The Relationships between the Rotational Axes of the Distal Femur in the Arthritic Caucasian Knee: A Magnetic Resonance Imaging Analysis.
Four distal femoral axes have been described to aid in the accuracy of transverse plane component alignment in total knee arthroplasty (TKA). These include the surgical epicondylar axis (SEA), the posterior condylar axis (PCA), and the anteroposterior (AP) axis. Therefore, the primary purpose of this study is to identify the axial femoral relationship with the least variation in a Caucasian population awaiting TKA for osteoarthritis. Secondarily, we further plan to determine if these femoral axis relationships differ with respect to sex or preoperative coronal alignment. These anatomic relationships were measured using preoperative magnetic resonance imaging, which was performed within 2 months of the planned operation date for patient specific instrumentation templating. In terms of our primary outcome, the mean SEA/AP angle was 92.8 degrees (standard deviation [SD]: 2.5 degrees), the mean PCA/AP angle was 95.7 degrees (SD: 2.8 degrees), and the mean PCA/SEA angle was 3.4 degrees (SD: 1.8 degrees). Overall, the PCA/SEA relationship had the smallest variance, while the PCA/AP had the most variance for all comparisons. In terms of our secondary outcome, there was no statistical difference between femoral axis relationships based on preoperative coronal plane alignment. In terms of sex differences, the PCA/SEA was significantly higher in female knees compared with males. Females had a PCA/SEA relationship of 4.7 degrees (SD: 1.3 degrees) compared with 2.6 degrees (SD: 1.2 degrees) for males (p < 0.05). By using the PCA/AP axes, the AP axis was externally rotated by 96.7 degrees (SD: 2.3 degrees) in females, compared with 93.2 degrees (SD: 2.1 degrees) in males, from the PCA. In conclusion, our results demonstrate that the PCA/SEA relationship should be used to determine axial rotation in TKA as it shows the least variation. When using the PCA, approximately 5 degrees of external rotation for Caucasian women and 3 degrees of external rotation for the Caucasian men should be dialed into the femoral cutting block to restore anatomic axial rotation. Further evaluation is needed to determine to role of preoperative coronal alignment on distal femoral axial alignment.


Asymmetric protonation of ketone enolates using chiral beta-hydroxyethers: acidity-tuned enantioselectivity.
New chiral hydroxyethers 1a-f were prepared for asymmetric protonation of achiral enolates prepared from prochiral ketones. The enantioselectivity of protonation was highly dependent upon the acidity of the chiral alcohols, the highest enantioselectivity (90% ee) being achieved with 3,5-dichloro-substituted beta-hydroxyether 1c. A salt-free enolate generated from trimethylsilyl enol ether 4 provided product of the highest ee. Unlike other reagents, chloro-substituted alcohols provided almost consistent enantioselections throughout the reaction temperatures examined (-25 to -98 degrees C). Protonation of other aromatic ketones showed selectivity similar to that of 2-methyl-1-tetralone.


Important clinicopharmacological aspects of captopril.
With a brief description of the physiological role of the renin-angiotensin-aldosterone system in the regulation of blood pressure the most important clinicopharmacological aspects of the converting enzyme inhibitor, captopril, is outlined. Hemodynamic and humoral effects, pharmacokinetics, indications, contraindications, dosage, side effects, drug interactions and usage in diagnostic procedures of captopril is described. The possibility of captopril therapy in children is also discussed.


Intravenous magnesium supplementation during cisdiammine-dichloroplatinum administration prevents hypomagnesemia.
Ten patients with disseminated testicular cancer were studied during 3 cycles of 20 mg/m2/day x 5 d CDDP combined with bleomycin and vinblastine or etoposide. Five of the patients (= group A) received 0.4 mmol KCl/kg/day and 0.3 mmol MgCl2/kg/day; the other five (= group B) received only KCl intravenously during the CDDP infusions. In group A no decrease of serum and red blood cell Mg concentration was noted. In group B the serum Mg concentration decreased from 0.84 +/- 0.04 mmol/l to 0.57 +/- 0.10 (p less than 0.001) on day 47, to 0.64 +/- 0.08 (p less than 0.005) on day 50 and to 0.72 +/- 0.02 (p less than 0.05) on day 57. The Mg concentration in the red blood cells decreased, but not significantly in group B. Furthermore, the fractional calcium excretion in group B was significantly lower than in group A during the CDDP infusions.


Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency in vitro and in vivo.
Photoacoustic flow cytometry is one of the most effective approaches to detect "alien" objects in the bloodstream, including circulating tumor cells, blood clots, parasites, and emboli. However, the possibility of detecting high-amplitude signals from these objects against the background of blood depends on the parameters of the laser pulse. So, the dependencies of photoacoustic signals amplitude and number on laser pulse energy (5-150 μJ), pulse length (1, 2, 5 ns), and pulse repetition rate (2, 5, 10 kHz) for the melanoma cells were investigated. First, the PA responses of a melanoma cell suspension in vitro were measured to directly assess the efficiency of converting laser light into an acoustic signal. After it, the same dependence with the developed murine model based on constant rate melanoma cell injection into the animal blood flow was tested. Both in vivo and in vitro experiments show that signal generation efficiency increases with laser pulse energy above 15 μJ. Shorter pulses, especially 1 ns, provide more efficient signal generation as well as higher pulse rates. A higher pulse rate also provides more efficient signal generation, but also leads to overheating of the skin. The results show the limits where the photoacoustic flow cytometry system can be effectively used for the detection of circulating tumor cells in undiluted blood both for in vitro experiments and for in vivo murine models.


Sources of innovation: an assessment of intellectual property.
An analysis of US Food and Drug Administration (FDA)-approved new molecular entities (NMEs) reveals dynamism in terms of new innovation. An assessment of the first patent for each drug shows that the pharmaceutical industry, particularly large, established companies in North America, tend to dominate the field. Over the past 10-15 years, European and Asian organizations have begun to close the gap. A dynamic inventive environment in drug discovery is suggested by the fact that NMEs for biologics or awarded to biotechnology companies often have inventors from the pharmaceutical and academic sectors. Whereas inventors continue to found biotechnology companies at a steady rate, recent trends suggest these inventors more often come from the private sector.


Interventions aimed at improving reading success: an evidence-based approach.
There is a consensus among researchers about the critical elements for effective reading instruction. These elements are the integration of explicit instruction in the alphabetic principle, reading for meaning, and opportunity to learn. These critical elements are present in classroom instruction that prevents reading difficulties as well as effective small-group and one-on-one interventions. Research on effective classroom instruction and reading interventions is described, and the case is argued that the most effective intervention is provided early--in kindergarten through 2nd grade--rather than after 3rd grade, and allows for sufficient intensity, duration, and supportiveness that no child is left behind. Policy implications for changes in (a) the way learning disabilities are identified and (b) the content of professional development of teachers are discussed.


N-Terminal Truncated Aβ4-42 Is a Substrate for Neprilysin Degradation in vitro and in vivo.
In sporadic Alzheimer's disease (AD), an imbalance between production and clearance of amyloid-β (Aβ) peptides seems to account for enhanced Aβ accumulation. The metalloprotease neprilysin (NEP) is an important Aβ degrading enzyme as shown by a variety of in vitro and in vivo studies. While the degradation of full-length Aβ peptides such as Aβ1-40 and Aβ1-42 is well established, it is less clear whether NEP is also capable of degrading N-terminally truncated Aβ species such as the common variant Aβ4-42. In the present report, we confirmed the degradation of Aβ4-x species by neprilysin using in vitro digestion and subsequent analysis using gel-based assays and mass spectrometry. By crossing Tg4-42 mice expressing only Aβ4-42 peptides with homozygous NEP-knock-out mice (NEP-/-), we were able to demonstrate that NEP deficiency increased hippocampal intraneuronal Aβ levels and aggravated neuron loss in the Tg4-42 transgenic mouse model of AD.


Knowledge, perceptions and effects of Ebola virus disease outbreak on the pig value chain in the agro-pastoralist district of Luwero, Central Uganda.
Ebola Virus Disease (EVD) outbreaks have a significant impact on the health and wellbeing, and livelihoods of communities. EVD response interventions particularly affect the food value chain, and income security of pig farmers in agro-pastoral communities. Despite the enormous effort of EVD response interventions, there is paucity of information towards EVD among those involved in the pig value chain, as well as the effect of EVD outbreaks on the pig value chain. This study therefore, assessed the knowledge, perceptions on the occurrence of Ebola and its effects on the pig value chain in the agro-pastoral district of Luweero, Central Uganda. A cross sectional study was conducted in two parishes of Ssambwe and Ngalonkulu, Luwero district. A total of 229 respondents were included in the study. Structured questionnaires, key informant interviews and focus group discussions were conducted to collect data. Quantitative data was analysed using SPSS version 22 while qualitative data was analysed using thematic content analysis. Of the 229 respondents, 95.6% could recall the occurrence of the last EVD outbreak in their locality. About 24.5% associated EVD with touching pigs or eating pork. Regarding knowledge, 194 (84.7%) correctly associated EVD with handling Ebola infected persons, 191 (83.4%) with migration of people from endemic areas, 148 (64.9%) eating monkey meat, 127 (55.5%) with eating bats, and 198 (64.9%) with conducting public meetings where there is an Ebola infected person. Out of 142 farmers, 55 (38.7%) believed that Ebola outbreaks affected demand and sale of pigs. The EVD outbreak significantly led to a reduction in the average number of pigs sold (P = 0.001), the average number of pigs bought by traders (P = 0.04), and the number of pigs sold/ slaughtered by butcher men at pork eating places (P = 0.03). This study showed that EVD outbreak negatively affected the pig value chain i.e., the demand and supply of pigs and pork. Therefore, there is need to sensitize the stakeholders in the pig value chain on EVD in order to minimize the negative economic impacts associated with EVD outbreaks.


Angiosarcoma of the heart - a diagnostic pitfall.
Primary tumours of the heart are extremely rare. Sarcomas are considered to be the most frequent histological type. This study presents two cases with a two-week and two-month history of fatigue, fever and shortness of breath. In both cases, cardiac tumours with pericardial effusion were diagnosed by means of echocardiography, being responsible for the above-mentioned symptoms. At the beginning of the diagnostic process, sarcomas seemed to be the likeliest cause of these symptoms. Establishment of the histopathological diagnosis based on the tumour biopsy turned out to be very difficult, and this delayed further therapeutic procedures.


