Muscle dystroglycan organizes the postsynapse and regulates presynaptic neurotransmitter release at the Drosophila neuromuscular junction.
The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila. We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site. Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg.


Phylogeny of bumble bees in the New World subgenus Fervidobombus (Hymenoptera: Apidae): congruence of molecular and morphological data.
We present new DNA sequence data (12S, 16S, and opsin gene fragments) and morphological characters of the male genitalia for a phylogenetic analysis of the bumble bee subgenus Fervidobombus. There is no significant incongruence between the three molecular data sets, and little incongruence between the DNA and morphology. Simultaneous analysis of all the data partitions resulted in a tree that was entirely congruent with the All-DNA tree. Optimization of the geographic locations of the taxa onto the tree topology using dispersal/vicariance analysis suggests a complex picture of spread and diversification of Fervidobombus from the Old World into the southern New World. There is a phylogenetic component to their spread into tropical rain forest, as the two primary rain forest species (Bombus transversalis and Bombus pullatus) comprise a monophyletic clade, along with a third species, Bombus atratus, which is widely distributed in South America, including lowland subtropical habitats.


The mycotoxin deoxynivalenol predisposes for the development of Clostridium perfringens-induced necrotic enteritis in broiler chickens.
Both mycotoxin contamination of feed and Clostridium perfringens-induced necrotic enteritis have an increasing global economic impact on poultry production. Especially the Fusarium mycotoxin deoxynivalenol (DON) is a common feed contaminant. This study aimed at examining the predisposing effect of DON on the development of necrotic enteritis in broiler chickens. An experimental Clostridium perfringens infection study revealed that DON, at a contamination level of 3,000 to 4,000 µg/kg feed, increased the percentage of birds with subclinical necrotic enteritis from 20±2.6% to 47±3.0% (P<0.001). DON significantly reduced the transepithelial electrical resistance in duodenal segments (P<0.001) and decreased duodenal villus height (P = 0.014) indicating intestinal barrier disruption and intestinal epithelial damage, respectively. This may lead to an increased permeability of the intestinal epithelium and decreased absorption of dietary proteins. Protein analysis of duodenal content indeed showed that DON contamination resulted in a significant increase in total protein concentration (P = 0.023). Furthermore, DON had no effect on in vitro growth, alpha toxin production and netB toxin transcription of Clostridium perfringens. In conclusion, feed contamination with DON at concentrations below the European maximum guidance level of 5,000 µg/kg feed, is a predisposing factor for the development of necrotic enteritis in broilers. These results are associated with a negative effect of DON on the intestinal barrier function and increased intestinal protein availability, which may stimulate growth and toxin production of Clostridium perfringens.


Reduced adherence to antiretroviral therapy among HIV-infected Tanzanians seeking cure from the Loliondo healer.
: The predictors for seeking alternative therapies for HIV-infection in sub-Saharan Africa are unknown. Among a prospective cohort of 442 HIV-infected patients in Moshi, Tanzania, 249 (56%) sought cure from a newly popularized religious healer in Loliondo (450 km away), and their adherence to antiretrovirals (ARVs) dropped precipitously (odds ratio = 0.20, 95% confidence interval: 0.09 to 0.44, P < 0.001) after the visit. Compared with those not attending Loliondo, attendees were more likely to have been diagnosed with HIV more remotely (3.8 vs. 3.0 years before, P < 0.001), have taken ARVs longer (3.4 vs. 2.5 years, P < 0.001), have higher median CD4 lymphocyte counts (429 vs. 354 cells/mm, P < 0.001), be wealthier (wealth index: 10.9 vs. 8.8, P = 0.034), and receive care at the private versus the public hospital (P = 0.012). In multivariable logistic regression, only years since the start of ARVs remained significant (odds ratio = 1.49, 95% confidence interval: 1.23 to 1.80). Treatment fatigue may play a role in the lure of alternative healers.


[Do Capsicum spp. trichomes influence the biological aspects of the broad mite, Polyphagotarsonemus latus Banks (Acari: Tarsonemidae)?].
Plant morphology traits can affect the feeding preference, oviposition choice and the vulnerability of herbivores to natural enemies. At long term, these plant variations may influence herbivore population dynamics due to the interference on their development, survival and reproduction. In this paper, the development of the broad mite Polyphagotarsonemus latus (Banks) was evaluated on five species of Capsicum with different density of trichomes. We tested the hypothesis that P. latus population growth has a negative relationship with the increase trichome density on leaves. It was assessed a decrease in the intrinsic growth rate (r m) of P. latus with the increase of trichome density on the leaves tested. The lower r m was measured in leaves of C. praetermissum (r m = 0.46), which has the highest trichome density among the assessed Capsicum species. The highest values of r m were observed on Capsicum species with intermediate densities of trichomes on leaves such as Capsicum frutescens (r m = 0.77) and Capsicum chinense (r m = 0.76). Capsicum spp. trichomes acted as a limiting plant trait for the development of P. latus when they were in higher densities and better distributed on the leaf surface. We also discuss the role of morphologic and chemical plant defenses on P. latus development.


The mechanism of Ca2+i increase in blood cells of spontaneously hypertensive rats.
Cytoplasmic free calcium (Ca2+i) is increased in platelets and lymphocytes of spontaneously hypertensive rats (SHR) and, to a lesser extent, in essential hypertensive patients. In this study, a method was devised to evaluate cellular Ca fluxes and the cellular Ca buffering power by means of the intracellular Ca indicator Quin-2. Ca influx was measured under conditions of Ca-pump inhibition, either by vanadate or ATP depletion. Lymphocytes of 5-month-old SHR were compared with those of normotensive Wistar-Kyoto rats (WKY). In both strains, the Ca entry rate and the cellular buffering capacity were higher in vanadate-treated than in ATP-depleted cells. SH rats exhibited a higher Ca influx and a greater intracellular Ca buffering power when vanadate was used to stop the Ca pump; these differences, however, were abolished in ATP-depleted lymphocytes. It is suggested that Ca entry in lymphocytes is ATP-dependent. Accelerated Ca entry in SHR can account for the previously reported higher levels of intracellular free Ca.


Implementing change in physiotherapy: professions, contexts and interventions.
The purpose of this paper is to report findings from qualitative interviews with physiotherapists to demonstrate why even minor changes to clinical work resulting from the introduction of new interventions, are often difficult to implement. The paper seeks to illustrate how some of the obstacles to implementing change were managed by physiotherapists. A total of 32 qualitative interviews with participating physiotherapists were conducted, 12 interviews prior to the introduction of the new system, and 20 afterwards. The interviews were coded and analysed thematically. The findings reveal a number of perceived limitations of current management of low back pain and identify key themes around convergence with the new approach, such as willingness by physiotherapists to adopt the new approach, the perception of benefits to adopting the new approach, as well as some difficulty in adjusting to it. The authors refer to the positive and negative elements as "soft" and "hard" disruption. The adoption of the new approach is explored with reference to the "situated" dimensions of physiotherapy practice and normalisation process theory. The study raises the need to conduct future observational research to support the interview findings. The study describes the "situated" components of physiotherapy work, which have received limited research attention. The value of the study lies less in its ability to explain specifically why physiotherapists adopted or rejected the new system, but in describing the conditions and consequences of change that might be translated to other professions, contexts and interventions.


Empathic Engagement With the COVID-19 Vaccine Hesitant in Private Facebook Groups: A Randomized Trial.
Vaccine misinformation has been widely spread on social media, but attempts to combat it have not taken advantage of the attributes of social media platforms for health education. The objective was to test the efficacy of moderated social media discussions about COVID-19 vaccines in private Facebook groups. Unvaccinated U.S. adults were recruited using Amazon's Mechanical Turk and randomized. In the intervention group, moderators posted two informational posts per day for 4 weeks and engaged in relationship-building interactions with group members. In the control group, participants received a referral to Facebook's COVID-19 Information Center. Follow-up surveys with participants (N = 478) were conducted 6 weeks post-enrollment. At 6 weeks follow-up, no differences were found in vaccination rates. Intervention participants were more likely to show improvements in their COVID-19 vaccination intentions (vs. stay same or decline) compared with control (p = .03). They also improved more in their intentions to encourage others to vaccinate for COVID-19. There were no differences in COVID-19 vaccine confidence or intentions between groups. General vaccine and responsibility to vaccinate were higher in the intervention compared with control. Most participants in the intervention group reported high levels of satisfaction. Participants engaged with content (e.g., commented, reacted) 11.8 times on average over the course of 4 weeks. Engaging with vaccine-hesitant individuals in private Facebook groups improved some COVID-19 vaccine-related beliefs and represents a promising strategy.


Dissecting the cyclic di-guanylate monophosphate signalling network regulating motility in Salmonella enterica serovar Typhimurium.
Flagella-mediated swimming and swarming motility in Salmonella enterica serovar Typhimurium is intercalated with the cyclic di-guanylate monophosphate (c-di-GMP) signalling network. In this study, we identified the GGDEF domain proteins STM2672, STM4551 and STM1987 as key di-guanylate cyclases involved in regulation of motility in a ΔyhjH phosphodiesterase gene deletion mutant with elevated c-di-GMP levels inhibiting motility. Surprisingly, these di-guanylate cyclases distinctively inhibited motility through the c-di-GMP receptors YcgR and the cellulose synthase BcsA, whereby STM2672 corresponded to YcgR, STM1987 to BcsA and STM4551 to both receptors. Although downregulation of motility is believed to prepare the bacterial cells for surface adhesion and biofilm formation, the major biofilm regulator CsgD of S. sv. Typhimurium was not involved in the regulation of swimming or swarming motility. Together with previously identified c-di-GMP networks regulating flagella-related phenotypes, flagella biosynthesis is a major target of c-di-GMP signalling in S. sv. Typhimurium.


