Effect of lecithin nanoliposome or soybean lecithin supplemented by pomegranate extract on post-thaw flow cytometric, microscopic and oxidative parameters in ram semen.
This investigation was carried out to study the effect of soybean lecithin 1.5% (wt/vol) (0, 2.5, 5 and 7.5 mg l-1 pomegranate extract (PE)) or PE-loaded lecithin nanoliposome (0, 2.5, 5 and 7.5 mg l-1) to Tris-based extender. Sperm motility (CASA), viability, membrane integrity (HOS test), abnormalities, mitochondrial activity, apoptosis status, lipid peroxidation, total antioxidant capacity (TAC)) and antioxidant activities (GPX, SOD) were investigated following freeze-thawing. No significant differences were detected in motility parameters, viability, membrane integrity, and mitochondria activity after thawing sperm between soybean lecithin and lecithin nanoliposomes. It was shown that PE5 significantly improved sperm total and progressive motility, membrane integrity, viability, mitochondria activity, TAC and reduced lipid peroxidation (malondialdehyde concentration). Moreover, the percentage of apoptotic sperm in PE5 extenders was significantly the lowest among other treatments. Sperm abnormalities, SOD and GPX were not affected by the antioxidant supplements. For apoptotic status, no differences were observed between soybean lecithin and lecithin nanoliposome. We showed that lecithin nanoliposome extender can be a beneficial alternative extender to protect ram sperm during cryopreservation without any adverse effects. It was also observed that regarding pomegranate concentration, PE5 can improve the quality of ram semen after thawing.


Early video-assisted thoracic surgery for primary spontaneous hemopneumothorax.
Primary spontaneous hemopneumothorax (PSHP) is a rare surgical emergency. The aim of this study was to compare the previous strategy of tube thoracostomy followed by thoracotomy when complications developed with early video-assisted thoracic surgery (VATS) for PSHP. Between November 1989 and May 2005, a total of 24 consecutive patients with PSHP were retrospectively reviewed. Before January 2000, there were 13 patients who were subjected to the treatment strategy of initial tube thoracostomy and underwent operation if the condition deteriorated or later complications occurred (group T). Under this strategy, all of these patients later required operations. After January 2000, another 11 patients were treated with VATS as soon as their condition stabilized after tube thoracostomy and resuscitation (group V). The data for the two groups were compared: sex, age, involved side, initial heart rate (HR) and mean blood pressure (BP), initial hemoglobin (Hb), preoperative blood loss, operating time, amount of blood transfusion, period of chest tube drainage (POD), length of hospital stay (LOS), complications, and length of follow-up. The sex, age, involved side, and the initial HR, BP, and Hb of the two groups were similar. The patients of group V had a significantly longer operating time [group V, 111 minutes (mean); group T, 85 minutes, P = 0.002]; less preoperative blood loss (group V, 946 ml; group T, 1687 ml, P = 0.003); less blood transfusion (group V, 465 ml; group T, 1044 ml, P = 0.002); shorter POD (group V, 4 days; group T, 7 days, P = 0.011); and shorter LOS (group V, 5 days; group T, 10 days, P = 0.002). No mortality or recurrence was noted in the entire series. Our study suggests that surgery should be undertaken for PSHP as soon as possible after the clinical condition has stabilized. Under this strategy, VATS is an acceptable approach. It allows a shorter hospital stay and is exempt from unnecessary blood transfusion. Later complications, such as empyema and impaired lung reexpansion, can also be avoided.


3-D printout of a DICOM file to aid surgical planning in a 6 year old patient with a large scapular osteochondroma complicating congenital diaphyseal aclasia.
A 6 year old girl presented with a large osteochondroma arising from the scapula. Radiographs, CT and MRI were performed to assess the lesion and to determine whether the lesion could be safely resected. A model of the scapula was created by post-processing the DICOM file and using a 3-D printer. The CT images were segmented and the images were then manually edited using a graphics tablet, and then an STL-file was generated and a 3-D plaster model printed. The model allowed better anatomical understanding of the lesion and helped plan surgical management.


Cx30.2 deletion causes imbalances in testicular Cx43, Cx46, and Cx50 and insulin receptors. Reciprocally, diabetes/obesity alters Cx30.2 in mouse testis.
Cx30.2 protein content and localization were assessed during development. An account of Cx30.2, Cx43, Cx46, and Cx50, and insulin receptor (IR) responses to Cx30.2, Cx46, or Cx50 deficiency in mouse interstitial tissue (ITf)- and seminiferous tubule-enriched fractions (STf) is given. The impact of high glucose/insulin on Cx30.2 was investigated in spontaneously diabetic and obese db/db and ob/ob mouse testis and anterior pituitary (AP). Cx30.2 labeled contacts in vascular endothelial and Leydig cells and Sertoli cell junctions in stage V-VII. Cx30.2 expression is regulated differently in the interstitium and tubules. Cx30.2 at 30-kDa levels peaked by 28 days in ITf and by 14 days in STf. In STf, deleting Cx30.2 decreased Cx43 and Cx50, whereas deleting Cx50 downregulated Cx30.2. The opposite occurred in ITf. In STf, deleting Cx30.2 upregulated Cx46 except the full-length reciprocally, deleting Cx46 upregulated Cx30.2. In ITf, Cx30.2 deficiency upregulated full-length and phosphorylated Cx46, whereas deleting Cx46 downregulated 48- to 50-kDa Cx30.2. The db/db and ob/ob mouse ITf, STf, and AP showed imbalanced Cx30.2 levels. IRα levels at 135 kDa declined in Cx30.2-/- and Cx50-/- mouse ITf and Cx46-/- and Cx50-/- STf. IRβ at 98 to 110 kDa dropped in Cx30.2-/- and Cx46-/- mice STf suggesting that Cx30.2 deficiency decreases active IR sites. The results show the connexins interdependence and interaction and that altering a single connexin changes the remaining connexins expression, which can modify gap junction-mediated glucose exchanges in contacting cells. Data suggest that glucose/insulin influences Cx30.2 turnover in testis and AP and, reciprocally, that connexins modulate testis glucose uptake and response to insulin.


Mechanical neural networks: Architected materials that learn behaviors.
Aside from some living tissues, few materials can autonomously learn to exhibit desired behaviors as a consequence of prolonged exposure to unanticipated ambient loading scenarios. Still fewer materials can continue to exhibit previously learned behaviors in the midst of changing conditions (e.g., rising levels of internal damage, varying fixturing scenarios, and fluctuating external loads) while also acquiring new behaviors best suited for the situation at hand. Here, we describe a class of architected materials, called mechanical neural networks (MNNs), that achieve such learning capabilities by tuning the stiffness of their constituent beams similar to how artificial neural networks (ANNs) tune their weights. An example lattice was fabricated to demonstrate its ability to learn multiple mechanical behaviors simultaneously, and a study was conducted to determine the effect of lattice size, packing configuration, algorithm type, behavior number, and linear-versus-nonlinear stiffness tunability on MNN learning as proposed. Thus, this work lays the foundation for artificial-intelligent (AI) materials that can learn behaviors and properties.


Gene networks for total number born in pigs across divergent environments.
For reproductive traits such as total number born (TNB), variance due to different environments is highly relevant in animal breeding. In this study, we aimed to perform a gene-network analysis for TNB in pigs across different environments using genomic reaction norm models. Thus, based on relevant single-nucleotide polymorphisms and linkage disequilibrium blocks across environments obtained from GWAS, different sets of candidate genes having biological roles linked to TNB were identified. Network analysis across environment levels resulted in gene interactions consistent with known mammal's fertility biology, captured relevant transcription factors for TNB biology and pointing out different sets of candidate genes for TNB in different environments. These findings may have important implication for animal production, as optimal breeding may vary depending on later environments. Based on these results, genomic diversity was identified and inferred across environments highlighting differential genetic control in each scenario.


The solar dynamo.
The origins of solar magnetism lie below the visible surface of the Sun, in the highly turbulent convection zone. Turbulent convection operates in conjunction with rotational shear, global circulations and intricate boundary layers to produce the rich diversity of magnetic activity we observe. Here, we review recent insights into the operation of the solar dynamo obtained from solar and stellar observations and numerical models.


Neuropathy in prediabetes: does the clock start ticking early?
Between 25% and 62% of patients with idiopathic peripheral neuropathy are reported to have prediabetes, and among individuals with prediabetes 11-25% are thought to have peripheral neuropathy, and 13-21% have neuropathic pain. Population-based studies suggest a gradient for the prevalence of neuropathy, being highest in patients with manifest diabetes mellitus, followed by individuals with impaired glucose tolerance then impaired fasting glucose and least in those with normoglycemia. The most sensitive test to assess glucose metabolism status is the oral glucose tolerance test. Pathogenesis involves hyperglycemia, microvascular abnormalities, dyslipidemia and the metabolic syndrome. Individuals with prediabetes have less severe neuropathy than those with manifest diabetes mellitus. Sensory modalities are more frequently affected than motor modalities, but impairment of small nerve fibers could be the earliest detectable sign. Diagnosis should rely on careful clinical examination, with emphasis on the evaluation of small fibers. An oral glucose tolerance test should be performed in patients with idiopathic neuropathy. The only treatment with any efficacy is lifestyle modification to improve control of hyperglycemia and cardiovascular risk factors, but long-term efficacy of this approach has not been established. This Review summarizes the current evidence on the association between prediabetes and neuropathy.


Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.
Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier.


