Effectiveness of two-liquid silane primers on bonding sintered feldspathic porcelain with a dual-cured composite luting agent.
The purpose of the current study was to evaluate the effect of two-component ceramic primers on the bond strength of a composite material joined to a sintered porcelain material. Two sizes of porcelain discs (VMK 68; 10 and 8 mm in diameter by 2.5 mm thick) were ground (No. 1000 SiC), and surface-conditioned using one of the following systems: (i) unprimed, (ii) Liquid A of the Porcelain Liner M material (PLM-A), (iii) Liquid B of Porcelain Liner M (PLM-B), (iv) Liquids A and B of Porcelain Liner M (PLM-AB), (v) Liquid A of the Tokuso Ceramics Primer material (TCP-A), (vi) Liquid B of Tokuso Ceramics Primer (TCP-B) and (vii) Liquids A and B of Tokuso Ceramics Primer (TCP-AB). All specimens were bonded with the Bistite II dual-cured composite luting agent, and shear bond strengths were determined both after 24 h immersion in water and after subsequent thermocycling (4-60 degrees C, 1 min each, 20,000 cycles). Of the seven groups assessed, two groups (PLM-AB and TCP-AB) showed the greatest bond strength both before (30.7 MPa for PLM-AB and 29.7 MPa for TCP-AB) and after (19.7 MPa for PLM-AB and 22.4 MPa for TCP-AB) thermocycling (P < 0.05). No significant differences were found between the PLM-AB and TCP-AB groups regardless of the application of thermocycling (P > 0.05). It can be concluded that both of the acid-catalysed two-liquid ceramic primers showed superior bonding to the unhydrolysed single-liquid silane agents (PLM-B and TCP-A) when the feldspathic porcelain was bonded with the Bistite II luting composite.


An integrative genomics approach identifies novel pathways that influence candidaemia susceptibility.
Candidaemia is a bloodstream infection caused by Candida species that primarily affects specific groups of at-risk patients. Because only small candidaemia patient cohorts are available, classical genome wide association cannot be used to identify Candida susceptibility genes. Therefore, we have applied an integrative genomics approach to identify novel susceptibility genes and pathways for candidaemia. Candida-induced transcriptome changes in human primary leukocytes were assessed by RNA sequencing. Genetic susceptibility to candidaemia was assessed using the Illumina immunochip platform for genotyping of a cohort of 217 patients. We then integrated genetics data with gene-expression profiles, Candida-induced cytokine production capacity, and circulating concentrations of cytokines. Based on the intersection of transcriptome pathways and genomic data, we prioritized 31 candidate genes for candidaemia susceptibility. This group of genes was enriched with genes involved in inflammation, innate immunity, complement, and hemostasis. We then validated the role of MAP3K8 in cytokine regulation in response to Candida stimulation. Here, we present a new framework for the identification of susceptibility genes for infectious diseases that uses an unbiased, hypothesis-free, systems genetics approach. By applying this approach to candidaemia, we identified novel susceptibility genes and pathways for candidaemia, and future studies should assess their potential as therapeutic targets.


Development of novel fortified beef patties with added functional protein ingredients for the elderly.
The effects of clean label functional protein ingredients; pea protein isolate (PPI), rice protein (RP) and lentil flour (LF), at 3% and 7% inclusion levels on technological and shelf life parameters of beef patties were evaluated over 12days. Protein content in the RP7 treatment was higher (P<0.05) than controls, but did not differ significantly from PPI7 and RP3. No effects on moisture, fat or ash content were detected. LF addition reduced product hardness, cohesiveness, gumminess and chewiness compared with controls. RP-enriched and control patties were associated with lower lipid oxidation over storage than PPI- and LF-enriched patties. RP had a differential effect on (L*), (a*) and (b*) when compared with controls. Microbiological characteristics for all treatments were acceptable after 12days. Protein fortified beef patties with a softer texture and acceptable technological properties targeted for ease of consumption by older adults were produced in an attempt to reach dietary targeted protein requirements for this segment.


Validation of measured microwave absorption and temperature change for development of a single-mode-type microwave heating thermogravimetry apparatus.
The temperature distribution, microwave absorption efficiency, and dielectric properties of a copper (ii) oxide (CuO) pellet heated by microwave irradiation were investigated for use in developing a single-mode-type microwave heating thermogravimetry apparatus. The validity of the apparatus was confirmed by comparing the measured data with the results of numerical simulations. The dielectric properties and error margins of other parameters estimated using the apparatus were also examined. The temperature distribution of the CuO pellet was observed to decrease monotonously on moving from the outlet to the inlet side of the apparatus. A three-dimensional numerical simulation of the electromagnetic field accurately reproduced this temperature distribution, suggesting the one-way movement of microwaves in the single-mode-type microwave apparatus. The numerically determined dependency of the CuO absorption efficiency was also found to be in very good agreement with published data. The same was the case with the permittivity loss of the CuO at various temperatures, as estimated from the measured microwave absorption efficiency. However, a larger error was observed in the estimation of the permittivity loss of a material with a lower microwave absorption efficiency, which was apparently due to the measurement error of the absorption efficiency of such a material.


Benzodiazepine and Z-drug use and risk of pneumonia in patients with chronic kidney disease: A population-based nested case-control study.
Concerns were raised about pneumonia development from benzodiazepines (BZDs) and Z-drugs, but direct evidence is limited, conflicting and without examining the highly susceptible patients with chronic kidney disease (CKD) nor specifying the risk for different drug utilizations. This study aimed to investigate whether use of BZDs and Z-drugs was each associated with an increased risk of pneumonia in a CKD population. We performed a nested case-control study of 36,880 CKD patients analyzing the Taiwan National Health Insurance Database between 01/1/2000 and 12/31/2011. Among the study cohort, we identified 4,533 cases of pneumonia based on validated disease codes, chest x-ray examination, and prescriptions of respiratory antibiotics, and randomly selected 16,388 controls from risk sets, matched by sex, age, and number of CKD-related hospitalizations. All prescription filling records of BZDs and Z-drugs in the year before the event/index date were analyzed for cases and controls. Conditional logistic regressions were performed to estimate the odds ratios (ORs). Current use of BZDs was associated with a 1.31-fold (95% CI, 1.18-1.26) increased risk of pneumonia compared to nonuse, but not for recent and past use. The risk from current BZD use was confined to new initiation (adjusted OR, 2.47; 95% CI, 2.02-3.03) or use for ≤ 30 days, and elevated to 2.88-fold (95% CI, 1.87-4.42) with parenteral administration. New initiation and current short-term use of Z-drugs was associated with a 2.94-fold (95% CI, 1.65-5.26) and 1.75-fold (95% CI, 1.13-2.72) increased risk of pneumonia, respectively. The findings were robust to adoption of a case-crossover study that analyzed cases only. Use of BZRAs is associated with an increased risk of pneumonia in CKD patients, especially for patients newly initiating BZDs or Z-drugs or those injected with BZDs. Physicians should exercise cautions for signs of pneumonia when prescribing BZDs or Z-drugs to CKD patients.


Vitamin D supplementation can enhance therapeutic effects of excimer laser in patients with vitiligo.
Vitiligo is a disease of acquired depigmentation characterized by the destruction of melanocytes. A theoretical association between low level of 25-hydroxyvitamin D [25(OH)D] and vitiligo has been previously suggested. The objective of this study was to determine the efficacy of intramuscular injection of cholecalciferol with excimer laser compared with the excimer laser alone for vitiligo treatment. This study included 26 patients diagnosed with non-segmental vitiligo and low serum 25(OH)D levels (<20 ng/mL). The participants were randomly divided into two groups through randomization. The treatment using a 308-nm excimer laser was administered to both groups, and the study group additionally received cholecalciferol injection. The Vitiligo Area Scoring Index (VASI) scores showed an 83.6% improvement over the initial score in the study group, whereas the control group showed a 54.7% improvement after 6 months of treatment. After 6 months of treatment, the study group showed a significantly higher proportion of patients who achieved VASI50 and VASI75 compared with the control group. Intramuscular injection of cholecalciferol can be a supplemental option for the treatment of vitiligo patients with vitamin D deficiency with excimer laser therapy.


Perceived live interaction modulates the developing social brain.
Although children's social development is embedded in social interaction, most developmental neuroscience studies have examined responses to non-interactive social stimuli (e.g. photographs of faces). The neural mechanisms of real-world social behavior are of special interest during middle childhood (roughly ages 7-13), a time of increased social complexity and competence coinciding with structural and functional social brain development. Evidence from adult neuroscience studies suggests that social interaction may alter neural processing, but no neuroimaging studies in children have directly examined the effects of live social-interactive context on social cognition. In the current study of middle childhood, we compare the processing of two types of speech: speech that children believed was presented over a real-time audio-feed by a social partner and speech that they believed was recorded. Although in reality all speech was prerecorded, perceived live speech resulted in significantly greater neural activation in regions associated with social cognitive processing. These findings underscore the importance of using ecologically-valid and interactive methods to understand the developing social brain.