Rationale and Description of Right Ventricle-Protective Ventilation in ARDS.
Pulmonary vascular dysfunction is associated with ARDS and leads to increased right-ventricular afterload and eventually right-ventricular failure, also called acute cor pulmonale. Interest in acute cor pulmonale and its negative impact on outcome in patients with ARDS has grown in recent years. Right-ventricular function in these patients should be closely monitored, and this is helped by the widespread use of echocardiography in intensive care units. Because mechanical ventilation may worsen right-ventricular failure, the interaction between the lungs and the right ventricle appears to be a key factor in the ventilation strategy. In this review, a rationale for a right ventricle-protective ventilation approach is provided, and such a strategy is described, including the reduction of lung stress (ie, the limitation of plateau pressure and driving pressure), the reduction of PaCO2 , and the improvement of oxygenation. Prone positioning seems to be a crucial part of this strategy by protecting both the lungs and the right ventricle, resulting in increased survival of patients with ARDS. Further studies are required to validate the positive impact on prognosis of right ventricle-protective mechanical ventilation.


Effect of salts, solvents and buffer on miRNA detection using DNA silver nanocluster (DNA/AgNCs) probes.
MicroRNAs (miRNAs) are small regulatory RNAs (size ~21 nt to ~25 nt) which regulate a variety of important cellular events in plants, animals and single cell eukaryotes. Especially because of their use in diagnostics of human diseases, efforts have been directed towards the invention of a rapid, simple and sequence selective detection method for miRNAs. Recently, we reported an innovative method for the determination of miRNA levels using the red fluorescent properties of DNA/silver nanoclusters (DNA/AgNCs). Our method is based on monitoring the emission drop of a DNA/AgNCs probe in the presence of its specific target miRNA. Accordingly, the accuracy and efficiency of the method relies on the sensitivity of hybridization between the probe and target. To gain specific and robust hybridization between probe and target, we investigated a range of diverse salts, organic solvents, and buffer to optimize target sensing conditions. Under the newly adjusted conditions, the target sensitivity and the formation of emissive DNA/AgNCs probes were significantly improved. Also, fortification of the Tris-acetate buffer with inorganic salts or organic solvents improved the sensitivity of the DNA/AgNC probes. On the basis of these optimizations, the versatility of the DNA/AgNCs-based miRNA detection method can be expanded.


[Translated article] Design and validation of two instruments to analyze and evaluate the formal quality in the informed consent process of clinical trials with medicinal products.
The activity of sponsors and Ethics Committees for Research with medicines has increased in recent years. The objective was to design and validate 2 instruments to analyze and evaluate the formal quality of the patient information sheet and the informed consent form of clinical trials with drugs, in accordance with the legislation. Design (Guideline for good clinical practice and European and Spanish regulations); validation (Delphi method and expert consensus: concordance ≥ 80%); reliability (inter-observer method, Kappa index). 40 patient information sheets/informed consent forms were evaluated. Very good concordance was obtained in both checklists (k ≥ 0.81, p b 0.001). The final versions consisted of checklist-patient information sheet: 5 sections, 16 items and 46 sub-items; and checklist-informed consent form: 11 items. The instruments developed are valid, reliable and facilitate the analysis, evaluation, and decision-making on the patient information sheets/informed consent forms of clinical trials with drugs.


Mechanism for giant enhancement of transport induced by active fluctuations.
Understanding the role of active fluctuations in physics is a problem in statu nascendi appearing both as a hot topic and a major challenge. The reason for this is the fact that they are inherently nonequilibrium. This feature opens a landscape of phenomena yet to be explored that are absent in the presence of thermal fluctuations alone. Recently a paradoxical effect has been briefly communicated in which a free-particle transport induced by active fluctuations in the form white Poisson shot noise can be enormously boosted when the particle is additionally subjected to a periodic potential. In this work we considerably extend the original predictions and investigate the impact of statistics of active noise on the occurrence of this effect. We construct a toy model of the jump-relaxation process that allow us to identify different regimes of the free-particle transport boost and explain their corresponding mechanisms. Moreover, we formulate and interpret the conditions for statistics of active fluctuations that are necessary for the emergence of giant enhancement of the free-particle transport induced by the periodic potential. Our results are relevant not only for microscopic physical systems but also for biological ones such as, e.g., living cells where fluctuations generated by metabolic activities are active by default.


Highly Efficient and Stable CdZnSeS/ZnSeS Quantum Dots for Application in White Light-Emitting Diode.
Semiconductor quantum dots (QDs) are a promising luminescent phosphor for next-generation lightings and displays. In particular, QD-based white light-emitting diodes (WLEDs) are considered to be the candidate light sources with the most potential for application in displays. In this work, we synthesized quaternary/ternary core/shell alloyed CdZnSeS/ZnSeS QDs with high bright emission intensity. The QDs show good thermal stability by performing high temperature-dependent experiments that range from 295 to 433 K. Finally, the WLED based on the CdZnSeS/ZnSeS QDs exhibits a luminous efficiency (LE) of 28.14 lm/W, an external quantum efficiency (EQE) of 14.86%, and a warm bright sunlight close to the spectrum of daylight (Commission Internationale de l'éclairage (CIE) coordinates 0.305, 0.371). Moreover, the photoluminescence (PL) intensity, LE, EQE, and correlated color temperature (CCT) of as-prepared QD WLED remained relatively stable with only slight changes in the luminescence stability experiment.


Challenges in Assessing Outcomes among Infants of Pregnant HIV-Positive Women Receiving ART in Uganda.
Since 2012, the WHO recommends lifelong ART with TDF+FTC/3TC+EFV for all HIV-positive pregnant and breastfeeding women (Option B-plus). In this analysis we describe the proportion of early and late transmission in mothers with high retention in Kampala, Uganda. We included 700 pregnant women from January 2012 to August 2014 with a follow-up extended to August 2016; the median age was 31 years (IQR: 26-35), 36.3% in WHO stage 3/4; median CD4 count was 447 cells/μL (IQR: 301-651) and 73.3% were already on ART for a median time of 28 (IQR: 10-57) months; 52% infants were male and median weight was 3.2 Kg (IQR: 2.5-3.5). Five hundred and sixty-five (80.7%) infants had at least one test for HIV; 22 (3.1%) infants died, all with unknown serostatus; 3 tested positive at week 6 and one additional at months 12 and 18. Two of the mothers of the 4 HIV-positive infants were ART-naïve at the time of pregnancy. We report very low documented HIV transmission comparable with those reported in clinical trials settings; however, demonstrating the efficacy of Option B-plus in terms of averted transmission in routine settings is challenging since high proportion of infants do not have documented HIV tests.


In vivo biological effects of stereotactic radiosurgery: a primate model.
Single-fraction, closed skull, small-volume irradiation (radiosurgery) of intact intracranial structures requires accurate knowledge of radiation tolerance. We have developed a baboon model to assess the in vivo destructive radiobiological effects of stereotactic radiosurgery. Three baboons received a single-fraction, 150-Gy lesion of the caudate nucleus, the thalamus, or the pons using the 8-mm diameter collimator of the gamma unit. Serial standard neurodiagnostic tests (neurological examination, computed tomographic scan, magnetic resonance imaging, stable xenon-enhanced computed tomographic scan of cerebral blood flow, somatosensory and brain stem evoked potentials, and myelin basic protein levels of cerebrospinal fluid) were compared with preoperative studies. Magnetic resonance imaging revealed the development of a lesion at the target site between 45 and 60 days after irradiation. Deterioration of the brain stem evoked potentials preceded imaging changes when the lesion encroached on auditory pathways. Myelin basic protein levels increased subsequent to imaging changes. Postmortem neuropathological examination confirmed a well-demarcated radionecrosis of the target volume. The baboon model appears to be an excellent method to study the in vivo biological effects of radiosurgery.


Evaluation of Health Care Disparities for Individuals with Intellectual and Developmental Disabilities in Ohio.
The purpose of the study was to determine the acute and long term services and supports (LTSS) utilization, cost of health care and disparities in access of care for individuals with Intellectual and Developmental Disabilities (IDD). Individuals with IDD on a waiver (receiving Medicaid-funded LTSS in community settings) compared to non-IDD individuals on a waiver control group were compared using Ohio Medicaid claims data from calendar year 2013. Results found the IDD Waiver population had lower utilization rates for emergency department visits, hospital admissions, and hospital readmissions within 30 days compared to the Non-IDD Waiver population and lower PMPM expenditures across all medical service categories except pharmacy. However, the IDD Waiver population possessed greater PMPM costs for LTSS and therefore greater overall costs of care. Furthermore, 94% of IDD Waiver individuals had an episode of care for neurological conditions, with the second most frequent episode of care being for mental health services. The two most frequent episodes of care for individuals in the Non-IDD Waiver group were for conditions related to treatment (medical/surgical) and musculoskeletal conditions. The goal of this research was to investigate the health care needs of individuals with IDD that may vary from other long term care populations. The differences in health care needs for individuals with IDD require health systems and care management that is tailored to the sub-population, with an emphasis on treatment for neurological and mental health conditions. The typical focus of care management efforts on reducing unnecessary utilization of hospital services may be less relevant to the IDD Waiver population. The results of this study will be used to make recommendations regarding the unique health care needs of individuals with IDD.


An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13.
The hypothesis that increased ADAMTS13 (a disintegrin and metalloprotease with thrombospondin repeats) activity or increased susceptibility of von Willebrand factor (VWF) to proteolysis by ADAMTS13 may underlie type I von Willebrand disease (VWD) in some patients was investigated. Plasma from 4 patients with type I VWD was cryoprecipitated. ADAMTS13 activity in the VWF-poor cryodepleted fraction was assessed by incubation with purified VWF; susceptibility to proteolysis of the VWF in the VWF-rich cryoprecipitate was assessed by incubation with a normal, group O cryodepleted plasma. ADAMTS13 activity was similar in all 4 type I VWD cryodepleted plasmas and comparable to a normal control plasma. In contrast, the VWF of one patient showed increased susceptibility to proteolysis by ADAMTS13. Investigation of additional family members indicated that increased susceptibility was heritable, but it did not track uniquely with type I VWD. Sequence analysis of VWF exon 28 indicated that increased susceptibility to proteolysis tracked with the "G" allele of the A/G polymorphism at position 24/1282, encoding the amino acid polymorphism Tyr/Cys1584 ("G" = Cys1584). A prospective study of 200 individuals yielded 2 Tyr/Cys1584 heterozygotes; for both, plasma VWF showed increased susceptibility to proteolysis. The finding that an amino acid polymorphism in VWF may influence susceptibility to ADAMTS13 has potentially significant implications in diverse areas.