Genome-wide transcriptome profiles of rice hybrids and their parents.
Heterosis is a widely studied phenomenon in several plant species. However, its genetic basis still remains to be elucidated. In this study, we used RNA-seq data from two rice genotypes and their reciprocal hybrids, and used a combination of transcriptome profiling and allele-specific expression analysis to identify genes that are differentially expressed in the hybrids and their parents or expressed in an allele-specific manner. The differentially expressed genes (DEGs) were identified by a pairwise comparison of the four genotypes. Detailed annotation of DEGs suggested that these genes showed enrichment in some gene ontology categories, and they tend to have tissue-specific expression patterns compared to all genes. A total of 1033 (10.24%) of 10,195 genes with informative single nucleotide polymorphism (SNPs) were identified as ASE genes. These allele-specific expessed (ASE) genes showed a broader expression breadth suggesting that they function in diverse developmental stages. Among 1033 ASE genes, we also identified 45 ASE transcription factors belonging to 17 transcription factor families. These ASE transcription factors may act in trans to regulate gene expression in filial 1 (F1) hybrids. Our analyses provide a comprehensive transcriptome profile of rice hybrids and their parents, and would be a useful resource for the rice research community.


Nanoscale Restructuring of Polymer Materials to Produce Single Polymer Composites and Miscible Blends.
I summarize work conducted in our laboratories over the past 30 years using small host molecules to restructure polymer materials at the nanometer level. Certain small molecules, such as the cyclic starches cyclodextrins (CDs) and urea (U) can form non-covalent crystalline inclusion compounds (ICs) with a range of guest molecules, including many polymers. In polymer-CD- and -U-ICs, guest polymer chains reside in narrow channels created by the host molecule crystals, where they are separated and highly extended. When the host crystalline lattice is carefully removed, the guest polymer chains coalesce into a bulk sample with an organization that is distinct from that normally produced from its melt or from solution. Amorphous regions of such coalesced polymer samples have a greater density, likely with less chain entanglement and more chain alignment. As a consequence, after cooling from their melts, coalesced amorphous polymers show glass-transition temperatures (Tgs) that are elevated above those of samples prepared from their solutions or melts. Upon cooling from their melts, coalesced samples of crystallizable polymers show dramatically-increased abilities to crystallize more rapidly and much closer to their melting temperatures (Tms). These unique behaviors of polymers coalesced from their CD- and U-ICs are unexpectedly resistant to extended annealing above their Tgs and Tms. Taking advantage of this behavior permits us to create polymer materials with unique and improved properties. Among these are amorphous polymers with elevated Tgs and semi-crystalline polymers with finer more uniform morphologies. Improved mechanical properties can be achieved through self-nucleation with small amounts of the same polymer made rapidly crystallizable through coalescence from its CD- or U-IC. This can lead to single polymer composites with as-received polymer matrices and self-nucleated reinforcements. Through simultaneous formation and subsequent coalescence from their common CD-ICs, stable well-mixed blends can be achieved between any two or more polymers, despite their inherent immiscibilities. Such coalesced and well-mixed blends are also resistant to phase segregation when heated for extensive periods well above their Tgs and Tms.


Accuracy of vital status ascertainment using the Social Security Death Master File in a deceased population.
Both insurance and clinical studies depend on the Social Security Death Master File (SSDMF) to provide vital status on subjects that are unavailable for direct ascertainment. Using the Gen Re individual life claims data, we analyzed the accuracy of vital status determination in a population known to be deceased. Overall, only 75% of claims appeared in the SSDMF. The detection rate is highly skewed by age of the decedent. This systematically reduced ascertainment of mortality at younger ages could cause misleading conclusions in studies that measure absolute mortality rates, especially when they include a wide age span.


Multiferroicity in TTF-CA organic molecular crystals predicted through ab initio calculations.
We show by means of ab initio calculations that the organic molecular crystal TTF-CA is multiferroic: it has an instability to develop spontaneously both ferroelectric and magnetic ordering. Ferroelectricity is driven by a Peierls transition of the TTF-CA in its ionic state. Subsequent antiferromagnetic ordering strongly enhances the opposing electronic contribution to the polarization. It is so large that it switches the direction of the total ferroelectric moment. Within an extended Hubbard model, we capture the essence of the electronic interactions in TTF-CA, confirm the presence of a multiferroic groundstate, and clarify how this state develops microscopically.


The CD4/CD8 ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults.
We explored the associations of the CD4/CD8 ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 ratio may identify patients with higher immunoactivation despite ART.


Concurrent Signals and Behavioral Plasticity in Blue Crab (Callinectes sapidus Rathbun) Courtship.
Behavioral flexibility and behavioral regulation through courtship signals may both contribute to mating success. Blue crabs (Callinectes sapidus) form precopulatory pairs after courtship periods that are influenced by female and perhaps male urine-based chemical signals. In this study, male and female crabs were observed in 1.5-m circular outdoor pools for 45 min while the occurrence and sequence of courtship behaviors and pairing outcomes were recorded. These results were then compared with trials in which males or females were blindfolded; lateral antennule (outer flagellum) ablated; blindfolded and lateral antennule ablated; or had received nephropore blocks. The relative importance of visual and chemical sensory systems during blue crab courtship were then determined and urine and non-urine based chemical signals for both males and females were examined. Courtship behaviors varied considerably in occurrence and sequence; no measured behavior was necessary for pairing success. Male or female blindfolding had no effect on any measured behavior. Males and females required chemical information for normal courtship behaviors, yet blocking male or female urine release did not affect courtship behaviors. Males required chemical information to initiate pairing or to maintain stable pairs. Male urine release was necessary for stable pairing, suggesting that male urine signals may be involved in pair maintenance rather than pair formation. Females that could not receive chemical information paired faster and elicited fewer male agonistic behaviors. The results demonstrate a great variability and flexibility in blue crab courtship, with no evidence for stereotyped behavioral sequences. However, these behaviors appear regulated by urine- and nonurine-based redundant chemical signals emanating from both males and females. Although urine-based signals play roles in blue crab courtship, chemical signals from other sites appear to carry sufficient information to elicit a full range of behavioral responses in males and females.


Iron deficiency anemia (IDA) perceptions and dietary iron intake among young women and pregnant women in Jordan.
To determine Iron Deficiency Anemia (IDA) perceptions and iron dietary practices of Jordanian female students and pregnant women, a descriptive quantitative questionnaire was administered to 271 participants: 206 female students and 65 pregnant women. This pilot study found that most participants can identify foods containing iron, but lack appropriate iron intake, because of eating habits and finances; more than 50% report daily symptoms of IDA, including dizziness, fatigue, depression, headaches, and loss of concentration and memory. There are no statistically significant differences in IDA perceptions and iron-related dietary practices based on education, and relatively few based on where participants live, their available financial resources, or their position (pregnant women or young women). Culturally sensitive intervention research, which addresses application of IDA education principles, temporary supplementation, and adequate income for dietary modification and long-term iron supplementation to prevent IDA is warranted.


Rational construction of a CNTs@VO2 nanosheets modified separator for enhancing the performance of lithium-sulfur batteries.
Although lithium-sulfur (Li-S) batteries possess great potential to become the next generation of energy storage technology due to their fivefold higher energy density than commercial lithium-ion batteries, their practical application is still hindered by their poor cycling stability, especially resulting from the disturbing shuttle effect of soluble intermediates. In this study, vanadium dioxide (VO2) nanosheets were successfully grown onto CNTs to form CNTs@VO2 through hydrothermal and calcining processes. The hollow structure of the high conductive CNTs offers internal space and mesopores to accommodate the electrolyte combined with the polar metal oxide VO2 nanosheets providing the chemical anchoring. The hollow binary core-shell host acting as the nanoreactor that serves as the modifier of the separator results in the intensive physical and chemical dual adsorption of lithium polysulfide species (LiPSs), promoting the conversion of long-chain LiPSs to alleviate the shuttle effect significantly and boosting the performance. In addition, the CNTs enhance the electronic conductivity and the electrolyte infiltration of the separator. Notably, the modified separator demonstrates a high initial discharge capacity of 1397 mA h g-1 at 0.2C and retains a stable cycling ability with a reversible capacity of 965 mA h g-1 over 200 cycles at 1C. Even for the high sulfur loading of 7.4 mg cm-2, it can deliver a high areal capacity of 5.4 mA h cm-2 at 0.5C.


Impact of moving target on measurement accuracy in 3D and 4D PET imaging-a phantom study.
The purpose of this study was to evaluate the impact of tumor motion on maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) measurements in both 3-dimensional and respiratory-correlated, 4-dimensional positron emission tomography (PET) imaging. We also evaluated the effect of implementing different attenuation correction methods in 4-dimensional PET image reconstruction on SUVmax and MTV. An anthropomorphic thorax phantom with a spherical ball as a surrogate for a tumor was used. Different types of motion were imposed on the ball to mimic a patient's breathing motion. Three-dimensional PET imaging of the phantom without tumor motion was performed and used as the reference. The ball was then set in motion with different breathing motion traces and imaged with both 3- and 4-dimensional PET methods. The clinical 4-dimensional PET imaging protocol was modified so that 3 different types of attenuation correction images were used for reconstructions: the same free-breathing computed tomography (CT) for all PET phases, the same average intensity projection CT for all PET phases, and 4-dimensional CT for phase-matched attenuation correction. Tumor SUVmax and MTV values that were measured from the moving phantom were compared with the reference values. SUVmax that was measured in 3-dimensional PET imaging was different from the reference value by 20.4% on average for the motions that were investigated; this difference decreased to 2.6% with 4-dimensional PET imaging. The measurement of MTV in 4-dimensional PET also showed a similar magnitude of reduction of deviation compared with 3-dimensional PET. Four-dimensional PET with use of phase-matched 4-dimensional CT for attenuation correction showed less variation in SUVmax and MTV among phases compared with 4-dimensional PET with free-breathing CT or average intensity projection CT for attenuation correction. Four-dimensional PET imaging reduces the impact of motion on measured SUVmax and MTV when compared with 3-dimensional PET imaging. Clinical 4-dimensional PET imaging protocols should consider phase-matched 4-dimensional CT imaging for attenuation correction to achieve more accurate measurements.


