The role of TrkA in the promoting wounding-healing effect of CD271 on epidermal stem cells.
CD271, a receptor of nerve growth factor (NGF), affects the biological properties of epidermal stem cells (eSCs) which are essential for skin wound closure. Tropomyosin-receptor kinase A (TrkA), another receptor of NGF, combined with CD271 has been involved with nervous system and skin keratinocytes. However, the exact role of TrkA combined with CD271 in eSCs during skin wound closure is still unclear. This study aimed to reveal the role of TrkA in the promoting wounding-healing effect of CD271 on eSCs. We obtained CD271-vo (over-expression of CD271) eSCs by lentiviral infection. K252a was used to inhibit TrkA expression. Full-thickness skin mouse wound closure model (5 mm in diameter) was used to detect the ability of CD271 over-expressed/TrkA-deficient during wound healing. The biological characteristics of eSCs and their proliferation and apoptosis were detected using immunohistochemistry and western blot. The expressions of protein kinase B (pAkt)/Akt, phosphorylated extracellular-signal-related kinase (pERK)/ERK1/2, and c-Jun N-terminal kinase (pJNK)/JNK were also detected by western blot. We found that over-expression of CD271 promoted the biological functions of eSCs. Interestingly, over-expression of CD271 in the absence of TrkA neither promoted eSCs' migration and proliferation nor promoted wound healing in a mouse model. In addition, we observed the reduced expression of pAkt/Akt and pERK/ERK1/2 following TrkA inhibition in vitro. Our studies demonstrated that the role of TrkA in the promoting wounding-healing effect of CD271 on eSCs.


Physicochemical properties of whey protein, lactoferrin and Tween 20 stabilised nanoemulsions: Effect of temperature, pH and salt.
Oil-in-water nanoemulsions were prepared by emulsification and solvent evaporation using whey protein isolate (WPI), lactoferrin and Tween 20 as emulsifiers. Protein-stabilised nanoemulsions showed a decrease in particle size with increasing protein concentration from 0.25% to 1% (w/w) level with Z-average diameter between 70 and 90 nm. However, larger droplets were produced by Tween 20 (120-450 nm) especially at concentration above 0.75% (w/w). The stability of nanoemulsions to temperature (30-90°C), pH (2-10) and ionic strength (0-500 mM NaCl or 0-90 mM CaCl2) was also tested. Tween 20 nanoemulsions were unstable to heat treatment at 90°C for 15 min. WPI-stabilised nanoemulsions exhibited droplet aggregation near the isoelectric point at pH 4.5 and 5 and they were also unstable at salt concentration above 30 mM CaCl2. These results indicated that stable nanoemulsions can be prepared by careful selection of emulsifiers.


Environmental modifications and 2-year measured and self-reported stair-use: a worksite randomized trial.
Environmental modifications have been shown to increase short-term stair use, longer-term success is unclear. This study assessed the 2-year effectiveness of an environmental intervention promoting worksite stair use. We assessed stair use at work by means of self-reports and infrared beam counters (which send a safe and invisible beam of infrared light from one side of a stairwell to a reflector on the other side; when an individual uses the stairs, the infrared beam is disrupted and an instance of stair use is recorded) at six worksites (three intervention, three control) in a group randomized, controlled worksite weight-gain prevention trial in Minneapolis/St. Paul, MN. Intervention modifications were signs encouraging stair use, music, and art posters in stairwells. We collected data before environmental modifications (2006-2007) and at the end of the 2-year intervention (2008-2009). The intervention had a significant positive effect on stair use measured both objectively and via self-report, with greatest increases reported among those participants who used the stairs least at baseline. Following 2-years of continuously-maintained stairwell modifications, increases in both objectively-measured and self-reported stair use were significantly larger at intervention than control worksites. Study findings suggest that the positive impact of environmental modifications on stair use persist over a longer time period than has been previously demonstrated. Results also indicate that infrequent stair users may be most amenable to the behavior changes encouraged by these environmental enhancements.


Collapsing-based and kernel-based single-gene analyses applied to Genetic Analysis Workshop 17 mini-exome data.
Recently there has been great interest in identifying rare variants associated with common diseases. We apply several collapsing-based and kernel-based single-gene association tests to Genetic Analysis Workshop 17 (GAW17) rare variant association data with unrelated individuals without knowledge of the simulation model. We also implement modified versions of these methods using additional information, such as minor allele frequency (MAF) and functional annotation. For each of four given traits provided in GAW17, we use the Bayesian mixed-effects model to estimate the phenotypic variance explained by the given environmental and genotypic data and to infer an individual-specific genetic effect to use directly in single-gene association tests. After obtaining information on the GAW17 simulation model, we compare the performance of all methods and examine the top genes identified by those methods. We find that collapsing-based methods with weights based on MAFs are sensitive to the "lower MAF, larger effect size" assumption, whereas kernel-based methods are more robust when this assumption is violated. In addition, many false-positive genes identified by multiple methods often contain variants with exactly the same genotype distribution as the causal variants used in the simulation model. When the sample size is much smaller than the number of rare variants, it is more likely that causal and noncausal variants will share the same or similar genotype distribution. This likely contributes to the low power and large number of false-positive results of all methods in detecting causal variants associated with disease in the GAW17 data set.


New 'marker swap' plasmids for converting selectable markers on budding yeast gene disruptions and plasmids.
Marker swap plasmids can be used to change markers for genes disrupted with nutritional markers in the yeast Saccharomyces cerevisiae. We describe 18 new marker swap plasmids, and we also review other plasmids available for marker conversions. All of these plasmids have long regions of flanking sequence identity, and thus the efficiency of homologous recombination mediated by marker conversion is very high. Marker swaps allow one to easily perform crosses to construct double mutant strains even if each of the disrupted strains contains the same marker, as is the case with the KanMX marker used in the yeast knockout collection. Marker swaps can also be used to change the selectable marker on plasmids, eliminating the need for subcloning.


Hypogonadotropic Hypogonadism in Infants with Congenital Hypopituitarism: A Challenge to Diagnose at an Early Stage.
Combined pituitary hormone deficiency (CPHD) presents a wide spectrum of pituitary gland disorders. The postnatal gonadotropic surge provides a useful period to explore the gonadotropic axis for assessing the presence of congenital hypogonadotropic hypogonadism (CHH). To explore the functioning of the hypothalamic-pituitary-gonadal axis in the postnatal gonadotropic surge for an early diagnosis of CHH in newborns or infants suspected of having CPHD. A cohort of 27 boys under 6 months and 19 girls under 24 months of age with suspected hypopituitarism was studied. Serum concentrations of LH, FSH, testosterone, inhibin B, anti-Müllerian hormone (AMH) and estradiol were measured, and male external genitalia were characterized as normal or abnormal (micropenis, microorchidism and/or cryptorchidism). CPHD was confirmed in 36 out of 46 patients. Low LH and testosterone levels were found in 66% of the hypopituitary males, in significant association with the presence of abnormal external genitalia. This abnormality had a positive predictive value of 93% for CHH. No significant association was observed between serum FSH, AMH and inhibin B and the patient's external genitalia. In newborn or infant boys with CPHD, LH and testosterone concentrations measured throughout the postnatal gonadotropic surge, together with a detailed evaluation of the external genital phenotype, facilitate the diagnosis of CHH at an early stage.


