Age-related differences in corpus callosum area of capuchin monkeys.
Capuchin monkeys (Cebus apella) are New World primates with relatively large brains for their body size. The developmental trajectories of several brain regions-including cortical white matter, frontal lobe white matter, and basal ganglia nuclei-are similar to humans. Additionally, capuchins have independently evolved several behavioral and anatomical characteristics in common with humans and chimpanzees-including complex manipulative abilities, use of tools, and the use of precision grips-making them interesting species for studies of comparative brain morphology and organization. Here, we report the first investigation into the development of the corpus callosum (CC) and its regional subdivisions in capuchins. CC development was quantified using high-resolution structural magnetic resonance imaging (MRI) images from 39 socially reared subjects (male n=22; female n=18) ranging in age from 4 days (infancy) to 20 years (middle adulthood). The total area of the CC and the subdivisions of the genu, rostral midbody, medial midbody, caudal midbody, and splenium were traced from the midsagittal section. Total CC area displayed significant differences across this time span and was best explained by quadratic growth. Sustained linear growth was observed in the subdivisions of the genu, rostral midbody, and splenium; sustained quadratic growth was seen in the subdivision of the medial midbody. Differences in growth were not detected in the subdivision of the caudal midbody. Females had a larger raw area of the total CC and of the medial midbody and caudal midbody throughout the lifespan. Our results indicate that capuchins show continued white matter development beyond adolescence in regions related to cognitive and motor development.


"It runs in my family …": The association of perceived family history with body dissatisfaction and weight bias internalization among overweight women.
Aspects of poor body acceptance (BA), such as internalized weight bias and dissatisfaction with one's shape and size, are the strongest predictors of disordered eating and are associated with reduced engagement in healthy behaviors. Perceiving oneself as having a family history of overweight (PFH) could boost BA by increasing attributions for inherited, biological causes of weight. A community sample of 289 women who were overweight from the Washington, DC metropolitan area who were dissatisfied with their current weight (68% Black; 32% White) enrolled in this study in 2012. PFH of overweight was associated with decreased internalized weight bias among white women and marginally increased body shape satisfaction generally. The relationship between PFH and BA was not explained by biological attributions for weight. Perceptions that overweight runs in one's family can be protective with respect to BA. This is suggestive of the potential benefit of integrating family-based approaches into weight management interventions.


Adaptive Bayesian Time-Frequency Analysis of Multivariate Time Series.
This article introduces a nonparametric approach to multivariate time-varying power spectrum analysis. The procedure adaptively partitions a time series into an unknown number of approximately stationary segments, where some spectral components may remain unchanged across segments, allowing components to evolve differently over time. Local spectra within segments are fit through Whittle likelihood based penalized spline models of modified Cholesky components, which provide flexible nonparametric estimates that preserve positive definite structures of spectral matrices. The approach is formulated in a Bayesian framework, in which the number and location of partitions are random, and relies on reversible jump Markov chain and Hamiltonian Monte Carlo methods that can adapt to the unknown number of segments and parameters. By averaging over the distribution of partitions, the approach can approximate both abrupt and slow-varying changes in spectral matrices. Empirical performance is evaluated in simulation studies and illustrated through analyses of electroencephalography during sleep and of the El Niño-Southern Oscillation.


Roles of substance P and NK(1) receptor in the brainstem in the development of emesis.
The emetic response is primarily a protective reflex occurring in a wide variety of vertebrates in response to the ingestion of toxic compounds. The role of the nuclei in the brainstem, including the area postrema, nucleus tractus solitarius, the dorsal motor nucleus of the vagus, and the central pattern generator for vomiting, as well as the involvement of the abdominal visceral innervation relevant to the emetic reflex, have all been discussed by many researchers. The introduction of serotonin 5-HT(3)-receptor antagonists into clinical practice allowed for a dramatic improvement in the management of vomiting. However, vomiting still remains a significant problem. The mechanism of the emetic response is even more complicated than was first thought. This review attempts to bring together some of the evidence suggesting the roles of substance P and its receptor, neurokinin NK(1) receptor, in the brainstem nuclei in the development of emesis. Accordingly, NK(1)-receptor antagonists might represent novel drugs for the management of major types of emesis.


Free fatty acid composition of human and rat peripheral nerve.
The free fatty acid (FFA) composition of peripheral nerve resembles that of erythrocytes but the composition of both is different from that of brain and other tissues. Approximately 75% of FFAs of nerve and erythrocytes are saturated and less than 5% are polyunsaturated whereas in brain and other tissues, 30-45% of FFAs are saturated and 25-50% are polyunsaturated. Approximately 10-15% of the total FFA of nerve have very long chain lengths [C24, C26, C28, and C30]. The presence of these very long-chain FFAs in endoneurium cannot be accounted for by the retention of erythrocytes or by lipid degradation. During Wallerian degeneration a significant increase of 18:1, associated with a decrease of saturated FFAs, was found in rat sciatic endoneurium, but normal values were approached when fiber regeneration was well under way. The FFA composition with chain length greater than or equal to C26 were not, however, significantly altered with degeneration or repair of nerves. The metabolic significance of this striking difference between nerve and brain FFA composition is unknown but may reflect different functional properties.


Fertility of dairy cows in Northern Ireland.
A comprehensive database was established on the milk production and reproductive performance of dairy cows in 19 selected herds in Northern Ireland, varying in size, management system and genetic merit. Data were obtained for 2471 cows, 1775 of which calved in a second year, and 693 were culled from the herd for specific reasons. The estimated mean rate of heat detection (assessed by the interheat interval during the main breeding season) in all the herds was 71 per cent, with a range from 53 to 92 per cent The average conception rate to first insemination was 37.1 per cent (range 21 to 66 per cent). The average calving interval for the retained cows was 407.2 days (range 359 to 448 days). Twenty-eight per cent of the cows that calved were culled, with infertility being the largest single reason (26.8 per cent of the cows culled). There were major differences in reproductive performance between the herds, but heat detection rate, conception rate and calving interval did not appear to be affeded by a herd's genetic merit. The herds with shorter calving intervals were characterised by better heat detection efficiency (83 v 61 per cent, P<0.01), a shorter interval from calving to first insemination (74 v 97 days; P<0.05), a higher conception rate to first insemination (45 v 34 per cent, P>0.10) and a lower removal rate (23 v 37 per cent, P<0.01). Furthermore, the cows in these herds had lower body condition scores (BCS) in the dry period (3.0 v 3.3; P<0.05) but lost less body condition in early lactation (0.3 v 0.6 BCS units, P<0.05). These results show that dairy herd fertility in Northern Ireland is generally low and similar to that previously reported for England and the USA, but that in some herds changes in herd management practices improved the cows' fertility.


Controlled generation of ultrafast vector vortex beams from a mode-locked fiber laser.
We report on a new class of mode-locked fiber lasers that allow direct creation of ultrafast vector vortex beams at arbitrary positions on the higher-order Poincaré sphere. The on-demand generation of space-variant polarization patterns was realized by controlling geometric phases inside the laser resonator to map polarization to orbital angular momentum. Thanks to the special cavity design, the required intracavity manipulation of the geometric phase imposed no disturbance on the passively mode-locked operation, thus demonstrating robust and flexible switching of vectorial modes with an 8.5 ps pulse duration. Analytical expressions were deduced to model the generated cylindrically symmetric polarization profiles, which are in agreement with experimental observations. The presented fiber laser would constitute a compact light source for producing ultrafast pulses in high-purity structured modes, which may find broad applications in classical and quantum optics.


An improved protein decoy set for testing energy functions for protein structure prediction.
We have improved the original Rosetta centroid/backbone decoy set by increasing the number of proteins and frequency of near native models and by building on sidechains and minimizing clashes. The new set consists of 1,400 model structures for 78 different and diverse protein targets and provides a challenging set for the testing and evaluation of scoring functions. We evaluated the extent to which a variety of all-atom energy functions could identify the native and close-to-native structures in the new decoy sets. Of various implicit solvent models, we found that a solvent-accessible surface area-based solvation provided the best enrichment and discrimination of close-to-native decoys. The combination of this solvation treatment with Lennard Jones terms and the original Rosetta energy provided better enrichment and discrimination than any of the individual terms. The results also highlight the differences in accuracy of NMR and X-ray crystal structures: a large energy gap was observed between native and non-native conformations for X-ray structures but not for NMR structures.


Strobe rearing prevents the convergence of inputs with different response timings onto area 17 simple cells.
Strobe rearing prevents the convergence of inputs with different response timings onto area 17 simple cells. J. Neurophysiol. 80: 3005-3020, 1998. The preceding paper showed that the loss of direction selectivity in simple cells induced by strobe rearing reflects the elimination of spatially ordered response timing differences across the receptive field that underlie spatiotemporal (S-T) inseparability. Here we addressed whether these changes reflected an elimination of certain timings or an alteration in how timings were associated in single cells. Timing in receptive fields was measured using stationary bars undergoing sinusoidal luminance modulation at different temporal frequencies (0.5-6 Hz). For each bar position, response phase versus temporal frequency data were fit by a line to obtain two measures: absolute phase and latency. In normal cats, many individual simple cells display a wide range of timings; in layer 4, the mean range for absolute phase and latency was 0.21 cycles and 39 ms, respectively. Strobe rearing compressed the mean timing ranges in single cells, to 0.08 cycles and 31 ms, respectively, and this compression accounted for the loss of inseparability. A similar compression was measured in layer 6 cells. In contrast, the range of timing values across the simple-cell population was relatively normal. Single cells merely sampled narrower than normal regions of the timing space. We sought to understand these cortical changes in terms of how inputs from the lateral geniculate nucleus (LGN) may have been affected by strobe rearing. In normal cats, a wide range of absolute phase and latency values exists among lagged and nonlagged LGN cells, and these thalamic timings account for most of the cortical timings. Also, S-T inseparability in many simple cells can be attributed to the convergence of lagged and/or nonlagged inputs. Strobe rearing did not change the sampling of lagged and nonlagged cells, and the geniculate timings continued to account for most of the cortical timings. However, strobe rearing virtually eliminated cortical receptive fields with mixed lagged and nonlagged timing, and it compressed the timing range in cells dominated by one or the other geniculate type. Thus strobe rearing did not eliminate certain timings in LGN or cortex, but prevented the convergence of different timings on single cells. To account for these results, we propose a developmental model in which strobe stimulation alters the correlational structure of inputs based on their response timing. Only inputs with similar timing become associated on single cortical cells, and this produces S-T separable receptive fields that lack the ability to confer a preferred direction of motion.


