohorts (n = 38). Nineteen hens (13 dead, 6 culled) had intussusceptions of the proventriculus into the ventriculus. Mean age of affected hens was 154 wk (range 110-204 wk). None of the hens in the study had an intestinal intussusception, and none of the hens euthanized at the end of the study had a proventricular intussusception. Hens with proventricular intussusceptions were severely emaciated; mean body weights were 1040 and 1736 g for affected and cohort hens, respectively. Necropsy findings included prominent keel, marked muscle atrophy, generalized serous atrophy of fat, no visible proventriculus, esophagus directly entering the ventriculus, and an enlarged, spherical, firm ventriculus, which contained an invaginated, swollen, diffusely ulcerated proventriculus. Eighteen affected hens were anovulatory (94.7%) compared to 27 cohorts (71.1%). Severe, diffuse necrosis and ulceration of the proventricular mucosa was confirmed microscopically, but no etiologic agent was identified. In conclusion, proventricular intussusception of undetermined etiology was identified as a cause of sporadic emaciation, culling, and mortality in older laying hens.


Artificial liver support in acute and acute-on-chronic liver failure.
Liver failure is a life-threatening condition, and an artificial liver is highly desirable to replace the failing liver-functions in the waiting time for liver regeneration to happen or until liver transplantation can be undertaken. This review focuses on the efficacy of using artificial extracorporeal liver support devices. Artificial liver support devices such as the molecular adsorbent recirculating system (MARS), fractionated plasma separation and adsorption, and therapeutic plasma exchange (TPE) are well tolerated. MARS and TPE improve systemic haemodynamics and the grade of hepatic encephalopathy. However, randomized, controlled trials of MARS and fractionated plasma separation and adsorption have failed to show improvement in survival in patients with acute liver failure (ALF) and patients with acute-on-chronic liver failure (ACLF). Only TPE improves survival in patients with ALF by ameliorate the release of ammonia, damage-associated molecular patterns and sB7 (CD80/86) from the necrotic liver. No randomized, controlled trials on survival in patients with ACLF using TPE have been done. Liver support systems such as MARS and TPE may temporarily improve systemic haemodynamics and the degree of encephalopathy. However, TPE is the only procedure that improves survival in patients with ALF. The role of TPE in ACLF remains unknown.


Characterization and Correction of Errors in Computing Contact Location Between Curved Articular Surfaces: Application to Total Knee Arthroplasty.
In total knee arthroplasty (TKA), one common metric used to evaluate innovations in component designs, methods of component alignment, and surgical techniques aimed at decreasing the high rate of patient-reported dissatisfaction is tibiofemoral contact kinematics. Tibiofemoral contact kinematics are determined based on the movement of the contact locations in the medial and lateral compartments of the tibia during knee flexion. A tibial force sensor is a useful instrument to determine the contact locations, because it can simultaneously determine contact forces and contact locations. Previous reports of tibial force sensors have neither characterized nor corrected errors in the computed contact location (i.e., center of pressure) between the femoral and tibial components in TKA that, based on a static analysis, are caused by the curved articular surface of the tibial component. The objectives were to experimentally characterize these errors and to develop and validate an error correction algorithm. The errors were characterized by calculating the difference between the errors in the computed contact locations when forces were applied normal to the tibial articular surface and those when forces were applied normal to the tibial baseplate. The algorithm generated error correction functions to minimize these errors and was validated by determining how much the error correction functions reduced the errors in the computed contact location caused by the curved articular surface. The curved articular surface primarily caused bias (i.e., average or systematic error) which ranged from 1.0 to 2.7 mm in regions of high curvature. The error correction functions reduced the bias in these regions to negligible levels ranging from 0.0 to 0.6 mm (p < 0.001). Bias in the computed contact locations caused by the curved articular surface of the tibial component as small as 1 mm needs to be accounted for, because it might inflate the computed internal-external rotation and anterior-posterior translation of femur on the tibia leading to false identifications of clinically undesirable contact kinematics (e.g., internal rotation and anterior translation during flexion). Our novel error correction algorithm is an effective method to account for this bias to more accurately compute contact kinematics.


Ornithine decarboxylase as a marker for colorectal polyps and cancer.
There is as yet no specific chromosomal abnormality or gene marker identified for colorectal polyps and cancer. Thus available markers include only phenotypic markers. Tumor markers that have been studied include tetraploidy and increased colonic mucosal proliferation; and these markers have identified those patients that are at high risk for colon cancer. The current "gold standard" of colorectal cancer markers is the carcinoembryonic antigen (CEA). CEA is best used as a monitor of disease and recurrence, and not as a screening or diagnostic test. Newer carbohydrate markers include CA 19-9, incompatible A and B antigens, and T and Lewis antigens. These markers have not shown increased specificity or sensitivity compared to CEA. An interesting recently described marker is ornithine decarboxylase (ODC), which serves as a simple overall index of colonic mucosal proliferation. Ornithine decarboxylase levels have shown correlation with the progression from normal mucosa to adenoma and carcinoma, especially in hereditary polyposis syndromes. This enzyme may also serve as a potential therapeutic target. Many markers have been found useless in further clinical trials. Ornithine decarboxylase needs to be studied in greater detail to determine its sensitivity and specificity, in patients with hereditary colonic neoplasia and in patients without genetic syndromes.