Resection of the patellar ligament: a complication of arthroscopic synovectomy.
Knee arthroscopy has evolved over the years to a point where most orthopaedic surgeons feel comfortable with both diagnostic and operative arthroscopy. As a result of the more powerful and sophisticated instrumentation available today, the role of operative arthroscopy has far surpassed original expectations. Certain instrumentation carries with it increased risk of both intraarticular and extraarticular injury if the surgeon fails to pay attention to anatomic landmarks. In this communication, we report a previously undescribed complication of operative arthroscopy--resection of the patellar ligament.


Intraspecific interference among larvae in a semivoltine dragonfly population.
This study focuses on ways that the size distribution of individuals influences the types and intensities of competitive interactions within a population of aquatic arthropod predators. Three field experiments and one laboratory experiment were designed to test for feeding interference, interference mortality, and dispersal effects within and between larval size classes of the primarily semivoltine dragonfly Tetragoneuria cynosura in Bays Mountain Lake. One field experiment documented the temporal pattern of colonization of large-mesh cylinders by the small, first-year-class larvae during a 30-day period; the results are consistent with passive (density-independent) colonization. A second field experiment examined the effect of large, second-year-class larvae at densities of 1 or 3 per cylinder (14 or 42 m-2) on colonization by small larvae; this colonization was inhibited at the high density of large larvae. In the laboratory experiment, when larvae of the two size-classes were together in the same aquarium, small larvae moved around less than when by themselves (dispersal inhibition). Thus the inhibition of colonization observed in the field may result from interference mortality, rather than from a flight response to the presence of larger conspecifics.To evaluate this interpretation, the third field experiment measured the in-situ functional response of large larvae to each other and to their small conspecific prey. Results suggest a type 1 (linear) functional response, with feeding inteference among large larvae. Moreover, the interference mortality inflicted by larger larvae on smaller conspecifics was apparently more intense on larger individuals within the small size-class. Taken together, the three field experiments and a statistical power analysis show how colonization and interference interact to determine the local density of small larvae, and why such interference effects are difficult to detect experimentally in the field.


High field magnetic resonance imaging of rodents in cardiovascular research.
Transgenic and gene knockout rodent models are primordial to study pathophysiological processes in cardiovascular research. Over time, cardiac MRI has become a gold standard for in vivo evaluation of such models. Technical advances have led to the development of magnets with increasingly high field strength, allowing specific investigation of cardiac anatomy, global and regional function, viability, perfusion or vascular parameters. The aim of this report is to provide a review of the various sequences and techniques available to image mice on 7-11.7 T magnets and relevant to the clinical setting in humans. Specific technical aspects due to the rise of the magnetic field are also discussed.


Effects of simulated microgravity on the expression of presynaptic proteins distorting the GABA/glutamate equilibrium--A proteomics approach.
Microgravity may cause cognition-related changes in the animal nervous system due to the resulting uneven flow of fluids in the body. These changes may restrict the long-term stay of humans in space for various purposes. In this study, a rat tail suspension model (30°) was used to explore the effects of 21 days of prolonged simulated microgravity (SM) on the expression of proteins involved in cognitive functions in the rat hippocampus. SM decreased the content of γ-aminobutyric acid (GABA) and increased the content of glutamate (Glu) in the rat hippocampus. A comparative (18)O-labeled quantitative proteomics strategy was applied to detect the differential expression of synaptic proteins under SM. Fifty-three proteins were found to be differentially expressed under SM. Microgravity induces difficulty in the formation of the SNARE complex due to the down-regulation of vesicle-associated membrane protein 3(VAMP3) and syntaxin-1A. Synaptic vesicle recycling may also be affected due to the dysregulation of syntaxin-binding protein 5 (tomosyn), rab3A and its effector rim2. Both processes are disturbed, indicating that presynaptic proteins mediate a GABA/Glu imbalance under SM. These findings provide clues for understanding the mechanism of the GABA/Glu equilibrium in the hippocampus induced by microgravity in space and represent steps toward safe space travel.


The fate of N-nitrosodiethanolamine after oral and topical administration to rats.
14C-labelled N-nitrosodiethanolamine ([14C]NDELA) was given to Osborne-Mendel rats at two dose levels, 0.5 or 50 mg/kg, by oral or topical administration. The excreta and tissues were analysed at various times from 4 hr to 1 wk after administration to determine the distribution of radioactivity. After oral administration, [14C]NDELA was rapidly absorbed from the gastro-intestinal tract, distributed throughout all organs and tissues, and then excreted, mainly via the kidneys. The tissue concentration reached a peak at 8 hr, but some activity remained after 1 wk. After topical application NDELA was slowly absorbed percutaneously, but once absorbed was distributed as in the orally dosed rats. Metabolic profiles of urine and bile samples from both the orally and topically dosed rats were identical, although the quantities varied. In addition to unchanged NDELA, one metabolite was present. The dose level had little effect on the quantities of unchanged NDELA or the metabolite present.


A radiographic study of dental development in the hypopituitary dwarf mouse.
Growth in body length, skeletal lengths, incisor lengths and molar root lengths were retarded in dwarf mice. The root lengths of third molars were more severely affected than those of other molars. The crown lengths at the enamel-cementum junction of upper and lower molars of most dwarf mice were significantly shorter than normal. The root canals of dwarf mice were smaller, apical closure was delayed and there was a delay in their eruption to the occlusal level. Although the size of the dentition was markedly affected in the dwarf mice, the functional relationship appeared to be unchanged.


Efficacy of Rho kinase inhibitor on cognitive impairment induced by chronic cerebral hypoperfusion in rats.
This work aims to explore the efficacy of Rho kinase inhibitor Fasudil on cognitive impairment induced by chronic cerebral hypoperfusion in rats. A total of 32 male adult Sprague Dawley (SD) rats were randomly divided into three groups: treatment group, control group and sham-operated group for severe carotid artery stenosis model. After two weeks, 8.35 mg/kg Fasudil and physiological saline were intraperitoneally applied twice per day in treatment group and control group, respectively. Morris water maze test was performed in each group to detect the changes of cognitive function and observe the hippocampal pathomorphology in rats after eight weeks. The average escape latency distinctly shortened (P < 0.01) and the percentage of swimming distance in the platform quadrant significantly increased (P < 0.01) in treatment group compared with those at corresponding time points in control group. The rate of carotid artery stenosis in rats had no statistical difference between treatment and control groups (P > 0.05). Fasudil effectively improved hippocampal pathomorphology. Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats.


How to determine if PPS will provide adequate resources for your population: one agency's experience.
Extensive research was conducted to develop the proposed Prospective Payment System (PPS) and to ensure that it will adequately cover the costs of care for Medicare beneficiaries receiving the home health benefit. However, there is tremendous variation among the patients served by agencies, meaning that the system will impact each agency somewhat differently. Using the methods outlined in this article, agencies can determine potential problem areas under PPS, enabling them to develop and implement solutions before October 1, 2000.