Stability of rubella virus after long-term persistence in human cell line.
Primary infection of HEp-2 cells with rubella virus resulted in non-cytophatic long-term persistent infection. During four years of persistence the virus was produced in sufficient quantities (up to 6 logs PFU/ml) and did not differ from the parental variant in its pathogenicity for BHK-21 or RK-13 cells, or hemagglutinating activity, but formed smaller plaques. Persistent virus preserved the original antigenicity as judged from reciprocal hemagglutination-inhibition or plaque reduction-neutralization tests with polyclonal antisera. Both original and persistent rubella viruses were thermoresistant (T 56 degrees C) and slightly temperature-sensitive. Clonal analysis revealed presence of ts-mutants among both original and persistent virus clones with different degrees of plating efficiency at 40 degrees/34 degrees C. RNA fingerprinting showed only minor changes in persistent rubella virus.


Factors affecting the component community structure of haemoparasites in bank voles (Clethrionomys glareolus) from the Mazury Lake District region of Poland.
The prevalence and abundance of infections with haemoparasites were studied over a 3 year period in Clethrionomys glareolus (bank vole, n = 420) sampled from forests in the NE of Poland. Total species richness was 5 (Prevalence = Haemobartonella sp. 63.1%, Bartonella grahamii 27.4%, Hepatozoon erhardovae 31.4%, Trypanosoma evotomys 15% and Babesia microti 1.0%) with 81.9% of the voles carrying at least 1 species and a mean infracommunity species richness of 1.4. Variation in species richness was determined primarily by season and year, and the interaction of these factors. The observed frequency distribution of infracommunity species richness did not differ from that predicted by a null model, suggesting that there were no marked associations between the species. Analyses of prevalence and abundance of infection with each species in turn, revealed that overall the principal causes of variation were temporal and seasonal and their interaction, intrinsic factors such as age and sex playing only a minor role. However, the relative importance of specific extrinsic, and rarely intrinsic, factors varied and was distinct for each of the species in the study. Prevalence data revealed 4 sets of 2-way associations between species, mostly varyingly dependent on combinations of intrinsic and extrinsic factors. Analysis of quantitative associations suggested 4 sets of positive 2-way interactions, 3 of which remained after controlling for the effect of extrinsic and intrinsic factors on the abundance of each species, but only one could be unequivocally accepted (Haemobartonella sp. +B. grahamii) after correction for multiple comparisons. These data are discussed in the context of the changing ecological profiles in this region of Eastern Europe and, in a wider context, in relation to current understanding of the factors which shape component community structures of haemoparasites in wild rodents.


Desulfonispora thiosulfatigenes gen. nov., sp. nov., a taurine-fermenting, thiosulfate-producing anaerobic bacterium.
Strain GKNTAUT has been described as a bacterium able to ferment the organosulfonate taurine (2-aminoethanesulfonate) quantitatively to acetate, ammonia and thiosulfate, an unusual metabolic product. This novel fermentation has now also been observed in four independent isolates from two continents. All five organisms were strictly anaerobic, Gram-positive, motile, spore-forming bacteria. Enrichments with isethionate (2-hydroxyethanesulfonate) and cysteate (2-amino-3-sulfopropionate), in contrast, yielded bacteria that disproportionated the sulfonate to sulfate and sulfide. The phylogenetic location of the taurine fermenters was analysed on the basis of 16S rDNA sequences. Strain GKNTAUT (= DSM 11270T = ATCC 700533T) is described as the type strain of a new genus and species, for which the name Desulfonispora thiosulfatigenes gen. nov., sp. nov. is proposed.


Mental health correlates of intimate partner violence in marital relationships in a nationally representative sample of males and females.
It is important to understand the epidemiology of intimate partner violence (IPV) experienced by both males and females. Data were drawn from the U.S. National Comorbidity Survey Replication. The relationships between physical IPV and child abuse, mental disorders, and suicidal ideation and attempts among males and females were examined. The results indicate that child sexual abuse was associated with IPV among males, whereas child physical and sexual abuse was associated with IPV among females. IPV was associated with poor mental health outcomes for males and females, although sex differences are noted. The sex differences indicate that females experience a wider range of poor mental health outcomes compared to males. Knowledge about correlates of IPV can be useful in identifying individuals exposed to violence. Further research is required to identify effective methods to reduce exposure to IPV and to adequately address the specific needs of male and female victims of IPV.


Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation.
Recessive mutations in the ubiquitously expressed POLR3A gene cause one of the most frequent forms of childhood-onset hypomyelinating leukodystrophy (HLD): POLR3-HLD. POLR3A encodes the largest subunit of RNA Polymerase III (Pol III), which is responsible for the transcription of transfer RNAs (tRNAs) and a large array of other small non-coding RNAs. In order to study the central nervous system pathophysiology of the disease, we introduced the French Canadian founder Polr3a mutation c.2015G > A (p.G672E) in mice, generating homozygous knock-in (KI/KI) as well as compound heterozygous mice for one Polr3a KI and one null allele (KI/KO). Both KI/KI and KI/KO mice are viable and are able to reproduce. To establish if they manifest a motor phenotype, WT, KI/KI and KI/KO mice were submitted to a battery of behavioral tests over one year. The KI/KI and KI/KO mice have overall normal balance, muscle strength and general locomotion. Cerebral and cerebellar Luxol Fast Blue staining and measurement of levels of myelin proteins showed no significant differences between the three groups, suggesting that myelination is not overtly impaired in Polr3a KI/KI and KI/KO mice. Finally, expression levels of several Pol III transcripts in the brain showed no statistically significant differences. We conclude that the first transgenic mice with a leukodystrophy-causing Polr3a mutation do not recapitulate the childhood-onset HLD observed in the majority of human patients with POLR3A mutations, and provide essential information to guide selection of Polr3a mutations for developing future mouse models of the disease.


The Giardia lamblia vsp gene repertoire: characteristics, genomic organization, and evolution.
Giardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response. The variable expression of the variant-specific surface protein (VSP) genes may contribute to this prolonged infection. Only one is expressed at a time, and switching expression from one gene to another occurs by an epigenetic mechanism. The WB Giardia isolate has been sequenced at 10x coverage and assembled into 306 contigs as large as 870 kb in size. We have used this assembly to evaluate the genomic organization and evolution of the vsp repertoire. We have identified 228 complete and 75 partial vsp gene sequences for an estimated repertoire of 270 to 303, making up about 4% of the genome. The vsp gene diversity includes 30 genes containing tandem repeats, and 14 vsp pairs of identical genes present in either head to head or tail to tail configurations (designated as inverted pairs), where the two genes are separated by 2 to 4 kb of non-coding DNA. Interestingly, over half the total vsp repertoire is present in the form of linear gene arrays that can contain up to 10 vsp gene members. Lastly, evidence for recombination within and across minor clades of vsp genes is provided. The data we present here is the first comprehensive analysis of the vsp gene family from the Genotype A1 WB isolate with an emphasis on vsp characterization, function, evolution and contributions to pathogenesis of this important pathogen.


The state of U.S. living kidney donors.
Increasing living kidney donation mandates ongoing assessment of living donors for future health risks and revision of national health policy. Living kidney donors as reported to the Organ Procurement and Transplant Network database from January 1988 through December 2008 were reviewed for minor medical abnormalities, presence of donor health care coverage, and occurrence of surgical complications and death. At donation in 2008, 19.5% were obese, 2.0% had a history of hypertension, and 3.5% had proteinuria. The median estimated GFR of living donors was 92.2 ml/min. Additionally, 12.2% of donors were reported not to have health insurance at the time of donation. By racial background, 14.9% of black and 17.0% of Hispanic donors did not have insurance at donation. Perioperative complications included blood transfusion (0.4%), reoperation (0.5%), and vascular complications (0.2%). Death occurred within 30 days of donation in 0.03% donating between October 1999 and December 2008. During those same years, overall donor death was 2.8%. Almost one quarter of living donors have medical conditions that may be associated with future health risk. Close follow-up and a registry of these donors are necessary. Only then will we be able to inform prospective living donors most accurately of the real risk of donation on their health and survival. Additionally, these data speak to the need for a national discussion on the provision of health insurance for living donors.


Diagnosis of twin reversed arterial perfusion sequence in the first trimester by transvaginal color Doppler ultrasound.
A case of twin reversed arterial perfusion (TRAP) sequence was diagnosed at 12 weeks' gestation using transvaginal color Doppler ultrasound, which demonstrated the presence of retrograde perfusion in the umbilical artery of the abnormal twin. Ultrasound imaging showed a monochorionic-diamniotic twin pregnancy with an inappropriately grown second twin, the morphological evaluation of which revealed an abnormal cephalic pole with acrania, diffuse subcutaneous edema and the presence of cardiac activity in an abnormal heart with a single chamber.