Calpain localization changes in coordination with actin-related cytoskeletal changes during early embryonic development of Drosophila.
Calpain, a calcium-dependent intracellular protease, was identified in Drosophila melanogaster. Drosophila calpain has an amino acid sequence highly homologous to those of mammalian calpains and exhibits a distinct domain structure consisting of cysteine protease and calcium-binding domains. Specific antibodies raised against a recombinant calpain fragment were used to identify the localization of calpain in developing Drosophila embryos. Calpain was first detected near the anterior pole and in posterior region of the embryo just after fertilization. The anterior calpain disappeared during the cleavage cycles. On the other hand, the posterior calpain moved to the posterior pole when polar buds were formed, and condensed just below the pole cells. At cleavage cycles 8 and 9, when nuclei reached the egg surface, calpain was localized between the nuclei at the surface beneath the precleavage furrows. Co-staining experiments with anti-actin antibody revealed that calpain condenses specifically at the edge of and between actin caps that underlie the plasma membrane immediately above each nucleus. These results indicate that calpain is involved in the dynamic changes in the embryonic cytoskeleton, especially actin-related structures, during early embryogenesis prior to cellularization.


Alcoholism and homicide with respect to the classification systems of Lesch and Cloninger.
Worldwide criminal statistics show a disproportionately high incidence of violent offences committed under the influence of alcohol. A psychopathological subtyping of alcohol dependence in offenders who committed homicide has mainly been related to impulsive and dissocial personalities up to now. In an investigation on 48 alcohol-dependent offenders who committed homicide, a subtyping according to the multidimensional classification systems of Lesch and Cloninger has now been conducted for the first time. In Lesch's classification, there was a high incidence of homicides committed by type II and type III subjects with the comorbidity anxiety and cyclothymia. While type III offenders were more often repeat offenders, there was a remarkably high rate of first offenders among type II subjects (Chi-squared test; chi(2) = 30.0, df = 3, P < 0.001). With respect to Lesch's typology, the blood alcohol concentrations did differ significantly in the group of offenders (Kruskal-Wallis, chi(2) = 18.3, df = 3, P < 0.001), whereas the blood alcohol concentration of type II offenders at the time of offence was significantly lower than in type III offenders (Mann-Whitney-U, Z = -3.47; P = 0.001). Regarding to the Cloninger's typology, no significant differences in the aforementioned parameters could be found. An excessive noradrenergic reaction of anxiety offenders with initial withdrawal is discussed as a possible explanatory model.


Age-related changes in pharyngeal and supraglottic sensation.
As one ages, sensory discrimination in the oral cavity progressively diminishes, and dysphagia and aspiration are more likely to occur. Whether similar age-related laryngeal and pharyngeal sensory abnormalities exist and contribute to dysphagia and aspiration is unknown. The purpose of this study was to determine if sensory discrimination in the area innervated by the superior laryngeal nerve diminishes with increasing age. By applying a previously described new device and technique that utilizes brief air pulse stimulation of the anterior wall of the pyriform sinus, sensory discrimination can be reliably determined. We carried out 672 trials in 56 healthy adults divided into three age groups: 20 to 40, 41 to 60, and 61 to 90 years of age. Overall, the average sensory discrimination was 2.30 +/- 0.50 mm Hg. In subjects 20 to 40 years of age, sensory discrimination was 2.07 +/- 0.20 mm Hg, while in subjects 61 to 90 years of age, sensory discrimination was 2.68 +/- 0.63 mm Hg (p < .05). There also was a statistically significant difference between the 41- to 60-year and 61- to 90-year age groups (p < .05). Progressive diminution in pharyngeal and supraglottic sensitivity with increasing age might be a contributing factor in the development of dysphagia and aspiration in the elderly.


Unsaturated binuclear cyclopentadienylrhenium carbonyl derivatives: metal-metal multiple bonds and agostic hydrogen atoms.
The cyclopentadienylrhenium carbonyls Cp 2Re 2(CO) n (Cp = eta (5)-C 5H 5; n = 5, 4, 3, 2) have been studied by density functional theory. The global minima for the Cp 2Re 2(CO) n ( n = 5, 4, 3, 2) derivatives are predicted to be the singly bridged structure Cp 2Re 2(CO) 4(mu-CO) with a formal Re-Re single bond; the doubly semibridged structure Cp 2Re 2(CO) 4 with a formal ReRe double bond; the triply bridged structure Cp 2Re 2(mu-CO) 3 with a formal ReRe triple bond; and the doubly bridged structure Cp 2Re 2(mu-CO) 2, respectively. The first three of these predicted structures have been realized experimentally in the stable compounds (eta (5)-C 5H 5) 2Re 2(CO) 4(mu-CO), (eta (5)-Me 5C 5) 2Re 2(CO) 4 and (eta (5)-Me 5C 5) 2Re 2(mu-CO) 3. In addition, structures of the type Cp 2Re-Re(CO) n with both rings bonded only to one metal and unknown in manganese chemistry are also found for rhenium but at energies significantly above the global minima. The unsaturated Cp 2Re-Re(CO) n structures ( n = 4, 3, 2) have agostic Cp hydrogen atoms forming C-H-Re bridges to the unsaturated Re(CO) n group with a Re-H distance as short as 2.04 A.


Mucosal exudation associated with a pulmonary delayed-type hypersensitivity reaction in the mouse. Role for the tachykinins.
In this study, the role for sensory neuropeptides in the induction of pulmonary inflammation associated with a delayed-type hypersensitivity (DTH) reaction in the mouse lung was investigated. Dinitrofluorobenzene (DNFB) was used as the sensitizing hapten and dinitrobenzene sulfonic acid was used as the intranasal challenge. Two hours after the challenge, no hapten-specific differences were observed between vehicle- and DNFB-sensitized mice. However, mucosal exudation and leukocyte accumulation (mononuclear leukocytes and neutrophils) were enhanced in the DNFB group 24 h after the challenge. In additional experiments we investigated whether the sensory nerves and specific sensory neuropeptides play a role in this pulmonary DTH reaction. The selective NK1 antagonist (RP 67580; 5.10(-9) mol/mouse), administered 5 min before and 1 h after the challenge, suppressed mucosal exudation and leukocyte accumulation in the airways 24 h after the challenge. In contrast, the selective calcitonin gene-related peptide (CGRP) antagonist, CGRP8-37 (5.10(-9) mol/mouse) had no effect on the pulmonary DTH reaction. Surprisingly, the depletion of all sensory neuropeptides resulted in an enhancement of mucosal exudation in vehicle- and DNFB-sensitized mice 24 h after the challenge. In conclusion, these results demonstrate that the tachykinins are important in mediating mucosal exudation and leukocyte accumulation associated with the DTH reaction in mouse airways. However, the findings in neuropeptide-depleted mice suggest that the sensory nerves may also play a protective role in mouse airways.


Promotion and guidance of neural network formation on SU-8 photoresist microchannels adjusted with multilayer films.
Induction of neural stem/progenitor cells (NSPCs) and establishment of neural network are important issues on neural engineering. In this work, a platform was designed to control and evaluate the differentiation of NSPCs, neurite direction, and to promote the neurite outgrowth. Polyelectrolyte multilayer (PEM) films provide surface properties by and have been used to regulate NSPCs differentiation in our previous study. Herein, a culture platform composed of SU-8 microchannel and PEM films was designed to achieve the goal of promoting NSPCs differentiation and to evaluate the effect of PEM films on the guidance of neural network formation. In this culture platform, NSPCs were induced into functional neurons, and neural network formation was accomplished on ITO glass-PEM films successfully.


Exploring the boundaries of additivity: mixtures of NADH: quinone oxidoreductase inhibitors.
The activity of mitochondrial complex I of the electron transport chain (ETC) is known to be affected by an extraordinarily large number of diverse xenobiotics, and dysfunction at complex I has been associated with a variety of disparate human diseases, including those with potentially environmentally relevant etiologies. However, the risks associated with mixtures of complex I inhibitors have not been fully explored, and this warrants further examination of potentially greater than additive effects that could lead to toxicity. A potential complication for the prediction of mixture effects arises because mammalian mitochondrial complex I has been shown to exist in two distinct dynamic conformations based upon substrate availability. In this study, we tested the accepted models of additivity as applied to mixtures of rotenone, deguelin, and pyridaben, with and without substrate limitation. These compounds represent both natural and synthetic inhibitors of complex I of the ETC, and experimental evidence to date indicates that these inhibitors share a common binding domain with partially overlapping binding sites. Therefore, we hypothesized that prediction of their mixtures effects would follow dose addition. Using human hepatocytes, we analyzed the effects of these mixtures at doses between 0.001 and 100 μM on overall cellular viability. Analysis of the dose-response curves resulting from challenge with all possible binary and ternary mixtures revealed that the appropriate model was not clear. All of the mixtures tested were found to be in agreement with response addition, but only rotenone plus deguelin and the ternary mixture followed dose addition. To determine if conformational regulation via substrate limitation could improve model selection and our predictions, we tested the models of additivity for the binary and ternary mixtures of inhibitors when coexposed with 2-deoxy-d-glucose (2-DG), which limits NADH via upstream inhibition of glycolysis. Coexposure of inhibitors with 2-DG did facilitate model selection: Rotenone plus pyridaben and the ternary mixture were in sole agreement with dose addition, while deguelin plus pyridaben was in sole agreement with response addition. The only ambiguous result was the agreement of both models with the mixture of rotenone plus deguelin with 2-DG, which may be explained by deguelin's well-known affinity for protein kinase B (Akt) in addition to complex I. Thus, our findings indicate that predictive models for mixtures of mitochondrial complex I inhibitors appear to be compound specific, and our research highlights the need to control for dynamic conformational changes to improve our mechanistic understanding of additivity with these inhibitors.