Is bone turnover a determinant of bone mass in rheumatoid arthritis?
To study the relationship between bone turnover markers and bone mineral density in patients with rheumatoid arthritis. We studied 54 patients, 24 of whom were receiving low dose steroids, and compared them to 54 age and sex matched controls. An 8.2% decrease of femoral neck bone mineral density (BMD) was found in patients not taking steroids compared with controls (confidence interval 1.2-15.3%). Serum markers of bone turnover -- namely, procollagen type I C-terminal propeptide (PICP) and procollagen type I N-terminal propeptide (PINP), which reflect bone formation, and procollagen type I C-terminal telopeptide, which reflects bone resorption -- were significantly increased compared with controls (p < 0.05, p < 0.01, p < 0.01, respectively). Both PINP levels and PICP levels were correlated with the femoral neck BMD as well as osteocalcin levels: R = -0.32 (p < 0.05), R = -0.29 (p < 0.05), and R = -0.42 (p < 0.01), respectively. The best independent predictors of bone mass (stepwise multiple regression analysis) at the femoral neck were steroid use, osteocalcin levels, age, height, the presence of rheumatoid factor, and the Health Assessment Questionnaire score, which explained 61.6% of the variance in femoral neck BMD. Elderly patients with RA using steroids with severe disease and high levels of osteocalcin have marked osteoporosis at the hip.


mKast is dispensable for normal development and sexual maturation of the male European honeybee.
The European honeybee (Apis mellifera L.) exhibits various social behaviors. The molecular and neural mechanisms underlying these behaviors have long been explored, but causal relations between genes or neurons and behaviors remain to be elucidated because effective gene manipulation methods in the honeybee have not been available until recently. We recently established a basic technology to produce mutant honeybee drones using CRISPR/Cas9. Here we produced mutant drones using CRISPR/Cas9 targeting mKast, which is preferentially expressed in a certain subtype of class I Kenyon cells that comprise the mushroom bodies in the honeybee brain. By immunoblot analysis, we showed that mKast protein expression was completely lost in the mutant drone heads. In addition, during the production process of homozygous mutant workers, we demonstrated that heterozygous mutant workers could be produced by artificial insemination of wild-type queens with the sperm of mutant drones, indicating that mKast mutant drones were sexually mature. These results demonstrate that mKast is dispensable for normal development and sexual maturation in drone honeybees, and allow us to proceed with the production of homozygous mutant workers for the analysis of a particular gene by gene knockout in the future.


A meta-analytic review of the Bethesda System for Reporting Thyroid Cytopathology: Has the rate of malignancy in indeterminate lesions been underestimated?
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a 6-tier diagnostic framework using uniform criteria in reports of thyroid aspirates. One of the major advantages of this framework is its association with defined risks of malignancy, allowing standardized management algorithms for each diagnosis. The objective of the current meta-analysis was to demonstrate the feasibility of using TBSRTC among specimens in the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for neoplasm (FN/SFN) categories. The authors also evaluated both the morphologic features and the risk of malignancy in the presence of Hurthle cells. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2008 to December2014. Studies were considered eligible only if they evaluated the risk of malignancy for specimens in the AUS/FLUS and/or FN/SFN categories and included surgical follow-up. In total, 51 articles were identified that used TBSRTC criteria and provided data for a total of 145,928 fine-needle aspiration (FNA) specimens. Of these, FNAs that had surgical follow-up were selected among the AUS/FLUS (N = 4475) and FN/SFN (N = 3202) specimens. The overall rate of malignancy was 27% for the AUS/FLUS category and 31% for the FN/SFN category. The AUS category was characterized by limited reported follow-up and surgical outcome. The data demonstrated that FNAs with an AUS diagnosis had a higher risk of malignancy than the risk according to published TBSRTC criteria, whereas the percentage of malignancy in FNAs with an FN/SFN diagnosis did not differ from that according to TBSRTC. Hurthle cell lesions represent a challenging category, underlying the importance of further studies to define whether they can be diagnosed in the AUS/FLUS category rather than the FN/SFN category.


Recovery of bioactive protein from bacterial inclusion bodies using trifluoroethanol as solubilization agent.
Formation of inclusion bodies poses a major hurdle in recovery of bioactive recombinant protein from Escherichia coli. Urea and guanidine hydrochloride have routinely been used to solubilize inclusion body proteins, but many times result in poor recovery of bioactive protein. High pH buffers, detergents and organic solvents like n-propanol have been successfully used as mild solubilization agents for high throughput recovery of bioactive protein from bacterial inclusion bodies. These mild solubilization agents preserve native-like secondary structures of proteins in inclusion body aggregates and result in improved recovery of bioactive protein as compared to conventional solubilization agents. Here we demonstrate solubilization of human growth hormone inclusion body aggregates using 30% trifluoroethanol in presence of 3 M urea and its refolding into bioactive form. Human growth hormone was expressed in E. coli M15 (pREP) cells in the form of inclusion bodies. Different concentrations of trifluoroethanol with or without addition of low concentration (3 M) of urea were used for solubilization of inclusion body aggregates. Thirty percent trifluoroethanol in combination with 3 M urea was found to be suitable for efficient solubilization of human growth hormone inclusion bodies. Solubilized protein was refolded by dilution and purified by anion exchange and size exclusion chromatography. Purified protein was analyzed for secondary and tertiary structure using different spectroscopic tools and was found to be bioactive by cell proliferation assay. To understand the mechanism of action of trifluoroethanol, secondary and tertiary structure of human growth hormone in trifluoroethanol was compared to that in presence of other denaturants like urea and guanidine hydrochloride. Trifluoroethanol was found to be stabilizing the secondary structure and destabilizing the tertiary structure of protein. Finally, it was observed that trifluoroethanol can be used to solubilize inclusion bodies of a number of proteins. Trifluoroethanol was found to be a suitable mild solubilization agent for bacterial inclusion bodies. Fully functional, bioactive human growth hormone was recovered in high yield from inclusion bodies using trifluoroethanol based solubilization buffer. It was also observed that trifluoroethanol has potential to solubilize inclusion bodies of different proteins.


Facial nerve neuroma: clinical, diagnostic, and surgical features.
Facial nerve neuromas are uncommon benign tumors. The diversity of tumor locations and their proximity to vital neurovascular structures create a variety of clinical situations, and the management strategy for each case differs. Two cases with tumors located at different sites and associated with different clinical presentations are discussed in terms of diagnosis and management.


Recurrent rewiring and emergence of RNA regulatory networks.
Alterations in regulatory networks contribute to evolutionary change. Transcriptional networks are reconfigured by changes in the binding specificity of transcription factors and their cognate sites. The evolution of RNA-protein regulatory networks is far less understood. The PUF (Pumilio and FBF) family of RNA regulatory proteins controls the translation, stability, and movements of hundreds of mRNAs in a single species. We probe the evolution of PUF-RNA networks by direct identification of the mRNAs bound to PUF proteins in budding and filamentous fungi and by computational analyses of orthologous RNAs from 62 fungal species. Our findings reveal that PUF proteins gain and lose mRNAs with related and emergent biological functions during evolution. We demonstrate at least two independent rewiring events for PUF3 orthologs, independent but convergent evolution of PUF4/5 binding specificity and the rewiring of the PUF4/5 regulons in different fungal lineages. These findings demonstrate plasticity in RNA regulatory networks and suggest ways in which their rewiring occurs.