Forming a stone in pelviureteric junction obstruction: Cause or effect?
To investigate a possible causal relationship for stone formation in pelviureteric junction obstruction and to outline management options. A literature search and evidence synthesis was conducted via electronic databases in the English language using the key words pelviureteric junction obstruction; urolithiasis; hyperoxaluria; laparoscopic pyeloplasty; flexible nephroscopy; percutaneous nephrolithotomy, alone or in combination. Relevant articles were analysed to extract conclusions. Concomitant pelviureteric junction obstruction (PUJO) and renal lithiasis has been reported only scarcely in the literature. Although PUJO has been extensively studied throughout the years, the presence of calculi in such a patient has not received equal attention and there is still doubt surrounding the pathophysiology and global management. Metabolic risk factors appear to play an important role, enough to justify metabolic evaluation in these patients. Urinary stasis and infection are well known factors predisposing to lithiasis and contribute to some extent. The choice for treatment is not always straightforward. Management should be tailored according to degree of obstruction, renal function, patient symptoms and stone size. Simultaneous treatment is feasible with the aid of minimally invasive operative techniques and laparoscopy in particular.


Caseload of a land-based trauma team.
Pre-hospital care is provided by a variety of models worldwide. The Tayside Trauma Team responds from Ninewells Hospital in Dundee to provide a physician-led pre-hospital care service targeted primarily at trauma patients. We present a description of the functions of the team, and data detailing the clinical work of the Team over a six-month period. The Team was called out 35 times in six months and attended 22 incidents, some involving multiple casualties. 34 patients received treatment at the scene of an incident. Most incidents were road traffic collisions, although the team also attended falls from height, an assault and a vascular injury. Eight patients (24%) met Injury Severity Score criteria for major trauma (ISS>15). Mean time from 999 calls to Team activation was 20 (range 4-79) min; and mean time from Team dispatch to 'Team mobile' was 4.6 (2-21) min. The Tayside Trauma Team provides a physician-led pre-hospital care response on demand from the Scottish Ambulance Service. It provides critical care interventions at the scene of various incidents (primarily traumatic) to attempt to improve patient outcome. Response times are favourable.


Adversarial Examples: Attacks and Defenses for Deep Learning.
With rapid progress and significant successes in a wide spectrum of applications, deep learning is being applied in many safety-critical environments. However, deep neural networks (DNNs) have been recently found vulnerable to well-designed input samples called adversarial examples. Adversarial perturbations are imperceptible to human but can easily fool DNNs in the testing/deploying stage. The vulnerability to adversarial examples becomes one of the major risks for applying DNNs in safety-critical environments. Therefore, attacks and defenses on adversarial examples draw great attention. In this paper, we review recent findings on adversarial examples for DNNs, summarize the methods for generating adversarial examples, and propose a taxonomy of these methods. Under the taxonomy, applications for adversarial examples are investigated. We further elaborate on countermeasures for adversarial examples. In addition, three major challenges in adversarial examples and the potential solutions are discussed.


Insights into the Role of Oxidative Stress in Hepatocellular Carcinoma Development.
Oxidative stress (OS) is linked to hepatocellular carcinoma (HCC) progression. HCC may develop as a result of genetic changes, including oxidative injury to both nuclear and mitochondrial DNA. Signaling pathways regulated by OS, such as Wnt/β-catenin and Notch pathways, are vital regulators in developing HCC. OS-mediated activation of transcription factors, including nuclear factor-κB and p53, among others, is capable of regulating the redox state of HCC cells. OS also affects the tumor microenvironment, which, in turn, regulates HCC progression. In HCC, reactive oxygen species (ROS) can potentially enhance tumor cell proliferation, metastasis, and resistance to treatment. However, elevated ROS levels can cause cytotoxicity and trigger apoptosis in HCC cells. This review highlights and explores potential oxidative stress-related treatment targets in HCC, offering novel insights for clinical therapies.


Addressing annotation and data scarcity when designing machine learning strategies for neurophotonics.
Machine learning has revolutionized the way data are processed, allowing information to be extracted in a fraction of the time it would take an expert. In the field of neurophotonics, machine learning approaches are used to automatically detect and classify features of interest in complex images. One of the key challenges in applying machine learning methods to the field of neurophotonics is the scarcity of available data and the complexity associated with labeling them, which can limit the performance of data-driven algorithms. We present an overview of various strategies, such as weakly supervised learning, active learning, and domain adaptation that can be used to address the problem of labeled data scarcity in neurophotonics. We provide a comprehensive overview of the strengths and limitations of each approach and discuss their potential applications to bioimaging datasets. In addition, we highlight how different strategies can be combined to increase model performance on those datasets. The approaches we describe can help to improve the accessibility of machine learning-based analysis with limited number of annotated images for training and can enable researchers to extract more meaningful insights from small datasets.


Diet diversity and colorectal cancer.
Food diversity has been recommended to achieve a healthy diet and prevent cancer. The relation between diet diversity and the risk of colorectal cancer was investigated using data from a multicenter case-control study carried out between 1992 and 1996 in Italy. The study included 1225 subjects with cancer of the colon (688 men and 537 women), 728 with cancer of the rectum (437 men and 291 women), and 4154 controls (2073 men and 2081 women) residing in the same geographical areas. Odds ratios (ORs) of colon and rectal cancer and the corresponding 95% confidence intervals (CI) according to food diversity were derived from unconditional multiple logistic regression equations. For colon cancer, an inverse association for total diversity was found in males (adjusted OR of 0.65 for the highest vs the lowest quintile of total diversity; 95% CI: 0.46-0.93) and in females (OR = 0.85; 95% CI: 0.57-1.26). With respect to specific food groups, there was an inverse association only with diversity within vegetables (OR = 0.66; 95% CI: 0.54-0.81 in colon cancer and OR = 0.71; 95% CI: 0.55-0.91 in rectal cancer). This study suggests that total diversity is moderately related to a decreased risk of colorectal cancer risk. A better understanding of the potential influence of dietary patterns on colorectal cancer is needed.


Structure of the S1 subunit C-terminal domain from bat-derived coronavirus HKU5 spike protein.
Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing question. Here, we solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain and those of other betacoronaviruses (betaCoVs) have a similar topology of the external subdomain, indicating the same ancestor of lineage C betaCoVs. However, two deletions in two respective loops located in HKU5-CTD result in conformational variations in CD26-binding interface and are responsible for the non-binding of HKU5-CTD to CD26. Combined with sequence variation in the HKU5-CTD receptor binding interface, we propose the necessity for surveilling the mutation in BatCoV HKU5 spike protein in case of bat-to-human interspecies transmission.


Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest after DNA methylating agent exposure.
Mouse fibroblasts, deficient in DNA polymerase beta, are hypersensitive to monofunctional DNA methylating agents such as methyl methanesulfonate (MMS). Both wild-type and, in particular, repair-deficient DNA polymerase beta null cells are highly sensitized to the cytotoxic effects of MMS by 4-amino-1,8-naphthalimide (4-AN), an inhibitor of poly(ADP-ribose) polymerase (PARP) activity. Experiments with synchronized cells suggest that exposure during S-phase of the cell cycle is required for the 4-AN effect. 4-AN elicits a similar extreme sensitization to the thymidine analog, 5-hydroxymethyl-2'-deoxyuridine, implicating the requirement for an intermediate of DNA repair. In PARP-1-expressing fibroblasts treated with a combination of MMS and 4-AN, a complete inhibition of DNA synthesis is apparent after 4 h, and by 24 h, all cells are arrested in S-phase of the cell cycle. Continuous incubation with 4-AN is required to maintain the cell cycle arrest. Caffeine, an inhibitor of the upstream checkpoint kinases ATM (ataxia telangiectasia-mutated) and ATR (ATM and Rad3-related), has no effect on the early inhibition of DNA synthesis, but cells are no longer able to maintain the block after 8 h. Instead, the addition of caffeine leads to arrest of cells in G(2)/M rather than S-phase after 24 h. Analysis of signaling pathways in cell extracts reveals an activation of Chk1 after treatment with MMS and 4-AN, which can be suppressed by caffeine. Our results suggest that inhibition of PARP activity results in sensitization to MMS through maintenance of an ATR and Chk1-dependent S-phase checkpoint.


Evaluation of animal and public health surveillance systems: a systematic review.
Disease surveillance programmes ought to be evaluated regularly to ensure they provide valuable information in an efficient manner. Evaluation of human and animal health surveillance programmes around the world is currently not standardized and therefore inconsistent. The aim of this systematic review was to review surveillance system attributes and the methods used for their assessment, together with the strengths and weaknesses of existing frameworks for evaluating surveillance in animal health, public health and allied disciplines. Information from 99 articles describing the evaluation of 101 surveillance systems was examined. A wide range of approaches for assessing 23 different system attributes was identified although most evaluations addressed only one or two attributes and comprehensive evaluations were uncommon. Surveillance objectives were often not stated in the articles reviewed and so the reasons for choosing certain attributes for assessment were not always apparent. This has the potential to introduce misleading results in surveillance evaluation. Due to the wide range of system attributes that may be assessed, methods should be explored which collapse these down into a small number of grouped characteristics by focusing on the relationships between attributes and their links to the objectives of the surveillance system and the evaluation. A generic and comprehensive evaluation framework could then be developed consisting of a limited number of common attributes together with several sets of secondary attributes which could be selected depending on the disease or range of diseases under surveillance and the purpose of the surveillance. Economic evaluation should be an integral part of the surveillance evaluation process. This would provide a significant benefit to decision-makers who often need to make choices based on limited or diminishing resources.