The role of surgery in primary syphilis of the anus.
Surgery has no role in the treatment of primary (infectious) syphilis of the anorectum. In this paper, we describe four patients who presented directly to the surgeon complaining of localized anal lesions. In three patients, the chancre was excised and in one patient the correct diagnosis was made prior to surgery. Rectal pain, which we attributed to secondary infection, was the chief complaint in three patients. Two patients also complained of tender lymphadenopathy. Darkfield examination is the most important diagnostic technique and penicillin remains the drug of choice. When treating diseases of the anorectum, the surgeon must maintain a high index of suspicion and a constant awareness of the manifold presentations of primary syphilis.


Major traumatic and septic genital injuries.
Major injuries to the testicles, penis, and genital skin from trauma and infection were seen in 62 patients over a 6-year period (1977 to 1983). Urethral injuries were excluded. In the past blunt testicle injuries were infrequently diagnosed and surgically ignored because of large surrounding hematomas. With the use of real-time ultrasound, 17 of 18 cases of testicle rupture were correctly diagnosed preoperatively. Surgical repair resulted in testicle salvage in 16 patients. Penetrating testicle injuries resulted in a high orchiectomy rate secondary to the infrequently described but recognized entity of self-emasculation in transsexuals. Penile rupture from blunt injuries (8) was successfully repaired and complete function was recovered. Penetrating penile injuries (4) were extensive and involved the urethra in two cases; full function returned after reconstruction. Major skin loss of the penis and/or scrotum (19) occurred from necrotizing fasciitis, burns, avulsion and penetrating injuries. Early debridement, bowel and urinary diversion followed by penile skin grafting, thigh pouches to protect testicles, and scrotal reconstruction resulted in acceptable cosmetic and functional results in all cases of major skin loss.


High-fat diet modifies expression of hepatic cellular senescence gene p16(INK4a) through chromatin modifications in adult male rats.
Liver is the crucial organ as a hub for metabolic reactions. p16(INK4a) is a well-established cyclin-dependent kinase (CDK) inhibitor that plays important role in the molecular pathways of senescence, which lead to irreversible cell cycle arrest with secretion of proinflammatory cytokines and mitochondrial dysfunction. This study tested the hypothesis that cellular senescence regulated by p16(INK4a) is associated with high-fat diet in adult male rats. Sprague Dawley rats were fed a high-fat (HF) diet or a control (C) diet for 9 weeks after weaning. At 12 weeks of age, liver samples of male rats were collected to investigate the key genes and liver physiological status. Both mRNA and protein expression level of cellular senescence marker, p16(INK4a), was increased significantly in HF group when compared to C group. A decrease of tri-methylated histone H3 lysine 27 (H3K27Me3) in the coding region of p16(INK4a) was observed. On the other hand, mRNA and protein expression of another inhibitor of cyclin-dependent kinase, p21(Cip1), was decreased significantly in HF group; however, no significant chromatin modification was found in this gene. Histological analysis demonstrated hepatic steatosis in HF group as well as severe fat accumulation. Our study demonstrated that HF diet regulated cellular senescence marker p16(INK4a) through chromatin modifications, which may promote hepatic fat accumulation and steatosis.


Ultrabroadband photonic structures to achieve high-performance daytime radiative cooling.
If properly designed, terrestrial structures can passively cool themselves through radiative emission of heat to outer space. For the first time, we present a metal-dielectric photonic structure capable of radiative cooling in daytime outdoor conditions. The structure behaves as a broadband mirror for solar light, while simultaneously emitting strongly in the mid-IR within the atmospheric transparency window, achieving a net cooling power in excess of 100 W/m(2) at ambient temperature. This cooling persists in the presence of significant convective/conductive heat exchange and nonideal atmospheric conditions.


Next-generation sequencing (NGS) for assessment of microbial water quality: current progress, challenges, and future opportunities.
Water quality is an emergent property of a complex system comprised of interacting microbial populations and introduced microbial and chemical contaminants. Studies leveraging next-generation sequencing (NGS) technologies are providing new insights into the ecology of microbially mediated processes that influence fresh water quality such as algal blooms, contaminant biodegradation, and pathogen dissemination. In addition, sequencing methods targeting small subunit (SSU) rRNA hypervariable regions have allowed identification of signature microbial species that serve as bioindicators for sewage contamination in these environments. Beyond amplicon sequencing, metagenomic and metatranscriptomic analyses of microbial communities in fresh water environments reveal the genetic capabilities and interplay of waterborne microorganisms, shedding light on the mechanisms for production and biodegradation of toxins and other contaminants. This review discusses the challenges and benefits of applying NGS-based methods to water quality research and assessment. We will consider the suitability and biases inherent in the application of NGS as a screening tool for assessment of biological risks and discuss the potential and limitations for direct quantitative interpretation of NGS data. Secondly, we will examine case studies from recent literature where NGS based methods have been applied to topics in water quality assessment, including development of bioindicators for sewage pollution and microbial source tracking, characterizing the distribution of toxin and antibiotic resistance genes in water samples, and investigating mechanisms of biodegradation of harmful pollutants that threaten water quality. Finally, we provide a short review of emerging NGS platforms and their potential applications to the next generation of water quality assessment tools.


Nitric oxide inhibits autophagy and promotes apoptosis in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide. The expression of nitric oxide synthase (NOS) and the inhibition of autophagy have been linked to cancer cell death. However, the involvement of serum nitric oxide (NO), the expression of NOS and autophagy have not been investigated in HCC. In the present study, we first established that the NO level was significantly higher in hepatitis B virus-related HCC than in the liver cirrhosis control (53.60 ± 19.74 vs 8.09 ± 4.17 μmol/L, t = 15.13, P < 0.0001). Using immunohistochemistry, we found that the source of NO was at least partially attributed to the expression of inducible NOS and endothelial NOS but not neuronal NOS in the liver tissue. Furthermore, in human liver cancer cells, NO-induced apoptosis and inhibited autophagy. Pharmacological inhibition of autophagy also induced apoptosis, whereas the induction of autophagy could ameliorate NO-induced apoptosis. We also found that NO regulates the switch between apoptosis and autophagy by disrupting the Beclin 1/Vps34 association and by increasing the Bcl-2/Beclin 1 interaction. Overall, the present findings suggest that increased NOS/NO promotes apoptosis through the inhibition of autophagy in liver cancer cells, which may provide a novel strategy for the treatment of HCC.


A fluid-dynamic interpretation of the asymmetric motion of singly flagellated bacteria swimming close to a boundary.
The singly flagellated bacterium, Vibrio alginolyticus, moves forward and backward by alternating the rotational direction of its flagellum. The bacterium has been observed retracing a previous path almost exactly and swimming in a zigzag pattern. In the presence of a boundary, however, the motion changes significantly, to something closer to a circular trajectory. Additionally, when the cell swims close to a wall, the forward and backward speeds differ noticeably. This study details a boundary element model for the motion of a bacterium swimming near a rigid boundary and the results of numerical analyses conducted using this model. The results reveal that bacterium motion is apparently influenced by pitch angle, i.e., the angle between the boundary and the swimming direction, and that forward motion is more stable than backward motion with respect to pitching of the bacterium. From these results, a set of diagrammatic representations have been created that explain the observed asymmetry in trajectory and speed between the forward and backward motions. For forward motion, a cell moving parallel to the boundary will maintain this trajectory. However, for backward motion, the resulting trajectory depends upon whether the bacterium is approaching or departing the boundary. Fluid-dynamic interactions between the flagellum and the boundary vary with cell orientation and cause peculiarities in the resulting trajectories.


Protein engineering through tandem transamidation.
Semisynthetic proteins engineered to contain non-coded elements such as post-translational modifications (PTMs) represent a powerful class of tools for interrogating biological processes. Here, we introduce a one-pot, chemoenzymatic method that allows broad access to chemically modified proteins. The approach involves a tandem transamidation reaction cascade that integrates intein-mediated protein splicing with enzyme-mediated peptide ligation. We show that this approach can be used to introduce PTMs and biochemical probes into a range of proteins including Cas9 nuclease and the transcriptional regulator MeCP2, which causes Rett syndrome when mutated. The versatility of the approach is further illustrated through the chemical tailoring of histone proteins within a native chromatin setting. We expect our approach will extend the scope of semisynthesis in protein engineering.


Platelets and atherosclerosis.
This discussion has centered about the consequences of the loss of endothelial integrity and how the blood platelet behaves under these circumstances. It is clear that the platelet can function as a participant in the development of the atherosclerotic lesion, can be an important contribution to mechanisms that operate to produce vascular spasm, and ultimately can play a major role in the development of thrombosis at the site of the complicated end-stage atherosclerotic lesion.


Multi-attribute decision-making: Use of scoring methods to choose the best form of dietary fat supplement in pregnant Saanen goats.
Nutritional manipulation with functional nutrients like polyunsaturated fatty acids can boost milk production efficiency in dairy farming. It is important to consider the animal's physiological periods, especially the second half of the first pregnancy for mammary gland development. By considering multiple factors and comparing them, multi-attribute decision-making (MADM) can be utilized to conduct further assessments and select the best diet for the animals. Forty primiparous Saanen does, from the last 2 months of pregnancy up to 4 months of lactation, have been assigned to four iso-energetic and iso-nitrogenous diets. Four dietary groups included: no external sources of fat (negative control, CT), saturated palm oil (positive control), roasted soybeans (omega-6, SB) and extruded flaxseed (omega-3, FS). Twenty-two performance criteria such as feed intake, milk yield and composition, body weight, blood metabolites and hormones, the milk fatty acid profile, as well as morphological and histological measurements of the mammary gland, in the form of least-square means, were considered. A decision-making tool was used to select the best form of fat supplements in late pregnancy and early lactation diets, to improve lactation performance in Saanen goats. For this purpose, a MADM method was applied to determine the order of preference similarity to the ideal solution. According to the score of this method, the FS group had the highest coefficients (0.689), and the CT group had the lowest coefficients (0.281). Incorporating flaxseed into the diets of Saanen goats during late pregnancy and early lactation is a valuable strategy for enhancing milk performance. This supplement is recommended as a source of fat. Additionally, the implementation of decision-making tools, such as the MADM method in animal science, can significantly improve management decision-making processes by reducing both time and cost. This presents a new avenue for making well-informed decisions.