Protocol for a Scalable StoryListening Intervention for Grief-Related Loneliness During COVID-19.
Social distancing during the COVID-19 pandemic limited how family, friends, and clinicians physically interacted with people who were dying and decreased communal opportunities for processing grief. These barriers can cause or exacerbate suffering due to loneliness while grieving. In this article, we describe the protocol for a brief storytelling intervention designed to reduce loneliness among families, friends, and clinicians grieving the death of a person during the time of COVID-19. We trained four StoryListening doulas (SLDs) to hold a welcoming space and listen to stories with curiosity and openness. The intervention included a video StoryListening session and two brief questionnaires, filled out before and two weeks after the encounter, assessing loneliness and quality of life. During sessions, SLDs invited participants to share their story of loss in their own words and in as much detail as preferred. When participants felt a sense of story completion, SLDs shared validating statements and expressed gratitude to the participant for sharing. The video and audio for each participant's StoryListening encounter were recorded and the participant was offered an audio copy of their session.


House modifications as a malaria control tool: how does local context shape participants' experience and interpretation in Uganda?
Evidence that house design can provide protection from malaria is growing. Housing modifications such as screening windows, doors, and ceilings, and attaching insecticide-impregnated materials to the eaves (the gap between the top of the wall and bottom of the roof), can protect against malaria. To be effective at scale, however, these modifications must be adopted by household residents. There is evidence that housing modifications can be acceptable, but in-depth knowledge on the experiences and interpretation of modifications is lacking. This qualitative study was carried out to provide a holistic account of the relationship between experiences and interpretations of four types of piloted housing modifications and the local context in Jinja, Uganda. Qualitative research was conducted between January to June 2021, before and during the installation of four types of housing modifications. The methods included nine weeks of participant observations in two study villages, nine focus group discussions with primary caregivers and heads of households (11-12 participants each), and nine key informant interviews with stakeholders and study team members. Most residents supported the modifications. Experiences and interpretation of the housing modifications were shaped by the different types of housing in the area and the processes through which residents finished their houses, local forms of land and property ownership, and cultural and spiritual beliefs about houses. To maximize the uptake and benefit of housing modifications against malaria, programme development needs to take local context into account. Forms of local land and house ownership, preferences, the social significance of housing types, and religious and spiritual ideas shape the responses to housing modifications in Jinja. These factors may be important in other setting. Trial registration Trial registration number is NCT04622241. The first draft was posted on November 9th 2020.


Microencapsulation of Aerococcus viridans with catalase and its application for the synthesis of dihydroxyacetone phosphate.
Dihydroxyacetone phosphate is essential for the synthesis of polyhydroxylated compounds used as components or precursors of active pharmaceutical substances, such as antibiotics or glycosidase inhibitors. Dihydroxyacetone phosphate was produced by enzymatic oxidation of L-alpha-glycerophosphate in the presence of glycerophosphate oxidase or Aerococcus viridans coimmobilized with a hydrogen peroxide-decomposing enzyme. The microencapsulation of A. viridans with catalase in sodium alginate showed a conversion of 98.5%; the conversion percentage remained constant in all five runs. Liquid chromatography of the product revealed that the product peak corresponded to that of the dihydroxyacetone phosphate internal standard. This indicated a high degree of product purity.


Synthesis and influencing factors of high-performance concrete based on copper tailings for efficient solidification of heavy metals.
Copper tailings containing a large amount of heavy metals such as Pb, Cu, As, Mn, and Cr discharged from its mining are a typical bulk solid waste, which is highly hazardous to human and the environment. This research proposed a sustainable and effective method for the environmentally sound utilization of copper tailings solid waste. A high-strength concrete material with copper tailings as the main raw material was successfully prepared, with a 28-day compressive strength of up to 85.35 MPa, the flexural strength reached 12.46 MPa, and the tailings utilization rate of 60%. The mechanical properties and heavy metal stabilization properties of the prepared high-performance concrete were obtained by adding coarse aggregates such as river sand, while changing the sand rate, cementitious material admixture and water-cement ratio. A long-term leaching experiment of the high-strength concrete material with 190 day was carried and proved that the material can be made with low or no risk of heavy metal contamination in copper tailings. Incorporation of copper tailings into the high-performance concrete hydration mainly contains three mechanisms: (i) Pore sealing effect generated by the formation of tailings geopolymer prompted the hardening of the geopolymer layer to form a monolithic package structure; (ii) The active SiO2 material in copper tailings reacts with Ca(OH)2 in the hydration products to produce a strong volcanic ash effect; (iii) the primary hydration of 3CaO·SiO2(C3S) and 3CaO·Al2O3(C3A) in the cement, and the secondary hydration reaction induced by the copper tailings and silica fume. These mechanisms are blended with each other to form a dense microstructure of the slurry, which embodies extremely high mechanical properties on a macroscopic scale, providing a reference role for the bulk utilization of copper tailings.


Aerobic decolorization of Acid Brilliant Scarlet GR by microbial community and the community dynamics during sequencing batch processes.
In this research, aerobic decolorization of Acid Brilliant Scarlet GR by microbial community was studied. Effects of conditions and dye concentraion on decolorization processes were investigated. Additionally, continuous decolorization was evaluated through sequencing batch tests and the microbial dynamics during this process was analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis. The results showed that 100 mg l⁻¹ of the dye was completely decolorized within 12 h, which was mainly caused by biodegradation. The optimal decolorization conditions were as follows: inoculation size 2.07 g l⁻¹ (wet cell pellet), rotation speed 150 r min⁻¹, pH 5.0-7.0 and 30 °C. The processes were well described by zero-order kinetics, and more than 700 mg l⁻¹ of the dye would inhibit the activity of the consortium. Furthermore, the microbial community exhibited high efficiency in sequencing batch processes for continuous decolorization. Microbial community structure shifted obviously when exposed to higher concentration of the dye (500 mg l⁻¹), and all the dominant microorganisms were affiliated with four different phyla of Actinobacteria, Bacteroidetes, Proteobacteria and Firmicutes.


The fate of sodium chlorite in simulated gastric and intestinal fluids and residues of chlorate in broiler chickens after oral administration of sodium chlorite.
The fate of sodium [36Cl]chlorite in simulated intestinal fluids and residues of chlorate in broiler chickens fed 0, 10, 100, or 1000 mg•kg-1 of dietary sodium chlorite for 7 days was determined. [36Cl]Chlorite was stable in water and simulated intestinal fluid during 6 h incubations but was rapidly degraded to chlorine dioxide, sodium chloride, and sodium chlorate in simulated gastric fluids. Addition of starch, citrate, or soybean shifted the relative proportions of chloroxyanions formed; addition of ferrous chloride caused quantitative formation of sodium chloride in gastric and intestinal fluids. [36Cl]Chlorite underwent reductive transformation when fortified into chicken serum. Residues of chlorate in broiler chickens ranged from 3.5 to 374 ng•g-1 in gizzard, were <6.8 to 126 ng•g-1 in liver and were <7.2 to 190 ng•g-1 in muscle when slaughtered with no withdrawal period. Data are presented suggesting that reductive processes govern the fate of chlorite when present in closed biological systems.