Identifying the inserted locus of randomly integrated expression plasmids by whole-genome sequencing of Aspergillus strains.
Whole-genome sequencing was conducted on two Aspergillus oryzae strains used for the manufacturing of food enzymes, Acrylaway® and Shearzyme®, with the aim of identifying the inserted locus of randomly integrated expression plasmid and obtaining flanking sequences for safety assessment. Illumina paired-end sequencing was employed, and the obtained reads were mapped to two references: the public genome sequence of Aspergillus oryzae RIB40 and the in-house sequence of the used expression plasmid. Introducing the concept of linking-reads, one locus for each was successfully identified as the integrated site. In the case of Acrylaway®, the obtained sequences suggested that the expression plasmid had been integrated as multiple copies in tandem form. In the case of Shearzyme®, however, information on one edge of the insert was missing, which required extra polymerase chain reaction (PCR) cloning for safety assessment. A 4-kb deletion was detected at the integrated site. There was also evidence of rearrangement occurring in Shearzyme® strain.


The Patterns, Risk Factors, and Prediction of Progression in Chronic Kidney Disease: A Narrative Review.
Chronic kidney disease (CKD) is a global public health problem that is associated with excess morbidity, mortality, and health resource utilization. The progression of CKD is defined by a decrease in glomerular filtration rate and leads to a variety of metabolic abnormalities including acidosis, hypertension, anemia, and mineral bone disorder. Lower glomerular filtration rate also bears a strong relationship with an increased risk of cardiovascular events, end-stage renal disease, and death. Patterns of CKD progression include linear and nonlinear trajectories, but kidney function can remain stable for years in some individuals. Addressing modifiable risk factors for the progression of CKD is needed to attenuate its associated morbidity and mortality. Developing effective risk prediction models for CKD progression is critical to identify patients who are more likely to benefit from interventions and more intensive monitoring. Accurate risk-prediction algorithms permit systems to best align health care resources with risk to maximize their effects and efficiency while guiding overall decision making.


Spectral CT of the Extremities with a Silicon Strip Photon Counting Detector.
Photon counting x-ray detectors (PCXDs) are an important emerging technology for spectral imaging and material differentiation with numerous potential applications in diagnostic imaging. We report development of a Si-strip PCXD system originally developed for mammography with potential application to spectral CT of musculoskeletal extremities, including challenges associated with sparse sampling, spectral calibration, and optimization for higher energy x-ray beams. A bench-top CT system was developed incorporating a Si-strip PCXD, fixed anode x-ray source, and rotational and translational motions to execute complex acquisition trajectories. Trajectories involving rotation and translation combined with iterative reconstruction were investigated, including single and multiple axial scans and longitudinal helical scans. The system was calibrated to provide accurate spectral separation in dual-energy three-material decomposition of soft-tissue, bone, and iodine. Image quality and decomposition accuracy were assessed in experiments using a phantom with pairs of bone and iodine inserts (3, 5, 15 and 20 mm) and an anthropomorphic wrist. The designed trajectories improved the sampling distribution from 56% minimum sampling of voxels to 75%. Use of iterative reconstruction (viz., penalized likelihood with edge preserving regularization) in combination with such trajectories resulted in a very low level of artifacts in images of the wrist. For large bone or iodine inserts (>5 mm diameter), the error in the estimated material concentration was <16% for (50 mg/mL) bone and <8% for (5 mg/mL) iodine with strong regularization. For smaller inserts, errors of 20-40% were observed and motivate improved methods for spectral calibration and optimization of the edge-preserving regularizer. Use of PCXDs for three-material decomposition in joint imaging proved feasible through a combination of rotation-translation acquisition trajectories and iterative reconstruction with optimized regularization.


Identification of bile biomarkers of biliary tract cancer through a liquid chromatography/mass spectrometry-based metabolomic method.
The incidence and mortality rate of biliary tract cancer have been increasing worldwide; however, its diagnosis and prognosis have not improved in recent years. A novel approach, termed 'metabolomics', may have the potential to be developed as an effective diagnostic tool. The present study prospectively obtained bile samples from 115 individuals, including 32 patients with biliary tract cancer, 61 patients with benign biliary tract diseases and 22 normal controls. A liquid chromatography/mass spectrometry (LC/MS)‑based approach was used to investigate the differences in bile samples between the three groups, followed by multivariate statistical analysis, which included partial least squares projection to latent structures with discriminant analysis (PLS‑DA) and orthogonal projection to latent structures with discriminant analysis (OPLS‑DA). The metabolomic 2D score plot and 3D plot revealed clear separation between the cancer, benign and normal control groups by PLS‑DA. To further address the significant difficulties in clinically differentiating between biliary tract cancer and benign biliary tract diseases, OPLS‑DA was performed to distinguish between the two disease groups and to select potential biomarkers. The cancer and benign groups were well differentiated. The metabolic analysis revealed significantly lower levels of lysophosphatidylcholine, phenylalanine, 2‑octenoylcarnitine, tryptophan and significantly higher levels of taurine‑ and glycine‑conjugated bile acids in the bile from patients with biliary tract cancer compared with those in the bile from patients with benign biliary tract disease. The present study suggested that an LC/MS‑based metabolomic investigation provides a potent and promising approach for discriminating biliary tract cancer from benign biliary tract diseases and the identified specific metabolites may offer potential as novel biomarkers for the early detection of biliary tract cancer.


'And then you can decide'--antenatal foetal diagnosis decision making in South Africa.
Decision making is integral to genetic counselling and the premise is that autonomous decisions emerge if patients are provided with information in a non-directive manner. The pivotal activity in antenatal diagnosis counselling with at-risk pregnant women is decision making regarding invasive procedures. This process is not well understood in multicultural settings. This study examined multicultural genetic counselling interactions with women of advanced maternal age (AMA). It aimed to investigate the participants' orientation towards the amniocentesis decision. Data were collected during 14 video-recorded consultations between six genetic counsellors and 14 women of AMA in a genetic counselling clinic in South Africa. The design was qualitative and conversation analysis was used for analysis. Analysis revealed that counsellors used several strategies to facilitate discussions and decision making. However, the invitation to make a decision regarding amniocentesis was not perceived as being neutral. Both the counsellors and the women appeared to treat the offer as one which should be accepted. This resulted in a paradox, as strategies intended to allow neutral discussion seem to achieve the opposite. It is suggested that these results may be linked to the local health-care setting. The results suggest that the understanding of decision-making processes and enhancing autonomy may require a more detailed investigation into psychosocial, political and historical factors in the local health-care setting. Models of practice as well as the training of genetic counsellors need to be sensitive to these influences. A closer examination of interactional variables may yield new and relevant insights for the profession.


Epicatechin gallate, a naturally occurring polyphenol, alters the course of infection with β-lactam-resistant Staphylococcus aureus in the zebrafish embryo.
(-)-epicatechin gallate (ECg) substantially modifies the properties of Staphylococcus aureus and reversibly abrogates β-lactam resistance in methicillin/oxacillin resistant (MRSA) isolates. We have determined the capacity of ECg to alter the course of infection in zebrafish embryos challenged with epidemic clinical isolate EMRSA-16. At 30 h post fertilization (hpf), embryos were infected by injection of 1-5 × 10(3) colony forming units (CFU) of EMRSA-16 into the circulation valley or yolk sac. Infection by yolk sac injection was lethal with a challenge dose above 3 × 10(3) CFU, with no survivors at 70 hpf. In contrast, survival at 70 hpf after injection into the circulation was 83 and 44% following challenge with 3 × 10(3) and 1-5 × 10(3) CFU, respectively. No significant increases in survival were noted when infected embryos were maintained in medium containing 12.5-100 μg/mL ECg with or without 4 or 16 μg/mL oxacillin. However, when EMRSA-16 was grown in medium containing 12.5 μg/mL ECg and the bacteria used to infect embryos by either the circulation valley or yolk sac, there were significant increases in embryo survival in both the presence and absence of oxacillin. ECg-modified and unmodified, GFP-transformed EMRSA-16 bacteria were visualized within phagocytic cells in the circulation and yolk sac; pre-treatment with ECg also significantly increased induction of the respiratory burst and suppressed increases in IL-1β expression typical of infection with untreated EMRSA-16. We conclude that exposure to ECg prior to infection reduces the lethality of EMRSA-16, renders cells more susceptible to elimination by immune processes and compromises their capacity to establish an inflammatory response in comparison to non-exposed bacteria.