[Gene fusion of egfp & kan and recombinant plasmid construction by red mediated in vivo homologous recombination].
Recombineering, a new genetic engineering technology based on high efficiency in vivo homologous recombination, can be used in target DNA knock-in, knock-out and gene cloning. In the process of gene subcloning mediated by Recombineering technique, high-quality target DNA fragments were difficult to obtain using in vitro overlapping PCR,therefore the efficiency of in vivo homologous recombination was severely interrupted. To solve this problem, some technology improvements have been established based on the principle of Red recombinases. The PCR DNA fragments of egfp and kan genes with complementary sequences on the end of each fragment were co-introduced into a pcDNA3.1 vector and Red recombinases containing E. coli DY331 host cells by electroporation. A recombinant plasmid pcDNA3.1-egfp-kan was screened directly by antibiotic marker. The positive rates can reach to 45%. The EGFP gene expression of pcDNA3.1-egfp-kan can be observed by transient transfection of 293 eukaryotic cells.


Effects of dietary combination of chromium and biotin on egg production, serum metabolites, and egg yolk mineral and cholesterol concentrations in heat-distressed laying quails.
Chromium picolinate is used in the poultry diet because of its antistress effects in addition to the fact that the requirement for it is increased during stress. This study was conducted to determine if the negative effects of high ambient temperature (34 degrees C) on egg production, egg quality, antioxidant status, and cholesterol and mineral content of egg yolk could be alleviated by combination of chromium picolinate and biotin (0.6/2.0; Diachrome, as formulated by Nutrition 21 Inc.), in laying Japanese quails (Coturnix coturnix japanica). Quails (n= 240; 50 d old) were divided into 8 groups, 30 birds per group. The quails were fed either a basal diet or the basal diet supplemented with 2, 4, or 8 mg of Diachrome/kg diet. Birds were kept at 22 degrees C and 53% relative humidity (RH). At 14 wk of age, the thermoneutral (TN) group remained in the same temperature as at the beginning of experiment, whereas the heat stress (HS) group was kept in an environment-controlled room (34 degrees C and 41% RH) for 3 wk. Heat exposure decreased performance when the basal diet was fed (p = 0.001). Diachrome supplementation at 4 and 8 mg/kg diet, increased feed intake (p = 0.05), egg production (p = 0.05), feed efficiency (p = 0.01), egg weight (p = 0.05), and Haugh unit (p = 0.01) in quails reared under heat stress conditions. Heat exposure increased concentrations of serum malondialdehyde (MDA) (p = 0.001), glucose, and cholesterol (p = 0.01), which were elevated by supplemental Diachrome (p < or = 0.05). Egg yolk Cr, Zn, and Fe (p = 0.01) concentrations increased linearly, whereas MDA and cholesterol concentrations decreased (p = 0.05) as dietary Diachrome supplementation increased in HS groups. Similar effects of supplementation on serum levels of glucose and cholesterol (p = 0.05) and egg yolk concentrations of cholesterol (p = 0.05) and Cr (p = 0.01) were observed in TN groups. No significant differences in other values were observed in the TN groups. Results of the present study suggest that supplementation with Diachrome protects the quail by reducing the negative effects of heat stress.


Evaluation of the validity of the different arms of the ASAS set of criteria for axial spondyloarthritis and description of the different imaging abnormalities suggestive of spondyloarthritis: data from the DESIR cohort.
The Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis (SpA) allows classification of patients with ('imaging' arm) and without ('clinical' arm) imaging abnormalities of the sacroiliac joints. To compare the phenotype of early axial SpA with regard to the two arms of the ASAS axial SpA criteria. Demographics, clinical and biological features of SpA, disease activity, severity parameters, and imaging abnormalities at the sacroiliac and spine levels were compared, in the two arms of the ASAS axial SpA criteria, in the patients of the French cohort of early SpA. Of the 615 patients analysed, 435 (70.7%) met the ASAS criteria (262 (60.2%) and 173 (39.8%) in the imaging and clinical arms, respectively). There were no major differences in the characteristics of the two groups except that those in the imaging arm were more likely to be younger, male and have higher concentrations of C-reactive protein. Imaging abnormalities other than those meeting the ASAS criteria for the imaging arm (ie, x-ray-determined structural damage or MRI-revealed inflammatory changes in the sacroiliac joint (SIJ)) were observed (MRI-SIJ structural damage (55.0% vs 3.5%), MRI-spine inflammatory changes (35.1% vs 12.9%), MRI-spine structural damage (10.3% vs 5.3%) and x-ray-syndesmophytes (11.8% vs 5.3%)) in the imaging versus clinical arm, respectively. Our study confirms the external validity of the clinical arm of the ASAS criteria. It is notable that many patients in the clinical arm showed other imaging changes in SIJs and spine.


Design and performance of a hyperspectral camera for full-face in vivo imaging.
Red, green, blue color photography is a mature technology and a powerful tool for the evaluation and understanding of the way an object reflects light and its related optical properties, but color photography fails to give a complete picture of these effects due to its inherent lack of spectral resolution. In this work, we update the L'OREAL reference device for skin color measurement, the Chromasphere, by replacing its current color camera system with an imaging spectrometer. This imaging spectrometer must provide a spatial resolution on par with the previous color cameras and a spectral resolution commensurate with a spectroradiometer while also achieving a time resolution suitable for in vivo studies of the human face. Due to these requirements, common spatial scanning techniques are not suitable for this application, and so we utilized a spectral-scanning approach based on a tunable liquid-crystal birefringent filter. We present the design and performance tests of a working prototype that is capable of measuring the spectrum in each of 4 MP with a nominal spectral resolution of 10 nm across the wavelength range from 420 to 730 nm in a total imaging time of less than 10 s. We cross-compared the spectral and color measurements obtained with this prototype, an industry-standard spectroradiometer, and a charge-coupled device color camera in order to assess the prototype's performance, and the results of this comparison show that our prototype is capable of taking spectral measurements near enough in quality to those of a spectroradiometer to successfully bridge the divide between such devices and conventional color cameras. Doing so, this instrument opens new possibilities for studies of complex in vivo phenomena that neither non-imaging spectrometers nor conventional cameras can pursue.


Investigations into the kinetics and thermodynamics of Sb(III) adsorption on goethite (alpha-FeOOH).
This study reports thermodynamic and kinetic data of Sb(III) adsorption from single metal solutions onto synthetic aqueous goethite (alpha-FeOOH). Batch equilibrium sorption experiments were carried out at 25 degrees C over a Sb:Fe molar range of 0.005-0.05 and using a goethite concentration of 0.44 g Fe/L. Experimental data were successfully modelled using Langmuir (R2 > or = 0.891) and Freundlich (R2 > or = 0.990) isotherms and the following parameters were derived from triplicate experiments: Kf = 1.903 +/- 0.030 mg/g and 1/n = 0.728 +/- 0.019 for the Freundlich model and b = 0.021 +/- 0.003 L/mg and Qmax = 61 +/- 8 mg/g for the Langmuir model. The thermodynamic parameters determined were the equilibrium constant, Keq =1.323 +/- 0.045, and the Gibb's free energy, DeltaG0 = -0.692 +/- 0.083 kJ/mol. The sorption process is very fast. At a Sb:Fe molar ratio of 0.05, 40-50% of the added Sb is adsorbed within 15 min and a steady state is achieved. The experimental data also suggest that desorption can occur within 24 h of reaction due to the oxidation of Sb(III) on the goethite surface. Finally, calculated pH of the aqueous solution using MINTEQ2 agrees well with the measured pH (3.9 +/- 0.7; n = 30). At pH 4, the dominant Sb species in solution are Sb(OH)3 and HSbO2 which both likely adsorb as inner sphere complexes to the positively charged goethite surface.


A comparison of two reciprocating instruments using bending stress and cyclic fatigue tests.
The aim of this study was to comparatively evaluate the bending resistance at 45º, the static and dynamic cyclic fatigue life, and the fracture type of the WaveOne (Dentsply Maillefer, Ballaigues, Switzerland) 25-08 and Reciproc (VDW, Munich, Germany) 25-08 instruments. A total of 60 nickel-titanium (NiTi) instruments (30 Reciproc and 30 WaveOne) from three different lots, each of which was 25 mm in length, were tested. The bending resistance was evaluated through the results of a cantilever-bending test conducted using a universal testing machine. Static and dynamic cyclic fatigue testing was conducted using a custom-made device. For the static and dynamic tests, a cast Ni-Cr-Mo-Ti alloy metal block with an artificial canal measuring 1.77 mm in diameter and 20.00 mm in total length was used. A scanning electron microscope was used to determine the type of fracture. Statistical analyses were performed on the results. The WaveOne instrument was less flexible than the Reciproc (p < 0.05). The Reciproc instrument showed better resistance in the static and dynamic cyclic fatigue tests (p < 0.05). The transverse cross-section and geometry of the instruments were important factors in their resistance to bending and cyclic fracture. Both of the instruments showed ductile-type fracture characteristics. It can be concluded that the Reciproc 25-08 instrument was more resistant to static and dynamic cyclic fatigue than the WaveOne 25-08 instrument, while the WaveOne 25-08 instrument was less flexible. Bending and resistance to cyclic fracture were influenced by the instruments' geometries and transverse cross-sections. Both of the instruments showed ductile-type fracture characteristics.


Gerontological research in China: The role of anthropological inquiry.
One fifth of the world's elderly population lives in China. Until recently political restrictions have hindered the conduct of research particularly ethnography. This piece provides an overview of recent research findings by Western scholars and of ethnographic research in progress in the areas of demography, state policy, age stratification, family planning, residence patterns, inter-generational transfers, patrilineality, health, illness, long term care, social welfare, and mortuary ritual. It analyzes the potential contributions of ethnography in this area.