Identification the Key Odorants in Different Parts of Hyla Rabbit Meat via Solid Phase Microextraction Using Gas Chromatography Mass Spectrometry.
The aim of this study was to explore the volatile compounds of hind leg, foreleg, abdomen and Longissimus dorsi in both male and female Hyla rabbit meat by solid phase microextraction tandem with gas chromatography mass spectrometry, and to seek out the key odorants via calculating the odor activity value and principal component analysis. Cluster analysis is used to study the flavor pattern differences in four edible parts. Sixty three volatile compounds were detected, including 23 aldehydes, 4 alcohols, 5 ketones, 11 esters, 5 aromatics, 8 acids and 7 hydrocarbons. Among them, 6 aldehydes and 3 acids were identified as the potential key odorants according to the ratio of concentration and threshold. The contents of volatile compounds in male Hyla rabbit meat were significantly higher than those in female one (p<0.05). The results of principal component analysis showed that the first two principal component cumulative variance contributions reach 87.69%; Hexanal, octanal, 2-nonenal, 2-decenal and decanal were regard as the key odorants of Hyla rabbit meat by combining odor activity value and principal component analysis. Therefore volatile compounds of rabbit meat can be effectively characterized. Cluster analysis indicated that volatile chemical compounds of Longissimus dorsi were significantly different from other three parts, which provide reliable information for rabbit processing industry and for possible future sale.


High-Flow Nasal Cannula Oxygenation in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.
In immunocompromised patients with acute respiratory failure, invasive mechanical ventilation remains associated with high mortality. Choosing the adequate oxygenation strategy is of the utmost importance in that setting. High-flow nasal oxygen has recently shown survival benefits in unselected patients with acute respiratory failure. The objective was to assess outcomes of immunocompromised patients with hypoxemic acute respiratory failure treated with high-flow nasal oxygen. We performed a post hoc analysis of a randomized controlled trial of noninvasive ventilation in critically ill immunocompromised patients with hypoxemic acute respiratory failure. Twenty-nine ICUs in France and Belgium. Critically ill immunocompromised patients with hypoxemic acute respiratory failure. A propensity score-based approach was used to assess the impact of high-flow nasal oxygen compared with standard oxygen on day 28 mortality. Among 374 patients included in the study, 353 met inclusion criteria. Underlying disease included mostly malignancies (n = 296; 84%). Acute respiratory failure etiologies were mostly pneumonia (n = 157; 44.4%) or opportunistic infection (n = 76; 21.5%). Noninvasive ventilation was administered to 180 patients (51%). Invasive mechanical ventilation was ultimately needed in 142 patients (40.2%). Day 28 mortality was 22.6% (80 deaths). Throughout the ICU stay, 127 patients (36%) received high-flow nasal oxygen whereas 226 patients received standard oxygen. Ninety patients in each group (high-flow nasal oxygen or standard oxygen) were matched according to the propensity score, including 91 of 180 (51%) who received noninvasive ventilation. High-flow nasal oxygen was neither associated with a lower intubation rate (hazard ratio, 0.42; 95% CI, 0.11-1.61; p = 0.2) nor day 28 mortality (hazard ratio, 0.80; 95% CI, 0.45-1.42; p = 0.45). In immunocompromised patients with hypoxemic acute respiratory failure, high-flow nasal oxygen when compared with standard oxygen did not reduce intubation or survival rates. However, these results could be due to low statistical power or unknown confounders associated with the subgroup analysis. A randomized trial is needed.


[Carbohydrate hydrolysis and absorption in the human small intestine in aging].
In old age, a significant increase of the starch hydrolysis and a decrease in the maltose hydrolysis occur, as well as lactose, glucose absorption, fructose and galactose. The starch hydrolysis decreases with further ageing, too, whereas saccharose hydrolysis and pure galactose absorption maintain their levels in old age. In ageing, the enzyme systems maintaining the membrane digestion undergo alterations earlier than the transport systems.


A self-hydrosilylation of phosphanylhydrosilylalkynes promoted by B(C6F5)3? An experimental and mechanistic study.
Phosphanylhydrosilylalkynes Me2HSiC[triple bond, length as m-dash]CPAr2 (Ar = Ph, 1a; 4-MeC6H4, 1b) were synthesized, which reacted with B(C6F5)3 to produce alkenes [(E)-(C6F5)3BCH[double bond, length as m-dash]C(PAr2)SiMe2]2 (2a and 2b) and (Z)-(C6F5)2BCH[double bond, length as m-dash]C(PAr2)SiMe2(C6F5) (3a and 3b). The formation of 2a (or 2b) involved a Wrackmeyer's SiHMe2 migration followed by Si-H addition across the C[triple bond, length as m-dash]C bond, whereas, that of 3a (or 3b) involved a similar mechanism with a further C6F5 migration. The B(C6F5)3-promoted reaction of the Si-centered geminal H and C[triple bond, length as m-dash]C groups is thus realized, which may be considered as a self-hydrosilylation. Mechanistic studies by both variable temperature NMR spectroscopy and DFT calculations were accomplished.


Probiotics in critically ill children.
Gut microflora contribute greatly to immune and nutritive functions and act as a physical barrier against pathogenic organisms across the gut mucosa. Critical illness disrupts the balance between host and gut microflora, facilitating colonization, overgrowth, and translocation of pathogens and microbial products across intestinal mucosal barrier and causing systemic inflammatory response syndrome and sepsis. Commonly used probiotics, which have been developed from organisms that form gut microbiota, singly or in combination, can restore gut microflora and offer the benefits similar to those offered by normal gut flora, namely immune enhancement, improved barrier function of the gastrointestinal tract (GIT), and prevention of bacterial translocation. Enteral supplementation of probiotic strains containing either Lactobacillus alone or in combination with Bifidobacterium reduced the incidence and severity of necrotizing enterocolitis and all-cause mortality in preterm infants. Orally administered Lactobacillus casei subspecies rhamnosus, Lactobacillus reuteri, and Lactobacillus rhamnosus were effective in the prevention of late-onset sepsis and GIT colonization by Candida in preterm very low birth weight infants. In critically ill children, probiotics are effective in the prevention and treatment of antibiotic-associated diarrhea. Oral administration of a mix of probiotics for 1 week to children on broad-spectrum antibiotics in a pediatric intensive care unit decreased GIT colonization by Candida, led to a 50% reduction in candiduria, and showed a trend toward decreased incidence of candidemia. However, routine use of probiotics cannot be supported on the basis of current scientific evidence. Safety of probiotics is also a concern; rarely, probiotics may cause bacteremia, fungemia, and sepsis in immunocompromised critically ill children. More studies are needed to answer questions on the effectiveness of a mix versus single-strain probiotics, optimum dosage regimens and duration of treatment, cost effectiveness, and risk-benefit potential for the prevention and treatment of various critical illnesses.


Local mate competition and parental investment in social insects.
Efforts to develop formulas for contrasting genetic interests of workers and queens in social Hymenoptera are complicated by many factors, including multiple matings by queens, oviposition by unmated females, and mating rivalry among genetic relatives (Hamilton's "local mate competition"). Because of haplodiploid sex determination in Hymenoptera, when such influences are absent, queens benefit from 1:1 sex ratios of investment (male: female) in reproductive offspring, workers from 1:3 ratios among reproductive siblings. Reports of variable ratios, including many well above 1:3, and female biases in nonsocial Hymenoptera and diplodiploid termites, implicate local mate competition and raises questions about previous interpretations that workers have their way.


Heart Histopathology and Mitochondrial Ultrastructure in Aged Rats Fed for 24 Months on Different Unsaturated Fats (Virgin Olive Oil, Sunflower Oil or Fish Oil) and Affected by Different Longevity.
Diet plays a decisive role in heart physiology, with lipids having especial importance in pathology prevention and development. This study aimed to investigate how dietary lipids varying in lipid profile (virgin olive oil, sunflower oil or fish oil) affected the heart of rats during aging. Heart histopathology, mitochondrial morphometry, and oxidative status were assessed. Typical histopathological features associated with aging, such as valvular lesions, endomyocardical hyperplasia, or papillary muscle calcification, were found at a low extent in all the experimental groups. The most relevant finding was that inflammation registered by fish oil group was lower compared to the other treatments. At the ultrastructural level, heart mitochondrial area, perimeter, and aspect ratio were higher in fish oil-fed rats than in those fed on sunflower oil. Concerning oxidative stress markers, there were differences only in coenzyme Q levels and catalase activity, lower in sunflower oil-fed animals compared with those fed on fish oil. In summary, dietary intake for a long period on dietary fats with different fatty acids profile led to differences in some aspects associated with the aging process at the heart. Fish oil seems to be the fat most protective of heart during aging.


Cyclobenzaprine in intractable pain syndromes with muscle spasm.
The effectiveness of cyclobenzaprine hydrochloride, a new tricyclic skeletal muscle relaxant, was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness. The investigation was double-blind and randomized, comparing cyclobenzaprine hydrochloride (10 mg three times a day) with diazepam (5 mg three times a day) and with placebo. After two weeks of treatment, the 16 patients in the cyclobenzaprine group showed an overall improvement in pain variables as did the 16 patients in the diazepam group. No serious adverse reactions to cyclobenzaprine were observed in the study. However, dry mouth due to cyclobenzaprine's anticholinergic action and mild degrees of drowsiness were encountered more often than with diazepam or placebo.


A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin.
The E-cadherin-catenin adhesion complex has been the subject of many structural and functional studies because of its importance in development, normal tissue function and carcinogenesis. It is well established that the cytoplasmic domain of E-cadherin binds either beta-catenin or plakoglobin, which both can assemble alpha-catenin into the complex. Recently we have identified an alpha-catenin binding site in beta-catenin and plakoglobin and postulated, based on sequence analysis, that these protein-protein interactions are mediated by a hydrophobic interaction mechanism. Here we have now identified the reciprocal complementary binding site in alpha-catenin which mediates its interaction with beta-catenin and plakoglobin. Using in vitro association assays with C-terminal truncations of alpha-catenin expressed as recombinant fusion proteins, we found that the N-terminal 146 amino acids are required for this interaction. We then identified a peptide of 27 amino acids within this sequence (amino acid positions 117-143) which is necessary and sufficient to bind beta-catenin or plakoglobin. As shown by mutational analysis, hydrophobic amino acids within this binding site are important for the interaction. The results described here, together with our previous work, give strong support for the idea that these proteins associate by hydrophobic interactions of two alpha-helices.