Porous graphene frameworks pillared by organic linkers with tunable surface area and gas storage properties.
We report the design and synthesis of two porous graphene frameworks (PGFs) prepared via covalent functionalization of reduced graphene oxide (RGO) with iodobenzene followed by a C-C coupling reaction. In contrast to RGO, these 3D frameworks show high surface area (BET, 825 m(2) g(-1)) and pore volumes due to the effect of pillaring. Interestingly, both the frameworks show high CO2 uptake (112 wt% for PGF-1 and 60 wt% for PGF-2 at 195 K up to 1 atm). PGFs show nearly 1.2 wt% H2 storage capacity at 77 K and 1 atm, increasing to ∼1.9 wt% at high pressure. These all carbon-based porous solids based on pillared graphene frameworks suggest the possibility of designing related several such novel materials with attractive properties.


In Vitro Validation of Patient-Specific Hemodynamic Simulations in Coronary Aneurysms Caused by Kawasaki Disease.
To perform experimental validation of computational fluid dynamics (CFD) applied to patient specific coronary aneurysm anatomy of Kawasaki disease. We quantified hemodynamics in a patient-specific coronary artery aneurysm physical phantom under physiologic rest and exercise flow conditions. Using phase contrast MRI (PCMRI), we acquired 3-component flow velocity at two slice locations in the aneurysms. We then performed numerical simulations with the same geometry and inflow conditions, and performed qualitative and quantitative comparisons of velocities between experimental measurements and simulation results. We observed excellent qualitative agreement in flow pattern features. The quantitative spatially and temporally varying differences in velocity between PCMRI and CFD were proportional to the flow velocity. As a result, the percent discrepancy between simulation and experiment was relatively constant regardless of flow velocity variations. Through 1D and 2D quantitative comparisons, we found a 5-17% difference between measured and simulated velocities. Additional analysis assessed wall shear stress differences between deformable and rigid wall simulations. This study demonstrated that CFD produced good qualitative and quantitative predictions of velocities in a realistic coronary aneurysm anatomy under physiological flow conditions. The results provide insights on factors that may influence the level of agreement, and a set of in vitro experimental data that can be used by others to compare against CFD simulation results. The findings of this study increase confidence in the use of CFD for investigating hemodynamics in the specialized anatomy of coronary aneurysms. This provides a basis for future hemodynamics studies in patient-specific models of Kawasaki disease.


Social functioning among older community-dwelling patients with schizophrenia: a review.
Social dysfunction is a hallmark of schizophrenia and a major constituent of its burden of disease. There is a need for more data on social functioning of older schizophrenic patients, because their numbers are rapidly growing and most are residing within the community. This article reviews existing evidence on social functioning in community-dwelling schizophrenic patients older than 55 years, focusing on social roles, social support, and social skills. Thirty-six publications proved fit for inclusion in the review. Studies from outside the United States were underrepresented. The available data suggest that the majority of older schizophrenic patients are well behind their healthy age-peers with respect to various aspects of social functioning. At the same time, a considerable heterogeneity among patients can be found. Cognitive abilities feature as a factor of major impact on social functioning, outweighing clinical symptoms. When evaluating social functioning both objective and subjective appraisals should be taken into account, because they may highlight different aspects of social functioning. Social support, impact of gender, and specific characteristics of older-old patients figure among areas that should be given priority in future research of social functioning in late life schizophrenia.


The polarographic behaviour of isocarboxazid (Marplan) and its hydrolytic products.
The polarographic reduction of isocarboxazid, (Marplan) and its hydrolytic product 5-methyl-3-isoxazolylcarboxylic acid was studied both in aqueous buffered and in nonaqueous methanolic solutions. In both media, reduction occurs in the isoxazole ring resulting in a single diffusion-controlled irreversible wave corresponding to the transfer of four electrons per molecule. Addition of surfaceactive agents to the experimental solutions, did not spilt the wave into separate acts. Addition of proton donors to the methanolic solutions did, however, confirm the transfer of four protons during reduction. In acid buffer solutions the recorded polarograms furnish good means for the quantitative estimation of both compounds in the concentration range used (10(-4)-10(-3).


Developmental regulation of genes mediating murine brain glucose uptake.
We examined the molecular mechanisms that mediate the developmental increase in murine whole brain 2-deoxyglucose uptake. Northern and Western blot analyses revealed an age-dependent increase in brain GLUT-1 (endothelial cell and glial) and GLUT-3 (neuronal) membrane-spanning facilitative glucose transporter mRNA and protein concentrations. Nuclear run-on experiments revealed that these developmental changes in GLUT-1 and -3 were regulated posttranscriptionally. In contrast, the mRNA and protein levels of the mitochondrially bound glucose phosphorylating hexokinase I enzyme were unaltered. However, hexokinase I enzyme activity increased in an age-dependent manner suggestive of a posttranslational modification that is necessary for enzymatic activation. Together, the postnatal increase in GLUT-1 and -3 concentrations and hexokinase I enzymatic activity led to a parallel increase in murine brain 2-deoxyglucose uptake. Whereas the molecular mechanisms regulating the increase in the three different gene products may vary, the age-dependent increase of all three constituents appears essential for meeting the increasing demand of the maturing brain to fuel the processes of cellular growth, differentiation, and neurotransmission.


Alpha-tocopherol as a modulator of smooth muscle cell proliferation.
The effects of alpha-tocopherol and beta-tocopherol have been studied in rat and human aortic smooth muscle cells. Alpha-tocopherol, but not beta-tocopherol, inhibited smooth muscle cell proliferation and protein kinase C in a dose-dependent manner, at concentrations ranging from 10 to 50 microM. Beta-tocopherol added simultaneously with alpha-tocopherol prevented both proliferation and protein kinase C inhibition. Protein kinase C inhibition was cell cycle-dependent and it was prevented by okadaic acid, a protein phosphatase inhibitor. Protein kinase C activity measured from aortas of cholesterol-fed rabbits was also inhibited by alpha-tocopherol. By using protein kinase C (PKC) isoform-specific inhibitors and immunoprecipitation reactions it was found that PKC-alpha was selectively inhibited by alpha-tocopherol. Further, an activation of protein phosphatase 2A by alpha-tocopherol was found, which caused PKC-alpha dephosphorylation and inhibition. Ultimately, this cascade of events at the level of cell signal transduction leads to the inhibition of smooth muscle cell proliferation.


[The microbiocenosis of intestine and immune status of children of primary school age].
The article deals with the study of species and quantitative structure of microbiocenosis of intestine and characteristics of immune status in children aged 8-10 years. In children with chronic tonsillitis pharyngitis and bronchitis and with diseases of gastro-intestinal tract (biliary dysfunction, chronic gastroduodenitis and gastritis) the microbe imbalance of various degree of manifestation was established which was prevailing in cases of children with pathology of gastrointestinal tract. The increase of quantity of opportunistic microflora induces the production of both immunoglobulins and cytotoxic lymphocytes and cells-natural killers.


Genome-wide localization of protein-DNA binding and histone modification by a Bayesian change-point method with ChIP-seq data.
Next-generation sequencing (NGS) technologies have matured considerably since their introduction and a focus has been placed on developing sophisticated analytical tools to deal with the amassing volumes of data. Chromatin immunoprecipitation sequencing (ChIP-seq), a major application of NGS, is a widely adopted technique for examining protein-DNA interactions and is commonly used to investigate epigenetic signatures of diffuse histone marks. These datasets have notoriously high variance and subtle levels of enrichment across large expanses, making them exceedingly difficult to define. Windows-based, heuristic models and finite-state hidden Markov models (HMMs) have been used with some success in analyzing ChIP-seq data but with lingering limitations. To improve the ability to detect broad regions of enrichment, we developed a stochastic Bayesian Change-Point (BCP) method, which addresses some of these unresolved issues. BCP makes use of recent advances in infinite-state HMMs by obtaining explicit formulas for posterior means of read densities. These posterior means can be used to categorize the genome into enriched and unenriched segments, as is customarily done, or examined for more detailed relationships since the underlying subpeaks are preserved rather than simplified into a binary classification. BCP performs a near exhaustive search of all possible change points between different posterior means at high-resolution to minimize the subjectivity of window sizes and is computationally efficient, due to a speed-up algorithm and the explicit formulas it employs. In the absence of a well-established "gold standard" for diffuse histone mark enrichment, we corroborated BCP's island detection accuracy and reproducibility using various forms of empirical evidence. We show that BCP is especially suited for analysis of diffuse histone ChIP-seq data but also effective in analyzing punctate transcription factor ChIP datasets, making it widely applicable for numerous experiment types.


Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.
To study the inhibitory effects of some agents or drugs (inhibitors) on benzo(e)pyrene (B(e)P)-induced cell death and apoptosis on human retinal pigment epithelial (ARPE-19) cells in vitro. ARPE-19 cells were pretreated with varying concentrations of different classes of inhibitors (calpain, benzyl isothiocyanate [BITC], simvastatin, epicatechin, genistein, resveratrol, and memantine) before B(e)P exposure. Cell viability (CV) was determined by a trypan blue dye-exclusion assay. Caspase-3/7 and caspase-9 activities were measured by fluorochrome assays. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with 2',7'-dicholorodihydrofluorescein diacetate dye assay. At 30-microM concentrations, the genistein, resveratrol, and memantine inhibitors were able to reverse significantly the loss of cell viability, the activation of caspase-3/7 and caspase-9, and the production of ROS/RNS in ARPE-19 cell cultures. Memantine was the most potent and genistein was the least effective inhibitor in blocking the B(e)P-induced effects. Calpain, BITC, simvastatin, and epicatechin did not reverse the loss of cell viability in B(e)P-treated ARPE-19 cells. As a matter of fact, at the concentrations studied (15, 30, 45 microM), the BITC plus B(e)P-treated cultures showed significantly lower cell viability than the B(e)P-treated culture alone, suggesting BITC-related toxicity. Genistein, resveratrol, and memantine can reverse the apoptosis and oxidant production generated by B(e)P, a toxic element of smoking. These inhibitors may be beneficial against retinal diseases associated with the loss of RPE cells.