Virus hijacking of host epigenetic machinery to impair immune response.
Epigenetic modifications, such as DNA hypermethylation, histone acetylation/methylation, or nucleosome positioning, result in differential gene expression. These modifications can have an impact on various pathways, including host antiviral immune responses. In this review, we summarize the current understanding of epigenetic modifications induced by viruses to counteract host antiviral immune responses, which are crucial for establishing and maintaining infection of viruses. Finally, we provide insights into the potential use of epigenetic modulators in combating viral infections and virus-induced diseases.


Parents' perception and willingness to maintain provider care continuity for their children under universal health coverage.
Provider continuity of care (COC) is closely related to patient outcome in pediatrics. However, no study has investigated how parents perceive the importance of COC and whether their perceptions affect their willingness to make effort to maintain good provider COC for their children under universal health coverage. A cross-sectional survey was conducted between August 2017 and February 2018 across 6 different practices: 2 medical centers, 2 regional hospitals, 1 district hospital, and 1 clinic (n = 825). Parents' and caregivers' perceptions and perceived value of COC were evaluated using 7 items. The contingent valuation method was used to estimate willingness to pay and spend time. Of all respondents, only 47% (n = 394) were willing to spend >30 minutes to have their children see the regular physician if the regular physician relocated. Approximately 38% (n = 302) respondents were willing to pay more than New Taiwan Dollar (NT$) 300 per month to maintain provider COC. The perception that high COC is important was associated with willingness to spend more time for maintaining high provider COC. Parents' perception of COC does not affect their willingness to pay for maintaining high provider COC for their children but affects their willingness to spend more time to maintain COC.


Interventional Radiologic Treatment of Hepatocellular Carcinoma.
The current treatment modalities for patients with hepatocellular carcinoma are discussed in this review. Hepatocellular carcinoma arises in up to 90% of cirrhotic patients, mainly due to chronic viral hepatitis and alcohol abuse. Nearly two-thirds of all patients with hepatocellular carcinoma are diagnosed at advanced stages, thus causing problems with treatment. Regardless of the stage of the disease, interventional radiology offers both curative and palliative treatment options in the management of this disease. Selecting the most appropriate treatment requires an initial staging assessment and detailed clinical and radiologic workup. Treatment allocation is based on liver function, size and number of tumors, macrovascular invasion, and extrahepatic spread of disease.


Acquisition and use of DNA-based HLA typing data in bone marrow registries.
The increased use of DNA-based typing techniques has improved the accuracy and reliability of HLA types assigned to patients requiring an allogeneic bone marrow transplant and their potential donors, facilitating better donor selection. The benefits of this technology, which will completely replace serologic typing within the next few years, have not yet been fully exploited since the typing information obtained in the form of DNA sequence polymorphisms is presently converted to an HLA allelic type for submission to a registry. Furthermore, within the registry, the allelic type may be further converted to a serologic antigen for use in the search and match process. Because the current nomenclature system makes selection of donors who are likely to provide optimal matches difficult, it is critical that DNA-based HLA typing data be recorded by registries as sequence polymorphisms tested as positive or negative rather than interpreted HLA types and that searching and matching utilize these polymorphisms. Until this transition is complete, we will not fully utilize this powerful HLA typing technology to best serve those patients seeking unrelated donors.


Transcriptional Responses of Candida albicans to Antimicrobial Peptide MAF-1A.
Candida albicans is a major fungal pathogen in humans. Novel antifungal agents are urgent demanded due to the challenges of the resistance. Antimicrobial peptides (AMPs) are critical components of the innate immune system against pathogenic microorganism infection. MAF-1A is a novel cationic AMP that comes from Musca domestica and is effective against C. albicans, but the antifungal mechanism remains unclear. In this study, we performed a transcriptomics analysis in C. albicans using RNA-seq technique under the treatment of MAF-1A. A total of 5654 genes were identified. Among these, 1032 were differentially expressed genes (DEGs), including 575 up-regulated genes and 457 down-regulated genes. In these DEGs, genes encoding ergosterol metabolism and fatty acid biosynthesis were identified to be significantly down-regulated, while genes associated with oxidative stress response and cell wall were identified to be significantly up-regulated. Using pathway enrichment analysis, 12 significant metabolic pathways were identified, and ribosome, oxidative phosphorylation, citrate cycle were mainly involved. The results revealed that MAF-1A induces complex responses in C. albicans. This study provides evidence that MAF-1A may inhibit the growth through affect multi-targets in C. albicans cells.


Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1-Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort.
Little evidence is available for the incidence of chronic kidney disease (CKD) and rate of estimated glomerular filtration rate (eGFR) decrement among Asians with low body weight who are susceptible to tenofovir disoproxil fumarate (TDF) nephrotoxicity. In this 12-year observational cohort in Tokyo, we examined 1383 treatment-naïve HIV-1-infected Asians [720 started TDF-containing (TDF group) and 663 started non-TDF-containing (control) combination antiretroviral therapy (cART)]. The CKD incidence was calculated, and the effect of TDF use on CKD development was estimated using logistic regression. The eGFR slopes, before and after cART initiation, were estimated using mixed-effects linear spline models. Most patients were males (median weight, 62.6 kg; 83% started ritonavir-boosted protease inhibitors; median observation duration, 5.08 years). CKD developed in 150 patients (10.8%), with an incidence of 20.6 per 1000 person-years [confidence interval (95% CI), 17.6-24.2]. None developed end-stage renal disease. TDF use was associated with CKD [odds ratio (OR), 1.8; 95% CI, 1.00-3.13; p = 0.052]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (-3.8, -5.5, and -9.0 mL/min/1.73 m2, respectively; p < 0.0001). The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (-26.4 vs. -7.4 mL/min/1.73 m2/year in the control). In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from -0.44 to -2.11 mL/min/1.73 m2/year; p = 0.010), whereas in the control, the difference was not significant. For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR declines.


Health care costs and utilization prior to diagnosis of antineutrophil cytoplasmic antibody vasculitis in Medicare beneficiaries.
BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA) vasculitis (AV) is a complex group of autoimmune disorders affecting blood vessels in multiple organ systems. Delays in diagnosis are common because AV symptoms can be nonspecific and present heterogeneously. This may result in increased health care utilization in the months preceding diagnosis. OBJECTIVE: To examine whether Medicare beneficiaries with AV experienced increased health care utilization and costs in the year before the first diagnosis recorded in claims, relative to beneficiaries without AV. METHODS: This retrospective cohort study used 2015-2016 Medicare Part A/B claims and Part D prescription drug data. Beneficiaries with newly diagnosed AV were identified by having 1 or more inpatient claims or 2 or more noninpatient claims 7 or more days apart in 2016 with an International Classification of Diseases, Tenth Revision, Clinical Modification code for AV, with no AV claims in the year prior. Beneficiaries with AV were matched 1:1 on age and sex to beneficiaries without any diagnoses for any type of systemic vasculitis in 2016. Beneficiaries with Part A/B coverage (AB, n = 1,460) and Part A/B/D coverage (ABD, n = 3,252) were analyzed separately. We estimated generalized linear mixed models with a negative binomial distribution to compare health care costs and utilization by AV status. RESULTS: Beneficiaries with AV had approximately 3 times higher Medicare Part A/B payments (incidence rate ratio [95% CI]: AB: 2.94 [2.44-3.53]; ABD: 2.95 [2.64-3.29]) and 2.5 times higher beneficiary Part A/B payments (AB: 2.47 [2.14-2.84]; ABD: 2.62 [2.40-2.87]) vs beneficiaries without AV. Beneficiaries with AV experienced significantly higher utilization across all categories, with the largest differences observed in hospital outpatient visits (AB: 2.69 [2.22-3.27]; ABD: 3.08 [2.73-3.47]). CONCLUSIONS: In the year prior to AV diagnosis, Medicare beneficiaries have significantly higher health care costs and utilization than beneficiaries without AV. DISCLOSURES: Dr Huang was supported by the University of North Carolina and GlaxoSmithKline Health Outcomes Fellowship during the time of the study and reports current employment at Horizon Therapeutics, Deerfield, IL. Dr Nguyen received predoctoral funding through a fellowship appointment sponsored by Bristol Myers Squibb during the time of the study and reports current employment at GlaxoSmithKline, Collegeville, PA. Dr Derebail receives personal fees from Travere Therapeutics, Bayer, and UpToDate, outside of the submitted work. The views expressed are those of the authors and do not represent the views of the Department of Veteran Affairs. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Maximum likelihood estimation in meta-analytic structural equation modeling.
Meta-analytic structural equation modeling (MASEM) involves fitting models to a common population correlation matrix that is estimated on the basis of correlation coefficients that are reported by a number of independent studies. MASEM typically consist of two stages. The method that has been found to perform best in terms of statistical properties is the two-stage structural equation modeling, in which maximum likelihood analysis is used to estimate the common correlation matrix in the first stage, and weighted least squares analysis is used to fit structural equation models to the common correlation matrix in the second stage. In the present paper, we propose an alternative method, ML MASEM, that uses ML estimation throughout. In a simulation study, we use both methods and compare chi-square distributions, bias in parameter estimates, false positive rates, and true positive rates. Both methods appear to yield unbiased parameter estimates and false and true positive rates that are close to the expected values. ML MASEM parameter estimates are found to be significantly less bias than two-stage structural equation modeling estimates, but the differences are very small. The choice between the two methods may therefore be based on other fundamental or practical arguments. Copyright © 2016 John Wiley & Sons, Ltd.


Endovaginal sonography for the early diagnosis of intrauterine and ectopic pregnancies.
Endovaginal sonography, together with beta-HCG titre, was used to diagnose ectopic pregnancy in 58 patients. Transabdominal ultrasound failed to conclude this diagnosis. The data from endovaginal sonography revealed the presence of a gestational sac in all 15 patients with normal pregnancies at a beta-HCG level of 1042 mIU/ml. Of the 23 patients with pathological pregnancies only 61% had an intrauterine gestational sac. Only 15% of the 20 patients with ectopic pregnancies showed an increase in beta-HCG greater than 66% in 48 h, while in normal pregnancy, this increase was found in 71% of the patients. The endovaginal findings of the ectopic gestation revealed a complex adnexal mass in 55%, a cystic mass in 30% and fluid in the cul-de-sac in 20%. The diagnostic indices of adnexal and cul-de-sac sonographic findings in the ectopic group further improved specificity and positive predictive accuracy. The detection of ectopic versus intrauterine gestation showed a high sensitivity of 95%, a specificity of 100%, a positive predictability of 100% and a negative predictability of 97%. The data confirm the value and reliability of endovaginal and cul-de-sac sonography, combined with measurement of the beta-HCG level in the early diagnosis of ectopic pregnancy. This combined approach not only makes the differentiation between normal and extrauterine gestation more accurate but also helps to avoid unnecessary diagnostic laparoscopy and hospitalization.