Clinic and care: associations with adolescent antiretroviral therapy adherence in a prospective cohort in South Africa.
Adolescent antiretroviral treatment (ART) adherence remains critically low. We lack research testing protective factors across both clinic and care environments. A prospective cohort of adolescents living with HIV (sample n = 969, 55% girls, baseline mean age 13.6) in the Eastern Cape Province in South Africa were interviewed at baseline and 18-month follow-up (2014-2015, 2015-2016). We traced all adolescents ever initiated on treatment in 52 government health facilities (90% uptake, 93% 18-month retention, 1.2% mortality). Clinical records were collected; standardized questionnaires were administered by trained data collectors in adolescents' language of choice. Probit within-between regressions and average adjusted probability calculations were used to examine associations of caregiving and clinic factors with adherence, controlling for household structure, socioeconomic and HIV factors. Past-week ART adherence was 66% (baseline), 65% (follow-up), validated against viral load in subsample. Within-individual changes in three factors were associated with improved adherence: no physical and emotional violence (12.1 percentage points increase in adjusted probability of adherence, P < 0.001), improvement in perceived healthcare confidentiality (7.1 percentage points, P < 0.04) and shorter travel time to the clinic (13.7 percentage points, P < 0.02). In combination, improvement in violence prevention, travel time and confidentiality were associated with 81% probability of ART adherence, compared with 47% with a worsening in all three. Adolescents living with HIV need to be safe at home and feel safe from stigma in an accessible clinic. This will require active collaboration between health and child protection systems, and utilization of effective violence prevention interventions.


[Prior authorisation to visit the neurologist from primary care may not be necessary: the findings of a prospective, controlled study].
The system by which approval must be given by the primary care physician before a patient can visit a specialist is known as gatekeeping and is aimed at preventing the mistaken or simple referral of patients to the next stage of health care services. We present a study that compares the final diagnoses of 400 patients who used a direct access model of referral (DAM) with those of 400 patients referred by a primary care physician in a prior authorisation model (PAM). We conducted a prospective analysis of two cohorts of patients who visited the same neurologist in a PAM system versus a DAM system. The 800 patients were evaluated following similar diagnostic criteria. The primary objective of the study was to compare the patients who were referred with a final diagnosis of 'non-neurological pathology' in the PAM and the DAM systems. Secondary aims consisted in conducting an analysis of the diagnoses by different pathologies between the two models. No significant differences were found between the referrals that were considered to be non-neurological in the PAM and the DAM systems (27.0% versus 26.3%; p = 0.48). A logistic regression model was performed with 'non-neurological pathology' as the dependent variable and age, sex and type of model (PAM or DAM) as the independent variables, similar results being obtained in both cases. Our data suggest that the role played by the primary care physician is not effective when it comes to preventing mistaken referrals to the neurologist in our area. A populational study would be needed to evaluate the rate at which resources are used and the spending on health care in the two models.


Molecular and phylogenetic characterization of bovine coronavirus virus isolated from dairy cattle in Central Region, Thailand.
Bovine coronavirus (BCoV) is involved mainly in enteric infections in cattle. This study reports the first molecular detection of BCoV in a diarrhea outbreak in dairy cows in the Central Region, Thailand. BCoV was molecularly detected from bloody diarrheic cattle feces by using nested PCR. Agarose gel electrophoresis of three diarrheic fecal samples yielded from the 25 samples desired amplicons that were 488 base pairs and sequencing substantiated that have BCoV. The sequence alignment indicated that nucleotide and amino acid sequences, the three TWD isolated in Thailand, were more quite homologous to each other (amino acid at position 39 of TWD1, TWD3 was proline, but TWD2 was serine) and closely related to OK-0514-3strain (virulent respiratory strain; RBCoV).The amino acid sequencing identities among TWD1, TWD2,TWD3, and OK-0514-3 strain were 96.0 to 96.6%, those at which T3I, H65N, D87G, H127Y, andQ136R were changed. In addition, the phylogenetic tree of the hypervariable region S1subunit spike glycoprotein BCoV gene was composed of three major clades by using the 54 sequences generated and showed that the evolutionally distance, TWD1, TWD2, and TWD3 were the isolated group together and most similar to OK-0514-3 strain (98.2 to 98.5% similarity). Further study will develop ELISA assay for serologic detection of winter dysentery disease.


Impairments of spatial working memory and attention following acute psychosocial stress.
Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory.


Nanoparticles of Pd: synthesis by microwave-solvothermal method and optical properties.
Well-dispersed Pd nanoparticles were synthesized by microwave-assisted solvothermal technique using methanol and ethanol. Particle size and morphology were controlled mainly by the reaction temperature. Particle size of Pd nanoparticles was controlled in the range of 2 to 11 nm by manipulating the reaction conditions. The Pd nanoparticles were characterized by transmission electron microscopy for particle size and shape and UV-Vis spectroscopy for optical properties. UV-Vis spectra showed that synthesized Pd nanoparticles stabilized with PVP had absorption bands at around 280 to 290 nm.


IL-18 gene expression pattern in exogenously treated AML cells.
IL-18 production may enhance immune system defense against KG-1 cells ; NB4 cells, which are associated with good prognosis, do not produce IL-18. In this study, we treated KG-1 cells with IL-18 and used microarray technology to assess subsequent effects on gene expression. In UniGene-array of 7488 human genes, expression of 57 genes, including stress related genes, increased at least 2-fold, whereas expression of 48 genes decreased at least 2-fold. Following exogenous exposure of KG-1 cells to IL-18, expression of CRYGC, NF(kappa)BIA and NACA gene were monitored. The latter is a transcriptional coactivator potentiating c-Jun-mediated transcription. NF(kappa)BIA is an inhibitor of NF(kappa)B, and affects growth regulation, apoptosis and hypoxic stress. Studies, such as this one, are beginning to clarify the differences between cells associated with good and bad cancer prognoses, which may ultimately assist in medical treatment for acute myeloid leukemia.


Musculoskeletal injuries in physical education versus non-physical education teachers: a prospective study.
Physical education (PE) teachers have a physically demanding job, putting them at a considerable risk for musculoskeletal injuries. To structurally develop tailored injury prevention programmes for PE teachers, a clear understanding of the extent, characteristics and underlying factors of their musculoskeletal injuries compared to referents is necessary. Therefore, the current study prospectively followed 103 PE teachers and 58 non-PE teachers, who registered musculoskeletal injuries and time of exposure to sports participation during one school year. Pearson χ(2)-tests and independent samples t-tests determined significant differences between PE and non-PE teachers regarding demographics and variables possibly related to injury occurrence. PE teachers had 1.23 and non-PE teachers 0.78 injuries/teacher/school year. This difference was significantly different after adjustment for hours spent weekly on intracurricular teaching during the career and for injury history during the preceding six months (P = 0.009; OR = 0.511; 95% CI = 0.308-0.846). PE teachers' most affected body parts were the knee and the back. PE teachers had a more extensive injury history (P < 0.001), a higher work- (P < 0.001) and sport index (P < 0.001), practiced more sports (P < 0.002) and taught more extracurricular sports (P = 0.001). Future injury prevention programmes should take account for the great injury history and heavy physical load in PE teachers.


A Hybrid Online Off-Policy Reinforcement Learning Agent Framework Supported by Transformers.
Reinforcement learning (RL) is a powerful technique that allows agents to learn optimal decision-making policies through interactions with an environment. However, traditional RL algorithms suffer from several limitations such as the need for large amounts of data and long-term credit assignment, i.e. the problem of determining which actions actually produce a certain reward. Recently, Transformers have shown their capacity to address these constraints in this area of learning in an offline setting. This paper proposes a framework that uses Transformers to enhance the training of online off-policy RL agents and address the challenges described above through self-attention. The proposal introduces a hybrid agent with a mixed policy that combines an online off-policy agent with an offline Transformer agent using the Decision Transformer architecture. By sequentially exchanging the experience replay buffer between the agents, the agent's learning training efficiency is improved in the first iterations and so is the training of Transformer-based RL agents in situations with limited data availability or unknown environments.


Spontaneous cancer and its possible relationship to oxygen metabolism.
Mortality statistics for cancer in various countries and periods of time indicate that there has been little effect of industrialization on the inherent or spontaneous rate of occurrence of cancer. From U.S. cancer statistics and the BEIR values [Report of the Advisory Committee on the Biological Effects of Ionizing Radiation (1979)] for radiation dose response, the ionizing radiation exposure required to produce a number of cancers equal to this spontaneous incidence was estimated to lie between 450 and 2100 rads (1 rad = 0.01 J/kg). From these "cancer equivalent" doses the number of single-strand DNA breaks required to produce the spontaneous cancers is estimated to be 0.26-1.3 per cell DNA per day. It is suggested that the univalent reduction of oxygen in normal metabolism to O2- and subsequent production of more harmful radicals is the source of the DNA defects that, in cases where the defense mechanisms fail, lead to spontaneous cancer in the individual.


[Role of the echocardiogram in adults with congenital cardiopathy].
Advances in cardiac surgery, intensive care and non-invasive diagnostic methods in congenital heart diseases have allowed ford a high percentage of these patients to arrive to adult hood. Initial presentation of this type of anomalies in adult life is now uncommon. Most of these lesions are not arribe complex and easily acknowledged, but occasionally complex defects that represent a challenge for the diagnostic and treatment options. The handling of this groups of patients requires detailed information of the cardiac anatomy and cardiovascular pathophysiology. Transthoracic echocardiography (TEE) is a widely used method considered the initial method of choice. The transesophageal echocardiography (ETE) in combination with pulsed and continuous wave Doppler and color flow mapping provide high image resolution, in real time, of the cardiac structures to establish the diagnosis and hemodynamic repercussion, offering besides an important support during interventional cardiac catheterization procedures and monitoring during surgical procedures. To perform and interpret the studies of congenital heart disease, it must be acknowledged that this is a highly specialized technique that requires in depth knowledge of the spatial cardiac anatomy and pathology of the lesions, as well as the understanding of the different options of treatment and complications. Recently a it three-dimensional reconstruction of cardiac ultrasound image has which permits the spatial recognition of the intracardiac anatomy and provides additional information for the understanding of the congenital heart disease.