First Report of Fusarium oxysporum and F. proliferatum Causing Postharvest Corm Rot on Taro in China.
Taro (Colocasia esculenta), a perennial tuberous herb of the family Araceae, is cultivated widely in southern China. In December 2020, postharvest corm rot occurred on taro of 5 tons with approximately 70% incidence in a 18 square meter cellar in the Qingshanhu District (115°83'E, 28°76'N) of Nanchang City, Jiangxi Province, China. Infected corms had round, soft and slightly sunken lesions covered with white mycelia. The lesions gradually expanded, causing part or whole corm to become soft and shrink, and the inner corm tissue turned brown and rotten. To isolate the pathogen, a total of 30 diseased corm samples were collected. The corms were surface-disinfected by wiping them with 70% ethanol and then passing them over flame back and forth for 5 s. After epidermal tissue of the corms was removed using a sterilized scalpel, small portions of the inner tissue were transferred onto potato dextrose agar (PDA) and incubated at 25°C in the dark. A total of 27 isolates forming Fusarium-like colonies were obtained using monosporic isolation, of which 11 isolates were identified as F. oxysporum and 16 isolates were identified as F. proliferatum based on the colony characteristics and conidial morphology (Leslie and Summerell, 2006). Colonies of F. oxysporum isolates produced dense whitish to light purple mycelia with dark red pigments. Macroconidia were sickle-shaped, straight to slightly curved, 3-5 septa, measuring 25.6 to 45.8 × 3.3 to 6.1 µm. Microconidia were hyaline, oval or ellipsoid, aseptate, and measured 5.2 to 11.8 × 2.2 to 3.5 µm. Chlamydospores were round, 3.5 to 7.6 µm in diameter. Colonies of F. proliferatum isolates were whitish with abundant aerial mycelia and orange pigments. Numerous oval unicellular microconidia were 4.5 to 11.8 × 1.9 to 4.2 µm, and sparse falcate macroconidia with 3-4 septa were 19.4 to 39.2 × 1.9 to 5.2 µm in size. No chlamydospores were observed. Genomic DNA of two representative isolates (F. oxysporum isolate YTU1 and F. proliferatum isolate YTH1) was extracted, and the internal transcribed spacer (ITS) region and translation elongation factor 1-α (TEF1-α) gene were amplified and sequenced using primers ITS1/ITS4 and EF-1H/EF-2T (White et al., 1990; Zhang et al., 2014) respectively. Using BLAST analysis, the ITS sequences of isolates YTU1 (506 bp) and YTH1 (508 bp) exhibited 100% homology with F. oxysporum (MN633363) and F. proliferatum (MT534188), respectively, and the TEF1-α sequences of YTU1 (712 bp) and YTH1 (703 bp) shared 100% homology with F. oxysporum (MN507110) and F. proliferatum (MK952799), respectively. Sequences were deposited in GenBank with the Accession Nos. MZ157124 and MZ310443 for ITS, and MZ383814 and MZ383815 for TEF1-α. The pathogenicity of each isolate was determined on six healthy taro corms. All the taro corms were surface-disinfected with 70% alcohol and two locations from each corm were inoculated. One location was inoculated with 20 μl of conidial suspension (1×105 conidia/ml) and the other was inoculated with sterilized water as a control. All corms were incubated in a growth chamber at 25℃ and 95% relative humidity in the dark. After 15 days, all inoculated corms developed brown rot symptoms, while the non-inoculated control corms remained symptomless. The original isolates were successfully reisolated from all symptomatic corms and identified by sequencing, fulfilling Koch's postulates. F. oxysporum has been reported causing postharvest corm rot of taro in Bogor, Japan, and British Solomon Islands (Widodo et al., 2011). However, to our knowledge, this is the first report of F. oxysporum causing postharvest corm rot of taro in China and F. proliferatum causing postharvest corm rot of taro in the world. The disease poses a potential threat to taro production and should be timely assessed and properly managed.


Epigenetics in Gastrointestinal Health and Disease: Spotlight on DNA Methylation in the Intestinal Epithelium.
Epigenetics can be defined as stable, potentially heritable changes in cellular phenotype caused by mechanisms other than alterations in the underlying DNA sequence. DNA methylation is amongst the most intensely studied epigenetic mechanisms and has been shown to play a major role in regulating fundamental aspects of cell biology including cellular differentiation, organ development, and cell type-specific gene expression. Importantly, it is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment and are able to mediate environmental changes into stable phenotypic alterations. Given existing evidence supporting the important effects of environmental factors (e.g., diet, nutrition, and infections) on human health, epigenetic mechanisms provide a plausible mechanistic framework for the development of many multifactorial diseases including inflammatory bowel disease (IBD). Impaired function of the intestinal epithelium has been implicated in IBD pathogenesis, yet underlying mechanisms remain ill defined. The work of our group focuses on investigating the role of DNA methylation in regulating cellular function of the human intestinal epithelium during gastrointestinal health and IBD. In addition to performing an analysis of primary human intestinal epithelium, we utilize human intestinal organoid culture systems allowing us to perform functional analysis in a patient-derived ex vivo model.


Orchestration an extracellular lipase production from Aspergillus niger MYA 135: biomass morphology and fungal physiology.
The impact of biomass morphology and culture conditions on fungal fermentation was widely reviewed in the literature. In this work, we presented three independent experiments in order to evaluate the influence of some of those input factors on a lipase production separately by using the Aspergillus niger MYA 135 and the two-stage fermentation technique. Regarding the culture modality, the biomass was pre-grown in a first reactor. Then, the washed mycelium was transferred to a second reactor to continue the study. Firstly, linear effects of fungal morphology and several physiological parameters on a lipase production were explored using the Plackett-Burman design. The dispersed fungal morphology was confirmed as a proper quality characteristic for producing an extracellular lipase activity. Concerning the impact of the carbon source on the biomass pre-growth, the sucrose (E = 9.923, p < 0.001) and the L-arabinose (E = 4.198, p = 0.009) presented positive and significant effects on the enzyme production. On the contrary, the supplementation of 0.05 g/L CaCl2 displayed a highly negative and significant effect on this process (E = - 7.390, p < 0.001). Secondly, the relationship between the enzyme production and the input variables N:C ratio, FeCl3 and olive oil was explored applying the central composite design. Among the model terms, the N:C ratio of the production medium had the most negative and significant influence on the enzyme synthesis. Thus, it was concluded that a low N:C ratio was preferable to increase its production. In addition, the bifunctional role of FeCl3 on this fungus was presented. Thirdly, a prove of concept assay was also discussed.


iPS cells for transplantation.
The induced pluripotent stem (iPS) cells from patient's somatic cells could be a useful source for drug discovery and cell transplantation therapies. However, there are still several problems to be solved in terms of safety concerns. We herein summarize the current knowledge about iPS cells and the obstacles that must be overcome before the cells can be used for medical applications. Recent progress has enabled us to generate integration-free iPS cells from noninvasive tissues. Several studies have also uncovered differences in iPS cells and ES cells in terms of gene expression, epigenetic modification, and differentiation potentials. Tissue origin affects the quality of iPS cells. However, in a rodent disease model, the transplantation of differentiated cells derived from iPS cells ameliorated their symptoms. Methods for gene correction and direct cell fate switching have also been reported. The successful generation of human leukocyte antigen (HLA)-typed iPS cells has been described. These findings should therefore facilitate the further application of iPS cells. Human iPS cells are able to provide functional neuronal cells, blood cells, and retinal cells, which would be a useful source for transplantation. Although recent reports have shown that it may be possible to overcome several difficulties associated with iPS cells, further improvements are needed, not only regarding safety aspects, but also in quality, before they can be medically applied.


A COF template-derived mesoporous CeO2-supported Au nanoparticles catalyst for the oxidative esterification of benzaldehydes and benzyl alcohols.
The direct oxidative esterification of benzaldehydes and benzyl alcohols to high value-added aromatic esters under mild and green reaction conditions is significant in the fine chemical industry. The accurate design of catalysts with high catalytic performance is crucial for this process. Herein, 2,4,6-trimethylpyridine, benzoic anhydride, and terephthalaldehyde were used to prepare a covalent organic framework (COF) material, which was then used as a template to construct a mesoporous CeO2-supported Au nanoparticles catalyst. The obtained Au@CeO2 catalyst was thoroughly characterized, and it possessed a mesoporous structure with a high surface area. Meanwhile, the as-prepared Au@CeO2 exhibited excellent catalytic performance in the oxidative esterification of benzaldehydes and benzyl alcohols with methanol, affording the corresponding aromatic esters under mild and green reaction conditions. Furthermore, the Au@CeO2 catalyst could also be recycled. Therefore, this study provides a green and sustainable pathway for the synthesis of high-value-added esters through a direct oxidative esterification strategy.


Gender-related differences in a process of the age-dependent alterations of the elements in monkey sino-atrial node.
Gender differences in the trace elements of monkey sino-atrial (SA) node were investigated in a process of age-dependent alterations. Sixty hearts from Japanese and rhesus monkeys (30 male and 30 female) used were aged ranging from 1-day- to 30-year-old. The elements were analyzed using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). Advancing age decreased all the trace elements. Ca, P, S and Mg significantly decreased. The correlation coefficients of Ca and P were -0.178±0.081 (p<0.05) and -0.088±0.022 (p<0.05) in male (n=30), and -0.095±0.026 (p<0.05) and -0.069±0.017 (p<0.05) in female (n=30), respectively. The age-dependent coefficients for Fe/Ca, Zn/Ca, Fe/P, Fe/S, Zn/S, Fe/Mg and Zn/Mg were exhibited markedly in male, but all was less in female. In gender-related differences, only a ratio of P/Ca (p<0.05) was significantly observed with ageing. The trace elements such as Cu, Se and Sn were less detected in the SA nodes. These results indicate that the age-dependent changes in the ratios of elements are appeared more rapidly in male monkey SA node, and the gender difference is observed in ratio of P/Ca. The different attenuations may be involved with the age- and gender-related SA nodal functions.


Virtually complete control of simple and face diastereoselectivity in the Michael addition reactions between achiral equivalents of a nucleophilic glycine and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: practical method for preparation of beta-substituted pyroglutamic acids and prolines.
This study demonstrates a new strategy for controlling the stereochemical outcome of the Michael addition reactions between nucleophilic glycine equivalents and alpha,beta-unsaturated carboxylic acid derivatives: The addition reactions between achiral Ni(II)-complex of the Schiff base of glycine with o-[N-alpha-pycolylamino]acetophenone and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones were shown to occur at room temperature in the presence of nonchelating organic bases and, most notably, with very high stereoselectivity at both newly formed stereogenic centers. Thus, the chiral 4-phenyl-1,3-oxazolidin-2-one moiety was found to control efficiently both face diastereoselectivities of the glycine derived enolate and the C,C double bond of the Michael acceptor. The new strategy developed in this work is methodologically superior to previous methods, most notably in terms of generality and synthetic efficiency. Excellent chemical yields and diastereoselectivities, combined with the simplicity of the experimental procedures, render the present method of immediate use for preparing various 3-substituted pyroglutamic acids and related amino acids (glutamic acids, glutamines, prolines, etc.) available via conventional transformations of the former.


[Application of proximal correction osteotomy of the tibia in treatment of the knee joint osteoarthrosis].
High osteotomy of tibia is the method of choice in patients with osteoarthrosis (OA) of the knee joint (KJ) medial portion of I and II stage. To secure positive postoperative result achievement high proximal osteotomy was combined with other interventions, directed on elimination of other morphological or functional disorders of the KJ. We have performed treatment of 43 patients with OA of KJ of II stage with the varus deformity, to whom correcting osteotomy "Opening Wedge". In all of them arthroscopy of the KJ was done, in 14--with stimultant arthroscopic plasty of anterior cruciform ligament, in 17--arthroscopic chondroplasty of articular surface defects of processus lateralis os femoris, in 12--arthroscopic KJ debridement, in 24--partial meniscusectomy. An excellent and good result was noted in 33 patients. Miniinvasive combined reconstructive-restorational interventions are effective in OA of II stage with disorder of an axis or an axis and the KJ stability.