Parental perceptions of barriers to blood lead testing.
This study identified barriers to blood lead testing from the perspective of parents of young children eligible for Medicaid. Data were gathered from three focus groups. Participants were asked if they were familiar with the dangers of high blood lead levels, rationale for not having a child tested for blood lead, what would facilitate having blood lead testing, and how they wanted to learn about blood lead poisoning. Most parents (n=30) were unfamiliar with the causes and effects of lead poisoning. While many reported their child had been tested for lead, others were unsure because they were not told the purpose of blood draws. Participants suggested that having all services in one facility would decrease travel and thus facilitate blood lead testing; others wanted the discomfort associated with phlebotomy minimized. Participants preferred to learn about lead poisoning from low-literacy brochures, videos, and television ads. Nurses should institute measures in their practice sites to improve blood lead poisoning prevention education and blood lead testing rates and to reduce the pain and anxiety associated with this procedure.


Strain-selective effects of corticosterone on locomotor sensitization to cocaine and on levels of tyrosine hydroxylase and glucocorticoid receptor in the ventral tegmental area.
We have studied biochemical and behavioral effects of chronic corticosterone administration in two inbred rat stains (Fischer 344 and Lewis), known to differ in their hypothalamic-pituitary-adrenal axis and in their behavioral responses to drugs of abuse. First, we studied corticosterone regulation of phosphoproteins in the ventral tegmental area of sham- and corticosterone-treated Fischer and Lewis rats, by means of back-phosphorylation and two-dimensional gel electrophoresis and Western blotting analysis. Corticosterone administration upregulated tyrosine hydroxylase immunoreactivity and decreased glial-fibrillary acidic protein phosphorylation state in the ventral tegmental area of Fischer rats only, with no changes seen in Lewis rats. We also studied corticosterone effects on locomotor sensitization to cocaine, a behavior known to be regulated by the ventral tegmental area. In Fischer rats, chronic corticosterone pretreatment resulted in development of cocaine sensitization, which was absent in sham-pretreated Fischer rats. In contrast, Lewis rats developed cocaine sensitization either with or without corticosterone pretreatment. Thus, both biochemical and behavioral effects of corticosterone observed in Fischer rats were absent in Lewis rats. We next studied the possibility that certain transcription factors, thought to play a role in tyrosine hydroxylase expression, could be involved in these strain-selective effects of corticosterone. Corticosterone treatment decreased levels of glucocorticoid receptor immunoreactivity in the ventral tegmental area of Lewis rats, but not of Fischer rats. In addition, drug-naive Fischer rats showed higher ventral tegmental area levels of immunoreactivity of cyclic AMP response element binding protein than Lewis rats, with no effect of corticosterone observed in either strain. These findings suggest that hypothalamic-pituitary-adrenal axis modulation of responses to drugs of abuse is a genetically determined characteristic seen in Fischer rats, but absent in Lewis rats. We propose that corticosterone administration down-regulates the glucocorticoid receptor in the ventral tegmental area of Lewis rats, and thereby prevents other adaptations to corticosterone treatment, while in the ventral tegmental area of Fischer rats the lack of glucocorticoid receptor down-regulation and the high basal levels of cyclic AMP response element binding protein could facilitate the transcriptional, biochemical and behavioral actions of glucocorticoids.


Development of a novel vaccine against canine parvovirus infection with a clinical isolate of the type 2b strain.
In spite of an extensive vaccination program, parvoviral infections still pose a major threat to the health of dogs. We isolated a novel canine parvovirus (CPV) strain from a dog with enteritis. Nucleotide and amino acid sequence analysis of the isolate showed that it is a novel type 2b CPV with asparagine at the 426th position and valine at the 555th position in VP2. To develop a vaccine against CPV infection, we passaged the isolate 4 times in A72 cells. The attenuated isolate conferred complete protection against lethal homologous CPV infection in dogs such that they did not develop any clinical symptoms, and their antibody titers against CPV were significantly high at 7-11 days post infection. These results suggest that the virus isolate obtained after passaging can be developed as a novel vaccine against paroviral infection.


Multidrug-resistant Pseudomonas aeruginosa isolated from the urine of patients with urinary tract infection.
We report the clinical courses of 3 patients with urinary obstruction who developed acute pyelonephritis caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Genome fingerprinting was performed to clarify the route of cross-infection, and an imipenem-resistance gene was detected by the polymerase chain reaction (PCR) method. The study included 17 patients at our institute who had urinary tract infections caused by P. aeruginosa between January and December 1997. MDR was defined as that when all the minimum inhibitory concentrations (MICs) were determined to show resistance according to the breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS) for P. aeruginosa. Pulse-field gel electrophoresis (PFGE) was carried out for genome fingerprinting. PCR was used to detect the metallo-beta-lactamase gene ( bla(IMP)). Three strains were revealed for MDR. The strains were isolated from the 3 patients with urinary tract obstruction who developed acute pyelonephritis. The treatment consisted of urinary drainage for the obstructed urinary tract and parenterally administered antimicrobials. Although none of the strains was susceptible to any antimicrobials, all patients had favorable outcomes. PFGE revealed that two strains had an identical genotype, implying cross-infection between the patients. The bla(IMP) gene was not detected in any of the three strains. In febrile patients with urinary tract infection caused by MDR P. aeruginosa, treatment for urinary obstruction is strongly recommended. Initial empirical chemotherapy with antimicrobials to which the organism is not susceptible is often inevitable. Because there was epidemiological evidence of cross-infection with MDR P. aeruginosa, countermeasures against nosocominal infection are warranted.


Effect of protein kinase inhibitors on IL-8/NAP-1 release from human umbilical vein endothelial cells.
Several protein kinase inhibitors (PKIs) were investigated for their effects on IL-1 beta, TNF alpha and PMA-induced IL-8 production from human umbilical vein endothelial cells (HUVEC). IL-1 beta (ED50 0.07 ng/ml), TNF alpha (ED50 100 ng/ml) and PMA (ED50 20 ng/ml) induced IL-8 production that could be detected as early as 2 h following stimulation. Staurosporine, a potent but non-specific inhibitor of protein kinases, inhibited PMA-induced (IC50 2 nM) but not IL-1 beta or TNF alpha (IC50 > 200 nM) induced IL-8 production. Neither the cAMP-dependent PKI, KT5720, nor the tyrosine PKIs, genistein, tyrphostin (1-100 microM) or lavendustin A (0.0001-1 microM), inhibited IL-8 production elicited by IL-1 beta. However, the macrolide protein kinase inhibitor geldanamycin (IC50 = 30 nM), but not the closely related analog herbimycin A (5-500 nM), inhibited IL-8 production by 60%. Northern blot analysis of IL-8 mRNA revealed that staurosporine suppressed mRNA increase following stimulation by PMA but not by IL-1. It is proposed that a novel protein kinase susceptible to geldanamycin inhibition may be involved in IL-1-mediated signal transduction.