Early recovery after cerebral ischemia risk of subsequent neurological deterioration.
Given the high short-term risk of stroke after transient ischemic attack, we hypothesized that substantial acute neurological recovery in patients presenting with cerebral ischemia would be associated with a greater risk of subsequent neurological deterioration due to recurrent cerebral ischemia. Data from the Trial of ORG10172 in Acute Stroke Treatment, a randomized trial of the heparinoid danaparoid, were analyzed to determine whether substantial acute recovery, defined as an improvement of greater than or equal to 75% on National Institutes of Health Stroke Scale (NIHSS) between baseline and 24 hours, was associated with a greater risk of subsequent deterioration, defined as a worsening on the NIHSS between day 1 and day 90. Of 1,184 subjects meeting entry criteria, 63 (5.3%) had substantial acute recovery. Subsequent deterioration was more common in those with substantial acute recovery compared with others (48 vs 33%; p = 0.028 by Fisher's exact test). In multivariable models, substantial acute recovery remained an independent predictor of subsequent deterioration (odds ratio, 3.0; 95% confidence interval, 1.7-5.2; p < 0.001). Among patients with acute cerebral ischemia, those who recover substantially within 24 hours may be at greater risk of subsequent neurological deterioration due to causes other than hemorrhage.


Simple and complex genetics of colorectal cancer susceptibility.
There are several hereditary conditions associated with an increased risk of colorectal cancer (CRC). These include well-characterized autosomal dominant syndromes, such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). A novel autosomal recessive form of FAP, caused by mutations in the base excision repair gene MYH, has recently been recognized. This discovery has provided further evidence for the importance of DNA repair mechanisms in CRC development, already documented by the involvement of the mismatch repair in HNPCC. Additional CRC-predisposing conditions, such as hyperplastic polyposis and hereditary mixed polyposis syndrome, are being outlined. Heterogeneity of genetic mechanisms has important consequences for counseling and surveillance in hereditary CRC. Nevertheless, classical mendelian conditions represent only a minor share of the total CRC population burden. Alleles of the same genes that are involved in hereditary syndromes might also act as low penetrance variants, as shown for APC 1307K in the Ashkenazi. However, the level of complexity of multifactorial CRC is such that current tools appear inadequate to pinpoint all the involved components. A combination of different strategies, including careful clinical observation, analysis of homogeneous patient populations, and critical evaluation of data derived from experimental models, along with methodological improvements in nucleic acid analysis, will probably be necessary to unravel the basis of nonmendelian CRC. Once this is achieved, it will be possible to realize the ultimate goal of targeted CRC prevention, with the adoption of measures tailored according to individual risk levels. .


A new ONO3- trianionic pincer-type ligand for generating highly nucleophilic metal-carbon multiple bonds.
Appending an amine to a C═C double bond drastically increases the nucleophilicity of the β-carbon atom of the alkene to form an enamine. In this report, we present the synthesis and characterization of a novel CF(3)-ONO(3-) trianionic pincer-type ligand, rationally designed to mimic enamines within a metal coordination sphere. Presented is a synthetic strategy to create enhanced nucleophilic tungsten-alkylidene and -alkylidyne complexes. Specifically, we present the synthesis and characterization of the new CF(3)-ONO(3-) trianionic pincer tungsten-alkylidene [CF(3)-ONO]W═CH(Et)(O(t)Bu) (2) and -alkylidyne {MePPh(3)}{[CF(3)-ONO]W≡C(Et)(O(t)Bu)} (3) complexes. Characterization involves a combination of multinuclear NMR spectroscopy, combustion analysis, DFT computations, and single crystal X-ray analysis for complexes 2 and 3. Exhibiting unique nucleophilic reactivity, 3 reacts with MeOTf to yield [CF(3)-ONO]W═C(Me)(Et)(O(t)Bu) (4), but the bulkier Me(3)SiOTf silylates the tert-butoxide, which subsequently undergoes isobutylene expulsion to form [CF(3)-ONO]W═CH(Et)(OSiMe(3)) (5). A DFT calculation performed on a model complex of 3, namely, [CF(3)-ONO]W≡C(Et)(O(t)Bu) (3'), reveals the amide participates in an enamine-type bonding combination. For complex 2, the Lewis acids MeOTf, Me(3)SiOTf, and B(C(6)F(5))(3) catalyze isobutylene expulsion to yield the tungsten-oxo complex [CF(3)-ONO]W(O)((n)Pr) (6).


Detecting Signals of Dietary Supplement Adverse Events from the CFSAN Adverse Event Reporting System (CAERS).
Dietary supplement adverse events are potentially severe, yet knowledge regarding the safety of dietary supplements is limited. The CFSAN Adverse Event Reporting System (CAERS) contains records of adverse events attributed to supplements and is potentially useful for dietary supplement pharmacovigilance. This study investigates the feasibility of mining CAERS for dietary supplement adverse events as well as for monitoring the safety of dietary supplement products. Using three online resources, we mapped products in CAERS to their listed ingredients. We then ran four standard signal detection algorithms over the ingredient-adverse event and product-adverse event pairs extracted from CAERS and ranked the detected associations. Comparing 130 signals detected by all four algorithms with a dietary supplement resource, we found evidence for 73 (56%) associations. In addition, some detected product-adverse event signals were consistent with product safety information. We have made a database of the detected adverse events publicly available at https://github.com/zhang-informatics/DDSAE.


SPREADSHEET-BASED PROGRAM FOR ERGONOMIC ADJUSTMENT OF NOTEBOOK COMPUTER AND WORKSTATION SETTINGS.
This paper discusses a computer program, ErgoNBC, which provides suggestions regarding the ergonomic settings of a notebook computer (NBC), workstation components, and selected accessories in order to help computer users to assume an appropriate work posture during the NBC work. From the users' body height, NBC and workstation component data, ErgoNBC computes the recommended tilt angle of NBC base unit, NBC screen angle, distance between the user and NBC, seat height and work surface height. If necessary, the NBC base support, seat cushion and footrest, including their settings, are recommended. An experiment involving twenty-four university students was conducted to evaluate the recommendations provided by ErgoNBC. The Rapid Upper Limb Assessment (RULA) technique was used to analyze their work postures both before and after implementing the Ergo NBC's recommendations. The results clearly showed that ErgoNBC could significantly help to improve the subjects' work postures.


Identification and characterization of several forms of phospholipase A2 in mouse epidermal keratinocytes.
The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated the release of arachidonic acid (AA) from mouse keratinocytes. A distinct difference was observed between the fatty acid release profile elicited by TPA and other stimuli. These findings led to the investigation of keratinocyte phospholipase A2 (PLA2), which catalyzes the release of sn-2 fatty acids from membrane phospholipids and regulates the production of eicosanoids. We characterized and identified several forms of PLA2 in mouse keratinocytes, a cytosolic or cPLA2 and two secretory or sPLA2s in the membrane. The PLA2 in keratinocyte cytosol is sensitive to heating and acid treatment, while resistant to reducing reagent. The PLA2 in keratinocyte membrane is resistant to heating and acid treatment, while sensitive to reducing reagent. These characteristics suggested the presence of a cPLA2 and at least one type of sPLA2. Inhibitor data further confirmed the identities of these PLA2s. The cPLA2 was activated by TPA, and appeared to be responsible for the majority of the specific release of AA observed in mouse keratinocytes treated with TPA. The calcium ionophore A23187, and 4alpha-TPA did not elicit the selectivity towards AA observed with TPA. The release of linoleic acid (LA) and oleic acid (OA) from A23187- and 4alpha-TPA-treated keratinocytes suggests activation of sPLA2. These activities may be due to the existence of both type I and type II sPLA2, as both were identified by polymerase chain reactions. In conclusion, keratinocytes express several forms of phospholipase A2 that differ in their substrate specificities and mechanisms of activation, resulting in distinct agonist-specific fatty acid release profiles.


The effect of therapy on tumour vascular function.
It has been established that malignant tissue as a consequence of abnormal morphogenesis has a structurally abnormal blood supply. These structural and as a consequence functional differences between normal and neoplastic vasculature provide a basis for selective modulation of tumour vascular function. Agents have been identified which can induce both irreversible and reversible effects on tumour blood flow. Hyperthermia, photodynamic therapy, tumour necrosis factor and flavone acetic acid are known to elicit most of their anti-tumour effect via irreversible changes in tumour vascular function. In addition to the extensive tumour cell kill and thus therapeutic potential provided by such chronic modulation of blood flow, acute transient changes in macroregional and microregional tumour blood flow could also play an important role if used appropriately with conventional therapies. The use of this latter type of modulation is discussed with reference to known examples of such 'vasoactive' compounds. It is also emphasized that blood flow changes induced in tumour tissue can be a 'double-edged sword' with detrimental consequences for therapeutic outcome if inappropriate changes are induced, for example, reductions in flow at the time of conventional radiotherapy or chemotherapy by agents not considered to be 'vasoactive'. To emphasize this point examples of blood flow modulation by pimonidazole and cis-platinum, agents that are used in conjunction with radiotherapy, are described.


Dual-light photodynamic therapy administered daily provides a sustained antibacterial effect on biofilm and prevents Streptococcus mutans adaptation.
Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.