The needs of adolescent girls who self-harm.
People who self-harm are typically intelligent, adolescent or young adult, middle to upper class girls, who do so to feel something or, paradoxically, to stop feeling and calm down. Girls who self-harm need to feel understood, listened to non-judgmentally, and responded to in relation to the unspoken suffering behind the self-harm behavior. The aim of treatment of girls who self-harm is to facilitate understanding of the act and provide alternative, healthier coping strategies.


Implementation and data processing of a five-channel microwave interferometer with high temporal resolution and low noise on Sino-UNIted Spherical Tokamak.
A five-channel microwave interferometer with high temporal resolution and high phase resolution has been developed for measuring electron density profiles and fluctuations on the Sino-UNIted Spherical Tokamak. A correction algorithm, based on the low signal amplitude detection, is proposed to eliminate the fringe jump errors. The correction algorithm achieves an accuracy of 92%. The density profile is reconstructed through the Park-matrix method, with the geometry of magnetic surfaces calculated by the equilibrium fitting. The reconstructed density profiles for discharges with supersonic molecular beam injection are in good agreement with the results of another 94 GHz single-channel horizontal interferometer and the Langmuir probes. The temporal resolution of the system is 0.5 µs and the line-integrated electron density resolution is 1 × 1015 m-2, which benefits from the single sideband modulation technique. Therefore, the multichannel interferometer system is capable of studying the details of the high-frequency (up to 200 kHz) density fluctuation such as that in the minor disruption event.


A Single-Centered Randomized Controlled Trial of Primary Pediatric Intensivists and Nurses.
Background: For long-stay patients (LSP) in pediatric intensive care units (PICU), frequently rotating providers can lead to ineffective information sharing and retention, varying goals and timelines, and delayed decisions, likely contributing to prolonged admissions. Primary intensivists (one physician serves as a consistent resource for the patient/family and PICU providers) and primary nurses (a small team of PICU nurses provide consistent bedside care) seek to augment usual transitory PICU care, by enhancing continuity and, potentially, decreasing length of stay (LOS). Methods: A single-centered, partially blinded randomized controlled trial of primary intensivists and nurses versus usual care. PICU patients admitted for or expected to be admitted for >10 days and who had ≥1 complex chronic condition were eligible. A block randomization with 1:1 allocation was used. The primary outcome was PICU LOS. Multiple secondary outcomes were explored. Results: Two hundred LSPs were randomized-half to receive primaries and half to usual care. The two groups were not significantly different in their baseline and admission characteristics. LSPs randomized to receive primaries had a shorter, but non-significant, mean LOS than those randomized to usual care (32.5 vs. 37.1 days, respectively, p = .19). Compared to LSPs in the usual care group, LSPs in the primary group had fewer unplanned intubations. Among LSPs that died, DNR orders were more prevalent in the primary group. Other secondary outcome and balance metrics were not significantly different between the two groups. Conclusion: Primary intensivists and nurses may be an effective strategy to counteract transitory PICU care and serve the distinctive needs of LSPs. However, additional studies are needed to determine the ways and to what extent they may accomplish this.


Emerging arboviral human diseases in Southern Europe.
Southern Europe is characterized by unique landscape and climate which attract tourists, but also arthropod vectors, some of them carrying pathogens. Among several arboviral diseases that emerged in the region during the last decade, West Nile fever accounted for high number of human cases and fatalities, while Crimean-Congo hemorrhagic fever expanded its geographic distribution, and is considered as a real threat for Europe. Viruses evolve rapidly and acquire mutations making themselves stronger and naive populations more vulnerable. In an effort to tackle efficiently the emerging arboviral diseases, preparedness and strategic surveillance are needed for the early detection of the pathogen and containment and mitigation of probable outbreaks. In this review, the main human arboviral diseases that emerged in Southern Europe are described.


Respiratory transition in infants delivered by cesarean section.
One of the biggest challenges a newborn faces after birth is the task of making a smooth transition to air breathing. This task is complicated by the fact that fetal lungs are full of fluid which must be cleared rapidly to allow for gas exchange. Respiratory morbidity as a result of failure to clear fetal lung fluid is not uncommon, and can be particularly problematic in some infants delivered by elective cesarean delivery (ECS). Given the high rates of cesarean deliveries in the USA and worldwide, the public health and economic impact of morbidity in this subgroup is considerable. Whereas the occurrence of birth asphyxia, trauma, and meconium aspiration is reduced by elective Cesarean delivery, the risk of respiratory distress secondary to transient tachypnea of the newborn, surfactant deficiency, and pulmonary hypertension is increased. It is clear that physiologic events in the last few weeks of pregnancy coupled with the onset of spontaneous labor are accompanied by changes in the hormonal milieu of the fetus and its mother, resulting in preparation of the fetus for neonatal transition. Rapid clearance of fetal lung fluid is a key part of these changes, and is mediated in large part by transepithelial Na reabsorption through amiloride-sensitive Na channels in the alveolar epithelial cells, with only a limited contribution from mechanical factors and Starling forces. This chapter discusses the physiologic mechanisms underlying fetal lung fluid absorption and explores potential strategies for facilitating neonatal transition when infants are delivered by ECS before the onset of spontaneous labor.


Sleep characteristics modify the association of genetic predisposition with obesity and anthropometric measurements in 119,679 UK Biobank participants.
Background: Obesity is a multifactorial condition influenced by genetics, lifestyle, and environment.Objective: We investigated whether the association of a validated genetic profile risk score for obesity (GPRS-obesity) with body mass index (BMI) and waist circumference (WC) was modified by sleep characteristics.Design: This study included cross-sectional data from 119,859 white European adults, aged 37-73 y, participating in the UK Biobank. Interactions of GPRS-obesity and sleep characteristics (sleep duration, chronotype, day napping, and shift work) with their effects on BMI and WC were investigated. Results: β Values are expressed as the change in BMI (in kg/m2) or WC per 1-SD increase in GPRS-obesity. The GPRS-obesity was associated with BMI (β: 0.57; 95% CI: 0.55, 0.60; P = 6.3 × 10-207) and WC (1.21 cm; 95% CI: 1.15, 1.28 cm; P = 4.2 × 10-289). There were significant interactions of GPRS-obesity and a variety of sleep characteristics with their relation with BMI (P-interaction < 0.05). In participants who slept <7 or >9 h daily, the effect of GPRS-obesity on BMI was stronger (β: 0.60; 95% CI: 0.54, 0.65 and β: 0.73; 95% CI: 0.49, 0.97, respectively) than in normal-length sleepers (7-9 h; β: 0.52; 95% CI: 0.49, 0.55). A similar pattern was observed for shift workers (β: 0.68; 95% CI: 0.59, 0.77 compared with β: 0.54; 95% CI: 0.51, 0.58 for non-shift workers) and for night-shift workers (β: 0.69; 95% CI: 0.56, 0.82 compared with β: 0.55; 95% CI: 0.51, 0.58 for non-night-shift workers), for those taking naps during the day (β: 0.65; 95% CI: 0.52, 0.78 compared with β: 0.51; 95% CI: 0.48, 0.55 for those who never or rarely had naps), and for those with a self-reported evening chronotype (β: 0.72; 95% CI: 0.61, 0.82 compared with β: 0.52; 95% CI: 0.47, 0.57 for morning chronotype). Similar findings were obtained by using WC as the outcome.Conclusion: This study shows that the association between genetic risk for obesity and phenotypic adiposity measures is exacerbated by adverse sleeping characteristics.


Explaining the primate extinction crisis: predictors of extinction risk and active threats.
Explaining why some species are disproportionately impacted by the extinction crisis is of critical importance for conservation biology as a science and for proactively protecting species that are likely to become threatened in the future. Using the most current data on threat status, population trends, and threat types for 446 primate species, we advance previous research on the determinants of extinction risk by including a wider array of phenotypic traits as predictors, filling gaps in these trait data using multiple imputation, and investigating the mechanisms that connect organismal traits to extinction risk. Our Bayesian phylogenetically controlled analyses reveal that insular species exhibit higher threat status, while those that are more omnivorous and live in larger groups have lower threat status. The same traits are not linked to risk when repeating our analyses with older IUCN data, which may suggest that the traits influencing species risk are changing as anthropogenic effects continue to transform natural landscapes. We also show that non-insular, larger-bodied, and arboreal species are more susceptible to key threats responsible for primate population declines. Collectively, these results provide new insights to the determinants of primate extinction and identify the mechanisms (i.e. threats) that link traits to extinction risk.


Determinants of Medication Non-Adherence Among the Elderly with Co-Existing Hypertension and Type 2 Diabetes Mellitus in Rural Areas of Udupi District in Karnataka, India.
Medication adherence is a crucial component in the management of elderly with co-morbid chronic conditions. Hence, this study aimed to investigate the determinants of medication non-adherence among rural elderly with co-morbid chronic conditions of hypertension (HTN) and type 2 diabetes mellitus (T2DM) in India. This cross-sectional study adopted the probability proportional to size (PPS) sampling technique to find the determinants of medication non-adherence among elderly residing in rural coverage areas of five randomly selected primary health centres (PHC) in Udupi district, Karnataka, India. A total of 360 elderly (72 samples from each cluster) who met the inclusion criteria and consented were interviewed using predesigned prevalidated and standardized or reliable tools. The data were coded and entered in SPSS version 16.0 and analyzed using both descriptive and inferential statistics. The study found that 55.6% (n=200) of rural elderly with co-morbid conditions HTN and T2DM were non-adherent to their medications and established Spearman correlation coefficient rank (r) value between undesirable person-related factors (r=-0.444); good family support (including financial support) (r=0.185); poor accessibility to healthcare facility (r=-0.209); detrimental medication-related factors including high cost of medication (r=-0.237) were found to be significant at 0.05 level of confidence (p < 0.05). Further, the study depicted that the chi-square test (χ2) was identified to be significantly associated (p<0.05) with a variable such as education, knowledge, number of illnesses and impairments, vision, memory, and physical impairments. Medication adherence could be improved among rural elderly with co-morbid conditions by identifying and addressing the determinants at the earliest. Further, it is vital to identify the suitable intervention program to address these avoidable problems.