Folate targeting of drug carriers: a mathematical model.
The binding of folate-targeted drug carriers to a receptor-bearing cell surface is modeled using a deterministic approach. The model accounts for the presence of multiple folate ligands on the carrier surface, the anchoring and presentation of the ligands on flexible polymeric tethers, and the combination of both clustered and homogeneous spatial distributions of receptors on the cell surface. The model was validated against an experimental system where folate-bearing liposomes were used as delivery vehicles to deliver drug to tumor cells in vitro. Unknown parameters of the model were then estimated by a least-squares fit to the experimental data. A parametric study systematically varying the estimated parameters around the best-fit values indicated that the model was sensitive to these parameters, lending credence to their estimated values. This study indicates that drug uptake is dependent on several factors including the ligand number, the exposure time, and carrier concentration. For the specific case of folate targeting, the cumulative uptake of folate ligands is important, causing a decrease in the carrier uptake rate once a threshold cumulative uptake is crossed.


Visual and haptic integration in the estimation of softness of deformable objects.
Softness perception intrinsically relies on haptic information. However, through everyday experiences we learn correspondences between felt softness and the visual effects of exploratory movements that are executed to feel softness. Here, we studied how visual and haptic information is integrated to assess the softness of deformable objects. Participants discriminated between the softness of two softer or two harder objects using only-visual, only-haptic or both visual and haptic information. We assessed the reliabilities of the softness judgments using the method of constant stimuli. In visuo-haptic trials, discrepancies between the two senses' information allowed us to measure the contribution of the individual senses to the judgments. Visual information (finger movement and object deformation) was simulated using computer graphics; input in visual trials was taken from previous visuo-haptic trials. Participants were able to infer softness from vision alone, and vision considerably contributed to bisensory judgments (∼35%). The visual contribution was higher than predicted from models of optimal integration (senses are weighted according to their reliabilities). Bisensory judgments were less reliable than predicted from optimal integration. We conclude that the visuo-haptic integration of softness information is biased toward vision, rather than being optimal, and might even be guided by a fixed weighting scheme.


Risk modification for diabetic patients. Are other risk factors treated as diligently as glycemia?
The importance of glucose control is recognized both by patients with diabetes and their physicians. However, other preventative interventions, such as using medications to manage lipid and blood pressure levels, are underused for diabetic patients. To determine whether patients with diligent glucose management are more likely to use medications that treat lipids and blood pressure. Administrative data records were evaluated for all diabetic patients aged 65 or older residing in Ontario in 1999 without pre-existing coronary artery disease (n=161,553). Measures of diligent glucose management were insulin use and frequent capillary glucose testing ((3) 2 per day). Outcomes were prescription of a lipid-lowering drug or antihypertensive drug. Using multivariate modeling, odds ratios for each diligence measure were determined for each outcome, adjusting for age, sex, comorbidities, and other covariates. Patients using insulin did not have a clinically important difference in lipid-lowering drug use (adjusted odds ratio 0.9, 99% confidence interval 0.9 - 1.0, P=0.002) or antihypertensive drug use (adjusted odds ratio 1.1, 99% confidence interval 1.0 - 1.1, P<0.001) versus non-users. Adjusted odds ratios for frequent glucose testing were not significantly different from unity for either lipid-lowering or antihypertensive drug use. Patients who required and were capable of diligent glucose management, which is invasive, expensive and time-consuming, were no more likely to use medications to control lipids or blood pressure. Preventative care for patients with diabetes may be too focused on glycemic control, and may be neglecting the management of other cardiovascular risk factors.


Brain and Quantum Dots: Benefits of Nanotechnology for Healthy and Diseased Brain.
The brain is the most complicated organ in a vertebrate's organism. In a human, it contains about two hundred billions of neurons and non-neuronal cells. To understand the mechanisms of the brain functions is the great challenge for the researchers. Much is already done on this way; however, it remains a lot to do still, and to get deeper knowledge, new approaches should be developed. One of this is to use benefits that nanotechnology brings in this area. Nanotechnology opens up unique opportunities, not only for material science research, but also for biology, medicine, and many other disciplines. There are several kinds of nanoparticles that can be applied in brain studies, Quantum Dots (QD) being so far most often used. QD are semiconductor light emitting nanocrystals with nanometer-sized structures of unique optical properties. They have bright fluorescence, are resistant to bleaching and able of emitting fluorescent light of different wavelengths. These properties make QD perfect tools for visualization of brain structures and mechanisms underlying its functions. Due to unique QD properties, even single molecules under study can be observed. Moreover QDs can be used for brain-targeted drug delivery. In this review, the application of quantum dots for the brain research is considered and benefits that it can bring are discussed.


EMG-based neuromuscular modeling with full physiological dynamics and its comparison with modified Hill model.
EMG-based muscle model has many applications in human-machine interface and rehabilitation robotics. For the muscular force estimation, so-called Hill-type model has been used in most of the cases. It has already shown its promising performance, however it is known as a phenomenological model considering only macroscopic physiology. In this paper, we discuss EMG-force estimation with the full physiology based muscle model in voluntary contraction. In addition to Hill macroscopic representation, a microscopic physiology description as stated by Huxley and Zahalak is integrated. It has significant meaning to realize the same kind of EMG-force estimation with multiscale physiology based model not with a phenomenological Hill model, because it brings the understanding of the internal biophysical dynamics and new insights about neuromuscular activations.


Treatment of poor-grade subarachnoid hemorrhage trial.
Management of poor-grade subarachnoid hemorrhage is based on limited evidence from small single-center retrospective observational studies. The purpose of this study was to undertake a single-center randomized controlled feasibility trial comparing a strategy of early endovascular aneurysm treatment with treatment after neurologic recovery in this group of patients. Patients with poor-grade SAH were randomized within 24 hours of admission to early treatment or treatment after neurologic recovery. If a patient was randomized to early treatment, the aneurysm was treated endovascularly within 24 hours of randomization. Recruitment rate, safety profile, and functional outcome at the time of discharge and at 6 months were assessed. Fourteen of 51 patients screened were eligible for the trial. Of these 14, 8 patients were randomized (57%). All patients in the early coiling arm received treatment within 24 hours of randomization. There was no treatment-related complication. Overall, good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in the early treatment arm (n = 5) had a good outcome rate of 20%, while those in treatment after neurologic recovery arm (n = 3) had a good outcome rate of 33.3%. This was a feasibility study that demonstrated that recruitment and randomization for comparing management strategies in poor-grade SAH are feasible. The recruitment rate among eligible patients was encouraging (57%), though a number of patients had to be excluded due to ineligibility. A multicenter study is necessary to recruit the numbers required to compare the clinical outcomes of these management strategies.


Cost-utility of Intravenous Immunoglobulin (IVIG) compared with corticosteroids for the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Canada.
Intravenous immunoglobulin (IVIG) has demonstrated improvement in chronic inflammatory demyelinating polyneuropathy (CIDP) patients in placebo controlled trials. However, IVIG is also much more expensive than alternative treatments such as corticosteroids. The objective of the paper is to evaluate, from a Canadian perspective, the cost-effectiveness of IVIG compared to corticosteroid treatment of CIDP. A markov model was used to evaluate the costs and QALYs for IVIG and corticosteroids over 5 years of treatment for CIDP. Patients initially responding to IVIG could remain a responder or relapse every 12 week model cycle. Non-responding IVIG patients were assumed to be switched to corticosteroids. Patients on corticosteroids were at risk of a number of adverse events (fracture, diabetes, glaucoma, cataract, serious infection) in each cycle. Over the 5 year time horizon, the model estimated the incremental costs and QALYs of IVIG treatment compared to corticosteroid treatment to be $124,065 and 0.177 respectively. The incremental cost per QALY gained of IVIG was estimated to be $687,287. The cost per QALY of IVIG was sensitive to the assumptions regarding frequency and dosing of maintenance IVIG. Based on common willingness to pay thresholds, IVIG would not be perceived as a cost effective treatment for CIDP.


Lack of correlation between prostate-specific antigen and the presence of measurable soft tissue metastases in hormone-refractory prostate cancer.
Appropriate staging procedures for patients with hormone-refractory prostate cancer are poorly defined. In particular, there are no studies correlating prostate-specific antigen (PSA) with more traditional methods of staging. We have evaluated the abdominal/pelvic CT scan, bone scan, and PSA results following initial diagnosis of hormone-refractory prostate cancer in 177 consecutive patients (median age = 63.1 years, range 45-80). Thirty-four patients (19.2%) had measurable lesions (> or = 2 cm) on CT scan compatible with metastatic disease. Of the patients with measurable lesions, 29/34 (85.3%) had retroperitoneal and/or pelvic adenopathy; 5 patients (14.7%) had measurable lesions in the liver. Other sites of metastatic disease were detected in less than 1% of the patients receiving scans. All patients had bone scan abnormalities compatible with metastatic disease. Results of these imaging studies were then compared to PSA serum concentration (Abbott IMx). The mean PSA concentration was not different in those patients with soft tissue disease as compared to those without soft tissue involvement and there was no correlation between PSA concentration and the presence or absence of measurable soft tissue disease. In contrast to previously published studies in hormone-naïve prostate cancer patients, these studies in hormone-refractory patients indicate that the detection of metastatic disease by standard radiological procedures cannot be predicted by measurement of serum PSA.