Synthesis and Antimicrobial Activity of the Hybrid Molecules between Sulfonamides and Active Antimicrobial Pleuromutilin Derivative.
A series of novel hybrid molecules between sulfonamides and active antimicrobial 14-o-(3-carboxy-phenylsulfide)-mutilin were synthesized, and their in vitro antibacterial activities were evaluated by the broth microdilution. Results indicated that these compounds displayed potent antimicrobial activities in vitro against various drug-susceptible and drug-resistant Gram-positive bacteria such as Staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus, and mycoplasma. In particular, sulfapyridine analog (6c) exhibited more potent inhibitory activity against Gram-positive bacteria and mycoplasma, including Staphylococcus aureus (MIC = 0.016-0.063 μg/mL), methicillin-resistant Staphylococcus aureus (MIC = 0.016 μg/mL), Streptococcus pneumoniae (MIC = 0.032-0.063 μg/mL), Mycoplasma gallisepticum (MIC = 0.004 μg/mL), with respect to other synthesized compounds and reference drugs sulfonamide (MIC = 8-128 μg/mL) and valnemulin (MIC = 0.004-0.5 μg/mL). Furthermore, comparison between MIC values of pleuromutilin-sulfonamide hybrids 6a-f with pleuromutilin parent compound 3 revealed that these modifications at 14 position side chain of the pleuromutilin with benzene sulfonamide could greatly improve the antibacterial activity especially against Gram-positives.


Enhancing growth of Chlamydomonas reinhardtii and nutrient removal in diluted primary piggery wastewater by elevated CO2 supply.
The coupling of primary piggery wastewater as a culture medium with elevated CO2 aeration is thought to be an economically feasible option for the cultivation of microalgae. However, little information is available regarding the photosynthetic characteristics of microalgae and nutrient removal from wastewater at different CO2 concentrations. It was found that elevated CO2 aeration provided sustained growth at CO2 concentrations ranging from 5% to 15% and performed best with 5% CO2 aeration in primary piggery wastewater for Chlamydomonas reinhardtii growth. Photosynthesis, respiration, and nutrient uptake (total nitrogen and total phosphorus) were stimulated in response to CO2 enrichment, thus increasing nutrient uptake in primary piggery wastewater, particularly total nitrogen and total phosphorus. A study of carbon-concentrating mechanism-related gene expression revealed that the levels of mRNAs, such as CAH1, LCIB and HLA3, were significantly downregulated. This represents a possible method for the reconciliation of CO2-stimulated growth with mixotrophic cultivation of C. reinhardtii in diluted primary piggery wastewater.


Attitudes and practices of registered nurses toward women who have experienced abuse/domestic violence.
To compare the education, attitudes, and practices related to domestic violence of perinatal nurses from three types of practice sites. A descriptive study of responses to a questionnaire administered to a convenience sample and through a mailing. Education conferences and responses to a mailing. Two hundred seventy-five nurses in perinatal practice (87 public health, 71 hospital, 117 private office). Primary outcomes were attitudes and beliefs about domestic violence and nursing behavior when domestic violence was identified. The effects of education about domestic violence on practice and the effect of a personal/family history of domestic violence on practice were examined. Some differences were found in the attitudes and beliefs of nurses from different practice sites, but more differences were found in their behaviors. Only 54% of the total sample reported having education about domestic violence, received in formal or continuing education programs. Public health nurses were the most likely to have such education. Education affected both attitudes and behavior. In the total sample, 31% of nurses reported abuse of themselves or family members. Nursing care for women who have experienced domestic violence includes assessment and appropriate counseling. Many nurses in this study lacked education about domestic violence. The provision of education about abuse and domestic violence is a first step toward a change in nursing practice.


Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature.
Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes.


Association of PIN3 16-bp duplication polymorphism of TP53 with breast cancer risk in Mali and a meta-analysis.
Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08-4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05-3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15-1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02-1.19; P = 0.01) models. The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.


Lifesource XL-18 pedometer for measuring steps under controlled and free-living conditions.
The primary aim was to examine the criterion and construct validity and test-retest reliability of the Lifesource XL-18 pedometer (A&D Medical, Toronto, ON, Canada) for measuring steps under controlled and free-living activities. The influence of body mass index, waist size and walking speed on the criterion validity of XL-18 was also explored. Forty adults (35-74 years) performed a 6-min walk test in the controlled condition, and the criterion validity of XL-18 was assessed by comparing it to steps counted manually. Thirty-five adults participated in the free-living condition and the construct validity of XL-18 was assessed by comparing it to Yamax SW-200 (YAMAX Health & Sports, Inc., San Antonio, TX, USA). During the controlled condition, XL-18 did not significantly differ from criterion (P > 0.05) and no systematic error was found using Bland-Altman analysis. The accuracy of XL-18 decreased with slower walking speed (P = 0.001). During the free-living condition, Bland-Altman analysis revealed that XL-18 overestimated daily steps by 327 ± 118 than Yamax (P = 0.004). However, the absolute percent error (APE) (6.5 ± 0.58%) was still within an acceptable range. XL-18 did not differ statistically between pant pockets. XL-18 is suitable for measuring steps in controlled and free-living conditions. However, caution may be required when interpreting the steps recorded under slower speeds and free-living conditions.


Discovery of age-related early-stage glycated proteins based on deep quantitative serum glycated proteome analysis.
Aging is a pressing global health issue that is linked to various diseases, such as diabetes and Alzheimer's disease. It is well known that glycation plays a pathological role in the aging process and age-related diseases. Thus, it is of great significance to discover protein glycation at an early stage for monitoring and intervention in the aging process. However, the endogenous age-related early-stage glycated proteome remains insufficiently profiled. To address this research gap, our study focuses on assessing glycated proteomics profiles in the serum of mice. We employ a robust and quantitative strategy previously developed by our team, to analyze endogenous glycated proteome in serum samples of 4 age groups of mice (10 weeks, 16 weeks, 48 weeks and 80 weeks). In total, 2959 endogenous glycated peptides corresponding to 296 serum proteins are identified from 48 runs of serum samples from 16 mice across the four age groups. By comparing these glycated peptides between adjacent age groups, we discover 49 glycated peptides from 35 proteins that show significant upregulation between the 48-week and 80-week age groups. Furthermore, we identify 10 glycated proteins (or protein groups) that are significantly upregulated only between the 48-week and 80-week age groups, including lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-II (Apo A-II). These novel findings provide unique signatures for understanding the aging process and age-related diseases. By shedding light on the early-stage glycated proteome, our study contributes valuable insights that may have implications for future interventions and therapeutic approaches.


Development of Novel PET Probes for Central 2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid Receptors.
We document the development of PET probes for central AMPA receptors and their application to in vivo animal imaging. An initial screening of perampanel derivatives was performed to identify probe candidates. Despite the high autoradiographic contrast yielded by several radioligands, rat PET scans did not support their in vivo suitability. Further focused derivatization and a second screening by ex vivo LC-MS measurements led to the selection of 2-[1-(3-methylaminophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl]benzonitrile, 21a, and its analogues as candidates. [(11)C]21a was shown by autoradiography to specifically bind to the neocortex and hippocampus, consistent with AMPA receptor localization. PET imaging with [(11)C]21a demonstrated moderate uptake of radioactivity in rat and monkey brains, with the retention of radiosignals being consistent with that from the autoradiogram data, and the uptake was blocked by pretreatment with unlabeled 21a in a dose-dependent manner. The current approach has facilitated the discovery of a PET probe potentially suitable for translational research and development focused on AMPA receptors.


Vitamin B12 deficiency - why refugee patients are at high risk.
Vitamin B12 is one of the most complex vitamins. The measurement of serum levels and the significance of the results are much debated in the literature. This article discusses testing for vitamin B12 deficiency, its clinical manifestations and the possible repercussions for Australia's refugee population. Full blood count and blood film, iron studies and haemoglobinopathy studies are routinely performed for newly arrived refugees in Australia. At the Migrant Health Service in Adelaide, South Australia, a young woman was found to have a very unusual blood picture with a normal mean cell volume, despite quite severe iron deficiency and thalassaemia trait. Her vitamin B12 was found to be 75 pmol/L. The following week there arose another case of an 11 month old breastfed baby with a vitamin B12 level of 52 pmol/L, whose mother had a level of 300 pmol/L. Understanding the clinical manifestations of vitamin B12 deficiency and how it is relevant to Australia's refugee population might assist to resolve some of the difficulties that refugees face in Australia.


Chronic ocular lesions associated with bi-directional microbeam radiation therapy in an experimental rat study for therapy of C6 and F98 gliomas.
To describe the chronic ocular lesions associated with microbeam radiation therapy (MRT) in an experimental rat study. MRT was administered bi-directionally with a skin entry dose of 350 Gy. During laterally directed irradiation, the beam entered the head on the right with the center of the beam array 3 mm posterior to the center of the right eye. During irradiation in anterior-posterior direction, the right eye was almost completely in the path of the beam array. Twelve months after MRT ophthalmic examinations were completed on 37 treated (MRT+) and 16 control (MRT-) rats. Electroretinography (ERG) was completed in two MRT+ and one MRT- rat. Histopathology was performed on eyes of 16 MRT+ and 9 MRT- rats, and retinal and choroidal thicknesses were measured. Biomicroscopic and indirect ophthalmoscopic examinations revealed fundus pallor and retinal vascular attenuation in 33 of 37 right and 2 of 37 left eyes of MRT+ rats. Cataracts were present in the right eyes of 12 of 37 MRT+ rats. ERG amplitudes were reduced in the eyes of MRT+ rats. Light microscopy revealed retinal lesions ranging in severity with loss of outer to inner retinal cell layers, in 16 of 16 right and of 8 of 16 left eyes MRT+ rats. The mean right retinal thickness of MRT+ rats was reduced. Eyes within the field treated with MRT at a dose of 350 Gy develop retinal degeneration and occasionally, cataract.