Dietary supplements and health: the research agenda.
Research needs to evaluate the role of dietary supplements in human health abound, yet funds to support all of the possible opportunities do not. Government agencies, such as the National Institutes of Health (NIH) in the USA, remain the chief sponsors of research in this area. They face the challenge of competing priorities, such as critical disease-oriented research, basic biomedical and technological development, and prevention-related research. Dietary supplements are widely used for health promotion and disease prevention, sometimes with minimal science to support their use. There is a need for focused research efforts to better address issues of efficacy, safety and quality of dietary supplements. At the same time, fundamental studies of their mechanisms of action are needed. In addition, resources to support research in this area are required: on the one hand, basic tools (analytical methods, characterization of ingredients) need to be developed and validated, and on the other, tools to understand patterns of supplement use in populations and study designs to assess their efficacy and safety need refining. These efforts benefit greatly from partnerships among government agencies and with the academic and private sectors.


In vitro folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells.
The genetic and epigenetic effects of nutritional folate deficiency were studied in two Chinese hamster ovary (CHO) cell lines. The CHO-AA8 cell line (hemizygous at the aprt locus) and CHO-UV5 (DNA repair-deficient mutant of AA8) were cultured in Ham's F-12 medium or in custom-prepared Ham's F-12 medium lacking folic acid, thymidine, and hypoxanthine. Cells cultured acutely in the folate deficient medium exhibited initial growth arrest, followed by massive cell death and DNA fragmentation into nucleosomal multimers characteristic of apoptosis. Although prolonged culture in the folate deficient medium was cytostatic and lethal to the majority cells, minor subpopulations in both cell lines failed to initiate cell death, exhibited phenotypic abnormalities, and adapted a selective growth advantage under marginal folate conditions. These "resistant" clones exhibited major alterations in deoxynucleotide pools associated with an increase in mutant frequency at the aprt locus as detected by resistance to cytotoxicity in 8-azaadenosine. The mutation frequency in the DNA repair-deficient CHO-UV5 cells was approximately 100-fold greater than that in the parental AA8 clones, underscoring the importance of DNA repair under conditions of folate deficiency and nucleotide pool imbalance. The enhanced mutation frequency in the DNA repair-competent folate-deficient CHO-AA8 cells suggests that DNA repair activity is less effective under folate-deficient conditions. These results add to the accumulating clinical and experimental evidence relating chronic folate deficiency to genomic instability and carcinogenesis.


Designing effective 'frustrated Lewis pair' hydrogenation catalysts.
The past decade has seen the subject of transition metal-free catalytic hydrogenation develop incredibly rapidly, transforming from a largely hypothetical possibility to a well-established field that can be applied to the reduction of a diverse variety of functional groups under mild conditions. This remarkable change is principally attributable to the development of so-called 'frustrated Lewis pairs': unquenched combinations of bulky Lewis acids and bases whose dual reactivity can be exploited for the facile activation of otherwise inert chemical bonds. While a number of comprehensive reviews into frustrated Lewis pair chemistry have been published in recent years, this tutorial review aims to provide a focused guide to the development of efficient FLP hydrogenation catalysts, through identification and consideration of the key factors that govern their effectiveness. Following discussion of these factors, their importance will be illustrated using a case study from our own research, namely the development of FLP protocols for successful hydrogenation of aldehydes and ketones, and for related moisture-tolerant hydrogenation.


Community determinants of health for rural elderly.
Although community health nursing practice supports community-level interventions, the influence of communities on the health of older members is not well known. Ethnographic design and methods were employed to study the health of older residents in a western plains farming community. Relationship was a key component for understanding life in this town. Reciprocal relationships in which older people and the community were mutual benefactors were crucial to the acceptability of help and support. Stressors were lack of privacy and isolation for those who did not conform to prevailing norms. Nurses in rural areas have to foster a sense of relationship and reciprocity within a community, since assistance is accepted most easily when older people can repay in kind. Advocating the use of government supports and programs may not be successful if the programs do not require such contributions. Close relationships can be stressful as well as supportive, and increasing social support and monitoring for an older person may inadvertently decrease privacy and promote stress.


The Pacific Center for Health Policy and Ethics.
The Pacific Center for Health Policy and Ethics has been created at the University of Southern California to address issues concerning health care and research from an ethical perspective. The Pacific Center is designed as an umbrella organization that will facilitate multidisciplinary work and inter-institutional collaboration through sponsorship of research and coalition building. The Center will also be a consultant to government and a resource on curriculum development and clinical ethics consultation. It will involve itself in a broad range of issues including control over dying, use of biotechnology, and access to health care and will bring diverse perspectives and values to these activities.


Valvuloplasty Without Prosthetic Ring or Band in Patients with Degenerative Mitral Regurgitation: Long-Term Results and Predictive Factors for Outcomes.
Mitral valvuloplasty including ring/band support is widely performed despite potential drawbacks of rings. Unsupported valvuloplasty is performed in only a few centers. This study aimed to report long-term outcomes of patients undergoing unsupported valvuloplasty for degenerative mitral regurgitation (MR) and to identify predictive factors for outcomes. This is a retrospective cohort including patients undergoing mitral valve repair for degenerative MR from 2000 to 2018. The main techniques were Wooler annuloplasty and quadrangular resection. Kaplan-Meier curves and Cox regression models were used for statistical analysis. One hundred fifty-eight patients were included (median age: 64.0 years). In-hospital mortality was 2.5%. Maximum followup was 19.6 years, with a median of 4.7 years (992 patient-years). Overall survival at 5, 10, and 15 years was 91.0% (95% confidence interval [CI]: 85.7-96.3), 87.6% (95% CI: 80.7-94.5), and 78.1% (95% CI: 65.9-90.3), respectively. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was an independent predictor of late death (hazard ratio [HR] 1.42; P=0.016). Freedom from mitral reoperation at 5, 10, and 15 years was 88.1% (95% CI: 82.0-94.2), 82.4% (95% CI: 74.6-90.2), and 75.7% (95% CI: 64.1-87.3), respectively. Left atrial diameter > 56 mm was associated with late reintervention in univariate analysis (HR 1.06; P=0.049). Degenerative MR can be successfully treated with repair techniques without annular support, thus avoiding the technical and logistical drawbacks of ring/band implantation while maintaining good long-term results. EuroSCORE II was a risk factor for late death, and larger left atrium was associated with late reoperation.


Analysis of membrane protein topography of Newcastle disease virus and cultured mammalian fibroblasts.
Diagonal electrophoresis, in conjunction with crosslinking by dimethyl-3,3'-dithiobispropionimidate (DTBP), has been used to probe membrane protein topography of Newcastle disease virus (NDV) and cultured mammalian fibroblasts (LM cells). Analysis of DTBP-treated NDV revealed crosslinking between a nucleocapsid protein, VP3, and an externally displayed glycoprotein, VP1, possessing hemagglutination and neuraminidase activities. Similar analysis of LM cells iodinated by the lactoperoxidase method indicated nearest-neighbor interactions of a noncovalent nature involving a major cell surface protein of 72,000 molecular weight. These studies illustrate the feasibility of this methodology for the study of membrane protein disposition in complex systems.


Total blood eosinophilia in allergic (type I allergy) and non-allergic asthma, rhinitis and cough.
p6tal blood eosinophil counts (TBE) were obtained in allergic and non-allergic patients suffering from asthma, rhinitis, cough, or various combinations of these disorders. As expected higher blood eosinophil counts were found in allergic patients. In the non-allergic patients however, significantly higher blood eosinophil counts were also found as compared to controls, which limits the possible role of TBE determination in the diagnosis of type I allergy. There is no significant correlation between TBE and total serum IgE. Atopic eczema is associated with higher TBE only in the group with allergic respiratory diseases. In allergic patients blood eosinophilia is steadily decreasing with age, where the inverse is observed in non-allergic patients. Our data suggest that for some reason TBE is increased in both allergic and non-allergic patients. A further increase of TBE in allergic patients is associated with a type I allergic reaction.


Biomechanics of cartilage articulation: effects of lubrication and degeneration on shear deformation.
To characterize cartilage shear strain during articulation, and the effects of lubrication and degeneration. Human osteochondral cores from lateral femoral condyles, characterized as normal or mildly degenerated based on surface structure, were selected. Under video microscopy, pairs of osteochondral blocks from each core were apposed, compressed 15%, and subjected to relative lateral motion with synovial fluid (SF) or phosphate buffered saline (PBS) as lubricant. When cartilage surfaces began to slide steadily, shear strain (Exz) and modulus (G) overall in the full tissue thickness and also as a function of depth from the surface were determined. In normal tissue with SF as lubricant, Exz was highest (0.056) near the articular surface and diminished monotonically with depth, with an overall average Exz of 0.028. In degenerated cartilage with SF as lubricant, Exz near the surface (0.28) was 5-fold that of normal cartilage and localized there, with an overall E(xz) of 0.041. With PBS as lubricant, Exz values near the articular surface were approximately 50% higher than those observed with SF, and overall Exz was 0.045 and 0.062 in normal and degenerated tissue, respectively. Near the articular surface, G was lower with degeneration (0.06 MPa, versus 0.18 MPa in normal cartilage). In both normal and degenerated cartilage, G increased with tissue depth to 3-4 MPa, with an overall G of 0.26-0.32 MPa. During articulation, peak cartilage shear is highest near the articular surface and decreases markedly with depth. With degeneration and diminished lubrication, the markedly increased cartilage shear near the articular surface may contribute to progressive cartilage deterioration and osteoarthritis.


Specificity of antibodies against rodent transforming growth factor-alpha protein.
We found that the immunohistochemical distribution of TGF-alpha varied in rodent tissues depending on the antibody used, suggesting that the specificity of anti-TGF-alpha antibodies differs significantly. To address this issue, we compared the specificity of two representative antibodies that have been widely used to detect rodent TGF-alpha. In a competition study, the antibodies were preincubated with an excess of synthetic rat TGF-alpha 34-50 and were used for staining of rat and mouse kidneys and/or uterus. The results revealed that one of the antibodies, anti-rat TGF-alpha polyclonal antibody, was neutralized by the peptide, whereas the other, anti-human TGF-alpha monoclonal antibody, was not absorbed by the peptide up to an excess of 100-fold. Western blotting analysis showed that the anti-rat TGF-alpha polyclonal antibody recognized both human and rat purified TGF-alpha. However, the anti-human TGF-alpha monoclonal antibody did not detect purified rat TGF-alpha, although the antibody reacted with mouse proteins other than TGF-alpha from kidneys and uterus, purified human TGF-alpha, and mouse carbonic anhydrase II. These data indicate that the anti-human TGF-alpha monoclonal antibody does not recognize rodent TGF-alpha under our experimental conditions and suggest that distribution of TGF-alpha in rodent tissues may need to be reexamined.