A cautionary note for retrocopy identification: DNA-based duplication of intron-containing genes significantly contributes to the origination of single exon genes.
Retrocopies are important genes in the genomes of almost all higher eukaryotes. However, the annotation of such genes is a non-trivial task. Intronless genes have often been considered to be retroposed copies of intron-containing paralogs. Such categorization relies on the implicit premise that alignable regions of the duplicates should be long enough to cover exon-exon junctions of the intron-containing genes, and thus intron loss events can be inferred. Here, we examined the alternative possibility that intronless genes could be generated by partial DNA-based duplication of intron-containing genes in the fruitfly genome. By building pairwise protein-, transcript- and genome-level DNA alignments between intronless genes and their corresponding intron-containing paralogs, we found that alignments do not cover exon-exon junctions in 40% of cases and thus no intron loss could be inferred. For these cases, the candidate parental proteins tend to be partially duplicated, and intergenic sequences or neighboring genes are included in the intronless paralog. Moreover, we observed that it is significantly less likely for these paralogs to show inter-chromosomal duplication and testis-dominant transcription, compared to the remaining 60% of cases with evidence of clear intron loss (retrogenes). These lines of analysis reveal that DNA-based duplication contributes significantly to the 40% of cases of single exon gene duplication. Finally, we performed an analogous survey in the human genome and the result is similar, wherein 34% of the cases do not cover exon-exon junctions. Thus, genome annotation for retrogene identification should discard candidates without clear evidence of intron loss. firstname.lastname@example.com; firstname.lastname@example.com


Stress-Mediated Enhancement of Ionic Conductivity in Fast-Ion Conductors.
Finding solid-state electrolytes with high ionic conductivity near room temperature is an important prerequisite for developing all-solid-state electrochemical batteries. Here, we investigate the effects of point defects (vacancies) and biaxial stress on the superionic properties of fast-ion conductors (represented by the archetypal compounds CaF2, Li-rich antiperovskite Li3OCl, and AgI) by using classical molecular dynamics and first-principles simulation methods. We find that the critical superionic temperature of all analyzed families of fast-ion conductors can be reduced by several hundreds of degrees through the application of relatively small biaxial stresses (|σ| ≤ 1 GPa) on slightly defective samples (cv ∼ 1%). In AgI, we show that superionicity can be triggered at room temperature by applying a moderate compressive biaxial stress of ∼1 GPa. In this case, we reveal the existence of a σ-induced order-disorder phase transition involving sizable displacements of all the ions with respect to the equilibrium lattice that occurs prior to the stabilization of the superionic state. In CaF2 and Li3OCl, by contrast, we find that tensile biaxial stress (σ < 0) favors ionic conductivity as due to an effective increase of the volume available to interstitial ions, which lowers the formation energy of Frenkel pair defects. Our findings provide valuable microscopic insight into the behavior of fast-ion conductors under mechanical constraints, showing that biaxial stress (or, conversely, epitaxial strain) can be used as an effective means to enhance ionic conductivity.


Are We Choosing Wisely in Lymphoma? Excessive Use of Surveillance CT Imaging in Patients With Diffuse Large B-cell Lymphoma (DLBCL) in Long-term Remission.
The use of surveillance computed tomography (CT) imaging in patients with diffuse large B-cell lymphoma in remission is neither effective nor cost-effective. The American Society of Hematology Choosing Wisely (CW) campaign, in particular, emphasizes the lack of benefit beyond 2 years of completion of therapy. We sought to describe the real-world practice of surveillance imaging. We used population-based health system administrative databases from Ontario, Canada. We studied a cohort of all adult patients ≥ 18 years with diffuse large B-cell lymphoma who received rituximab (R) with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) between 2004 and 2012. We defined an index date of 2 years after the last dose of RCHOP as the time frame beyond which surveillance imaging would be inappropriate. The cumulative incidence of receiving CT scans after the index date represented the primary outcome of interest. The cohort consisted of 2401 patients treated with RCHOP during the study period. The cumulative incidence reached 52.5% (range, 50.4%-54.6%) by 3 years of follow-up. On multivariable analysis, patients with more comorbidities and within certain geographic regions within the province were noted to have increased CT scanning. The cumulative incidence appeared to decrease over the study follow-up period (from 62.4% in 2006 to 48.0% in 2014; P < .001). During a timeframe in which surveillance imaging is deemed unnecessary by the CW campaign, the practice remains excessive. Regional variations in CT scanning suggest that local practice patterns can be targeted to reduce imaging. A recent decline in scanning may reflect a broadening appreciation for the evidence against surveillance or uptake of the CW campaign.


Ιmpact of sunitinib-induced hypothyroidism on survival of patients with metastatic renal cancer.
Sunitinib plays an important role in managing the metastatic renal cell cancer (mRCC). Sunitinib-induced hypothyroidism is a common side-effect of the drug. There have been attempts to link hypothyroidism with a better clinical outcome in sunitinib-treated (mRCC) patients. Our aim was to relate the impact of hypothyroidism to the survival of these patients. We have evaluated 70 patients with mRCC that received sunitinib as a first line treatment. Thyroid-stimulating hormone (TSH) was measured at baseline, after 15 days of treatment (day-15) and at the end of the second cycle (day-75). Biomarker data and correlations with response were analysed with Microsoft Excel. Comparison results from Student's t-test with a p less than 0.05 were considered statistically significant. Kaplan-Meyer and log-rank tests were performed using GraphPad Prism 5 for Windows. Regarding the response to treatment, a progression-free survival (PFS) of 9.47 months and an overall survival (OS) of 22.03 months were demonstrated. Our data are consistent with published data by other authors. On day-15 from the beginning of the treatment an important number of patients exhibited a TSH elevation. On day-15 42.86% had a TSH over the upper normal limit and 50.0% at the end of the second cycle (day-75). TSH increased earlier in patients that exhibited an objective response (× 3.33 times the baseline values on day-15) than patients that exhibited disease stabilisation (× 2.18) or disease progression (× 1.59). Early increases in TSH were associated with a longer PFS (11.92 vs. 8.82 months, p = 0.0476) and a longer OS (3.10 vs. 1.08 years, p = 0.0011). Early TSH-increase is associated with a clinical benefit. The patients that showed at least a twofold increase of their baseline TSH, responded to therapy by stabilisation or by regression of disease. This is the only study to our knowledge which shows that early increases - 2 weeks from starting the treatment - in TSH levels have a prognostic value. Both PFS and OS of the patients who demonstrated a higher than a twofold rise were significantly longer than the PFS and the OS of the patients that presented a lower or no TSH-increase.


Decomposition and organic amendments chemistry explain contrasting effects on plant growth promotion and suppression of Rhizoctonia solani damping off.
Organic Amendments (OAs) has been used in agroecosystems to promote plant growth and control diseases caused by soilborne pathogens. However, the role of OAs chemistry and decomposition time on plant growth promotion and disease suppression is still poorly explored. In this work, we studied the effect of 14 OAs at four decomposition ages (3, 30, 100, and 300 days) on the plant-pathogen system Lactuca sativa-Rhizoctonia solani. OAs chemistry was characterized via 13C-CPMAS NMR spectroscopy as well as for standard chemical (i.e. N content, pH, EC) and biological parameters (i.e. phytotoxicity and R. solani proliferation bioassay). OAs have shown variable effects, ranging from inhibition to stimulation of Lactuca sativa and Lepidium sativum growth. We recorded that N rich OAs with high decomposability were conducive in the short-term, while converting suppressive in the long term (300 days). On the other hand, cellulose-rich OAs with high C/N ratio impaired L. sativa growth but were more consistent in providing protection from damping-off, although this property has significantly shifted during decomposition time. These results, for the first time, highlight a consistent trade-off between plant growth promotion and disease control capability of OAs. Finally, we found that OAs effects on growth promotion and disease protection can be hardly predictable based on the chemical characteristic, although N content and some 13C CPMAS NMR regions (alkyl C, methoxyl C, and carbonyl C) showed some significant correlations. Therefore, further investigations are needed to identify the mechanism(s) behind the observed suppressive and conducive effects and to identify OAs types and application timing that optimize plant productivity and disease suppression in different agro-ecosystems.


The Impact of Oral-Gut Inflammation in Cerebral Palsy.
Background: Oral-gut inflammation has an impact on overall health, placing subjects at risk to acquire chronic conditions and infections. Due to neuromotor disturbances, and medication intake, cerebral palsy (CP) subjects present intestinal constipation, impacting their quality of life (QOL). We aimed to investigate how oral inflammatory levels predicted gut phenotypes and response to therapy. Methods: A total of 93 subjects aging from 5 to 17 years were included in the study, and assigned into one of the 4 groups: CP with constipation (G1, n = 30), CP without constipation (G2, n = 33), and controls without CP with constipation (G3, n = 07) and without CP and without constipation (G4, n = 23). In addition to characterizing subjects' clinical demographics, medication intake, disease severity levels, salivary cytokine levels [TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10], and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Statistical significance was evaluated by Shapiro-Wilks, Student's T-Test, ANOVA, and ANCOVA analysis. Results: Salivary proinflammatory cytokines were highly correlated with the severe form of gut constipation in G1 (P < 0.001), and out of all cytokines IL-1β levels demonstrated highest correlation with all gut constipation (P < 0.05). A significant relationship was found between the type of medication, in which subjects taking Gamma-Aminobutyric Acid (GABA) and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Cleary salivary inflammatory levels and gut constipation were correlated, and impacted QOL of CP subjects. G1 presented a lower QOL mean score of CPCHILD (49.0 ± 13.1) compared to G2 (71.5 ± 16.7), when compared to G3 (88.9 ± 7.5), and G4 (95.5 ± 5.0) (P < 0.01). We accounted for gingival bleeding as a cofounder of oral inflammation, and here were no differences among groups regarding gender (P = 0.332) and age (P = 0.292). Conclusions: Collectively, the results suggest that saliva inflammatory levels were linked to gut constipation, and that the clinical impact of medications that controlled gut was reliably monitored via oral cytokine levels, providing reliable and non-invasive information in precision diagnostics.