Mapmodulin: a possible modulator of the interaction of microtubule-associated proteins with microtubules.
We have purified and characterized a 31-kDa protein named mapmodulin that binds to the microtubule-associated proteins (MAPs) MAP2, MAP4, and tau. Mapmodulin binds free MAPs in strong preference to microtubule-associated MAPs, and appears to do so via the MAP's tubulin-binding domain. Mapmodulin inhibits the initial rate of MAP2 binding to microtubules, a property that may allow mapmodulin to displace MAPs from the path of organelles translocating along microtubules. In support of this possibility, mapmodulin stimulates the microtubule- and dynein-dependent localization of Golgi complexes in semi-intact CHO cells. To our knowledge, mapmodulin represents the first example of a protein that can bind and potentially regulate multiple MAP proteins.


[Interferon, ribavirin and amantadine in prior nonresponders to interferon and ribavirin therapy with chronic hepatitis C (genotype 1)].
Despite advances in the treatment of chronic hepatitis C virus (HCV), the disease persists after treatment with interferon and ribavirin in a large percentage of patients and other therapeutic options are lacking. We investigated the efficacy of retreatment with antiviral therapy including amantadine. prospective and open pilot study. Thirty-nine patients with chronic HCV, genotype 1, who were nonresponders to interferon and ribavirin were included. The patients were given repeat treatment with interferon-alpha 2A (9 MU/week), ribavirin (1,000-1,200 mg/day) and amantadine (200 mg/day) for 48 weeks. HCV-RNA was undetectable in 5 patients in week 48 (12.8%) and in only 2 patients after 24 weeks of follow-up (5.1% of sustained responses). In patients with basal viremia of < 8 105 U/ml the probability of response at the end of treatment and of sustained response was 26.3 and 10.5%, respectively; in patients with elevated viremias response was 0%. In patients with chronic HCV genotype 1 without response to interferon and ribavirin, triple antiviral therapy with interferon, ribavirin and amantadine is not useful.


Insulin releasing effects of adrenocorticotropin (ACTH 1-39) and ACTH fragments (1-24 and 18-39) in lean and genetically obese hyperglycaemic (ob/ob) mice.
An excessive insulin releasing effect of adrenocorticotropic hormone (ACTH) and ACTH fragments has been considered as a possible factor contributing to the hyperinsulinaemia of genetically obese hyperglycaemic (ob/ob) mice. To investigate this possibility, plasma glucose and insulin responses of 11- to 14-week-old fed lean and ob/ob mice were examined after intraperitoneal administration of ACTH 1-39, ACTH 1-24 and ACTH 18-39, each at a dose of 25 nmol/mouse (50-115 micrograms/mouse). ACTH 1-39 produced a marked and rapid increase of plasma insulin in both lean and ob/ob mice, the effect being much greater in the ob/ob mutant (maximum increases of 5.5 +/- 1.5 and 46.1 +/- 4.1 ng/ml at 10 min in lean and ob/ob mice respectively, P less than 0.001). In lean mice plasma glucose concentrations showed a protracted decreased (maximum decrease of 3.7 +/- 0.5 mmol/l at 120 min), whereas glucose concentrations were increased (maximum increase of 4.2 +/- 1.3 mmol/l at 60 min) in ob/ob mice. ACTH 1-24 produced qualitatively similar but generally smaller effects than ACTH 1-39, while ACTH 18-39 did not significantly affect glucose and insulin concentrations. In 24 h fasted mice, ACTH 1-39 produced similar but generally smaller effects than in fed mice. The results suggest that the effects of ACTH on glucose and insulin homoeostasis are conferred by the N-terminal 1-24 sequence, and ACTH may exert acute effects which contribute to the hyperinsulinaemia and hyperglycaemia of ob/ob mice.


Dosimetric Analysis and Normal-Tissue Complication Probability Modeling of Child-Pugh Score and Albumin-Bilirubin Grade Increase After Hepatic Irradiation.
This study aimed to develop robust normal-tissue complication probability (NTCP) models for patients with hepatocellular carcinoma treated with radiation therapy (RT) using Child-Pugh (CP) score and albumin-bilirubin (ALBI) grade increase as endpoints for hepatic toxicity. Data from 108 patients with hepatocellular carcinoma treated with RT between 2008 and 2017 were evaluated, of which 47 patients (44%) were treated with proton RT. Of these patients, 29 received stereotactic body RT and 79 moderately hypofractionated RT to median physical tumor doses of 43 Gy in 5 fractions and 59 Gy in 15 fractions, respectively. A generalized Lyman-Kutcher-Berman (LKB) model was used to model the NTCP using 2 clinical endpoints, both evaluated at 3 months after RT: CP score increase of ≥2 and ALBI grade increase of ≥1 from the pre-RT baseline. Confidence intervals on LKB fit parameters were determined using bootstrap resampling. Compared with previous NTCP models, this study found a stronger correlation between normal liver volume receiving low doses of radiation (5-10 Gy) and a CP score or ALBI grade increase. A CP score increase exhibited a stronger correlation to normal liver volumes irradiated than an ALBI grade increase. LKB models for CP increase found values for the volume-effect parameter of a = 0.06 for all patients, and a = 0.02/0.09 when fit to photon/proton patients separately. Subset analyses for patients with superior initial liver functions showed consistent dose-volume effects (a = 0.1) and consistent dose-response relationships. This study presents an update of liver NTCP models in the era of modern RT techniques using relevant endpoints of hepatic toxicity, CP score and ALBI grade increase. The results show a stronger influence of low-dose bath on hepatic toxicity than those found in previous studies, indicating that RT techniques that minimize the low-dose bath may be beneficial for patients.


Acid-sensing ion channel 3 deficiency increases inflammation but decreases pain behavior in murine arthritis.
Through its location on nociceptors, acid-sensing ion channel 3 (ASIC-3) is activated by decreases in pH and plays a significant role in musculoskeletal pain. We recently showed that decreases in pH activate ASIC-3 located on fibroblast-like synoviocytes (FLS), which are key cells in the inflammatory process. The purpose of this study was to test whether ASIC-3-deficient mice with arthritis have altered inflammation and pain relative to controls. Collagen antibody-induced arthritis (CAIA) was generated by injection of an anti-type II collagen antibody cocktail. Inflammation and pain parameters in ASIC-3(-/-) and ASIC-3(+/+) mice were assessed. Disease severity was assessed by determining clinical arthritis scores, measuring joint diameters, analyzing joint histology, and assessing synovial gene expression by quantitative polymerase chain reaction analysis. Cell death was assessed with a Live/Dead assay of FLS in response to decreases in pH. Pain behaviors in the mice were measured by examining withdrawal thresholds in the joints and paws and by measuring their physical activity levels. Surprisingly, ASIC-3(-/-) mice with CAIA demonstrated significantly increased joint inflammation, joint destruction, and expression of interleukin-6 (IL-6), matrix metalloproteinase 3 (MMP-3), and MMP-13 in joint tissue as compared to ASIC-3(+/+) mice. ASIC-3(+/+) FLS showed enhanced cell death when exposed to pH 6.0 in the presence of IL-1β, which was abolished in ASIC-3(-/-) FLS. Despite enhanced disease severity, ASIC-3(-/-) mice did not develop mechanical hypersensitivity of the paw and showed greater levels of physical activity. Our findings are consistent with the hypothesis that ASIC-3 plays a protective role in the inflammatory arthritides by limiting inflammation through enhanced synoviocyte cell death, which reduces disease severity, and through the production of pain, which reduces joint use.


Spatial integration and sensitivity changes in the human rod visual system.
1. The factor by which increment threshold rises with increasing background intensity is less if the target is small than if it is large. The difference is usually attributed to a reduction in the area over which visual signals are integrated as the visual system light adapts. Recently, however, it has been argued that the difference in slope may instead be caused by an increase in the gain of the local response function with light adaptation. 2. To test this hypothesis in the rod-driven visual system, we compared monoptic, small and large target increment thresholds, and dichoptic, large target brightness matches, measured as a function of background intensity in a typical, complete achromat, who has no cone vision. 3. The dichoptic brightness matches were made using a large target of a similar intensity to the threshold intensity of the small target. If local intensity is important, the large target brightness matching curve should be more similar to the shallow, small target threshold curve. But, if changes in spatial integration are important, the brightness matching curve should be similar to the steeper, large target threshold curve. 4. The slope of the large (1.85 deg) target increment threshold functions measured with either 200 or 50 ms test flashes were steeper than those of the small (10 min of arc) target functions by 0.10 (on logarithmic co-ordinates) or about 15%. 5. The logarithmic slopes of the dichoptic brightness curves were also slightly steeper than the small target increment functions. This is contrary to the local response (only) hypothesis, which predicts that the brightness curve should have the same slope as the small target function because the luminance of the targets in the two cases is the same. 6. We conclude that there must be a change in spatial integration in the rod visual system during light adaptation, over and above that due to local gain changes.


CR digital mammography: an affordable entry.
CR full-field digital mammography (FFDM) has been used extensively in other countries, and it was one of the 4 digital mammography technologies employed in the Digital Mammographic Imaging Screening Trial. Affordability and easy integration with pre-existing mammography systems makes CR FFDM an attractive way to secure the advantages of filmless mammography imaging. CR mammography is true digital mammography--it is merely a different way of acquiring the image. The FDA has recently approved the first CR FFDM system for sale in the United States. At Gundersen Lutheran Health System (La Crosse, Wisconsin), CR FFDM is the most practical technology for realizing the potential everyday clinical benefits of filmless mammography imaging.