Blood pressure and body mass index in Ethiopian immigrants: comparison of operations Solomon and Moses.
Blood pressure, height and weight of 122 male and 143 female Ethiopian Jews who immigrated to Israel in Operation Solomon (1991) were measured and compared with those of Ethiopian immigrants who arrived in Israel in 1984-85 (Operation Moses). Although the body mass indices of the Operation Solomon immigrants were much higher than those of Operation Moses, no significant differences were found in blood pressure measurements in any age-group or in either sex. Blood pressure in Operation Solomon immigrants increased with age and correlated with body mass index and triglyceride serum levels among males, but not females. No correlation was found between cholesterol levels and blood pressure measurements.


Interpreting dissociations between regular and irregular past-tense morphology: evidence from event-related potentials.
Neuropsychological dissociations between regular and irregular English past-tense morphology have been reported using a lexical decision task in which past-tense primes immediately precede present-tense targets. We present N400 event-related potential data from healthy participants using the same design. Both regular and irregular past-tense forms primed corresponding present-tense forms, but with a longer duration for irregular verbs. Phonological control conditions suggested that differences in formal overlap between prime and target contribute to, but do not account for, this difference, suggesting a link between irregular morphology and semantics. Further analysis dividing the irregular verbs into two categories (weak irregular and strong) revealed that priming for strong verbs was reliably stronger than that for weak irregular and regular verbs, which were statistically indistinguishable from one another. We argue that, although we observe a regular-irregular dissociation, the nature of this dissociation is more consistent with single- than with dual-system models of inflectional morphology.


Quantitative Proteomics Analysis of Herbaceous Peony in Response to Paclobutrazol Inhibition of Lateral Branching.
Herbaceous peony (Paeonia lactiflora Pall.) is an emerging high-grade cut flower worldwide, which is usually used in wedding bouquets and known as the "wedding flower". However, abundant lateral branches appear frequently in some excellent cultivars, and a lack of a method to remove Paeonia lactiflora lateral branches other than inefficient artificial methods is an obstacle for improving the quality of its cut flowers. In this study, paclobutrazol (PBZ) application was found to inhibit the growth of lateral branches in Paeonia lactiflora for the first time, including 96.82% decreased lateral bud number per branch, 77.79% and 42.31% decreased length and diameter of lateral branches, respectively, declined cell wall materials and changed microstructures. Subsequently, isobaric tag for relative and absolute quantitation (iTRAQ) technology was used for quantitative proteomics analysis of lateral branches under PBZ application and control. The results indicated that 178 differentially expressed proteins (DEPs) successfully obtained, 98 DEPs were up-regulated and 80 DEPs were down-regulated. Thereafter, 34 candidate DEPs associated with the inhibited growth of lateral branches were screened according to their function and classification. These PBZ-stress responsive candidate DEPs were involved in eight biological processes, which played a very important role in the growth and development of lateral branches together with the response to PBZ stress. These results provide a better understanding of the molecular theoretical basis for removing Paeonia lactiflora lateral branches using PBZ application.


Nonsyndromic tooth agenesis patterns and associated developmental dental anomalies: a literature review with radiographic illustrations.
Tooth agenesis is one of the most intriguing phenomena, because it is frequently associated with other oral anomalies, structural variations and malformations of other teeth, late eruption, transposition and crowding. The diagnosis can be quite challenging as radiographic examination is critical for the diagnosis but not always possible and the late developing teeth may be sometimes scored developmentally missing. Accurate diagnosis therefore requires radiographic, clinical, and dental cast examinations. It is an important clinical and public health problem. Patients with missing permanent teeth may suffer from a reduced chewing ability, inarticulate pronunciation, and an unfavorable aesthetic appearance. Clinically, early diagnosis of a dental anomaly can alert the clinician to the possible development of other associated dental anomalies in the same patient or family, and avoid the possible sequelae. Understanding of tooth agenesis patterns and their impact on diagnosis, prevention, and eventually therapeutics are becoming integral parts of comprehensive dental care. Dental examination with radiographic screening of hypodontia in early childhood should be emphasized as part of public oral health policy to allow early diagnosis and timely intervention.


[Questionnaire on the incidence and control of fleas in dogs and cats presented to German small animal practices].
2590 small animal practitioners in Germany have been asked by a questionnaire from which 1694 (65.4%) replied. 1186 of these veterinarians (70%) often see ectoparasite infestation. Fleas are predominant and occur on cats (1016/60%), followed by dogs (424/25%), small mammals and birds (254/15%). Flea infestations on dogs and cats are observed throughout the year, but the prevalences are generally higher during the summer season. The results reveal that topically administered spot-on formulations is the most popular method used for flea control. The most common applied antiparasitic substances both in dogs and in cats were fipronil (535/31.6%; 690/40.7%), imidacloprid (290/17.1%; 417/24.6%) and selamectin (267/15.8%; 319/18.8%). Due to 771 (45.5%) of the answering veterinarians the animal owner himself, and according 694 (41%) respectively 229 (13.5%) of the replies the veterinarian or the veterinary technician applies the antiparasiticide onto the skin. 1457 veterinarians (86%) administer compounds against adult fleas and their developmental stages also in the animal's environment.


Mechanistic Basis for the Differential Effects of Rivaroxaban and Apixaban on Global Tests of Coagulation.
Rivaroxaban and apixaban are both small molecules that reversibly inhibit factor Xa. Compared with rivaroxaban, apixaban has minimal effects on the prothrombin time and activated partial thromboplastin time. To investigate this phenomenon, we used a factor Xa-directed substrate in a buffer system. Although rivaroxaban and apixaban inhibited factor Xa with similar K i values at equilibrium, kinetic measurements revealed that rivaroxaban inhibited factor Xa up to 4-fold faster than apixaban ( p < 0.001). Using a discontinuous chromogenic assay to monitor thrombin production by prothrombinase in a purified system, rivaroxaban was 4-fold more potent than apixaban (K i values of 0.7 ± 0.3 and 2.9 ± 0.5 nM, respectively; p = 0.02). Likewise, in thrombin generation assays in plasma, rivaroxaban prolonged the lag time and suppressed endogenous thrombin potential to a greater extent than apixaban. To characterize how the two inhibitors differ in recognizing factor Xa, inhibition of prothrombinase was monitored in real-time using a fluorescent probe for thrombin. The data were fit using a mixed-inhibition model and the individual association and dissociation rate constants were determined. The association rates for the binding of rivaroxaban to either free factor Xa or factor Xa incorporated into the prothrombinase complex were 10- and 1,193-fold faster than those for apixaban, respectively, whereas dissociation rates were about 3-fold faster. Collectively, these findings suggest that rivaroxaban and apixaban differ in their capacity to inhibit factor Xa and provide a plausible explanation for the observation that rivaroxaban has a greater effect on global tests of coagulation than apixaban.


Relaxation of particles in the sloped region in a conserved growth model.
The dynamical scaling properties of conserved growth models, in which the downward (upward) movement of a particle dropped only on the sloped region occurs with a probability p (1-p), are investigated by simulations in the substrate dimension d=1. By direct analysis of the surface fluctuation W, the models with p>1/2 are clearly and cleanly shown to have crossover behavior from Mullins-Herring (MH) universality to Edwards-Wilkinson (EW) universality. In contrast, the models with p<1/2 are shown to have an instability eventually, even though they initially follow the MH equation. The model with p=1/2 is shown to belong to the MH universality class and to be the critical model that splits the models with EW behavior from those with the instability. From these results we explain the physical reason for the very slow crossover in models like the Wolf-Villain model.


[Clinical importance of screening differential gene set of monocytes based on single-cell sequencing and digital polymerase chain reaction technology for early diagnosis of sepsis].
To verify the specific differentiated subsets of monocytes in sepsis, and to screen and construct the differential gene set of monocytes used for early diagnosis of sepsis. Patients with sepsis admitted to Guangdong Provincial People's Hospital from June 2020 to March 2021 were enrolled, and peripheral blood mononuclear cells (PBMC) were extracted. Single-cell sequencing technology and pseudo-time analysis were used to verify the differential subsets of monocytes. Bioinformatics methods were used to analyze the expression of genes in differential subsets of monocytes and screen out differential genes for the preliminary construction of a candidate differential gene set. The digital polymerase chain reaction (PCR) technology was used to verify the candidate differential genes in PBMC of sepsis patients and sepsis human myeloid leukemia mononuclear cells (THP-1) models, and the Venn diagram was used to construct the final differential gene set of monocytes. Gene Expression Omnibus (GEO) database was used to validate the differential gene set of monocytes. (1) The results of cell annotation and pseudo-time analysis showed that the differentiation of NEAT1+CD163+ monocyte occurred in the early stage of sepsis was significantly different from other subsets, which validated that NEAT1+CD163+ monocyte was the characteristic subset in the pathological process of sepsis. (2) Twenty-two differential genes related to sepsis were screened out from the gene expression of NEAT1+CD163+ monocyte. After further verification by digital PCR, basic leucine zipper ATF-like transcription factor (BATF), JUNB proto-oncogene, carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4), chromosome 9 open reading frame 95 (C9orf95), G protein subunit alpha 15 (GNA15), complement C3a receptor 1 (C3AR1), transforming growth factor beta 1 (TGFB1) and mitochondrial carrier homolog 1 (MTCH1) were screened out to construct the final differential gene set of monocytes. (3) The external validation results showed that C9orf95 gene had no data in GSE154918 and GSE133822 from GEO, it was excluded during validation. In GSE154918, the expressions of BATF, JUNB, CEACAM4, GNA15, C3AR1, TGFB1, and MTCH1 in the sepsis group were significantly higher than those in the healthy control group (log2expression level: BATF was 12.78±0.08 vs. 11.39±0.35, JUNB was 16.88±0.07 vs. 16.04±0.03, CEACAM4 was 14.73±0.08 vs. 13.77±0.05, GNA15 was 13.16±0.06 vs. 12.30±0.04, C3AR1 was 14.62±0.13 vs. 12.87±0.05, TGFB1 was 16.95±0.05 vs. 16.57±0.36, MTCH1 was 14.80±0.02 vs. 14.61±0.15, all P < 0.05). In GSE133822, the expressions of BATF, CEACAM4, GNA15, and C3AR1 in the sepsis group were significantly higher than those in the health control group (log2expression level: BATF was 8.66±0.16 vs. 7.92±0.14, CEACAM4 was 9.20±0.16 vs. 8.36±0.20, GNA15 was 10.66±0.18 vs. 10.13±0.16, C3AR1 was 11.49±0.27 vs. 10.48±0.16, all P < 0.05), while the expressions of JUNB, TGFB1, and MTCH1 were not statistically different between two groups. The results of gene set variation analysis (GSVA) showed that the enrichment scores of monocytes differential gene set of sepsis group were significantly higher than those of the healthy control group in both GSE154918 (0.38±0.04 vs. -0.44±0.02) and GSE133822 (0.56±0.02 vs. 0.20±0.05, both P < 0.01). Receiver operator characteristic curve (ROC curve) analysis showed that the differential gene set of monocytes had a reliable diagnostic value for early sepsis with the area under ROC curve (AUC) of 0.993 [95% confidence interval (95%CI) was 0.980-1.000] in GSE154918 and 0.944 (95%CI was 0.873-1.000) in GSE133822. A differential gene set of monocytes (BATF, JUNB, CEACAM4, GNA15, C3AR1, TGFB1, and MTCH1) screened out by single-cell sequencing and digital PCR technology has a reliable diagnostic value for the early sepsis, and may provide a new idea for the early diagnosis of sepsis.