Prognostic significance of nucleolar assessment in invasive breast cancer.
Nucleolar morphometric features have a potential role in the assessment of the aggressiveness of many cancers. However, the role of nucleoli in invasive breast cancer (BC) is still unclear. The aims of this study were to investigate the optimal method for scoring nucleoli in IBC and their prognostic significance, and to refine the grading of breast cancer (BC) by incorporating nucleolar score. Digital images acquired from haematoxylin and eosin-stained sections from a large BC cohort were divided into training (n = 400) and validation (n = 1200) sets for use in this study. Four different assessment methods were evaluated in the training set to identify the optimal method associated with the best performance and significant prognostic value. These were: (i) a modified Helpap method; (ii) counting prominent nucleoli (size ≥2.5 µm) in 10 field views (FVs); (iii) counting prominent nucleoli in five FVs; and (iv) counting prominent nucleoli in one FV. The optimal method was applied to the validation set and to an external validation set, i.e. data from The Cancer Genome Atlas (n = 743). Scoring prominent nucleoli in five FVs showed the highest interobserver concordance rate (intraclass correlation coefficient of 0.8) and a significant association with BC-specific survival (P < 0.0001). A high nucleolar score was associated with younger age, larger tumour size, and higher grade. Incorporation of nucleolar score in the Nottingham grading system resulted in a higher significant association with survival than the conventional grade. Quantification of nucleolar prominence in five FVs is a cost-efficient and reproducible morphological feature that can predict BC behaviour and can provide an alternative to pleomorphism to improve BC grading performance.


Optimization of metals extraction from spent lithium-ion batteries by sulphuric acid and sodium metabisulphite through a techno-economic evaluation.
The main factors that affect the extraction of metals from spent lithium-ion batteries by acid leaching using H2SO4, and sodium metabisulphite, were evaluated and optimized through a set of experiments, framed by a techno-economic approach. The maximum value of the profit response was obtained with the highest possible values of acid concentration (2.5 M) and time (2 h), a liquid/solid ratio of 5 L/kg, and the lowest possible value of temperature (40 °C). After leaching, the electrodes active material contained in the metals decreased, while it was still significant in the graphite, as observed by scanning electron microscopy-energy dispersive spectrometry and x-ray powder diffraction. Even though the performed economic evaluation was a summarized outline it can be considered suitable to compare different leaching conditions and to determine the possible best combinations of factors that can optimize the profit response.


Sarcopenia provides extra value outside the PULP score for predicting mortality in older patients with perforated peptic ulcers.
Perforated peptic ulcer (PPU) remains challenging surgically due to its high mortality, especially in older individuals. Computed tomography (CT)-measured skeletal muscle mass is a effective predictor of the surgical outcomes in older patients with abdominal emergencies. The purpose of this study is to assess whether a low CT-measured skeletal muscle mass can provide extra value in predicting PPU mortality. This retrospective study enrolled older (aged ≥ 65 years) patients who underwent PPU surgery. Cross-sectional skeletal muscle areas and densities were measured by CT at L3 and patient-height adjusted to obtain the L3 skeletal muscle gauge (SMG). Thirty-day mortality was determined with univariate, multivariate and Kaplan-Meier analysis. From 2011 to 2016, 141 older patients were included; 54.8% had sarcopenia. They were further categorized into the PULP score ≤ 7 (n=64) or PULP score > 7 group (n=82). In the former, there was no significant difference in 30-day mortality between sarcopenic (2.9%) and nonsarcopenic patients (0%; p=1.000). However, in the PULP score > 7 group, sarcopenic patients had a significantly higher 30-day mortality (25.5% vs. 3.2%, p=0.009) and serious complication rate (37.3% vs. 12.9%, p=0.017) than nonsarcopenic patients. Multivariate analysis showed that sarcopenia was an independent risk factor for 30-day mortality in patients in the PULP score > 7 group (OR: 11.05, CI: 1.03-118.7). CT scans can diagnose PPU and provide physiological measurements. Sarcopenia, defined as a low CT-measured SMG, provides extra value in predicting mortality in older PPU patients.


Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial.
To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function. Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.v. injections. Transthoracic echocardiography imaging was acquired 3 days after arrival to altitude and prior to the first placebo or rHuEPO injection as well as one day after the last rHuEPO injection three weeks later. rHuEPO did not alter cardiovascular morphology parameters, systolic or diastolic function. In the placebo group, altitude exposure improved left ventricle (LV) systolic function due to an increased twist angle but rHuEPO had no additional effects. Pulmonary arterial systolic pressure was unaffected in either group. Notably, rHuEPO hampered LV untwist rate without affecting LV early filling. rHuEPO provided during mild altitude exposure does not cause any major effects on heart function. The observed alteration in LV untwist induced by rHuEPO is unlikely to have a meaningful clinical effect. Trial Registration Registered on www. gov (NCT04227665).


Effect of conditioned medium of mouse embryonic fibroblasts produced from EC-SOD transgenic mice in nuclear maturation of canine oocytes in vitro.
The rate of in vitro maturation (IVM) of canine oocytes has not improved in comparison to that of other mammalian species. This study aims to improve the efficiency of canine oocytes IVM using the antioxidant, extracellular superoxide dismutase (EC-SOD). Thus, the effect of conditioned medium of EC-SOD transgenic mouse embryonic fibroblasts cultured with MEF culture medium (DMEM + 5% FBS) for in vitro nuclear maturation in canine oocytes was investigated. In experiment I, oocytes were collected from the ovaries of domestic bitches, which were allotted to one of two groups: (1) TCM199 + 1% FBS (n = 108) or (2) DMEM + 5% FBS (n = 112), cultured for 48 h and investigated for in vitro nuclear maturation of canine oocytes using Hoechst staining. Meiotic progression to metaphase II in group 1 was 1.8% compared to 1.8% in group 2. In experiment II, EC-SOD levels were examined in NTg-CMEF and Tg-CMEF at 0, 2 and 4 days obtained from EC-SOD transgenic mice generated in our laboratory. The concentration of EC-SOD in Tg-CMEF at day 2 (371.7 +/- 3.1 ng/ml) was the highest for all groups (P < 0.05). EC-SOD levels in Tg-CMEF were higher than in NTg-CMEF; therefore, the efficiency of Tg-CMEF for IVM was investigated. In experiment III, oocytes were allotted to one of three groups: (1) Tg-CMEF at day 0 (n = 84), (2) Tg-CMEF at day 2 (n = 92) or (3) Tg-CMEF at day 4 (n = 98), cultured for 48 h and the IVM of canine oocytes investigated. The mean percentage of MII oocytes in IVM was 2.4, 4.4 and 2.0% for groups 1, 2 and 3, respectively. In experiment IV, the effects of conditioned medium of EC-SOD transgenic mouse embryonic fibroblasts (Tg-CMEF) cultured in MEF culture medium were compared with conditioned medium acquired from non-transgenic mouse embryonic fibroblasts (NTg-CMEF) on IVM of canine oocytes. In this experiment, meiotic progression to metaphase II was 7.1% in Tg-CMEF versus 0% in NTg-CMEF (P < 0.05). Tg-CMEF was more effective than NTg-CMEF. In conclusion, it was verified that canine oocytes were able to effectively progress to metaphase II in IVM when cultured in Tg-CMEF.


[Cellular primary cilia and human diseases].
Cellular primary cilium, located on the surface of virtually all mammalian cells, is a strictly conserved organelle which regulates cell biological process and maintains cell homeostasis by modulating cell proliferation, differentiation, migration, polarity, signal cascades and other life activities. Some diseases caused by mutations in genes encoding structural proteins or accessory proteins of primary cilia are collectively termed as "ciliopathies", which can occur in embryo, infancy and even adulthood. Ciliopathies not only involve a single organ, but also involve multiple organs and multiple systems, showing variable symptoms and overlapping symptoms. This review mainly summarizes the effects of ciliopathy-associated gene mutations on bone, tooth, skin, liver and bile duct, kidney, brain, retina, heart and other organs, uncovers their molecular mechanisms and provides some novel insights into therapy of ciliopathies.