Orthogonal Tyrosine and Cysteine Site-Directed Spin Labeling for Dipolar Pulse EPR Spectroscopy on Proteins.
Site-directed spin labeling of native tyrosine residues in isolated domains of the protein PTBP1, using a Mannich-type reaction, was combined with conventional spin labeling of cysteine residues. Double electron-electron resonance (DEER) EPR measurements were performed for both the nitroxide-nitroxide and Gd(III)-nitroxide label combinations within the same protein molecule. For the prediction of distance distributions from a structure model, rotamer libraries were generated for the two linker forms of the tyrosine-reactive isoindoline-based nitroxide radical Nox. Only moderate differences exist between the spatial spin distributions for the two linker forms of Nox. This strongly simplifies DEER data analysis, in particular, if only mean distances need to be predicted.


Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas.
Long non-coding RNAs (lncRNAs) comprise a family of non-coding transcripts that are emerging as relevant gene expression regulators of different processes, including tumour development. To determine the possible contribution of lncRNA to the pathogenesis of follicular lymphoma (FL) we performed RNA-sequencing at high depth sequencing in primary FL samples ranging from grade 1-3A to aggressive grade 3B variants using unpurified (n = 16) and purified (n = 12) tumour cell suspensions from nodal samples. FL grade 3B had a significantly higher number of differentially expressed lncRNAs (dif-lncRNAs) with potential target coding genes related to cell cycle regulation. Nine out of the 18 selected dif-lncRNAs were validated by quantitative real time polymerase chain reaction in an independent series (n = 43) of FL. RP4-694A7.2 was identified as the top deregulated lncRNA potentially involved in cell proliferation. RP4-694A7.2 silencing in the WSU-FSCCL FL cell line reduced cell proliferation due to a block in the G1/S phase. The relationship between RP4-694A7.2 and proliferation was confirmed in primary samples as its expression levels positively related to the Ki-67 proliferation index. In summary, lncRNAs are differentially expressed across the clinico-biological spectrum of FL and a subset of them, related to cell cycle, may participate in cell proliferation regulation in these tumours.


Occurrence, functions and biosynthesis of polyamides in microorganisms and biotechnological production.
Microorganisms are able to synthesize three different polyamides by enzymatic processes independently from ribosomal protein biosynthesis: poly(gamma-D-glutamic acid), poly(epsilon-L-lysine) and multi-L-arginyl-poly(L-aspartic acid) which is also referred to as cyanophycin. These polyamides, which occur mainly in Bacillus spp. (and only a few other eubacteria and the nematocysts of Cnidaria, in Streptomyces albulus or in cyanobacteria, respectively), have recently attracted considerable interest of the chemical industry and may be suitable for various applications. This review summarizes our current knowledge on the occurrence, biosynthesis, physiological functions, and biodegradation as well as on the properties and putative applications of these polyamides. Emphasis is placed on the enzymology of the polymerization and on the genes encoding the polymerizing enzymes, which have only recently become available for cyanophycin synthetases. Prospects for novel production processes. in particular for cyanophycin, are also presented.


Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow.
Human umbilical cord perivascular cells (HUCPVCs) have been shown to have a high proliferative potential and the capacity to differentiate into an osteogenic phenotype. HUCPVCs have thus been considered a possible extra-embryonic mesenchymal stem cell (MSC) source for cell-based therapies. To assess this potential, we compared HUCPVCs to the "gold standard" bone marrow mesenchymal stromal cells (BMSCs) with respect to their proliferation, differentiation, and transfection capacities. HUCPVCs showed a higher proliferative potential than BMSCs and were capable of osteogenic, chondrogenic, and adipogenic differentiation. Interestingly, osteogenic differentiation of HUCPVCs proceeded more rapidly than BMSCs. Additionally, HUCPVCs expressed higher levels of CD146, a putative MSC marker, relative to BMSCs. HUCPVCs showed comparable transfection efficiency as BMSCs using a nucleofection method but were more amenable to transfection with liposomal methods (FuGENE). Gene array analysis showed that HUCPVCs also expressed Wnt signaling pathway genes that have been implicated in the regulation of MSCs. The similar characteristics between HUCPVCs and MSCs support the applicability of HUCPVCs for cell-based therapies. Disclosure of potential conflicts of interest is found at the end of this article.


T lymphocytes of the normal human cornea.
Lymphocytes in the periphery of the normal human cornea are identified as being only T lymphocytes by immunohistochemical methods. OKT-4 positive cells (T-helper/inducer lymphocytes) and OKT-8 positive cells (T-suppressor/cytotoxic lymphocytes) are found in similar numbers in most of the corneas examined. OKT-4 positive cells in the cornea present a risk of transferring HTLV-III (HIV) by corneal grafting.


A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study.
To evaluate the efficacy and safety of a combined regimen of bendamustine (B) and rituximab (R) in Japanese patients with relapsed/refractory (r/r) indolent B-cell non-Hodgkin lymphomas (B-NHLs) and mantle cell lymphoma (MCL). Patients aged 20-79 years with pathologically confirmed B-NHLs or MCL, which were r/r after 1-2 R-containing regimens, were included in this study. The BR regimen consisted of B (90 mg/m(2)) for two consecutive days and R (375 mg/m(2)) on day 1, 2, or 3. The course was repeated every 4 weeks for up to four cycles. Fifty-three patients were enrolled in this study and analyzed. The diagnosis included follicular lymphoma (FL) (77 %), mucosa-associated lymphoid tissue lymphoma (13 %) and others (10 %). Forty-seven (90 %) patients completed four cycles of treatment as per schedule. Best overall response rate (ORR) and complete response rate (CRR) was 94 and 71 %, respectively (for FL, ORR 95 % and CRR 80 %). The treatment was well tolerated and the primary toxicity was myelosuppression; the incidence of grade 3/4 leukopenia and neutropenia were 42 and 40 %, respectively. There were no grade 5 toxicities. The BR regimen is safe in Japanese patients with r/r indolent B-NHLs and MCL, and is effective for those with r/r indolent B-NHLs. For the evaluation of late toxicity, especially infection, longer follow-up of this cohort is needed.


10-year changes in upper body strength and power in elite professional rugby league players--the effect of training age, stage, and content.
The purpose of this investigation was to observe changes in maximal upper body strength and power across a 10-year period in professional athletes who were experienced resistance trainers. Six professional rugby league players were observed with test data reported according to 2 important training stages in their professional careers. The first stage (1996-1998) monitored the changes as the subjects strived to establish themselves as elite professionals in their sport. The remaining test data are from the latter stage (2000-2006), which is characterized by a longer competition schedule and shorter periods devoted to improving physical preparation. The changes in upper body strength, assessed by the 1 repetition maximum bench press and mean maximum power during bench press throws with various barbell resistances of 40-80 kg, were assessed by effect size (ES) and smallest worthwhile change (SWC) statistics. Large increases in strength and power of approximately 22-23% were reported across the 10-year period, however, only small changes (as determined by ES) in strength or power occurred after year 2000 till 2006. This result of only small changes in strength or power despite 6 years of intense resistance training was attributed to 3 main factors. Key among them are the possible existence of a "strength ceiling" for experienced resistance trainers, the Long-term Athlete Development model, and possibly an inappropriate volume of strength-endurance training from 2004 to 2005. The fact that an SWC in strength and power occurred in the year after the cessation of strength-endurance training suggests that training program manipulation is still an influencing factor in continuing strength and power gains in experienced resistance trainers.


Public and patient involvement in the development of an internet-based guide for persistent somatic symptoms (GUIDE.PSS): A qualitative study on the needs of those affected.
Persistent somatic symptoms (PSS) frequently remain under-treated in health care settings. Evidence-based services that lead affected individuals to early guideline-based care are currently missing. This study aimed to identify the needs of those affected concerning an internet-based guide. The second aim was to evaluate public and patient involvement (PPI). Participants experiencing PSS for at least 6 months were recruited via hospitals, psychotherapeutic practices and self-help organizations. Qualitative data were gathered via ideation discussions and prioritization tasks. Thematic analysis was conducted to gain insight on the needs of people with lived experiences. PPI was quantitatively evaluated with the Public and Patient Engagement Evaluation Tool. A total of 12 individuals participated (eight females, ages 22-66 years, duration of symptoms 1-43 years). Participants wanted to feel more supported, validated, in control and engaged with managing their health. Content-related preferences included education, self-help, social support and contact addresses. The majority of participants (>90%) experienced their involvement as worthwhile. To the best of our knowledge, this is one of the first studies describing PPI in intervention development for PSS. The involvement was perceived as a valuable contribution to the development process. Adults with lived experiences were involved at the level of collaboration through the establishment of a participatory research team (PRT) and at the level of consultation through a workshop series, including one of the coauthors. They were involved in developing and validating intervention material and checking data interpretation.


Reducing Nitrogen and Phosphorus Losses from Different Crop Types in the Water Source Area of the Danjiang River, China.
Nitrogen and phosphorus are essential for plant growth and are the primary limiting nutrient elements. The loss of nitrogen and phosphorus in agricultural systems can cause the eutrophication of natural water bodies. In this paper, a field simulated rainfall experiment was conducted in a typical small watershed of the Danjiang River to study the nutrient loss process of nitrogen and phosphorus in slope croplands subjected to different crops and tillage measures. The characteristics of the runoff process and nutrient migration of different slope treatments were studied, which were the bare-land (BL, as the control), peanut monoculture (PL), corn monoculture (CL), bare land (upper slope) mixed with peanut monoculture (lower slope) (BP), corn and peanut intercropping (TCP), corn and soybean intercropping (TCS), downslope ridge cultivation (BS) slope, and straw-mulched (SC), respectively. The results showed that the runoff of CL, SC, TCS, BS, BP, PL and TCP slope types were 93%, 75%, 51%, 39%, 28%, 12%, and 6% of the those of the bare land, respectively. The total nitrogen concentration in runoff on different slope types decreased in the order of BP > PL > BS > SC > TCP > BL > CL > TCS. The BL was characterized with the highest NRL-TN (the loss of total nitrogen per unit area), with the value of 1.188 kg/hm2, while those of the TCP is the smallest with the value of 0.073 kg/hm2. The total phosphorus concentration in runoff decreasd in the order of BS > BP > PL > BL > TCP > SC > CL > TCS. The PRL-TP (the loss of total phosphorus per unit area) of BL is the largest (0.016 kg/hm2), while those of TCP is the smallest (0.001 kg/hm2). These indicate that the loss of nitrogen is much higer than that of phosphorus. The loss of nitrogen in runoff is dominated by nitrate nitrogen, which accounts for 54.4%-78.9% of TN. Slope croplands in the water source area should adopt the tillage measures of TCP and PL.These measures can reduce 85% of the runoff of nitrogen and phosphorus compared to the bare land. The results may assist in agricultural non-point source pollution control and help promote improved management of the water environment in the Danjiang River's water source area.