Setup for high-temperature surface Brillouin light scattering: Application to opaque thin films and coatings.
A setup combining surface Brillouin light scattering with a high-temperature chamber has been developed. The temperature of the sample is controlled with a Bühler HDK chamber for optical measurements (maximum temperature of 1600 °C), in controlled atmospheres or high vacuum (10-6 mbar). This setup allows the study of sound velocity of surface acoustic waves and of the elastic constants of opaque thin films and coatings in situ as a function of temperature from surface Brillouin light scattering, by analyzing the backscattered light from the sample at a fixed angle of incidence. In this paper, we will demonstrate the applications of this setup for metallic glass thin films devitrification study and evaluation of high temperature elastic properties of hard nitride coatings. This kind of study using surface acoustic waves is rare, in contrast to those made on transparent bulk materials.


Contrasting levels of DNA polymorphism at the autosomal and X-linked visual color pigment loci in humans and squirrel monkeys.
The X-linked color pigment (opsin) locus is known to be highly polymorphic in the squirrel monkey and other New World monkeys. To see whether this is also the case for the autosomal (blue) opsin locus, we obtained 32 squirrel monkey and 30 human blue opsin gene sequences. No amino acid polymorphism was found in either the squirrel monkey sample or the human sample, contrary to the situation at the X-linked opsin locus. This sharp contrast in the level of polymorphism might be due to differences in gene expression between the autosomal and the X-linked loci. At the X-linked locus, heterozygote advantage can occur because, owing to X-inactivation, the two alleles in a heterozygote are expressed in different cone cells, producing two types of cone cell, whereas at the autosomal locus, heterozygote advantage cannot occur because the two alleles in a heterozygote are expressed in the same cone cells, producing only one type of cone cell (i.e., phenotypically a homozygote). From the sequence data, the levels of nucleotide diversity (pi, i.e., the number of nucleotide differences per site) are estimated: for the human sample, pi = 0.00% per nondegenerate site, 0.00% per twofold degenerate site, and 0.04% per fourfold degenerate site in the coding regions and 0.01% per site in intron 4; for the squirrel monkey sample, pi = 0.00% per nondegenerate site, 0.00% per twofold degenerate site, and 0.15% per fourfold degenerate site in the coding regions and 0.17% per site in intron 4. The blue opsin genes from the common and pygmy chimpanzees, the gorilla, the capuchin, and the howler monkey were also sequenced. Features critical to the function of the opsin are well conserved in all known mammalian sequences. However, the interhelical loops are, on average, actually more conservative than the transmembrane helical regions. In addition, these sequence data and those from some other genes indicate that the common and pygmy chimpanzees are not closely related, their divergence data being from one third to one half the date of the human-chimpanzee divergence.


Endoscopic extraperitoneal radical prostatectomy: oncological and functional results after 700 procedures.
We review our experience with endoscopic (totally) extraperitoneal radical prostatectomy (EERPE) as first line therapy for localized prostate cancer. A total of 700 consecutive patients underwent EERPE. Mean patient age was 63.4 years (range 42 to 77). Mean preoperative prostate specific antigen was 10.7 ng/ml (range 1.4 to 82). A total of 206 patients (29.4%) had a history of previous lower abdominal or pelvic surgery including inguinal hernioplasty with mesh placement and 43 patients (6.1%) had a history of prostatic intervention (transurethral resection of the prostate, high intensity focused ultrasound, Millin prostatectomy, radiotherapy). After preparation of the preperitoneal space the technique of EERPE duplicates the steps of classic open descending retropubic radical prostatectomy including a nerve sparing EERPE when indicated. Mean operative time was 151 minutes (range 50 to 320). There was no conversion and the transfusion rate was 0.9% in 6. Four patients (0.6%) had intraoperative rectal injuries which were treated endoscopically with a 2-layer suture. A total of 14 patients (2%) required early and 3 patients (0.4%) required late postoperative reintervention. Pathological stage was pT2a in 89 patients (12.7%), pT2b in 54 (7.7%), pT2c in 245 (35%), pT3a in 229 (32.7%), pT3b in 79 (11.2%) and pT4 in 4 patients (0.6%). Positive surgical margins were found in 10.8% (42 of 388) of patients with a pT2 tumor and in 31.2% (96 of 308) of patients with a pT3 tumor. Pelvic lymph node dissection was performed in 266 patients (38%), of whom 14 (5.3%) were found to have lymph node involvement. Mean catheterization time was 6.2 days. Six months after surgery 83.8% of the patients were completely continent, 10.4% needed 1 to 2 pads daily and 5.8% of patients needed more than 2 pads daily. Of all patients who underwent nerve sparing procedures, 100 patients had a postoperative followup of 6 months. Of the 66 patients with the unilateral nerve sparing approach 8 (12.1%) had erections sufficient for intercourse and 16 of 34 patients (47.1%) with the bilateral nerve sparing procedure had erections sufficient for intercourse with or without the help of phosphodiesterase type 5 inhibitors. The results of this series are promising. Perioperative morbidity is low, and short-term oncological and functional results are favorable. Although the followup is too short to draw definite conclusions, it is obvious that a nerve sparing approach in EERPE is feasible and reproducible. Our data demonstrate that EERPE can be performed with equal efficacy and results compared with laparoscopic transperitoneal radical prostatectomy, while providing the ease and safety of a totally extraperitoneal approach, completely avoiding intraperitoneal complications.


Symptom validity indices in the Posttraumatic Stress Disorder Checklist for DSM-5.
The use of symptom validity tests (SVTs) is standard practice in psychodiagnostic assessments. Embedded measures are indices within self-report measures. To date, no embedded SVTs have been identified in the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5). This research aimed to develop and validate PCL-5 SVTs in two samples of veterans. Participants completed one of two prospective research studies that included cognitive and psychological tests. Participants in Study 1 were veterans (N = 464) who served following the September 11, 2001, terrorist attacks; participants in Study 2 were veterans or service members (N = 338) who had been deployed to Iraq and/or Afghanistan. Both studies included the PCL-5 and the Structured Inventory of Malingered Symptomatology (SIMS), the latter of which served as the criterion for identifying PCL-5 SVTs. For Study 1, two separate SVTs were developed: the PCL-5 Symptom Severity scale (PSS), based on the PCL-5 total score, and the PCL-5 Rare Items scale (PRI), based on PCL-5 items infrequently endorsed at the highest item ratings. At the most conservative SIMS cutoff score, the PSS achieved excellent discrimination for both the Study 1, AUC = .840, and Study 2 samples, AUC = .858, with specific cutoff scores of ≥ 51 and ≥ 56 maximizing sensitivity while maintaining a specificity of .90. The PRI achieved good discrimination, AUCs = .760 and.726, respectively, with a cutoff score of 2 or higher indicated by both studies. The results of these two studies provide provisional support for these two embedded SVTs in the PCL-5.


Silica Modified Chitosan/Polyethylenimine Nanogel for Improved Stability and Gene Carrier Ability.
Although chitosan-based hydrogel has been widely used as a gene carrier material, further improvement in this aspect is still needed. Herein a new method was proposed for preparing the effective chitosan-based gene carrier nanogel. The new method based on the fact that supra-molecular interactions between silica, polyethylenimine (PEI) and chitosan could be used to self-assemble them together to form a rigid and stable gene carrier material in the reverse microemulsion system. When compared with chemical cross-linking route, the proposed method is simple and easy to adjust components of the resulting nanogel and, therefore, can improve its gene carrying ability. Our results showed that, doping of the PEI and silica into the chitosan hydrogel obviously increased its strength, stability and gene carrying ability.


Emerging role of nanocarriers based topical delivery of anti-fungal agents in combating growing fungal infections.
The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.


The effect of acute and chronic exercise on steroid hormone fluctuations in young and middle-aged men.
The current study examine the effects of combined sprint and resistance training on serum total testosterone (TT), sex-hormone-binding globulin (SHBG) and cortisol (C), at rest, and in response to the Wingate Anaerobic-Test (WAnT) in 21 and 41 years old men. Forty moderately-trained men were randomly assigned to a young trained (YT), young control (YC), middle-aged trained (MAT), and middle-aged control (MAC) group. Before (P1), and after (P2) training, blood samples were collected at rest and after exercise. At P1, higher C and lower TT was observed in middle-aged groups compared to younger ones (P < 0.05). At P2, basal TT increased significantly (P < 0.05) in MAT and the age-difference was absent between trained groups (P > 0.05). Basal SHBG decreased significantly in YT at P2 (P < 0.05) but did not change in other groups from before to after training (P > 0.05). Free-testosterone was significantly (P < 0.05) higher in young compared to middle-aged groups at P1, but at P2, this age-related difference disappeared between YT and MAT (P > 0.05). C post-WAnT increased significantly for MAT only (P < 0.05) at P2, whilst no significant changes were observed in the other three groups (P < 0.05) at P2. In contrast, resting levels of C did not change in all groups at P2 (P > 0.05). The current study demonstrates that this training intervention may help increase steroids hormones in middle-aged men and counteract the negative effect of age on TT and free testosterone.


[Autophagy in chronic liver diseases: a friend rather than a foe?]
Within recycling damaged cell components, autophagy maintains cell homeostasis. Thus, it has been anticipated that autophagy would play an essential role in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most prevalent chronic liver diseases in Western countries, sharing common histopathologic features and a common disease progression. In this review, we discuss the role of autophagy at different stages of NAFLD and ALD as well as in liver regeneration and hepatocarcinogenesis.