Adaptive paradigms for mapping phonological regions in individual participants.
Phonological encoding depends on left-lateralized regions in the supramarginal gyrus and the ventral precentral gyrus. Localization of these phonological regions in individual participants-including individuals with language impairments-is important in several research and clinical contexts. To localize these regions, we developed two paradigms that load on phonological encoding: a rhyme judgment task and a syllable counting task. Both paradigms relied on an adaptive staircase design to ensure that each individual performed each task at a similarly challenging level. The goal of this study was to assess the validity and reliability of the two paradigms, in terms of their ability to consistently produce left-lateralized activations of the supramarginal gyrus and ventral precentral gyrus in neurologically normal individuals with presumptively normal language localization. Sixteen participants were scanned with fMRI as they performed the rhyme judgment paradigm, the syllable counting paradigm, and an adaptive semantic paradigm that we have described previously. We found that the rhyme and syllable paradigms both yielded left-lateralized supramarginal and ventral precentral activations in the majority of participants. The rhyme paradigm produced more lateralized and more reliable activations, and so should be favored in future applications. In contrast, the semantic paradigm did not reveal supramarginal or precentral activations in most participants, suggesting that the recruitment of these regions is indeed driven by phonological encoding, not language processing in general. In sum, the adaptive rhyme judgment paradigm was effective in localizing left-lateralized phonological encoding regions in individual participants, and, in conjunction with the adaptive semantic paradigm, can be used to map individual language networks.


Reactivity of adrenaline toward alkoxyl radicals and carbonyl triplet states.
The reactivities of adrenaline toward hydrogen abstraction by the tert-butoxyl radical and the excited triplet state of benzophenone have been examined in solution using laser flash photolysis techniques. The rate constants obtained in acetonitrile-rich solvents are 13 and 1.5 x 10(8) M(-1) s(-1) for benzophenone triplet and the tert-butoxyl radical, respectively. Adrenaline is a better hydrogen donor than phenol, but not as efficient as alpha-tocopherol.


Non-Hermitian degeneracies and unidirectional reflectionless atomic lattices.
Light propagation in optical lattices of driven cold atoms exhibits non-Hermitian degeneracies when the first-order modulation amplitudes of real and imaginary parts of the probe susceptibility are manipulated to be balanced. At these degeneracies, one may observe complete unidirectional reflectionless light propagation. This strictly occurs with no gain and can be easily tuned and fully reversed as supported by the transfer-matrix calculations and explained via a coupled-mode analysis.


Atomic-resolution crystal structure of thioredoxin from the acidophilic bacterium Acetobacter aceti.
The crystal structure of thioredoxin (AaTrx) from the acetic acid bacterium Acetobacter aceti was determined at 1 A resolution. This is currently the highest resolution crystal structure available for any thioredoxin. Thioredoxins facilitate thiol-disulfide exchange, a process that is expected to be slow at the low pH values encountered in the A. aceti cytoplasm. Despite the apparent need to function at low pH, neither the active site nor the surface charge distribution of AaTrx is notably different from that of Escherichia coli thioredoxin. Apparently the ancestral thioredoxin was sufficiently stable for use in A. aceti or the need to interact with multiple targets constrained the variation of surface residues. The AaTrx structure presented here provides a clear view of all ionizable protein moieties and waters, a first step in understanding how thiol-disulfide exchange might occur in a low pH cytoplasm, and is a basis for biophysical studies of the mechanism of acid-mediated unfolding. The high resolution of this structure should be useful for computational studies of thioredoxin function, protein structure and dynamics, and side-chain ionization.


[Systematic review on the characteristics of acute gastroenteritis outbreaks caused by sapovirus].
Objective: To understand the epidemiological and etiological characteristics of outbreaks on acute gastroenteritis caused by sapovirus (SaV) worldwide. Methods: Literature about the outbreaks on acute gastroenteritis caused by SaV were retrieved from the databases including WanFang, CNKI, PubMed and Web of Science after evaluation. Time, geography, setting and population distributions of outbreaks, transmission mode, SaV genotype and clinical characteristics of the patients were analyzed. Results: A total of 34 papers about SaV were included, involving 146 outbreaks occurred between October 1976 and April 2016. In these papers, 138 outbreaks were reported on the related months. All these outbreaks occurred in northern hemisphere. SaV outbreaks occurred all year around, but mainly in cold season, the incidence was highest in December (25 outbreaks) and lowest in in August (2 outbreaks). Most outbreaks were reported by Japan, followed by Canada, the United States of America and the Netherlands. There were 141 outbreaks for which the occurring settings were reported, child-care settings were most commonly reported setting (48/141, 34.04%), followed by long-term care facility (41/141, 29.08%) and hospital (16/141, 11.35%). Clinical symptoms of 1 704 cases in 31 outbreaks were reported, with the most common symptom was diarrhea (1 331/1 704, 78.12%), followed by nausea (829/1 198, 69.20%), abdominal pain (840/1 328, 63.25%), vomiting (824/1 704, 48.36%) and fever (529/1 531, 34.53%). Genotypes of SaV were determined for 119 outbreaks. GⅠ(51/119, 42.86%) and GⅣ (45/119, 37.82%) were predominant. The outbreaks of GⅣ SaV increased suddenly in 2007, and the outbreaks of GⅠ SaV mainly occurred in 2008 and during 2011-2013. Conclusions: SaV outbreaks were reported mainly by developed countries, with most outbreaks occurred in cold season, in child-care settings and long term care facility. GⅠ and GⅣ were the most common genotypes of SaV. Prevention and control of SaV outbreak in China seemed relatively weak, and it is necessary to conduct related training and to strengthen the SaV outbreak surveillance in areas where service is in need.


Note: A temperature-stable low-noise transimpedance amplifier for microcurrent measurement.
Temperature stability and noise characteristics often run contradictory in microcurrent (e.g., pA-scale) measurement instruments because low-noise performance requires high-value resistors with relatively poor temperature coefficients. A low-noise transimpedance amplifier with high-temperature stability, which involves an active compensation mechanism to overcome the temperature drift mainly caused by high-value resistors, is presented. The implementation uses a specially designed R-2R compensating network to provide programmable current gain with extra-fine trimming resolution. The temperature drifts of all components (e.g., feedback resistors, operational amplifiers, and the R-2R network itself) are compensated simultaneously. Therefore, both low-temperature drift and ultra-low-noise performance can be achieved. With a current gain of 1011 V/A, the internal current noise density was about 0.4 fA/√Hz, and the average temperature coefficient was 4.3 ppm/K at 0-50 °C. The amplifier module maintains accuracy across a wide temperature range without additional thermal stabilization, and its compact size makes it especially suitable for high-precision, low-current measurement in outdoor environments for applications such as electrochemical emission supervision, air pollution particles analysis, radiation monitoring, and bioelectricity.


Impact of allelic dropout on evidential value of forensic DNA profiles using RMNE.
Two methods are commonly used to report on evidence carried by forensic DNA profiles: the 'Random Man Not Excluded' (RMNE) approach and the likelihood ratio (LR) approach. It is often claimed a major advantage of the LR method that dropout can be assessed probabilistically. In this article, a new RMNE measure is proposed that like-wise accounts for allelic dropout in an observed forensic DNA profile. We discuss the necessary calculations, underline their simplicity and provide a tool for performing the calculations.


Modeling of inhibitor-metalloenzyme interactions and selectivity using molecular mechanics grounded in quantum chemistry.
We investigated the binding properties of the metalloprotease inhibitors hydroxamate, methanethiolate, and methylphosphoramidate to a model coordination site occurring in several Zn2+ metalloproteases, including thermolysin. This was carried out using both the SIBFA (sum of interactions between fragments ab initio-computed) molecular mechanics and the SCF/MP2 procedures for the purpose of evaluating SIBFA as a metalloenzyme modeling tool. The energy-minimized structures were closely similar to the X-ray crystallographic structures of related thermolysin-inhibitor complexes. We found that selectivity between alternative geometries and between inhibitors usually stemmed from multiple interaction components included in SIBFA. The binding strength sequence is hydroxamate > methanethiolate > or = methylphosphoramidate from multiple interaction components included in SIBFA. The trends in interaction energy components, rankings, and preferences for mono- or bidentate binding were consistent in both computational procedures. We also compared the Zn2+ vs. Mg2+ selectivities in several other polycoordinated sites having various "hard" and "soft" qualities. This included a hexahydrate, a model representing Mg2+/Ca2+ binding sites, a chlorophyll-like structure, and a zinc finger model. The latter three favor Zn2+ over Mg2+ by a greater degree than the hydrated state, but the selectivity varies widely according to the ligand "softness." SIBFA was able to match the ab initio binding energies by < 2%, with the SIBFA terms representing dispersion and charge-transfer contributing the most to Zn2+/Mg2+ selectivity. These results showed this procedure to be a very capable modeling tool for metalloenzyme problems, in this case giving valuable information about details and limitations of "hard" and "soft" selectivity trends.


Out in the cold: the hypothermic heart response.
We present an interesting case of a 49-year-old woman with hypothermia and associated Osborn waves (also called J waves) on ECG. She was found on the floor of her home and difficult to arouse. On arrival to the emergency department (ED), her rectal temperature was 87.5°F. ECG showed Osborn waves in diffuse leads. She was intubated in the ED and was started on vasopressor support for hypotension refractory to intravenous fluid boluses. She was transferred to the critical care unit for continued respiratory and cardiovascular support. With active external rewarming her core body temperature continued to improve. Blood pressure also improved and vasopressor was tapered off. She was extubated and was transferred to the medical floor for continued supportive care. Osborn waves on ECG resolved within 12 h of achieving normal range body temperature. The patient was eventually discharged home with medical follow-up.