Evaluation of Glycine max mRNA clusters.
Clustering the ESTs from a large dataset representing a single species is a convenient starting point for a number of investigations into gene discovery, genome evolution, expression patterns, and alternatively spliced transcripts. Several methods have been developed to accomplish this, the most widely available being UniGene, a public domain collection of gene-oriented clusters for over 45 different species created and maintained by NCBI. The goal is for each cluster to represent a unique gene, but currently it is not known how closely the overall results represent that reality. UniGene's build procedure begins with initial mRNA clusters before joining ESTs. UniGene's results for soybean indicate a significant amount of redundancy among some sequences reported to be unique mRNAs. To establish a valid non-redundant known gene set for Glycine max we applied our algorithm to the clustering of only mRNA sequences. The mRNA dataset was run through the algorithm using two different matching stringencies. The resulting cluster compositions were compared to each other and to UniGene. Clusters exhibiting differences among the three methods were analyzed by 1) nucleotide and amino acid alignment and 2) submitting authors conclusions to determine whether members of a single cluster represented the same gene or not. Of the 12 clusters that were examined closely most contained examples of sequences that did not belong in the same cluster. However, neither the two stringencies of PECT nor UniGene had a significantly greater record of accuracy in placing paralogs into separate clusters. Our results reveal that, although each method produces some errors, using multiple stringencies for matching or a sequential hierarchical method of increasing stringencies can provide more reliable results and therefore allow greater confidence in the vast majority of clusters that contain only ESTs and no mRNA sequences.


CN(-)-Induced degradation of nuclei in cells of pea leaves.
Degradation of nuclei in epidermal and guard cells of pea leaves was induced by NaCN. Guard cells were considerably more resistant to CN- than epidermal cells. CN--induced nucleus degradation in guard cells was accelerated by illumination. The effect of illumination was negligible in epidermal cells that, unlike guard cells, do not contain chloroplasts. These data may indicate a role of chloroplasts in CN--induced cell death. CN--induced nucleus degradation in epidermal cells was retarded by antioxidants (butylated hydroxytoluene and vitamin E). The effect of CN- in guard cells was largely removed by vitamin E. Salicylic acid, an inhibitor of catalase and ascorbate peroxidase, induced 100% degradation of nuclei in epidermal cells but did not significantly affect nuclei in guard cells. CN--induced inhibition of catalase and peroxidase is assumed to lead to generation and accumulation of reactive oxygen species inducing apoptosis. Like mitochondria, which play an important role in animal cell apoptosis, chloroplasts may take part in apoptosis in plant cells.


Type 2 diabetes self-management social support intervention at the U.S.-Mexico border.
To pilot test the efficacy of a culturally tailored diabetes self-management social support intervention for Mexican American adults with Type 2 diabetes (T2DM) living in the U.S.-Mexico border region and to test the feasibility of recruiting and training promotoras to participate in intervention delivery. This study used a single-group pretest and posttest design. The convenience sample consisted of 21 Mexican American adults with T2DM. The setting for the study was a community in the Arizona-Sonora, Mexico border region. A bilingual, bicultural certified diabetes educator (CDE) and a nurse researcher developed the intervention to improve T2DM self-management activities for Mexican Americans. Data were collected using self-report questionnaires, glycosolated hemoglobin (HbA(1c)), and anthropometric measures. Intervention efficacy was demonstrated by an increase in participants' diabetes self-management activities and diabetes knowledge and a decrease in diabetes-related distress and sedentary behaviors. There were no significant changes in physiologic outcomes. Feasibility of recruitment and training of 2 promotoras who participated in intervention delivery was established. Promotoras, in collaboration with a CDE, successfully delivered a culturally tailored diabetes self-management social support intervention for Mexican American adults with T2DM. This intervention positively affected diabetes self-management behaviors.


Anoctamin 6 is an essential component of the outwardly rectifying chloride channel.
Outwardly rectifying chloride channels (ORCC, ICOR) of intermediate single-channel conductance of around 50 pS, are ubiquitously expressed, but have remained a mystery since their description more than 25 y ago. These channels have been shown to be activated on membrane excision and depolarization of the membrane voltage and by cAMP in the presence of the cystic fibrosis transmembrane conductance regulator. We show that anoctamin 6 (Ano6), a member of the recently identified family of putative Cl(-) channels, is the crucial component of ORCC single-channel and whole-cell currents in airway epithelial cells and Jurkat T lymphocytes. Cystic fibrosis transmembrane conductance regulator augmented ORCC produced by Ano6 in A549 airway epithelial cells. Ano6 is activated during membrane depolarization or apoptosis of Jurkat T lymphocytes and epithelial cells, and is inhibited by 5-nitro-2-(3-phenylpropylamino) benzoic acid, 4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid, or AO1. Ano6 belongs to the basic equipment of any cell type, including colonic surface epithelial cells. It forms the essential component of ORCC and seems to have a role for cell shrinkage and programmed cell death.


Influence of mental health and substance use problems and criminogenic risk on outcomes in serious juvenile offenders.
To investigate the relations among certain mental health problems (MHPs; affective, anxiety, attention-deficit/hyperactivity disorder [ADHD], and substance use disorders), criminogenic risk, and outcomes in a sample of serious adolescent offenders. Using data from a longitudinal study of serious adolescent offenders (N = 949; mean age = 16 years, SD = 1.10 years; 84% male; 78% minority), we evaluated the association of MHPs with three distinct outcomes (rearrest, self-reported antisocial activity, and gainful activity), tested whether having an MHP contributed any unique explanatory power regarding these outcomes over and above criminogenic risk markers, and examined whether MHPs moderated the relationship between risk markers and outcomes. Negative binomial and ordinal regressions were used. Data for the study were derived primarily from youth self-report over a 7-year period, with parent collaterals reporting on ADHD, and official records as the source for rearrest information. Of the sample, 57.5% met the criteria for at least one of the assessed MPHs. The presence of a substance use disorder showed consistent associations with the outcomes. After controlling for risk markers and demographic characteristics, MHPs were not associated with most outcomes. The co-occurrence of a substance use disorder and an MHP moderated the relations between several risk markers and outcomes. Current juvenile justice policies that focus treatment efforts on both criminogenic and mental health factors (with particular emphasis on treating substance use disorders) appear to be well founded. It is unlikely that focusing solely on treating MHPs in serious offenders will have a distinct impact on later outcomes.


Protective efficacy of multiepitope vaccines constructed from common antigens of Eimeria species in chickens.
Clinical avian coccidiosis is typically caused by coinfection with several Eimeria species. Recombinant protein and DNA vaccines have shown promise in controlling coccidiosis. On this basis, DNA vaccines that encode multiple epitopes from different Eimeria species may provide broad protection against coinfections. In this study, we designed a fusion gene fragment, 14EGT, that contained concentrated T-cell epitopes from four common antigens of Eimeria species (14-3-3, elongation factor 2, glyceraldehyde-3-phosphate dehydrogenase, and transhydrogenase). The multiepitope DNA vaccine pVAX1-14EGT and recombinant protein vaccine pET-32a-14EGT (r14EGT) were then created based on the 14EGT fragment. Subsequently, cellular and humoral immune responses were measured in vaccinated chickens. Vaccination-challenge trials were also conducted, where the birds were vaccinated with the 14EGT preparations and later exposed to single or multiple Eimeria species to evaluate the protective efficacy of the vaccines. According to the results, vaccination with 14EGT preparations effectively increased the proportions of CD4+ and CD8+ T cells and the levels of Th1 and Th2 hallmark cytokines. The levels of serum IgG antibodies were also significantly increased. Animal vaccination trials revealed alleviated enteric lesions, weight loss, and oocyst output compared to those of the control groups. The preparations were found to be moderately effective against single Eimeria species, with the anticoccidial index (ACI) ranging from 160 to 180. However, after challenge with multiple Eimeria species, the protection provided by the 14EGT preparations was not satisfactory, with ACI values of 142.18 and 146.41. Collectively, the results suggest that a multiepitope vaccine that encodes the T-cell epitopes of common antigens derived from Eimeria parasites could be a potential and effective strategy to control avian coccidiosis.