Development of antibodies to axonal neurofilaments in the progression of chronic tick-borne encephalitis.
We followed the presence of autoantibodies to neurofilaments (NF) in the sera of patients with acute tick-borne encephalitis (TBE), chronic TBE, amyotrophic lateral sclerosis (ALS), and other diseases of CNS. The diagnosis was made according to clinical signs and based on virus neutralizing antibodies. Autoantibodies to NF were found in the majority of chronic TBE patients during disease progression, but were neither present in acute TBE nor in chronic TBE cases during the stabilization phase. Autoantibodies to NF found in a patient with acute TBE showed subsequent progression to a prolonged course. The data are discussed in order to assess the mechanisms of the chronic TBE process and its role in impairing the slow axonal transport.


Timing of onset affects arthritis presentation pattern in antisyntethase syndrome.
To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.


Sheep monoclonal antibodies prevent systemic effects of botulinum neurotoxin A1.
Botulinum neurotoxin (BoNT) is responsible for causing botulism, a potentially fatal disease characterized by paralysis of skeletal muscle. Existing specific treatments include polyclonal antisera derived from immunized humans or horses. Both preparations have similar drawbacks, including limited supply, risk of adverse effects and batch to batch variation. Here, we describe a panel of six highly protective sheep monoclonal antibodies (SMAbs) derived from sheep immunized with BoNT/A1 toxoid (SMAbs 2G11, 4F7) or BoNT/A1 heavy chain C-terminus (HcC) (SMAbs 1G4, 5E2, 5F7, 16F9) with or without subsequent challenge immunization with BoNT/A1 toxin. Although each SMAb bound BoNT/A1 toxin, differences in specificity for native and recombinant constituents of BoNT/A1 were observed. Structural differences were suggested by pI (5E2 = 8.2; 2G11 = 7.1; 4F7 = 8.8; 1G4 = 7.4; 5F7 = 8.0; 16F9 = 5.1). SMAb protective efficacy vs. 10,000 LD50 BoNT/A1 was evaluated using the mouse lethality assay. Although not protective alone, divalent and trivalent combinations of SMabs, IG4, 5F7 and/or 16F9 were highly protective. Divalent combinations containing 0.5–4 μg/SMAb (1–8 μg total SMAb) were 100% protective against death with only mild signs of botulism observed; relative efficacy of each combination was 1G4 + 5F7 > 1G4 + 16F9 >> 5F7 + 16F9. The trivalent combination of 1G4 + 5F7 + 16F9 at 0.25 μg/SMAb (0.75 μg total SMAb) was 100% protective against clinical signs and death. These results reflect levels of protective potency not reported previously.


Association between the CDC6 G1321A polymorphism and the risk of cervical cancer.
Cell division cycle protein 6 (CDC6) plays critical roles in DNA replication and carcinogenesis. The biological significance of the CDC6 G1321A polymorphism (V441I, rs13706) on cervical carcinogenesis is still unknown. Here, we examined the potential influence of this polymorphism on cell proliferation and the individual's susceptibility to cervical cancer. We genotyped the CDC6 G1321A polymorphism in 87 cervical cancer cases and 110 healthy female subjects. Unconditional logistic regression analysis was used to estimate the association between the genotypes and the risk of cervical cancer. The BrdU incorporation assay was applied to analyze the effect of this polymorphism on cell proliferation. Compared with the GG homozygotes, the cervical cancer risk was significantly reduced in the individuals with the heterozygous AG genotype (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.28-0.98; P = 0.042) or the homozygous AA genotype (OR, 0.29; 95% CI, 0.09-0.89; P = 0.030). Further stratified analyses showed that the decreased risk of cervical cancer was more evident among younger subjects (≤44 years old) with the AG or AA genotypes (OR, 0.44; 95% CI, 0.21-0.92; P = 0.029 and OR, 0.12; 95% CI, 0.03-0.61; P = 0.010, respectively). The BrdU incorporation assay showed that 293T cells transfected with CDC6-441I (1321A) had a lower proliferation rate in comparison with those transfected with CDC6-441V (1321G), although the difference did not reach statistical significance at the 0.05 level. The CDC6 G1321A polymorphism may contribute to the risk of cervical cancer. Further studies with more subjects and in diverse ethnic populations are necessary to confirm the general validity of our findings.


Autologous transplantation for aggressive non-Hodgkin's lymphoma: results of a randomized trial evaluating graft source and minimal residual disease.
To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) for aggressive non-Hodgkin's lymphoma (NHL). Of 105 high-risk, persistent, or relapsed NHL patients slated for an autologous HSCT entered onto this trial, 93 eligible patients were randomized to receive cytokine-naive autologous bone marrow transplantation (ABMT) (n = 46) or mobilized peripheral-blood stem-cell transplantation (PBSCT) (n = 47). All patients received carmustine, etoposide, cytarabine, and cyclophosphamide as the conditioning regimen. PBSCT patients also received identical mobilization with granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/d, and both groups received G-CSF 5 microg/kg/d after the infusion of the stem-cell product until neutrophil engraftment. PBSCT patients had significantly faster engraftment of all cell lineages: median time to absolute neutrophil count > or = 500/microL, 10 days versus 13 days on the ABMT arm; median time to platelet count greater than 20,000/microL untransfused, 11 days versus 15 days on the ABMT arm; and median time to RBC transfusion independence, 8 days versus 16 days on the ABMT arm. The complete response rate was 72% for PBSCT and 54% for ABMT. The death rate before posttransplant day 100 was 2% on the ABMT arm and 6% on PBSCT arm. Event-free survival was 37% for PBSCT and 37% for ABMT. However, overall survival for PBSCT was 61% compared with 43% for ABMT. Patients with aggressive NHL receiving HSCT randomized to PBSCT demonstrated improved neutrophil engraftment and platelet and RBC transfusion independence. The complete response rate and EFS were not statistically different by randomization arm. Patients whose harvests were positive for minimal residual disease by molecular analysis had poorer EFS.


Prevalence of Normal-Weight Obesity in Community-Dwelling Chinese Older Adults: Results from the Beijing Longitudinal Study of Aging.
Normal-weight obesity (NWO) is characterized by high body fat percentage (BFP) in individuals with normal body mass index (BMI). This condition may increase the risk of serious health problems, such as cardiovascular diseases, diabetes, insulin resistance, hypertension, and metabolic syndrome. However, the prevalence of NWO in older adults in Beijing remains unclear. This study aimed to investigate the prevalence of overweight and obesity among older adults in Beijing, using three obesity assessment indicators: BMI, waist circumference, and BFP. Cross-sectional study. Data were obtained from the 2012 Beijing Longitudinal Study of Aging, which used a stratified, sectional, random, and cluster sampling method. Questionnaires, physical examinations, and laboratory tests were completed. Obesity was divided into four categories based on combinations of BMI and BFP: non-obese, muscle-type obesity, NWO and fatty obesity. A total of 2393 community-dwelling older adults with an average age of 72.98±8.09 years old were recruited. Of them, 1051 were male (43.92%) and 1245 were living in rural areas (52.03%). The prevalence of overweight and obesity among older people in Beijing was 35.5% and 16.1%, respectively. When the sample was divided according to obesity classification, the proportion of muscular obesity, NWO and adipose obesity was 14.7%, 10.7%, and 41.8%, respectively. The prevalence of central obesity was 62.3%. The prevalence of obesity decreased with age, but it was higher in females than in males as well as among individuals living in urban areas than in individuals living in rural areas. The prevalence of NWO was 10.7% among older adults in Beijing and increased with age. Older adults who are female or living in urban areas should be instructed to take measures aimed at reducing body fat and increasing muscle strength.


Terahertz rare-earth orthoferrite metamaterials by 3-D direct writing technology.
Terahertz (THz) radiation excites electronic and optical modes of many materials, and controlling interaction of these materials with THz pulses provides a fascinating avenue to achieve unprecedented functionalities in return. Here, woodpile-structured rare-earth orthoferrite metamaterials built with 3-D direct ink writing technology are proposed and experimentally demonstrated. Polarization-independent THz refraction and switching of resonances by varying the number of layers in the structure, as well as the structural parameters and specimen support angle are achieved. Such all-rare-earth-orthoferrite dielectric metamaterials are easy to fabricate and can be very promising in developing efficient and low cost THz functional metadevices.


Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer.
To identify time trends and factors associated with breast-conserving surgery (BCS) and delivery of postoperative radiation therapy among women with stage I or II breast cancer. Survey. Population-based cancer registry in the Seattle-Puget Sound (Wash) region. The study included 8095 women diagnosed with stage I or II breast cancer (American Joint Committee on Cancer staging criteria) from 1983 through 1989. Breast-conserving surgery with or without radiation therapy vs mastectomy, and, among women with BCS, a comparison of radiation therapy vs no therapy. In 1985 when results from a US randomized clinical trial of BCS were published, the frequency of BCS peaked (46.3% of stage I; 30.1% of stage II) followed by a return to levels before 1985 for women with stage II breast cancer and a more moderate decline for stage I breast cancer. The likelihood of BCS decreased with increasing age (P less than .001), with stage II disease, and with residence outside the region's major urban center, and it increased with education (P less than .001) or median income (P less than .001) by census tract. The proportion of women who received radiation therapy after BCS decreased with age (P less than .001), was lower for women with stage II than stage I disease, and was lowest in counties without radiation therapy facilities. Despite scientific evidence of the equivalent efficacy of BCS with radiation therapy and mastectomy, BCS is not performed on the majority of women with stage I or II breast cancer as recommended by the National Institutes of Health, and factors are associated with its use that differ from selection criteria outlined by the National Institutes of Health.


Sero-prevalence of contagious bovine pleuropneumonia in dryland of Borana, southern Oromia, Ethiopia.
Ethiopia is one of the largest African countries where livestock farming represent a relevant resource for the economy and the livelihood of the population. Contagious bovine pleuropneumonia (CBPP) is among the transboundaries animal disease that is hindering cattle farming in Ethiopia. Due to the limited resources of veterinary services, disease control and surveillance is discontinuous and occasional field investigations of target areas contribute to depict disease spreading in the country. The study was conducted to determine the seroprevalence, at herd and animal level, and identify the risk factors involved in CBPP diffusion and persistence in the Borana pastoral zone. A total of 498 serum samples were collected from 120 cattle herds and tested using competitive Enzyme-Linked Immunosorbent Assay (c-ELISA). Of 120 herds sampled, 37 (30.83%; (95% CI = 22.73-39.91%) were tested positive to CBPP antibody. Out of 498 sera samples tested 46 (9.24%; 95% CI = 6.84-12.13%) were positive. The highest prevalence was observed in Teltele (12/95; 12.90%; 95% CI = 6.7-21%) followed by Yabello (12/104; 11.54%; 95% CI = 6.1-19.3%) and Arero (10/91; 10.99%; 95% CI = 95% CI = 5.4-19.3%), whereas the lowest prevalence was observed in Gomole (5/101; 6.42%; 95% CI = 1.6-11.2%) and Dubluk (7/109; 4.95%; 95% CI = 2.6-12.8%) districts and statistically not significant (p > 0.05). Results of multivariate logistic regression analysis revealed that, age, herd movement and herd size of the animals had statistically significant effect on sero-positivity to CBPP (p < 0.05). Sex, season and body condition were not significantly (p > 0.05) associated with the occurrence of CBPP. The study confirms that CBPP is persistent in the territory and remain as a major problem that affects health and productivity of cattle. Therefore, awareness creation to the pastoralists in the study area about the effect of CBPP and designing appropriate control methods has a paramount importance to improve the health and productivity of cattle production in the area.


Intraocular hypothalamic transplants containing histaminergic neurons: innervation of host iris and hippocampal cografts.
Hypothalamic tissue containing the tuberomammillary nucleus was dissected from fetuses of Embryonic Day 17 and inserted into the anterior chamber of the eye of young adult recipient rats. The growth of hypothalamic grafts was monitored through the translucent cornea and transplants were found to double in size over the 8 first weeks in oculo. After 4 weeks fetal hippocampal formation (Embryonic Day 18) was inserted into the eye chamber in half of the previously grafted animals and placed in contact with the first grafts. Double grafts were allowed to mature for up to 18 weeks before sacrifice. Recipient rats were anesthetized and superfused with carbodiimide and paraformaldehyde, after which transplants were removed, frozen, sectioned on a cryostat, and incubated with histamine antibodies. Immunohistochemical evaluations revealed a large number of histamine-positive nerve cell bodies with processes innervating the entire hypothalamic graft with a dense plexus of varicose fibers. Such histamine-positive fibers were also seen to invade the surrounding host iris in some cases with thick axon bundles as well as with single fibers. When hypothalamic transplants were combined with hippocampal grafts numerous histamine-immunoreactive fibers invaded the hippocampal tissue to form a plexus of varicose terminals throughout the cografts. After 4 weeks in oculo only a sparse histamine-positive innervation of hippocampal grafts was found, while 18-week-old double grafts contained a considerably larger amount of immunoreactive neurites.(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiac autonomic modulation assessed by heart rate variability in children with asthma.
To assess cardiac autonomic modulation, measured by short-term frequency domain analysis of heart rate variability (HRV), in children with asthma. We conducted an observational study at a tertiary care teaching hospital. The sample consisted of 119 children aged 7 to 15 years with asthma and 56 age-matched healthy controls. Frequency domain HRV measures included low-frequency (LF; 0.04-0.15 Hz), high-frequency (HF; 0.15-0.4 Hz), and LF/HF ratio. The LF and HF components were expressed in both absolute values of power (ms2 ) and in normalized units (nu). Compared with healthy controls, asthmatic children had significantly higher value of HF (nu) (mean ± standard deviation: 45.9 ± 14.6 vs 40.7 ± 13.6; P = .02), and lower values of LF (nu) (54.1 ± 14.6 vs 59.3 ± 13.6; P = .02) and LF/HF ratio (median, interquartile range: 1.12, 0.82-1.88 vs 1.59, 1.02-2.08; P = .03). We did not find significant differences between children with persistent and intermittent asthma, and between children with well-controlled and partially-controlled or uncontrolled asthma, in terms of HRV measures. Children with stable chronic asthma may have a cardiac autonomic imbalance with a possible enhanced parasympathetic modulation, as assessed by short-term frequency domain analysis of HRV. Neither asthma severity nor asthma control was significantly associated with HRV measures, but the study did not have enough power to draw a firm conclusion on this point.


Arthritis in idiopathic inflammatory myopathy: clinical features and autoantibody associations.
To determine the prevalence, distribution, and clinical manifestations of arthritis in a cohort of patients with idiopathic inflammatory myopathies (IIM). Associations with autoantibody status and HLA genetic background were also explored. Consecutive patients with IIM treated in a single center were included in this cross-sectional study (n = 106). History of arthritis, 68-joint and 66-joint tender and swollen joint index, clinical features of IIM, and autoantibody profiles were obtained by clinical examination, personal interview, and review of patient records. High-resolution genotyping in HLA-DRB1 and HLA-DQB1 loci was performed in 71 and 73 patients, respectively. A combination of patients' medical history and cross-sectional physical examination revealed that arthritis at any time during the disease course had occurred in 56 patients (53%). It was present at the beginning of the disease in 39 patients (37%) including 23 cases (22%) with arthritis preceding the onset of muscle weakness. On physical examination, 29% of patients had at least 1 swollen joint. The most frequently affected areas were wrists, and metacarpophalangeal and proximal interphalangeal joints. Twenty-seven out of the 29 anti-Jo1-positive patients had arthritis at any time during the course of their illness; this prevalence was significantly higher compared to patients without the anti-Jo1 autoantibody (p < 0.0001). No association of arthritis with individual HLA alleles was found. Our data suggest that arthritis is a common feature of myositis. It is frequently present at the onset of disease and it may even precede muscular manifestations of IIM. The most common presentation is a symmetrical, nonerosive polyarthritis affecting particularly the wrists, shoulders, and small joints of the hands. We have confirmed a strong association of arthritis with the presence of the anti-Jo1 antibody.


Progression of mitral regurgitation in patients with mitral valve prolapse.
Mitral valve prolapse (MVP) is a very common clinical entity which is frequently associated with mild mitral regurgitation (MR) and which most commonly becomes clinically manifest in the third and fourth decades of life. Severe MR associated with MVP, occurs much less frequently and is most commonly seen in patients above the age of 50 years. Relatively little information is available regarding the progression of mild to severe MR in patients with MVP. This report reviews a recent study which investigated the progression from mild to severe MR in patients with MVP. The study included 86 patients, average age 60 years, who presented with cardiac symptoms and severe MR. A high incidence of MVP was seen on echocardiograms (57 of 75 [75%]) and on left ventriculography (61 of 84 [73%]). Mitral valve replacement was performed in 75 patients. Pathologically all valves appeared grossly enlarged, severely floppy and had extensive myxomatous changes with collagen dissolution. 80 patients had a pre-existing heart murmur first detected at average age 34. Patients remained asymptomatic for an average of 25 years at which time clinical symptoms first appeared. After symptoms developed mitral valve surgery was necessary in most patients within one year. This rapid deterioration could partially be attributed to ruptured chordae in 39 of 76 patients (51%) or atrial fibrillation in 48 of 86 patients (56%). 28 patients had one or more serial clinical evaluations including auscultation, chest x-ray, echocardiography, and cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)


Increasing the size of portion options affects intake but not portion selection at a meal.
In an environment with large portion sizes, allowing consumers more control over their portion selection could moderate the effects on energy intake. We tested whether having subjects choose a portion from several options influenced the amount selected or consumed when all portion sizes were systematically increased. In a crossover design, 24 women and 26 men ate lunch in the lab once a week for 3 weeks. At each meal, subjects chose a portion of macaroni and cheese from a set of 3 portion options and consumed it ad libitum. Across 3 conditions, portion sizes in the set were increased; the order of the conditions was counterbalanced across subjects. For women the portion sets by weight (g) were 300/375/450, 375/450/525, and 450/525/600; for men the portions were 33% larger. The results showed that increasing the size of available portions did not significantly affect the relative size selected; across all portion sets, subjects chose the smallest available portion at 59% of meals, the medium at 27%, and the largest at 15%. The size of portions offered did, however, influence meal intake (P < 0.0001). Mean intake (±SEM) was 16% greater when the largest set was offered (661 ± 34 kcal) than when the medium and smallest sets were offered (both 568 ± 18 kcal). These results suggest that portions are selected in relation to the other available options, and confirm the robust effect of portion size on intake. Although presenting a choice of portions can allow selection of smaller amounts, the sizes offered are a critical determinant of energy intake. Thus, the availability of choices could help to moderate intake if the portions offered are within an appropriate range for energy needs.