Alcohol-induced miR-155 and HDAC11 inhibit negative regulators of the TLR4 pathway and lead to increased LPS responsiveness of Kupffer cells in alcoholic liver disease.
Inflammation promotes the progression of alcoholic liver disease. Alcohol sensitizes KCs to gut-derived endotoxin (LPS); however, signaling pathways that perpetuate inflammation in alcoholic liver disease are only partially understood. We found that chronic alcohol feeding in mice induced miR-155, an inflammatory miRNA in isolated KCs. We hypothesized that miR-155 might increase the responsiveness of KCs to LPS via targeting the negative regulators of LPS signaling. Our results revealed that KCs that were isolated from alcohol-fed mice showed a decrease in IRAK-M, SHIP1, and PU.1, and an increase in TNF-α levels. This was specific to KCs, as no significant differences were observed in these genes in hepatocytes. We found a causal effect of miR-155 deficiency on LPS responsiveness, as KCs that were isolated from miR-155 KO mice showed a greater induction of IRAK-M, SHIP1, and suppressor of cytokine signaling 1 after LPS treatment. C/EBPβ, a validated miR-155 target, stimulates IL-10 transcription. We found a higher induction of C/EBPβ and IL-10 in KCs that were isolated from miR-155 KO mice after LPS treatment. Gain- and loss-of-function studies affirmed that alcohol-induced miR-155 directly regulates IRAK-M, SHIP1, suppressor of cytokine signaling 1, and C/EBPβ, as miR-155 inhibition increased and miR-155 overexpression decreased these genes in LPS or alcohol-pretreated wild-type KCs. HDAC11, a regulator of IL-10, was significantly increased and IL-10 was decreased in KCs that were isolated from alcohol-fed mice. Functionally, knockdown of HDAC11 with small interfering RNA resulted in an IL-10 increase in LPS or alcohol-pretreated Mϕ. We found that acetaldehyde and NF-κB pathways regulate HDAC11 levels. Collectively, our results indicate that the alcohol-induced responsiveness of KCs to LPS, in part, is governed by miR-155 and HDAC11.


Acute Ochratoxin A exposure induces inflammation and apoptosis in human embryonic kidney (HEK293) cells.
Ochratoxin A (OTA), a common contaminant of grain and fruit and known carcinogen, has been linked to impaired antioxidant response and cellular repair. The effect of OTA on inflammation in cells has not been explored. This study investigated OTA's influence on inflammatory mediators using a range of OTA concentrations (0.5 μM (sub-IC50), 1.2 μm (IC50) and 2 μm (supra-IC50)) on human embryonic kidney (HEK293) cells over 24hr. The markers of inflammation in HEK293 cells were evaluated using the following techniques: western blotting (phosphorylated (p-)NFκB (Ser536), p-IKK (Ser176/180) and p-p53 (Ser392), total NFκB, IKK, IκBα and p53), luminometry (caspases 1, 3/7, 8, 9, ATP) and ELISA to determine IL-1β levels. The results indicate increased activation of the inflammatory pathway in the sub-IC50 concentration, evidenced by significant increases in p-NFκB (p = 0.0006). The IC50 concentration indicates decreased inflammatory induction supported by decreased levels of IL-1β and caspase 1 (p = 0.0186 and p = 0.0068 respectively) with decreased IKK and increased IκBα (p = 0.0046 and p = 0.0006 respectively). Furthermore, a decrease in inflammatory pathway activation was seen in O3 (increased IκBα, p < 0.05) coupled with increased apoptosis via elevated caspase 3/7 (p = 0.0002), 8 (p = 0.0011) and 9 activity (p = 0.0002); as well as decreased ATP levels. This data suggests a new mechanism of OTA toxicity and its involvement in inflammation, kidney disease and fibrosis.


Quality of life determinants in patients of a Psychosocial Care Center for alcohol and other drug users.
Quality of life assessments in patients receiving treatment for substance dependence can serve as one predictor of response to treatment. This study aimed to identify determinants of quality of life in patients of a Psychosocial Care Center for alcohol and other drug users (CAPSad). The sample consisted of 77 patients with a diagnosis of substance dependence being treated at CAPSad for more than six months. Severity of substance dependence was assessed using the Addiction Severity Index (ASI-6), quality of life was assessed using the World Health Organization Quality of Life assessment instrument-short version (WHOQOL-BREF), and depressive symptoms were assessed by the Beck Depression Inventory (BDI). Data on CAPSad activities, psychiatric diagnoses, and medications used were collected from the medical records. Quality of life was significantly impaired in more severe cases of substance dependence and in those with more severe depressive symptoms. As for other variables, poorer quality of life was significantly associated with a greater number of years of education, unemployment, use of medications, and greater use of individual sessions with the reference professional. Linear regression analysis revealed depressive symptom severity to be an independent determinant of quality of life impairment, accounting for over 50% of the variation in physical and psychological domains. These results demonstrate the need to consider other factors, such as depressive symptoms and quality of life, in the treatment of substance dependence.


Cable analysis in quiescent and active sheep Purkinje fibres.
Cable properties of sheep cardiac Purkinje fibres were studied under resting and paced conditions. Standard micro-electrode techniques were used to apply intracellular current pulses and record the resultant voltage changes at various distances from the current input. In a parallel set of experiments, fibre dimensions were measured after freezing and serial sectioning. Fibres selected on the basis of a cylindrical appearance had approximately uniform cross-sectional diameters which varied +/- 12% along their length. Electrotonic potentials recorded at rest and in diastole (under conditions that minimized diastolic depolarization) adhered quite closely to the behaviour expected for a unidimensional cable provided voltages were recorded greater than or equal to one fibre diameter from the current source. The unidimensional space constant, input resistance, and membrane time constant were significantly larger during quiescence than in diastole. These differences were accounted for by a 90% increase in membrane resistance at rest. There was no significant change in internal longitudinal resistance nor membrane capacitance associated with activity. The voltage distribution close to the current input (i.e. within one fibre diameter) strongly deviated from the theoretical three-dimensional voltage decay expected for a homogeneous cylinder. This finding suggests that the transverse resistance to current flow is much greater than the longitudinal resistance. The anisotropic behaviour within the cardiac Purkinje fibre may explain several previous observations: (i) the lack of a relationship between conduction velocity and fibre diameter; and (ii) the much shorter liminal length for excitation in Purkinje fibres than for point-stimulated squid axons.


NO EVIDENCE OF BOTTLENECK IN THE POSTGLACIAL RECOLONIZATION OF EUROPE BY THE NOCTULE BAT (NYCTALUS NOCTULA).
During the Pleistocene, the habitat of the noctule bat (Nyctalus noctula) was limited to small refuge areas located in Southern Europe, whereas the species is now widespread across this continent. Using mtDNA (control region and ND1 gene) polymorphisms, we asked whether this recolonization occurred through bottlenecks and whether it was accompanied by population growth. Sequences of the second hypervariable domain of the control region were obtained from 364 noctule bats representing 18 colonies sampled across Europe. This yielded 108 haplotypes that were depicted on a minimum spanning tree that showed a starlike structure with two long branches. Additional sequences obtained from the ND1 gene confirmed that the different parts of the MST correspond to three clades which diverged before the Last Glacial Maximum (18,000 yrC14 BP), leading to the conclusion that the noctule bat survived in several isolated refugia. Partitioning populations into coherent geographical groups divided our samples (φCT = 0.17; P = 0.01) into a group of highly variable nursing colonies from central and eastern Europe and less variable, isolated colonies from western and southern Europe. Demographic analyses suggest that populations of the former group underwent demographic expansions either after the Younger Dryas (11,000-10,000 yrC14 BP), assuming a fast mutation rate for HV II, or during the Pleistocene, assuming a conventional mutation rate. We discuss the fact that the high genetic variability (h = 0.69-0.96; π = 0.006-0.013) observed in nursing colonies that are located some distance from potential Pleistocene refugia is probably due to the combined effect of rapid evolution of the control region in growing populations and a range shift of noctule populations parallel to the recovery of forests in Europe after the last glaciations.


Use of shoulder flexors to achieve isometric elbow extension in C6 tetraplegic patients during weight shift.
The anterior deltoid muscle has been found to be active during elbow extension in normal volunteers and in C6 tetraplegic patients lacking a functional triceps. Using surface electromyography (EMG) on normal volunteers and on patients with spinal cord injury (SCI) at the C6 motor level, we evaluated whether the anterior deltoid and biceps brachii muscles are active during closed chain elbow extension in a simulated weight shift position. Thirteen normal volunteers performed isometric contractions at 5 submaximal levels of force ranging from 4-25 kg. Six SCI patients performed isometric contractions at force levels of 20%, 40%, 60%, 80% and 100% maximum voluntary contraction (MVC). Surface EMG over the right biceps, triceps, and anterior deltoid muscles was recorded for each participant and the root mean square (rms) electromyographic activity level for each muscle was determined at each level of force. Statistical analyses using repeated ANOVA with Tukey HSD post-hoc tests were performed for each level of force. The results indicated increasing rms activity of the triceps and anterior deltoid muscles with increasing force in normal volunteers to a significant degree (P < 0.05). SCI patients showed significant increasing activity of the anterior deltoid with increasing force, but showed minimal triceps rms activity. In both groups, the biceps showed minimal rms activity. SCI patients exhibited significantly greater rms activity of the anterior deltoid at low force compared with normal volunteers. The results suggest that the anterior deltoid aids in isometric elbow extension during a simulated weight shift maneuver.