Exploring Binding Mechanisms in Nuclear Hormone Receptors by Monte Carlo and X-ray-derived Motions.
In this study, we performed an extensive exploration of the ligand entry mechanism for members of the steroid nuclear hormone receptor family (androgen receptor, estrogen receptor α, glucocorticoid receptor, mineralocorticoid receptor, and progesterone receptor) and their endogenous ligands. The exploration revealed a shared entry path through the helix 3, 7, and 11 regions. Examination of the x-ray structures of the receptor-ligand complexes further showed two distinct folds of the helix 6-7 region, classified as "open" and "closed", which could potentially affect ligand binding. To improve sampling of the helix 6-7 loop, we incorporated motion modes based on principal component analysis of existing crystal structures of the receptors and applied them to the protein-ligand sampling. A detailed comparison with the anisotropic network model (an elastic network model) highlights the importance of flexibility in the entrance region. While the binding (interaction) energy of individual simulations can be used to score different ligands, extensive sampling further allows us to predict absolute binding free energies and analyze reaction kinetics using Markov state models and Perron-cluster cluster analysis, respectively. The predicted relative binding free energies for three ligands binding to the progesterone receptor are in very good agreement with experimental results and the Perron-cluster cluster analysis highlighted the importance of a peripheral binding site. Our analysis revealed that the flexibility of the helix 3, 7, and 11 regions represents the most important factor for ligand binding. Furthermore, the hydrophobicity of the ligand influences the transition between the peripheral and the active binding site.


Global determinants of prey naiveté to exotic predators.
Prey naiveté-the failure of prey to recognize novel predators as threats-is thought to exacerbate the impact that exotic predators exert on prey populations. Prey naiveté varies under the influence of eco-evolutionary mediating factors, such as biogeographic isolation and prey adaptation, although an overall quantification of their influence is lacking. We conducted a global meta-analysis to test the effects of several hypothesized mediating factors on the expression of prey naiveté. Prey were overall naive towards exotic predators in marine and freshwater systems but not in terrestrial systems. Prey naiveté was most pronounced towards exotic predators that did not have native congeneric relatives in the recipient community. Time since introduction was relevant, as prey naiveté declined with the number of generations since introduction; on average, around 200 generations may be required to erode naiveté sufficiently for prey to display antipredator behaviour towards exotic predators. Given that exotic predators are a major cause of extinction, the global predictors and trends of prey naiveté presented here can inform efforts to meet conservation targets.


Relative yield-per-recruit and management strategies for Cynoscion acoupa (Perciformes: Sciaenidae) in Lake Maracaibo, Venezuela.
Acoupa weakfish, Cynoscion acoupa, in Lake Maracaibo is subject to intense commercial fishing by an artisanal fleet, and a recent decrease in fish size observed from landings is of concern. This fishery has not yet been modeled, and its assessment and the establishment of management practices to overcome the current overfished condition are urgently needed. To address this, we used recent and past empirical growth estimates to model relative yield-per-recruit under different lengths at first capture. Our results from relative yield-per-recruit analysis showed evidence that growth and recruitment overfishing occur under current fishing practices in Lake Maracaibo. Particular attention was given to fishing practices in El Tablazo Bay where young, small fish predominate in the commercial catches (mean total length=33.7cm), well below the length at first sexual maturity (-40cm TL) for both sexes. As management strategies, we propose to set a mesh size limit at or above 8.89cm (3.5in), which will reduce fishing mortality of immature fish, increase yield-per-recruit, and will result in an increase of Acoupa weakfish recruitment for the long term in Lake Maracaibo.


Cost-Effectiveness Analysis of a National Newborn Screening Program for Biotinidase Deficiency.
There are conflicting views as to whether testing for biotinidase deficiency (BD) ought to be incorporated into universal newborn screening (NBS) programs. The aim of this study was to evaluate the cost-effectiveness of adding BD to the panel of conditions currently screened under the national NBS program in Spain. We used information from the regional NBS program for BD that has been in place in the Spanish region of Galicia since 1987. These data, along with other sources, were used to develop a cost-effectiveness decision model that compared lifetime costs and health outcomes of a national birth cohort of newborns with and without an early detection program. The analysis took the perspective of the Spanish National Health Service. Effectiveness was measured in terms of quality-adjusted life years (QALYs). We undertook extensive sensitivity analyses around the main model assumptions, including a probabilistic sensitivity analysis. In the base case analysis, NBS for BD led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of $24,677. Lower costs per QALY gained were found when conservative assumptions were relaxed, yielding cost savings in some scenarios. The probability that BD screening was cost-effective was estimated to be >70% in the base case at a standard threshold value. This study indicates that NBS for BD is likely to be a cost-effective use of resources.


[Determination of oligomycins hydrophobicity parameters].
The parameters of hydrophobicity of five oligomycins, i. e. A, B, C, F and SC-II were determined by HPLC. The location of the ascending hydrophobicity parameter was set: oligomycin B < oligomycin SC-II < oligomycin A < oligomycin F < oligomycin C.


Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: Impact of national programme of antifungal prophylaxis.
The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, paediatric hematology-oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of six consecutive years in nationwide study. A total number of 5628 patients with newly diagnosed malignancies and 971 patients after HCT (741 allo-HCT and 230 auto-HCT) were screened for infectious complications in biennial reports. IFD incidence was lower among PHO patients: 8.8% vs 21.2% (P < .0001) and survival from IFD was better: 94.2% vs 84.1% (P < .0001). Auto-HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo-HCT patients. Introduction of national antifungal prophylaxis programme in HCT and acute leukaemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients > 10 years old. Factors contributing to death with infection were as follows: undergoing HCT, diagnosis of acute leukaemia (ALL or AML) and duration of treatment of infection > 21 days. In conclusion, the incidence of IFD in allo-HCT and in AML patients on chemotherapy has decreased after introduction of national programme of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison with historical international data.


Experiences of participating in a vocational rehabilitation program in Singapore.
The purposes of this study were to (i) describe the lived experiences of participating in a Singaporean vocational rehabilitation (VR) program among individuals with stroke and spinal cord injury and (ii) identify salient features of the program that facilitated their return-to-work process. This was a qualitative phenomenological study. Participants were invited to complete an interview about their return-to-work process after acquiring a disability vis-à-vis their participation in a local VR program. The qualitative data were analyzed inductively. Twenty-four middle-aged participants with a stroke or spinal cord injury completed the interviews. The participants' experiences with the local VR program were largely positive. Several key features of the VR program were identified. These were: (i) providing a multi-disciplinary and individualized program; (ii) building positive collaborations between service providers and participants; and (iii) supporting personal growth among participants. The Singaporean VR program demonstrated internationally recommended best practices. These best practices were beneficial for the participants' return-to-work process, as reflected by their positive feedback about the program. Our study emphasizes the need for comprehensive and evidence-based VR programs to meet the complex needs of individuals with disabilities who want to return to work.Implications for rehabilitationMulti- or inter-disciplinary care services are needed in vocational rehabilitation (VR) programs to support the complex return-to-work process of clients.VR programs should have the capacity to provide client-centered care as their clients may experience diverse, yet unique challenges during their return-to-work processVR service providers play a crucial role in engaging and motivating their clients throughout the program to achieve their return-to-work goalsVR service providers should address concurrent or future concerns that could impact on their clients' ability to return to or remain at work.


Modeling the Impact of Newcastle Disease Virus Vaccinations on Chicken Production Systems in Northeastern Madagascar.
Chickens are a key source of nutrition for rural Malagasy communities. Due to high endemic rates of Newcastle disease, it remains challenging to raise sustainable chicken flocks as a consistent food source. Here, we explore the impact of triannual Newcastle disease virus (NDV) vaccine interventions on the growth and herd immunity acquisition of Malagasy chicken flocks. Between 2011 and 2018 we collected longitudinal data to assess the population dynamics of chicken populations in remote Malagasy communities. In 2016, we launched a pilot campaign for vaccination in six rural communities to determine the impacts on chicken survivorship and productivity. We used these data to specify a mathematical model of realistic Malagasy chicken population dynamics under a triannual vaccination regime. The mathematical model represents an extension to conventional SIR models that allows for modeling the impact of specific vaccinations on chicken flock dynamics, rather than estimation of parameters. Understanding chicken population dynamics is important for realizing the potential for domestic chicken flocks to serve as sustainable food sources. The results suggested that vaccination coverage of at least ~40% is necessary over 5+ years to achieve population doubling, while complete herd immunity may not be possible given the short duration of effectiveness of vaccination, and the high levels of births and deaths in the chicken flocks.


Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma.
The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.


Low-dose radioisotope scanning and quantitative analysis in the diagnosis of congenital hypothyroidism.
Quantitative thyroid scanning using low doses of 99mTc sodium pertechnetate (1.85-3.7 MBq) was performed in 38 cases of congenital hypothyroidism. Of these 38 cases, 29 were scanned at 14 +/- 6 days old, and 9 at 1 year old. The scans show the full range of gland anatomy from athyreotic to normal. All morphologically normal scans had grossly increased uptakes of 99mTc. The incidence of the various thyroid anatomies was different in each age group. The average radiation dose to the thyroid was 2.29 mGy, with at least 70% of patients receiving a dose of 3.0 mGy or less. Such low doses of 99mTc should allow further scanning in later life. Neonatal thyroid scanning reveals the aetiology of congenital hypothyroidism and enables the clinician to assess the short- and long-term needs of the child.


Herbs as an antioxidant arsenal for periodontal diseases.
Herbal medicines have long been used as a traditional mode of therapy for various ailments in India. They are being used increasingly as dietary supplements to ward off common diseases. Periodontal diseases are highly prevalent and can affect up to 90% of the world population. Gingivitis is the mild form whereas periodontitis results in an irreversible loss of supporting structures of the teeth. Even though periodontal pathogens form a crucial component in the etiopathogenesis of periodontitis, there is a growing body of evidence suggesting oxidative stress playing a pivotal role in the disease initiation and progression. Studies have shown a direct correlation between increased levels of biomarkers for tissue damage induced by reactive oxygen species (ROS) to the severity of periodontal disease. Thus, the focus of attention has revolved back to herbal medicines due to their wide spectrum of biological and medicinal activities, lower costs, and higher safety margin. Internet databases Pubmed and Google Scholar were searched, and the most relevant articles were considered for review. This review briefly describes the various herbs with antioxidant capacity and their potency in the treating periodontal disease.