Resection of a cardiac aneurysm in an infant with anomalous origin of the left coronary artery from the pulmonary trunk.
We describe an infant with an anomalous left coronary artery arising from the pulmonary trunk leading to myocardial ischaemia and development of an apical aneurysm of the left ventricle. Clinical presentation in general is based on myocardial hypoperfusion resulting in ischaemia and infarction. When presenting in infancy, however, then the features, as in our patient, may be tachypnea, dyspnea, failure to thrive and irritability, especially during feeding. Then, again as in our patient, it is possible to miss the definitive diagnosis, which is made by echocardiography and cardiac catheterization. Reimplantation of the anomalous left coronary artery into the aorta usually results in improvement of left ventricular function over time. In our patient, the myocardial infarction was complicated by formation of an aneurysm, and reimplantation alone was not sufficient to restore cardiac function. Resection of the aneurysm greatly improved the hemodynamics.


Quantitative electrostatic force microscopy with sharp silicon tips.
Electrostatic force microscopy (EFM) probes are typically coated in either metal (radius ∼ 30 nm) or highly-doped diamond (radius ∼ 100 nm). Highly-doped silicon probes, which offer a sharpened and stable tip apex (radius ∼ 1-10 nm) and are usually used only in standard atomic force microscopy, have been recently shown to allow enhanced lateral resolution in quantitative EFM and its application for dielectric constant measurement. Here we present the theoretical modelling required to quantitatively interpret the electrostatic force between these sharpened tips and samples. In contrast to a sphere-capped cone geometry used to describe metal/diamond-coated tips, modelling a sharpened silicon tip requires a geometry comprised of a cone with two different angles. Theoretical results are supported by experimental measurements of metallic substrates and ∼10 nm radius dielectric nanoparticles. This work is equally applicable to EFM and other electrical scanned probe techniques, where it allows quantifying electrical properties of nanomaterials and 3D nano-objects with higher resolution.


Investigation of the mechanism of triclosan induced mouse liver tumors.
Chronic dietary exposure to Triclosan (TCS) produced increased incidence of liver tumors in mice. The mechanism for liver tumor induction has been attributed to activation of either peroxisome proliferator activated receptor α (PPARα) or constitutive androstane receptor (CAR). To further define the mechanism of TCS induced liver tumors, male CD-1 and C57BL/6 mice were treated with TCS at 0, 10, 100 and 200 mg/kg diet/day for 14 or 28 days. In addition, a recovery group and positive control groups for CAR or PPARα activation with either phenobarbital or diethylhexyl-phthalate were included in the 14-day study. TCS induced a dose-dependent increase in relative liver weight and centrilobular hypertrophy in both strains of mice. Hepatocyte DNA synthesis (BrdU labeling) was also increased in a dose-related pattern. In comparison with previous studies, TCS induced a significant increase in CAR/PXR (Cyp2b10, Cyp3a11) and PPARα (Cyp4a10) responsive genes in both CD-1 and C57BL/6 mice. The corresponding enzyme activity for CAR (7-pentoxyresorufin-O-dealkylase) and PPARα (peroxisomal Acyl-CoA oxidase) were also significantly increased in a similar fashion. Oxidative stress related genes Gpx1 and Aox1 were increased in the C57BL/6 but not in CD-1 mice. The increases in gene expression and enzyme activities returned to control levels after 14-day recovery. The present results demonstrate that both CAR and PPARα activation are involved in the TCS induced mouse liver tumor.


History of radiation genetics: light and darkness.
Purpose: To review the history of radiation effects in germ cells and to attempt to discern future directions. Materials and methods: Review of published papers. Results: Recent mouse studies using microarray-based comparative genomic hybridization techniques revealed that germline mutations would occur much less frequently than would be expected from the results of past studies which used specific locus tests. The mean induction rate of deletion mutations was about 1%/genome per Gy. In other words, one out of 100 offspring following a parental (possibly only paternal) exposure to 1 Gy may be expected to have one deletion. This means that at low doses, the genetic risk of radiation is so small and difficult to detect, especially when we learn that our genomes are not perfect and carry as many as on average 80 inactivated genes under heterozygous conditions. Nevertheless, any radiation-induced de novo mutations can be deletions which may involve haploid-sensitive genes, and hence can be a threat to health. Conclusion: Although powerful methods such as whole-genome-sequencing techniques have become available to detect radiation effects in human germ cells, the mutation induction rate in the genome now appears to be much lower than was previously thought. Consequently, detecting radiation effects in human germ cells still remains a difficult task.


Developmental effects of vasotocin and nonapeptide receptors on early social attachment and affiliative behavior in the zebra finch.
Zebra finches demonstrate selective affiliation between juvenile offspring and parents, which, like affiliation between pair partners, is characterized by proximity, vocal communication and contact behaviors. This experiment tested the hypothesis that the nonapeptide arginine vasotocin (AVT, avian homologue of vasopressin) and nonapeptide receptors play a role prior to fledging in the development of affiliative behavior. Zebra finch hatchlings of both sexes received daily intracranial injections (post-hatch days 2-8) of either AVT, Manning Compound (MC, a potent V1a receptor antagonist) or saline (vehicle control). The social development of both sexes was assessed by measuring responsiveness to isolation from the family and subsequent reunion with the male parent after fledging. In addition, we assessed the changes in affiliation with the parents, unfamiliar males, and unfamiliar females each week throughout juvenile development. Compared to controls, MC subjects showed decreased attachment to the parents and MC males did not show the normal increase in affiliative interest in opposite sex individuals as they reached reproductive maturity. In contrast, AVT subjects showed a sustained affiliative interest in parents throughout development, and males showed increased interest in opposite sex conspecifics as they matured. These results provide the first evidence suggesting that AVT and nonapeptide receptors play organizational roles in social development in a bird.


Novel evidence suggesting an anti-oxidant property for erythropoietin on vancomycin-induced nephrotoxicity in a rat model.
1. The aim of the present study was to investigate the role of oxidative stress in renal injury and to determine whether erythropoietin (EPO) acts as an anti-oxidant in vancomycin (VCM)-induced renal impairment. 2. Twenty-four rats were divided into three groups as follows: (i) control (Group 1); (ii) VCM treated (Group 2); and (iii) VCM + EPO treated (Group 3). Vancomycin (200 mg/kg, i.p.) was administered to Groups 2 and 3 for 7 days. Erythropoietin (150 IU/kg, i.p.) treatment was started 24 h before VCM and lasted for 7 days. On Day 8, renal tissues were excised and blood samples were collected. Serum creatinine and blood urea nitrogen were measured, along with renal malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activity and tissue VCM levels. The kidneys were examined for any histopathological changes. 3. Renal MDA levels were found to be increased, whereas SOD and CAT activity was decreased, in the VCM-treated group compared with the control group. There was a marked decrease in MDA levels and an increase in SOD activity, but not CAT activity, after VCM + EPO treatment. Marked histopathological alterations, including interstitial oedema, tubular dilatation, tubular epithelial cell desquamation and vacuolization, were observed in VCM-treated rats. Histopathological changes were significantly improved after EPO administration. 4. In conclusion, the present data suggest that oxidative stress plays an important role in VCM-induced nephrotoxicity. Erythropoietin seems to act as an anti-oxidant, diminishing the toxic oxidative effects of VCM on renal tissues.


Systematic high-content genome-wide RNAi screens of endothelial cell migration and morphology.
Many cell types undergo migration during embryogenesis and disease. Endothelial cells line blood vessels and lymphatics, which migrate during development as part of angiogenesis, lymphangiogenesis and other types of vessel remodelling. These processes are also important in wound healing, cancer metastasis and cardiovascular conditions. However, the molecular control of endothelial cell migration is poorly understood. Here, we present a dataset containing siRNA screens that identify known and novel components of signalling pathways regulating migration of lymphatic endothelial cells. These components are compared to signalling in blood vascular endothelial cells. Further, using high-content microscopy, we captured a dataset of images of migrating cells following transfection with a genome-wide siRNA library. These datasets are suitable for the identification and analysis of genes involved in endothelial cell migration and morphology, and for computational approaches to identify signalling networks controlling the migratory response and integration of cell morphology, gene function and cell signaling. This may facilitate identification of protein targets for therapeutically modulating angiogenesis and lymphangiogenesis in the context of human disease.


Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression.
To investigate the therapeutic effect of hydrogen-rich water (HRW) on inflammatory bowel disease (IBD) and to explore the potential mechanisms involved. Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline (NS) intraperitoneally (ip); dextran sulfate sodium (DSS) group, in which the mice received NS ip (5 mL/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW (in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + ZnPP group, in which the mice received HRW (in the same volume as the NS treatment) and ZnPP [a heme oxygenase-1 (HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved. The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d (P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group (P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group (P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group (P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1β compared with the DSS group (P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum (ER) stress, including p-eIF2α, ATF4, XBP1s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group (P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of ZnPP obviously reversed the protective role of HRW. In the DSS + HRW + ZnPP group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group (P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group. HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.


Isolation and characterization of a filamentous phage, Vf33, specific for Vibrio parahaemolyticus.
Phage Vf33, a filamentous phage about 1,400 nm long and 7 nm wide, specific for Vibrio parahaemolyticus, was isolated and characterized. The buoyant density of Vf33 in CsCl was 1.292 g/cm3. As with other filamentous phages, the lytic activity of Vf33 was resistant to heating below 80 C and to treatment with diethylether, acetone or methanol but sensitive to chloroform. The nucleic acid of this phage is single-stranded circular DNA 8.4 kb in size. The viral genome was converted to a double-stranded replicative form in the host-cell. Among the strains tested, only V. parahaemolyticus strains possessing K38 antigen was sensitive to the phage.


Detection of bacteria in the presence of antibiotics by using specific monoclonal antibodies to neutralize the antibiotics.
Inactivation of penicillin and gentamicin in cultures was achieved by using monoclonal antibodies against these antibiotics. A viridans group streptococcus (penicillin MIC, less than or equal to 0.06 micrograms/ml) and Escherichia coli ATCC 35218 (gentamicin MIC, less than or equal to 1 microgram/ml) were able to grow in broth containing 0.25 micrograms of penicillin per ml and 4 micrograms of gentamicin per ml, respectively, when the specific antibodies were added. This procedure may be useful to increase the yield of bacteria from body fluid specimens that contain antibiotics.