Fabrication of novel poly(lactic acid)/amorphous magnesium phosphate bionanocomposite fibers for tissue engineering applications via electrospinning.
Fibrous bionanocomposites consisting of amorphous magnesium phosphate (AMP) nanospheres and polylactic acid (PLA) were fabricated by electrospinning. There are two important signatures of this paper. First, AMP, as an alternative to well-known calcium phosphate (CaP) materials, is added to PLA as the second phase. To the best of our knowledge, it is the first attempt to fabricate magnesium phosphate (MgP)/biopolymer composite. This is made possible by our previously reported research on the successful synthesis of AMP nanospheres via microwave processing. Second, the sustained release of magnesium and phosphate ions from PLA matrix can stimulate a series of cell responses. The structure of the composites and their bone-like apatite-forming abilities in simulated body fluid (SBF) were examined. Additionally, the effects on the proliferation and differentiation of preosteoblast cells were evaluated by performing in vitro cell culture and monitoring markers such as Osteocalcin (OCN), Osteopontin (OPN), Alkaline phosphatase (ALP) and Collagen type-I (Col I) using real-time polymerase chain reaction (PCR). For better dispersion of AMP in the fibers, a surfactant, 12-hydroxysteric acid (HSA), as previously reported in the literature, was used. However, HSA significantly inhibited the proliferation and differentiation of preosteoblast cells, indicating the potential risk in using HSA in the combination of AMP or MgP in tissue engineering applications.


Retinol-binding protein synthesis and secretion by the rat visceral yolk sac. Effect of retinol status.
Studies were conducted to explore in rats the role of retinol in the regulation of the synthesis and secretion of retinol-binding protein (RBP) by the visceral yolk sac compared to the liver. Previous studies have shown that in retinol deficiency, hepatic RBP secretion is specifically inhibited, whereas hepatic RBP synthesis rate is unchanged. Retinol-depleted, retinoic acid-supplemented female rats were mated, and maternal liver, fetal liver, and visceral yolk sac were obtained at 14 days of gestation (retinol-depleted group). A group of identically treated, retinol-depleted rats were repleted with retinol on the 14th day of gestation, and the same tissues were collected 6 h later (retinol-repleted group). Normal female rats were used as controls. RBP was assayed by radioimmunoassay and RBP mRNA levels by RNase protection assay using a rat RBP cDNA clone. RBP levels in the visceral yolk sac were elevated 10-fold in the retinol-depleted as compared to the control rats and had declined to near normal values in the retinol-repleted animals. The relative levels of RBP mRNA in the visceral yolk sac were very similar in all three groups of rats. Thus, as in the liver, in the visceral yolk sac retinol deficiency inhibits RBP secretion without altering RBP mRNA levels. In the visceral yolk sac, as in the liver, retinol status appears to regulate RBP secretion specifically, without affecting the rate of RBP biosynthesis.


Complete Genome Sequences of Two Shiga Toxin-Producing Escherichia coli O146:H10 Strains Recovered from a Foodborne Outbreak in China.
Shiga toxin-producing Escherichia coli (STEC) is one of the primary pathogenic contaminants of foods, contributing to several foodborne outbreaks in recent years. Here, we report the complete genome sequences of two non-O157 STEC strains isolated from an outbreak of diarrhea in the city of Guilin, Guangxi Zhuang Autonomous Region, China.


Molecular structure, expression analysis and functional characterization of APRIL (TNFSF13) gene in bat (Vespertilio superans Thomas).
A proliferation-inducing ligand (APRIL) is a novel member of the tumor necrosis factor (TNF) superfamily, which is involved in immune regulation. In the present study, the full-length cDNA of APRIL (designated bAPRIL) from bat was cloned using RT-PCR and its biological activities have been characterized. The open reading frame (ORF) of this cDNA consists of 753 bases, encoding a protein of 250 amino acids. This protein was found to contain a predicted transmembrane domain, a putative furin protease cleavage site, and a typical TNF homology domain corresponding to other, known APRIL homologs. Real-time quantitative PCR (qPCR) analysis indicated that bAPRIL mRNA was predominantly expressed in bat lymphoid tissue spleen. The SUMO-bsAPRIL was efficiently expressed in Escherichia coli BL21 (DE3) and confirmed by SDS-PAGE and Western blot analysis. Laser scanning confocal microscopy analysis showed that bsAPRIL could bind to its receptors on B cells. In vitro, MTT assays indicated that bsAPRIL could promote the survival/proliferation of mouse splenic B cells grown with anti-mouse IgM. These findings indicate that bsAPRIL plays an important role in the survival and proliferation of B cells and has functional cross-reactivity among mammalians. The present findings may provide valuable information for research into the immune system of the bat.


Regulation of noradrenaline release by S-nitroso-cysteine: inhibition in PC12 cells in a cyclic GMP-independent manner.
Nitric oxide (NO), including NO free radicals (*NO) and peroxynitrite (OONO-), modulates the release of neurotransmitters from neuronal tissues. Although we reported that S-nitroso-cysteine stimulated noradrenaline release in brain slices, we now show that only S-nitroso-cysteine inhibits noradrenaline release from PC12 cells. S-Nitroso-cysteine inhibited, in a dose-dependent manner (up to 0.6 mM), the Ca2+ -dependent [3H]noradrenaline release induced by ionomycin, adenosine 5'-O-(3-thiotriphosphate), or high K+, from PC12 cells labeled with [3H]noradrenaline. Sodium nitroprusside, S-nitroso-N-acetylpenicillamine, and 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene, which specifically release NO free radicals in neutral buffer, had minimal effects on [3H]noradrenaline release, although they markedly stimulated cyclic GMP accumulation. 3-Morpholinosydonimine, which releases peroxynitrite, had no effect on either [3H]noradrenaline release or cyclic GMP accumulation. S-Nitroso-cysteine inhibited phorbol 12-myristate 13-acetate- and mastoparan (wasp venom toxin)-induced [3H]noradrenaline release. These findings suggest that 1) S-nitroso-cysteine, but not other NO donors, inhibits some common process occurring during noradrenaline release in PC12 cells, 2) neither NO radicals, peroxynitrite, nor cyclic GMP mediate the inhibitory effects of S-nitroso-cysteine in PC12 cells.


Post-hypoxic myoclonus: Differentiating benign and malignant etiologies in diagnosis and prognosis.
Neurological function following cardiac arrest often determines prognosis. Objective tests, including formal neurological examination and neurophysiological testing, are performed to provide medical providers and decision-makers information to help guide care based on the extent of neurologic injury. The demonstration of post-hypoxic myoclonus on examination has been described to portend poor outcome after cardiac arrest, but recent studies have challenged this idea given that different forms of post-hypoxic myoclonus predict disparate prognoses. The presence of myoclonus status epilepticus (MSE) usually signals a poor outcome, especially if generalized. Lance-Adams syndrome (LAS), another form of post-hypoxic myoclonus, carries a better prognosis. Differentiating subtypes of post-hypoxic myoclonus is therefore critical. This can be difficult in the acute setting with clinical examination alone due to the use of sedation to facilitate mechanical ventilation, and neurophysiological studies may be more reliable. In this review, we describe and compare clinical and neurophysiological features of MSE and LAS. Generalized epileptiform activity and burst suppression on electroencephalography tend to be more common in MSE, and focal epileptiform activity at the vertex may define LAS. Those with multifocal MSE may have better outcomes than those with generalized MSE. We conclude that neurophysiological testing is vital acutely after cardiac arrest when post-hypoxic myoclonus is present to help determine prognostication and guide decision-making.