The kinematic differences between skill levels in the squash forehand drive, volley and drop strokes.
Knowledge of the kinematic differences that separate highly skilled and less-skilled squash players could assist the progression of talent development. This study compared trunk, upper-limb and racket kinematics between two groups of nine highly skilled and less-skilled male athletes for forehand drive, volley and drop strokes. A 15-camera motion analysis system recorded three-dimensional trajectories, with five shots analysed per participant per stroke. The highly skilled group had significantly (p < 0.05) larger forearm pronation/supination range-of-motion and wrist extension angles at impact than the less-skilled. The less-skilled group had a significantly more "open" racket face and slower racket velocities at impact than the highly skilled. Rates of shoulder internal rotation, forearm pronation, elbow extension and wrist flexion at impact were greater in the drive stroke than in the other strokes. The position of the racket at impact in the volley was significantly more anterior to the shoulder than in the other strokes, with a smaller trunk rotation angular velocity. Players used less shoulder internal/external rotation, forearm pronation/supination, elbow and wrist flexion/extension ranges-of-motions and angular velocities at impact in the drop stroke than in the other strokes. These findings provide useful insights into the technical differences that separate highly skilled from less-skilled players and provide a kinematic distinction between stroke types.


Quantification of an Adverse Outcome Pathway Network by Bayesian Regression and Bayesian Network Modeling.
The adverse outcome pathway (AOP) framework has gained international recognition as a systematic approach linking mechanistic processes to toxicity endpoints. Nevertheless, successful implementation into risk assessments is still limited by the lack of quantitative AOP models (qAOPs) and assessment of uncertainties. The few published qAOP models so far are typically based on data-demanding systems biology models. Here, we propose a less data-demanding approach for quantification of AOPs and AOP networks, based on regression modeling and Bayesian networks (BNs). We demonstrate this approach with the proposed AOP #245, "Uncoupling of photophosphorylation leading to reduced ATP production associated growth inhibition," using a small experimental data set from exposure of Lemna minor to the pesticide 3,5-dichlorophenol. The AOP-BN reflects the network structure of AOP #245 containing 2 molecular initiating events (MIEs), 3 key events (KEs), and 1 adverse outcome (AO). First, for each dose-response and response-response (KE) relationship, we quantify the causal relationship by Bayesian regression modeling. The regression models correspond to dose-response functions commonly applied in ecotoxicology. Secondly, we apply the fitted regression models with associated uncertainty to simulate 10 000 response values along the predictor gradient. Thirdly, we use the simulated values to parameterize the conditional probability tables of the BN model. The quantified AOP-BN model can be run in several directions: 1) prognostic inference, run forward from the stressor node to predict the AO level; 2) diagnostic inference, run backward from the AO node; and 3) omnidirectionally, run from the intermediate MIEs and/or KEs. Internal validation shows that the AOP-BN can obtain a high accuracy rate, when run is from intermediate nodes and when a low resolution is acceptable for the AO. Although the performance of this AOP-BN is limited by the small data set, our study demonstrates a proof-of-concept: the combined use of Bayesian regression modeling and Bayesian network modeling for quantifying AOPs. Integr Environ Assess Manag 2021;17:147-164. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Delineating the mTOR kinase pathway using a dual TORC1/2 inhibitor, AZD8055, in multiple myeloma.
Despite promising preclinical results with mTOR kinase inhibitors in multiple myeloma, resistance to these drugs may arise via feedback activation loops. This concern is especially true for insulin-like growth factor 1 receptor (IGF1R), because IGF1R signaling is downregulated by multiple AKT and mTOR feedback mechanisms. We have tested this hypothesis in multiple myeloma using the novel selective mTOR kinase inhibitor AZD8055. We evaluated p-mTOR S(2481) as the readout for mTORC2/Akt activity in multiple myeloma cells in the context of mTOR inhibition via AZD8055 or rapamycin. We next validated AZD8055 inhibition of mTORC1 and mTORC2 functions in multiple myeloma cells alone or in culture with bone marrow stroma cells and growth factors. Unlike rapamycin, AZD8055 resulted in apoptosis of multiple myeloma cells. AZD8055 treatment, however, induced upregulation of IGF1R phosphorylation in p-Akt S(473)-expressing multiple myeloma cell lines. Furthermore, exposure of AZD8055-treated cells to IGF1 induced p-Akt S(473) and rescued multiple myeloma cells from apoptosis despite mTOR kinase inhibition and TORC2/Akt blockage. The addition of blocking IGF1R antibody resulted in reversing this effect and increased AZD8055-induced apoptosis. Our study suggests that combination treatment with AZD8055 and IGF1R-blocking agents is a promising strategy in multiple myeloma with potential IGF1R/Akt signaling-mediated survival.


The relationship between maternal depression, in-home violence and use of physical punishment: what is the role of child behaviour?
The combined impact of maternal depression and in-home violence, and how their relationship with physical punishment varies with child behaviour are unknown. To determine the combined impact of maternal depression and violence exposure on smacking and explore the role of child behaviours in this relationship. Multivariable regression analysis of a sample of kindergarten children. Maternal depressive symptoms, violence exposure and smacking were measured by parent interview. Child behaviours were reported by teachers. 12,764 mother-child dyads were examined. The adjusted odds ratio (aOR) for smacking among depressed mothers was 1.59 (95% CI 1.40 to 1.80), mothers exposed to in-home violence 1.48 (95% CI 1.18 to 1.85) and dually exposed mothers 2.51 (95% CI 1.87 to 3.37). Adjusting for child self-control or externalising behaviour did not change these associations, and no effect modification by child behaviour was detected. Among mothers smacking children, depression was associated with increased smacking frequency (adjusted incident rate ratio (aIRR) 1.12; 95% CI 1.01 to 1.24), but became borderline significant after adjusting for child self-control or externalising behaviour (aIRRs 1.10; 95% CI 1.00 to 1.21). Depressed mothers exposed to violence demonstrated higher rates of smacking (aIRR 1.29; 95% CI 1.09 to 1.53); this remained stable when adjusting for child behaviours. Maternal depression and violence exposure are associated with smacking, particularly when depression and violence co-exist, when they are also associated with smacking frequency. Child self-control and externalising behaviour do not substantially impact the association between maternal depressive symptoms, violence exposure and smacking.


Enhanced ALP activity of MG63 cells cultured on hydroxyapatite-poly(ethylene glycol) hydrogel composites prepared using EDTA-OH.
In order to obtain a hydroxyapatite (HAp)-poly(ethylene glycol) (PEG) composite, tetra amine-terminated PEG was crosslinked using disuccinimidyl tartrate to obtain a PEG hydrogel. Using two kinds of chelators with different stability constants for Ca ion (N-(2-hydroxyethyl) ethylenediamine-N,N',N'-triacetic acid (EDTA-OH, 8.14), and ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA, 10.96)), calcium phosphate was deposited within PEG hydrogels by heating the chelator-containing calcium phosphate solution at 90 °C. X-ray diffraction analysis showed that the deposited calcium phosphate was HAp. The crystallinity of the HAp deposited using EDTA-OH was low compared with that obtained using EDTA, but the amount of HAp deposited within the PEG hydrogel using EDTA-OH was higher than that deposited using EDTA. Significantly more human osteoblast-like MG-63 cells adhered on the HAp-PEG composite prepared using EDTA-OH than on the HAp-PEG composites prepared using EDTA. Furthermore, the alkaline phosphatase activity of MG-63 cultured on the HAp-PEG composite prepared using EDTA-OH was four times higher than that on the HAp-PEG composite prepared using EDTA. Therefore, the HAp-PEG composite prepared using EDTA-OH has potential as a bone substitute material.


Increased-risk donors and solid organ transplantation: current practices and opportunities for improvement.
The development and implementation of 'increased risk donor' (IRD) status by the Centers for Disease Control (CDC) was intended to guide patients and providers in decision making regarding risk of infectious transmission via solid organ transplantation. Several contemporary studies have shown underutilization of these organs. This review summarizes the issues surrounding IRD status as well as recent advances in our understanding of the risks and benefits of increased risk organs and their appropriate utilization. Risk of window-period infection remains exceedingly low, and implementation of nucleic acid testing for HIV and hepatitis C virus (HCV) has resulted in decreasing risk of window-period infection often by an order of magnitude or more. Surgeons remain hesitant to utilize IRD organs. In addition, surgeon assessment of risk by donor behaviour was often discordant with known risks of those behaviours. Studies investigating outcomes of utilization of IRD organs suggest long-term mortality and graft survival is at least equivalent to non-IRD organs. Contemporary results suggest that IRD organs continue to be underutilized, particularly adult kidneys and lungs, with hundreds of wasted organs per year. CDC IRD labelling has led to an underutilization of organs for transplantation. The risks associated with acceptance of an IRD organ are inflated by surgeons and patients, and outcomes for patients who undergo transplantation with increased risk organs are similar to or better than those for patients whom accept standard risk organs. The rate of transmission of window-period infection from IRD organs is exceptionally low. The harms regarding the utility of Public Health Service increased risk classification outweigh the benefits for patients in need of transplant.