Interferon γ -induced chemokines in psoriatic arthritis.
Interferon γ-inducible protein (IP-10) chemokine is implicated in the pathogenesis of psoriatic arthritis (PsA). It was shown that chemokine (C-X-C motif) receptor (CXCR) 3 and CXCR4 were expressed by both blood-derived plasmacytoid dendritic cells (pDCs) and pDCs isolated from rheumatoid arthritis (RA) and PsA synovial fluid (SF) and that IP-10, chemokine (C-X-C motif) ligand (CXCL)-11, and CXCL-12 present in RA and PA SF stimulated chemotaxis of blood-derived pDCs. High circulating levels of IP-10 and chemokine (C-C motif) ligand (CCL) 2 have been found in PsA patients, with a T helper cells (Th) 1 immune predominance in the early phase of the disease. Moreover a decline of IP-10 levels has been observed in long lasting PsA, with a significant increase of the CCL2/IP-10 ratio, suggesting a shift from Th1 to Th2 immune response in long duration PsA. IP-10 levels in PsA patients are significantly higher in presence of autoimmune thyroiditis. IP-10 has been suggested to be a good marker to monitor the activity or progression of PsA. Attempts have been made to modulate or inhibit the production of IP-10 in PsA in order to modify the course of the disease.


Adrenopause - does it really exist?
In ageing human adrenal glands there occur some morphological changes which result in alterations of their cortex endocrine function. Glucocorticoid-excreting cells in the zona glomerulosa live longer than androgen-producing cells in the zona reticularis, which undergo significant apoptosis. Therefore, in elderly humans cortisol levels are normal (significantly higher than at young age), while adrenal androgen concentrations decline with ageing. Function of the zona glomerulosa is affected by the adrenal status, circulatory system condition, efficiency of the kidneys and liver and medication. An important problem of ageing is the rising incidence of non-secreting, incidentally detected, benign adrenal tumors, called incidentalomas. They necessitate clear-sighted radiological and hormonal diagnosis.


Acyclic nucleoside phosphonates containing a second phosphonate group are potent inhibitors of 6-oxopurine phosphoribosyltransferases and have antimalarial activity.
Acyclic nucleoside phosphonates (ANPs) that contain a 6-oxopurine base are good inhibitors of the Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) 6-oxopurine phosphoribosyltransferases (PRTs). Chemical modifications based on the crystal structure of 2-(phosphonoethoxy)ethylguanine (PEEG) in complex with human HGPRT have led to the design of new ANPs. These novel compounds contain a second phosphonate group attached to the ANP scaffold. {[(2-[(Guanine-9H-yl)methyl]propane-1,3-diyl)bis(oxy)]bis(methylene)}diphosphonic acid (compound 17) exhibited a Ki value of 30 nM for human HGPRT and 70 nM for Pf HGXPRT. The crystal structure of this compound in complex with human HGPRT shows that it fills or partially fills three critical locations in the active site: the binding sites of the purine base, the 5'-phosphate group, and pyrophosphate. This is the first HG(X)PRT inhibitor that has been able to achieve this result. Prodrugs have been synthesized resulting in IC50 values as low as 3.8 μM for Pf grown in cell culture, up to 25-fold lower compared to the parent compounds.


Exogeneous and endogenous CCK inhibit ethanol ingestion in Sardinian alcohol-preferring rats.
Ethanol ingestion, like food ingestion, stimulates release of the signaling molecule cholecystokinin (CCK) from the small intestine. Here, we investigated the possibility that ethanol-induced CCK release might be a negative-feedback control of ethanol ingestion, similar to its function as part of the mechanism by which ingested food produces meal-ending satiation. We used Sardinian alcohol-preferring (sP) and Marchesian Sardinian (msP) alcohol-preferring rats, two apparently identical substrains that spontaneously ingest pharmacologically relevant amounts of ethanol, as well as their background strain, Wistar (W) rats. We demonstrated that: (1) intraperitoneal (IP), but not intracerebroventricular, injections of 0.5-4 microg/kg CCK-8 produced transient, dose-related reductions in 10% ethanol ingestion; (2) this inhibitory effect of CCK-8 on ethanol intake appeared behaviorally similar to its inhibitory action on ingestion of sucrose solutions; (3) the inhibitory effect of IP CCK-8 on ethanol ingestion occurred without evidence of tolerance when tests were repeated on consecutive days; (4) IP CCK-8 reduced ethanol intake despite simultaneously reducing blood ethanol levels (BALs); and (5) antagonism of CCK1 receptors with devazepide increased ethanol intake, indicating that endogenous CCK normally limits the size of bouts of ethanol ingestion. These results implicate peripheral CCK in the control of ethanol ingestion in sP and msP alcohol-preferring rats.


Synthesis and Dual-Emission Feature of Salen-Al/Triarylborane Dyads.
Novel salen-Al/triarylborane dyad complexes were prepared and characterized with their corresponding mononuclear compounds. The UV-vis and photoluminescence experiments for dyads exhibited photoinduced energy transfer from borane to the salen-Al moiety in an intramolecular manner. Theoretical calculation and fluoride titration results further supported these intramolecular energy-transfer features.


End-of-life decisions: an important theme in the care for people with intellectual disabilities.
While end-of-life decisions in the general population have received attention in several countries, not much is known about this in people with intellectual disabilities (IDs). Therefore, the prevalence and nature of end-of-life decisions were investigated in a Dutch centre providing residential care for 335 people with IDs. A retrospective study of medical files of people who died between January 2002 and July 2007. One or more end-of-life decisions were taken in 27 out of 47 cases. A non-treatment decision was taken for seven residents, possibly shortening life expectancy in some cases. The family was involved in decision making in half of the 27 cases. No information was found about the process of end-of-life decision making. There was no evidence in the notes that any of the people with IDs was asked for his or her own opinion in taking an end-of-life decision. This study demonstrates that medical end-of-life decisions played a part in significant numbers of people with IDs who have died within this centre, but further studies are needed to establish decision-making processes.


Electrospun Fibers of Biocompatible and Biodegradable Polyesters, Poly(Ethylene Oxide) and Beeswax with Anti-Bacterial and Anti-Fungal Activities.
Fibrous materials composed of core-sheath fibers from poly(ethylene oxide) (PEO), beeswax (BW) and 5-nitro-8-hydroxyquinoline (NQ) were prepared via the self-organization of PEO and BW during the single-spinneret electrospinning of a homogeneous blend solution of the partners. Additionally, the application of the same approach enabled the preparation of fibrous materials composed of core-double sheath fibers from PEO, poly(L-lactide) (PLA) and NQ or 5-chloro-7-iodo-8-hydroxyquinoline (CQ), as well as from PEO, poly(ε-caprolactone) (PCL) and NQ. The consecutive selective extraction of BW and of the polyester with hexane and tetrahydrofuran, respectively, evidenced that core-double sheath fibers from PEO/polyester/BW/drug consisted of a PEO core, a polyester inner sheath and a BW outer sheath. In order to evaluate the possibility of the application of fibrous materials from PEO/BW/NQ, PEO/PLA/BW/NQ, PEO/PCL/BW/NQ and PEO/PLA/BW/CQ for plant protection, microbiological studies were performed using both phytopathogenic microorganisms (Pseudomonas corrugata, Fusarium graminearum and Fusarium avenaceum) and beneficial microorganisms (Pseudomonas chlororaphis, Bacillus amyloliquefaciens and Trichoderma asperellum). It was found that the fibrous materials had anti-bacterial and anti-fungal activity against both phytopathogenic and beneficial microorganisms. This is the first report on the activity of fibrous materials loaded with 8-hydroxyquinoline derivatives not only against phytopathogenic but also against beneficial microorganisms that are of importance in agriculture.


Development of a strategy to control the dissolved concentrations of oxygen and carbon dioxide at constant shear in a plant cell bioreactor.
To examine the effects of volatile components on plant cell growth, a bioreactor control system was developed to simultaneously control the dissolved concentrations of both oxygen and carbon dioxide. The first step in this work was to develop a mathematical model to account for gas-liquid mass transfer; biological utilization and production of O(2) and CO(2); and the series of chemical reactions of CO(2) in water. Using this model and dynamic measurements for dissolved O(2) and CO(2), it was observed that (1) both absorption and desorption of a volatile component could be described by a single mass transfer coefficient, K(l)a, and (2) K(l)a values for oxygen and carbon dioxide transfer were directly proportional. The second step of this work was to employ the mathematical model in an adaptive feed-forward strategy to control the dissolved O(2) and CO(2) concentrations by manipulating the inlet gas composition to the bioreactor. This strategy allowed dissolved concentrations to be controlled without the need for changing either the total gas flow rate or agitator speed. Adaptive control was required because the volumetric rates of O(2) and CO(2) consumption and production vary with time during long term operation and therefore these rates must be continually updated. As the final step, we demonstrated that this control strategy was capable of controlling the dissolved gas concentrations in both short- and long-term studies involving the cultivation of Catharanthus roseus plant cells.


Deficiency of intrarenal angiotensin II type 2 receptor impairs paired homeo box-2 and N-myc expression during nephrogenesis.
We previously demonstrated that angiotensin II (Ang II) stimulates paired homeo box-2 (Pax-2) via the Ang II type 2 receptor (AT(2)R). The Pax-2 gene and N-myc play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation in embryonic mesenchymal cells and embryonic mouse kidneys. Since AT(2)R knock-out (KO) mice have a phenotype that is similar to that of humans with congenital renal and urinary tract anomalies (CAKUT) and develop hypertension in adulthood, these mice and wild-type controls were used for this study. Embryonic kidneys isolated from E12 to term gestation were cultured in Dulbecco's modified Eagle's medium (DMEM) with or without Ang II (10(-6) M) for 24 h ex vivo. Renal morphogenesis was histologically assessed. Mean glomerular tuft volume was determined by the method of Weibel and Gomez with the aid of image analysis software. Pax-2 and N-myc gene expression were determined by immunostaining as well as by Western blotting and real-time-quantitative polymerase chain reaction (RT-qPCR). Glomerular size was significantly smaller, and Pax-2 and N-myc expression down-regulated, in kidneys of AT(2)R KO mice compared with those of wild-type mice. In ex vivo studies, Ang II stimulated Pax-2 and N-myc mRNA expression in embryonic kidneys of wild-type mice, but this stimulatory effect was absent in embryonic kidneys of AT(2)R KO mice. Taken together, these data indicate that intrarenal AT(2)R plays an important role in nephrogenesis. Deficiency of AT(2)R may impair both Pax-2 and N-myc expression, eventually resulting in glomerular hyperfiltration that may, ultimately, lead to later development of hypertension.