An Exploration of Nursing Assistants' Perceptions About Job Satisfaction.
High levels of staff turnover of certified nursing assistants (CNAs) are costly and disruptive to patient care. A variety of factors contribute to a 36% turnover rate of CNAs nationwide (2015 Staffing Report, 2015). According to Stone and Wiener, high rates of turnover and staff vacancies have multilayered consequences; patient care suffers, cost of constantly replacing workers soars, and worker job dissatisfaction increases. This study examined the CNAs' beliefs about job satisfaction as an approach to prevent job turnover and retain high achieving staff in one acute care hospital in a south eastern region. The goal was to determine how CNAs define job satisfaction, evaluate their understanding of and gauge interest in the career options presented at information sessions as well as listen to their ideas on how they believe are the best approaches to achieve job satisfaction for the CNAs at this facility. A qualitative key informant design was used to interview a purposive sample of 9 nursing assistants who were currently employed at the hospital for at least 6 months and who attended a brief information session. Individual 20-minute face-to-face interviews of consented participants were recorded, transcribed, and coded for themes using constant comparative analysis. Four major categories emerged from the interviews: CNA views of job satisfaction, clinical ladder option, support services option, and what CNAs want.


Measurement of the target-normal single-spin asymmetry in deep-inelastic scattering from the reaction (3)He(↑)(e,e')X.
We report the first measurement of the target-normal single-spin asymmetry in deep-inelastic scattering from the inclusive reaction 3)He(↑)(e,e')X on a polarized (3)He gas target. Assuming time-reversal invariance, this asymmetry is strictly zero in the Born approximation but can be nonzero if two-photon-exchange contributions are included. The experiment, conducted at Jefferson Lab using a 5.89 GeV electron beam, covers a range of 1.7<W<2.9 GeV, 1.0<Q(2)<4.0 GeV(2) and 0.16<x<0.65. Neutron asymmetries were extracted using the effective nucleon polarization and measured proton-to-(3)He cross-section ratios. The measured neutron asymmetries are negative with an average value of (-1.09±0.38)×10(-2) for invariant mass W>2 GeV, which is nonzero at the 2.89σ level. Our measured asymmetry agrees both in sign and magnitude with a two-photon-exchange model prediction that uses input from the Sivers transverse momentum distribution obtained from semi-inclusive deep-inelastic scattering.


Projecting disease when death is likely.
Projection disease incidence, prevalence, and net morbidity is often needed when individuals are likely to die, either disease free or after the disease has developed. Examples of this include remission of cancer or heart disease in elderly people who can die from these or other causes and occurrence of a particular acquired immune deficiency syndrome illness in human immunodeficiency virus type 1 (HIV-1) disease. Death is not an ancillary event but, rather, indicates either and end to disease morbidity or an end to risk to ever develop the disease. Thus, time to disease survival analyses that censor disease-free individuals at death can produce misleading results. The paper describes several useful quantifications of disease and death for this setting. A paradigm that utilizes Kaplan-Meier functions to estimate these quantities is introduced. The approach anchors on a four-stage disease/death model: stage A, living without disease; stage B, dead without ever developing disease; stage C, developed the disease and living; and stage D, dead after developing the disease. An application is made to projecting cytomegalovirus disease in a cohort of HIV-1-infected users of zidovudine and Pneumocystis prophylaxis from the Multicenter AIDS Cohort Study (MACS) during 1989-1993. At 3 years after a CD4+ count below 100/microliters, a man had an 18.7%, 46.3%, 5.3% or 29.9% chance, respectively, to be in stage A, B, C, or D. This man, on average, had 0.28 years of cytomegalovirus morbidity during these 3 years.


The Nasolabial Area Shown on Histology and P45 Sheet Plastination.
The aim of this study was to elucidate the relationships between the nasolabial fold and superficial fascia on histology and P45 sheet plastination.Two centimeter width specimen of the nasolabial area were harvested from the skin to periosteum. Then, 10-μm sections were made, stained with Masson trichrome, and observed under a light microscope. Three head and neck specimens were sliced in horizontal sections (46 slices) using P45 sheet plastination (polyester resin corrosion-resistant method designed to preserve biological sectional specimens in situ). Through slicing, bleaching, dehydration, casting, forced impregnation, curing, cutting, and sanding the molds, P45 plastination provided good light transmission, allowing the internal structures within the sheet to be revealed clearly in their intact form.The observations on histology and P45 sheet plastination correlated well. The nasolabial fold consisted of the superficial fatty layer of superficial fascia (SFS). At the beginning of the alar groove level, the nasolabial groove was located on the point where the medial limit of SFS met the levator labii superioris. At the alar base level, the nasolabial groove was located where the medial limit of the SFS met levator labii superioris. At the mouth corner level, the nasolabial groove was located where the medial limit of the SFS met the modiolus, including the orbicularis oris. The superficial fascia became scanty near the nasolabial groove, and the SFS comprised the nasolabial fold.The results of the present study may be helpful for applying subcutaneous dissection or sub-superficial muscular aponeurotic system dissection in rejuvenation of the nasolabial area.


The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia.
The prognosis of pulmonary fibrosis associated with scleroderma (PF-SSc) has been reported to be significantly better than that of IPF. Because the nonspecific interstitial pneumonia-pattern (NSIP), a newly defined subgroup of idiopathic interstitial pneumonias (IIP), has better prognosis than the usual interstitial pneumonia pattern (UIP), we postulated that NSIP may occur more frequently than UIP in patients with scleroderma who develop fibrosis. We reviewed the pathologic, radiologic and clinical outcomes in 19 patients with PF-SSc. Two pulmonary pathologists reclassified the histopathology of surgical lung biopsies (SLBx) and consensus diagnosis was achieved in all patients. Thirteen patients had NSIP, five had UIP, and remained one showed only nondiagnostic honeycombing. No significant difference was noted in the initial pulmonary function test (PFT), bronchoalveolar lavage (BAL) findings, or other clinical parameters between UIP and NSIP groups. Comparison of the clinical outcome of 12 patients who were followed for more than 12 months (mean: 34.5 +/- 26.0 months) suggested a better prognosis for NSIP than UIP. Five of the eight NSIP patients improved and three were stable, whereas in patients with UIP, one worsened and three were stable. NSIP seems to be the major histopathologic pattern in patients with PF-SSc.


Transforaminal lumbar interbody fusion: the effect of various instrumentation techniques on the flexibility of the lumbar spine.
In vitro comparison of four reconstruction techniques following transforaminal lumbar interbody fusion in a human cadaveric model. Transforaminal lumbar interbody fusion (TLIF) is a relatively new technique that avoids the morbidity of an anterior approach and the nerve root manipulation of a posterior interbody fusion. This study measured the effects of a TLIF on the overall and segmental flexibility of the lumbar spine using four different spinal implant configurations. Anterior lumbar interbody fusion, posterior lumbar interbody fusion, and combined anterior-posterior spinal procedures are gaining wide acceptance for the treatment of selected patients with segmental spinal instability and spondylolisthesis with associated degenerative changes. Each fusion technique may have different effects on the overall flexibility of the lumbar spine. The unilateral TLIF procedure with adjunctive pedicular fixation is one variation of an interbody fusion technique that requires less bony and soft tissue dissection and minimizes nerve root manipulation compared with other interbody fusion methods. Five fresh-frozen, human lumbar spines were nondestructively subjected to flexion, extension, lateral bending, and axial rotation moments using a previously validated spine flexibility tester, and displacements were measured. Testing the intact lumbar spine was followed by testing of a unilateral L4-L5 TLIF using a single ramp carbon fiber cage without adjunctive internal fixation. The single carbon fiber (Brantigan) cage was inserted obliquely in a posterolateral to anteromedial position in the L4-L5 disc space. Following testing of the cage alone, three different adjunctive stabilization techniques were tested. Posterior stabilization involved one of the following: a contralateral translaminar facet screw, single side/ipsilateral nonsegmental pedicle screw fixation, and bilateral nonsegmental pedicle screw fixation. The overall flexibility of each lumbar spine was calculated from load-displacement curves for each axis of rotation. The flexibility of the L4-L5 segment of each spine was computed from kinematic motion data acquired via attached LED sensors to the L4 and L5 vertebral bodies. Statistical testing was performed with paired t tests. The flexibility of the entire (T12-S1) destabilized spine after TLIF with interbody cage alone and with all three reconstructive techniques was comparable with the intact spine. However, the motion at the L4-L5 segment was significantly increased for the TLIF with interbody cage alone in axial rotation (299% of intact, P < 0.01), with no significant change in flexion-extension (79% of intact, P = 0.22) or lateral bending (87% of intact, P = 0.39). With the addition of a contralateral translaminar facet screw, the motion at the L4-L5 segment remained significantly more flexible in axial rotation (250% of intact, P = 0.06) although less than with the cage alone. With the unilateral pedicle screw construct, the L4-L5 segment remained more flexible in axial rotation (182% of intact, P = 0.07) although significantly less than with the facet screw construct (P < 0.05). The addition of bilateral pedicle screws most closely reapproximated the flexibility of the intact spine with no significant difference in axial rotation (91% of intact, P = 0.30), flexion-extension (93% of intact, P = 0.19), or lateral bending (99% of intact, P = 0.47). The motion at the L4-L5 segment with bilateral pedicle screws was not significantly different than for the intact specimen in axial rotation (144% of intact, P = 0.17), flexion-extension (81% of intact, P = 0.21), or lateral bending (86% of intact, P = 0.27). TLIF reconstruction with a solitary cage did not increase overall spine flexibility from the intact condition but significantly increased segmental flexibility at L4-L5 in axial rotation. A unilateral translaminar facet screw had minimal stabilizing effect at L4-L5. Unilateral pedicle screws frews further increased stiffness at the L4-L5 segment. However, TLIF with bilateral pedicle screws most closely approximated the L4-L5 segmental flexibility of the intact spine.


Apoptosis: future perspectives.
The field of apoptosis has expanded to include research in almost all subject areas of cell biology. Despite this growth, there are still many unanswered questions, some of which are fundamental to the development of therapeutic strategies. Most importantly, the underlying mechanisms involved in conferring specificity of apoptotic signals must be determined. This will allow the development of treatments to delete injured or transformed cells and minimize damage to other tissues. Such information is also necessary to combat degenerative diseases, to prevent critical loss of cells. In addition, it would be of therapeutic benefit to selectively induce apoptosis in specific cells where removal of unwanted cells is required (e.g. tumour cells in malignant tissue or inflammatory cells responsible for tissue damage in chronic inflammatory disease). Therefore we have to understand how the full complement of signalling pathways, and survival and apoptotic proteins determine the end effect of an apoptotic signal. Apoptotic cells are known to functionally influence phagocytes that ingest them, but little is known of the effect of apoptosis on neighbouring cells or of signals generated during the apoptotic process itself. Although the processes of mitosis and apoptosis would appear to be diametrically opposed, cell-cycle proteins are involved in apoptosis, and may be able to influence cell-death mechanisms; conversely, proliferation may be caspase-dependent in some cells. Further study is necessary to discover how these pathways are interlinked since such knowledge would be particularly useful in cancer treatment. The link between pathogen-survival strategies and apoptotic mechanisms will also reward further work. Viruses, in particular, exploit cellular survival and death pathways for replication purposes and may represent a targeting approach for specific treatments.


[Contribution of immunohistochemical methods to the study of central nervous system tumors].
The contributions of the immunoperoxidase technique for the demonstration of glial fibrillary acidic (GFA) protein, neuron specific enolase (NSE) and the Leu-7 (HNK-1) monoclonal antibody in central nervous system (CNS) tumors are reviewed. GFA protein is expressed in normal, reactive and neoplastic cells of astrocytic lineage. Its presence in nonastrocytic CNS tumors is related either to the development of gliofibrillogenesis (ependymomas), to ontogenetic factors (oligodendrogliomas; choroid plexus papillomas), or to uptake of the protein from adjacent reactive astrocytes (capillary hemangioblastomas). It has permitted the recognition of new entities such as the pleomorphic xanthoastrocytoma, and of little known variants such as lipidized glioblastomas. NSE is of diagnostic importance in peripheral neuronal, endocrine and neuroendocrine tumors, but of considerably less value in CNS tumors, since it may be found in the cells of a variety of glial and other cerebral neoplasma as well as in reactive astrocytes. It has also been found to be present in a number of unrelated tumors outside the nervous system. The Leu-7 (HNK-1) monoclonal antibody, a hematological marker, has been found to cross-react with a number of cells of schwannian origin and may be helpful in the differential diagnosis of schwannomas and neurofibromas from other soft tissue neoplasms. Its recognition of oligodendroglial tumor cells has been confirmed, but it is also frequently recognized by both reactive and neoplastic astrocytes. In addition to its reactivity with cells of the immune system, a number of epithelial tumors, in particular adenocarcinomas of the prostate, will also be recognized by the antibody.(ABSTRACT TRUNCATED AT 250 WORDS)


Willow wood sap promotes the density-dependent pathogenesis of Brenneria salicis.
Brenneria salicis resides in symptomless willow (Salix spp.) and other tree species, but only willow trees develop watermark disease. To understand the conversion of B. salicis into a pathogen, its pathogenicity and differential growth in the various tree species are studied. Brenneria salicis was detected by plating and polymerase chain reaction-based techniques. Cell wall degradation and quorum sensing (QS) were assayed as possible pathogenicity mechanisms in wood. Differences in B. salicis growth capacities were tested in wood sap of the trees. Watermark diseased willow wood contained high concentrations of B. salicis with QS-induced cellulase activity. In the fall, wood sap of willow, and not of poplar and alder, promoted high density growth of B. salicis. In situ, B. salicis was the dominant bacterial type in willow wood during the fall and winter period. Willow sustains high densities of B. salicis at the time of leaf shedding. The cellulase in the immobilized wood sap has then a long-lasting contact with the xylem cell wall. Timing of dormancy and subsequent winter conditions might interfere with sap composition, B. salicis density, activity and survival, and be the reason, at least partly, for the variable occurrence of the disease.


Transcranial Magnetic Stimulation Measures in the Elderly: Reliability, Smallest Detectable Change and the Potential Influence of Lifestyle Habits.
Background: Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to evaluate cortical function and corticospinal pathway in normal and pathological aging. Yet, the metrologic properties of TMS-related measurements is still limited in the aging population. Objectives: The aim of this cross-sectional study was to document the reliability and smallest detectable change of TMS measurements among community-dwelling seniors. A secondary objective was to test if TMS measurements differ between elders based on lifestyle, medical and socio-demographic factors. Methods: Motor evoked potentials (MEPs) elicited by single-pulse TMS were recorded in the first dorsal interosseous (FDI) in 26 elderly individuals (mean age = 70 ± 3.8 years). Resting motor threshold (rMT), MEP amplitudes and contralateral silent period (cSP) were measured on two separate occasions (1-week interval), and the standard error of the measurement (SEMeas), intraclass correlation coefficient (ICC), and smallest detectable change in an individual (SDCindv) were calculated. Lifestyle, medical and socio-demographic factors were collected using questionnaires. TMS-related outcomes were compared using independent sample t-test based on the presence of chronic health diseases, chronic medication intake, obesity, history of smoking, physical activity levels, gender, and level of education. Results: rMT and cSP measures were the most reliable outcomes, with the lowest SEMeas and highest ICCs, whereas MEP amplitude-related measures were less reliable. SDCindv levels were generally high, even for rMT (7.29 %MSO) and cSP (43.16-50.84 ms) measures. Although not systematically significant, results pointed toward a higher corticospinal excitability in elderly individuals who were regularly active, who had no chronic medical conditions and who did not take any medication. Conclusion: Even though SDCindv levels were relatively high, these results show that rMT and cSP are the most reliable outcomes to investigate age-related changes in the corticomotor system and suggest that the influence of factors such as lifestyle habits and medications on TMS measures should be investigated further.


[Remodeling of cardiac gap junctions and arrhythmias].
In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to-cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart failure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above-mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentration in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic spread of the impulse of ventricular myocardium. The dephosphorylation of CX43 not only reduces electrical conductance, but also decreases permeability of chemicals between cardiomyocytes. The lateralization of gap junctions may increase the number of hemichannels formed by CX43. The opening of hemichannels induces ATP efflux and Na(+) influx, which forms a delayed after-depolarization. The gap junction remodeling in pathological condition produces arrhythmia substrate in the ventricles. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and arrhythmias were summarized.


Generation of conditional knockout mice.
Conditional knockout mouse models are powerful tools to examine the biological and molecular function(s) of genes in specific tissues. The general procedure to generate such genetically engineered mouse models consists of three main steps. The first step is to find the appropriate genomic clone of the gene of interest and to design the cloning and Southern blot strategies. The second step is the cloning of the gene-targeting vector with all its essential components including positive and negative selection cassettes and the insertion of LoxP sites. Although conventional methods are still being widely used for DNA cloning, we describe in this book chapter the use of λ Red phage-based homologous recombination in Escherichia coli to capture the genomic DNA of the gene of interest and to assemble the gene-targeting vector. This new method provides several advantages as it does not require the presence of restriction sites within the gene of interest to insert LoxP-flanked DNA fragments. In the final step, the gene-targeting vector is transferred into embryonic stem (ES) cells, and successfully targeted ES cell clones are injected into mouse blastocysts to generate conditional knockout mice.


Attention-deficit hyperactivity disorder in elementary school students in Shantou, China: prevalence, subtypes, and influencing factors.
Attention-deficit hyperactivity disorder (ADHD) is a frequent childhood-onset psychiatric condition and categorized into three subtypes of predominantly inattentive (ADHD-I), hyperactive impulsive (ADHD-H), and combined (ADHD-C). The prevalence and subtypes of ADHD vary considerably. The primary aim of this study was to provide a prevalence estimate of ADHD in elementary school students living in Shantou, a district of China, and in addition to examine the influence of informants, age, and gender on the prevalence. A total of 3,497 students aged 7-12 years were enrolled by random and stratified sampling. In stage I, teachers and parents of all participating students in randomly selected schools were asked to complete Chinese versions of the Conners' 10-item scale. In stage II, students with high scores (>15) were interviewed by a psychiatrist for a diagnosis with or without ADHD. Parents rated many more students with high scores than teachers did in stage I. The prevalence of ADHD determined by Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) was 5.91% (5.27%-6.55%), which is comparable to the rates reported in previous studies with Chinese children. This hits the low border of the ADHD prevalence range from 5.9 to 7.1% worldwide, and is lower than that of Chinese children living in Hong Kong, suggesting an important influence of Chinese culture on the diagnosis of ADHD. The constituent ratios of ADHD-I, ADHD-C, and ADHD-H subtypes were 67.43, 24.57, and 8.00%, respectively. The rate of ADHD-H decreased with age, whereas that of ADHD-I remained at the highest levels in all age groups, suggesting that symptoms in the inattention domain are the most persistent and refractory.


Human tracking using convolutional neural networks.
In this paper, we treat tracking as a learning problem of estimating the location and the scale of an object given its previous location, scale, as well as current and previous image frames. Given a set of examples, we train convolutional neural networks (CNNs) to perform the above estimation task. Different from other learning methods, the CNNs learn both spatial and temporal features jointly from image pairs of two adjacent frames. We introduce multiple path ways in CNN to better fuse local and global information. A creative shift-variant CNN architecture is designed so as to alleviate the drift problem when the distracting objects are similar to the target in cluttered environment. Furthermore, we employ CNNs to estimate the scale through the accurate localization of some key points. These techniques are object-independent so that the proposed method can be applied to track other types of object. The capability of the tracker of handling complex situations is demonstrated in many testing sequences.