An antibody to the beta-secretase cleavage site on amyloid-beta-protein precursor inhibits amyloid-beta production.
Proteolytic cleavage of amyloid-beta-protein precursor (AbetaPP) by beta- and gamma-secretases results in production of the amyloid-beta peptide (Abeta) that accumulates in the brains of sufferers of Alzheimer's disease (AD). We have developed a monoclonal antibody, 2B12, which binds in the vicinity of the beta-secretase cleavage site on AbetaPP but does not bind within the Abeta region. We hypothesised that this antibody, directed against the substrate rather than the enzyme, could inhibit cleavage of AbetaPP by beta-secretase via steric hindrance and thus reduce downstream production of Abeta. The antibody would enter cells by binding to AbetaPP when it is at the cell surface and then be internalised with the protein. We subsequently demonstrated that, after addition of 2B12 to standard growth media, this antibody was indeed capable of inhibiting Abeta40 production in neuroblastoma and astrocytoma cells expressing native AbetaPP, as measured by an ELISA. This inhibition was both concentration- and time-dependent and was specific to 2B12. We were only able to inhibit approximately 50% of Abeta40 production suggesting that not all AbetaPP is trafficked to the cell surface. We propose that this antibody could be used as a novel, putative therapy for the treatment of AD.


High-spin electronic states of lanthanide-arene complexes: Nd(benzene) and Nd(naphthalene).
Neodymium (Nd) complexes of benzene and naphthalene were synthesized in a laser-ablation supersonic molecular beam source. High-resolution electron spectra of these complexes were obtained using pulsed-field ionization zero electron kinetic energy (ZEKE) spectroscopy. Second-order Møller-Plesset perturbation calculations were employed to aid spectral and electronic-state assignments. The adiabatic ionization energies were measured to be 38 081 (5) cm(-1) for Nd(benzene) and 37 815 (5) cm(-1) for Nd(naphthalene). For the Nd(benzene) complex, the observed frequencies of 831 and 286 cm(-1) were assigned to C-H out-of-plane bending and Nd(+)-C(6)H(6) stretching modes in the (6)A(1) ion state and 256 cm(-1) to the Nd-C(6)H(6) stretching mode in the (7)A(1) neutral state. To confirm these assignments, the ZEKE spectrum of the deuterated species was recorded, and the corresponding vibrational frequencies were measured to be 710 and 277 cm(-1) in the ion state and 236 cm(-1) in the neutral state. For the Nd(naphthalene) complex, the observed vibrational modes were C(10)H(8) bending (394 cm(-1)), Nd(+)-C(10)H(8) stretching (286 and 271 cm(-1)), Nd(+)-C(10)H(8) bending (80 cm(-1)), and C(10)H(8) twisting (105 cm(-1)) in the (6)A(') ion state and metal-ligand bending (60 cm(-1)) and ligand twisting (55 cm(-1)) in the (7)A(') neutral state. The formation of the ground state of the Nd(benzene) complex requires 4f → 5d and 6s → 5d electron excitation of the Nd atom, whereas the formation of the ground state of Nd(naphthalene) involves the 6s → 5d electron promotion.


Clinical study and results of surgical treatment in 146 oligospermic men with varicocele.
Data of 146 infertile men undergoing surgical treatment for varicocele are reported. Patients with the following features were treated by surgery: normal FSH (follicle-stimulating hormone) not severe hypotrophy of the left testis and normal right testis; absence of azoospermia; absence of autosome or sex chromosome alterations; absence of signs of genital inflammation. A clear-cut improvement in the condition of seminal secretion was obtained both in oligospermic patients with less than 10 millions spermatozoa per ml preoperatively, and in patients with a higher number of spermatozoa. Particularly, a marked improvement in the valid motility and morphology of spermatozoa was observed. The biological index of a successful treatment in correcting infertility is represented by the high number (51) of successful pregnancies in the wives of operated patients. It is to be underlined that measurements of spermatic vein pressure, phlebography and intraoperative cineradioscopy completely avoid recurrence that otherwise affects about 5 to 6% of operated patients.


[EFFECT OF DIFFERENT NECK-SHAFT ANGLE ON EFFICACY IN TREATMENT OF PROXIMAL HUMERAL FRACTURES WITH LOCKING PLATE].
To observe the influence of different humeral neck-shaft angle on the efficacy in the treatment of proximal humeral fractures with locking plate. A total of 106 patients with proximal humeral fractures were treated by locking plate between March 2009 and March 2013, and the clinical data were retrospectively analyzed. Of 106 cases, 58 were male and 48 were female, aged from 26 to 71 years (mean, 52.3 years). The causes were traffic accident injury in 54 cases, falling injury from height in 23 cases, falling injury in 21 cases, and others in 8 cases. According to the Neer classification, there were 32 cases of two-part fractures, 65 cases of three-part fractures, and 9 cases of four-part fractures. The time from injury to operation was 1-7 days (mean, 2.7 days). According to neck-shaft angle by X-ray measurements at 1-3 days after operation, the patients were divided into 3 groups: valgus group (> 145°), normal group (126-145°), and varus group (< 126°) to observe the influence of neck-shaft angle on efficacy. According to postoperative humeral neck-shaft angle, there were 10 cases in valgus group, 75 cases in normal group, and 21 cases in varus group. There was no significant difference in general clinical data among 3 groups (P > 0.05). The patients were followed up 6-12 months. The X-ray results showed fracture healing, and no significant difference was found in fracture healing time among 3 groups (P>0.05). After 6 months, the varus angle of femoral head and visual analogue scale (VAS) score of normal group were significantly lower than those of valgus group and varus group (P < 0.05). The excellent and good rate of Constant-Murley score was 78.67% (59/75) in normal group, and it was significantly higher than that in valgus group (60.00%, 6/10) and varus group (42.86%, 9/21) (P < 0.05), but there was no significant difference between valgus group and varus group (P > 0.05). The complication rate was 28.57% (6/21) in varus group, was 10.67% (8/75) in normal group, and was 20.00% (2/10) in valgus group, showing no significant difference among 3 groups (χ2 = 4.31, P = 0.12). Reconstruction of normal neck-shaft angle is the key to good shoulder function and clinical efficacy in the treatment of proximal humeral fracture.


A preliminary evaluation of immune stimulation following exposure to metal particles and ions using the mouse popliteal lymph node assay.
The objective of this preliminary study was to evaluate the threshold for immune stimulation in mice following local exposure to metal particles and ions representative of normal-functioning cobalt-chromium (CoCr) metal-on-metal (MoM) hip implants. The popliteal lymph node assay (PLNA) was used in this study to assess immune responses in BALB/c mice following treatment with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3 and NiCl2), or Cr2O3 particles together with metal salts using single-dose exposures representing approximately 10days (0.000114mg), 19years (0.0800mg), and 40years (0.171mg) of normal implant wear. The immune response elicited following treatment with Cr2O3 particles together with metal salts was also assessed at four additional doses equivalent to approximately 1.5months (0.0005mg), 0.6years (0.0025mg), 2.3years (0.01mg), and 9.3years (0.04mg) of normal implant wear. Mice were injected subcutaneously (50μL) into the right hind foot with the test article, or with the relevant vehicle control. The proliferative response of the draining lymph node cells (LNC) was measured four days after treatment, and stimulation indices (SI) were derived relative to vehicle controls. The PLNA was negative (SI<3) for all Cr2O3 particle doses, and was also negative at the lowest dose of the metal salt mixture, and the lowest four doses of the Cr2O3 particles with metal salt mixture. The PLNA was positive (SI>3) at the highest two doses of the metal salt mixture and the highest three doses of the Cr2O3 particles with the metal salt mixture. The provisional NOAEL and LOAEL values identified in this study for immune activation corresponds to Co and Cr concentrations in the synovial fluid approximately 500 and 2000 times higher than that reported for normal-functioning MoM hip implants, respectively. Overall, these results indicate that normal wear conditions are unlikely to result in immune stimulation in individuals not previously sensitized to metals.


Electronic effects of peripheral substituents at porphyrin meso positions.
Porphyrins are stable molecules with a macrocyclic conjugated system and often peripheral substituents. This unique structure makes the electronic properties of the four meso-carbons (the methine bridges) nearly identical. Replacement of the weakly electron-polarizing 2,4-vinyl groups of protoporphyrin IX with strongly electron-polarizing acetyl groups not only leads to much lower meso-carbon reactivities toward electrophilic aromatic substitution but also results in a significant meso-selectivity (the beta- and gamma-meso-positions become much more nucleophilic (basic) than the alpha- and delta-meso-positions). To further investigate the relationship between the porphyrin meso-carbon reactivities and the peripheral substituents, two monoacetylporphyrin analogues also were synthesized. This investigation not only leads to empirical rules for predicting porphyrin meso-carbon selectivities but also provides important models for theoretical calculations of porphyrin aromaticity.


Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and recombinant human beta interferon alone and in combination on simian varicella virus infection in monkeys.
Treatment of viral infections with combinations of antiviral agents may permit administration of reduced doses of either or both drugs. Lowered doses may reduce associated toxicity. Intravenous administration of substantial doses of either human recombinant beta interferon (rHuIFN-beta) or 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) prevents development of simian varicella virus infection in African green monkeys. Daily doses of 2 X 10(6) U of rHuIFN-beta/kg inhibited clinical disease in monkeys inoculated with simian varicella virus, and doses of DHPG between 20 and 60 mg/kg per day were necessary for similar antiviral effects. Intravenous administration of combinations of rHuIFN-beta and DHPG permitted an approximately 100-fold reduction in the effective dose of rHuIFN-beta and a 10-fold reduction in the effective dose of DHPG. Analysis of data relating to viremia by using the method of the median-effect principle showed the combination of rHuIFN-beta and DHPG was strongly synergistic in treatment of this infection.


[The role of salt regime and modulation of hemorheologic effects of trental in rats with experimental circulatory insufficiency].
Experiments on rats showed that experimental circulatory insufficiency negatively affects the hemorrcological properties. A change in the mineral intake influences some of the hemorreological characteristics. The sodium chloride substitute hyposol (giposol) increased the osmotic resistance reduced the cholesterol level in the erythrocyte membranes On the gyposol background, trental normalized the volume blood flow. Thus, balanced mineral compositions may be a useful additional component in the complex therapy of circulatory insufficiency.