In vitro DNA synthesis by megaloblastic bone marrow: effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis.
The de novo pathway of thymidylate synthesis (i.e., methylation of dUMP to dTMP) is directly folate dependent and indirectly vitamin B12 (cobalamins) dependent. In deficiency of these vitamins, this pathway is impaired, and exogenous deoxyuridine (dU) fails to suppress adequately in vitro incorporation of [3H]thymidine (3H-TdR) into DNA via the salvage pathway (i.e., abnormal dU suppression). This abnormality is corrected by the addition of folate compounds (analogues) and/or vitamin B12 depending on the nature of the underlying deficiency. We studied the effects of addition of PteGlu, 5-methyl THF (5-CH3-FH4), 5-formyl-THF (5-CHO-FH4), and hydroxy-cobalamin (OH-cbl) on 3H-TdR incorporation into DNA and thymidine kinase activity (salvage pathway), and on [3H]deoxyuridine (3H-dU) incorporation and dU suppression values (de novo pathway) in cultures of normal and megaloblastic bone marrows. The results showed that 3H-TdR incorporation into DNA and the salvage enzyme, thymidine kinase, activity were greater and 3H-dU incorporation into DNA less in megaloblastic cells as compared with normal cells. The addition of folates significantly reduced 3H-TdR incorporation and thymidine kinase activity and enhanced 3H-dU incorporation in folate and vitamin B12-deficient cells except that 5-CH3-FH4 had no effect on vitamin B12-deficient cells. None of these additives had any significant effect on normal cells. This study also showed that the addition of the deficient vitamin(s) to the "control tubes" in the dU suppression test is inappropriate, as these vitamins may at least partially correct the defect in cellular DNA synthesis caused by the deficiencies of these vitamins and may mask these deficiencies in the results of the in vitro correction of the dU suppression abnormalities in mild cases of megaloblastic anemia.


Lung cancer involving the superior vena cava: pneumonectomy with concomitant partial resection of superior vena cava.
We report two cases in which partial resection and reconstruction of the superior vena cava (SVC) were performed with the use of a temporary SVC-right atrial internal bypass for complete resection of carcinoma of the right lung. In the first case, the SVC was invaded by the primary tumor itself, arising in the anterior segment of the right upper lobe. In the second case a metastasized tracheobronchial lymph node had invaded the SVC. In both cases, partial resection of SVC was performed safely with the internal bypass technique.


[Diagnostic image (83). A girl with subfebrile temperature and ascites. Tuberculous peritonitis].
A subfebrile girl with ascites.--A 16-year-old Ethiopian girl who had been living in the Netherlands for 4 years had ascites and echogenic spots in the abdomen. Laparoscopy revealed peritonitis tuberculosa.


Chemical composition of heartwood and sapwood of Tectona grandis characterized by CG/MS-PY.
Teak wood has chemical compounds that can be used for pharmaceutical and textile industries, in addition, this compounds are related to resistance to biodeterioration, color and modification processes. Heartwood and sapwood of T. grandis (teak), 15 years-old, were characterized by Py-CG/MS analysis and syringyl (S)/guaiacyl (G) ratio was evaluated. Heartwood and sapwood were pyrolyzed at 550 °C and 62 and 51 compounds were identified from them, respectively. The acetic acid (10%) and levoglucosan (26.65%) were the most abundant compound in the sapwood and heartwood, respectively. The high acetic acid content enhances the use of teak wood to production of artificial essences for perfumery, paints, dyes. While levoglucosan can be used in the manufacture of epoxy resins, antiparasitic and insecticides. The organic compounds identified include 2-methylanthraquinone as one of the main component responsible for the resistance of the teak wood to biological factors (fungi and termites). The syringyl (S)/guaiacyl (G) ratio of heartwood and sapwood was 0.51 and 0.50, respectively.


Trends in extracellular matrix biology.
Extracellular matrixes (ECMs) are intricate 3-dimensional macromolecular networks of unique architectures with regulatory roles in cell morphology and functionality. As a dynamic native biomaterial, ECM undergoes constant but tightly controlled remodeling that is crucial for the maintenance of normal cellular behavior. Under pathological conditions like cancer, ECM remodeling ceases to be subjected to control resulting in disease initiation and progression. ECM is comprised of a staggering number of molecules that interact not only with one another, but also with neighboring cells via cell surface receptors. Such interactions, too many to tally, are of paramount importance for the identification of novel disease biomarkers and more personalized therapeutic intervention. Recent advances in big data analytics have allowed the development of online databases where researchers can take advantage of a stochastic evaluation of all the possible interactions and narrow them down to only those of interest for their study, respectively. This novel approach addresses the limitations that currently exist in studies, expands our understanding on ECM interactions, and has the potential to advance the development of targeted therapies. In this article we present the current trends in ECM biology research and highlight its importance in tissue integrity, the main interaction networks, ECM-mediated cell functional properties and issues related to pharmacological targeting.


[Remote presentation of thesis and final postgraduate works during the COVID-19 pandemic. Are there advantages in the non-face-to-face presentations?]
The COVID-19 pandemic limited in person presentation of final works and theses for the completion of specializations, masters and doctorates. To describe the experience in remote presentations of summative essays and thesis. A qualitative-quantitative cross-sectional study was carried out. Perceptions of graduates and examiner board members were explored through a questionnaire. 54 presentations were included: 53.7% specializations, 40.7% masters and 5.6% doctorates. The average audience number was 34 and distance to the university was 273.6 km. 116 professionals answered: graduates 28.4% and examiner board members 71.6%. They were female gender in 51.5% and 36.1%, respectively. 100% of graduates and 96.3% of examiner board members believed that they were able to present the results of the investigation, and only 3% and 7.3%, respectively, reported technical difficulties. Positive aspects identified by graduates were higher comfort (45.5%), and greater audience number (36.4%); while the examiner board members identified preventing transportation (37,8%) and taking advantage of technologies (35,4%). Graduates identified as negative aspects audience invisibility (33.3%), and potential threat of technical difficulties (27.3%); whilst the examiner board members identified none (31,7%), and potential threat of technical difficulties (20,7%). Remote presentations were successful for graduates and examiner board members, and allowed to continue and finish academic postgraduate training.


Effects of the environment on dog semen parameters and testosterone concentration.
Whether a mammal reproduces seasonally or continuously depends mostly on the environment and its effects on the endocrine pattern. Although the dog was the first species to have been domesticated, little information is available on the changes in reproduction that have occurred since. In this study, we evaluated whether environmental stimuli can act as modulators of male gonadal activity in the dog at the latitude of Bari (Italy). Therefore, for 1 year, serum and seminal testosterone (T) concentrations, together with seminal parameters, were recorded monthly and evaluated in relation to environmental variables such as temperature, humidity, and photoperiod. We found that, in temperate regions, the annual serum T profile is not affected by environmental conditions, whereas seminal T profile peaks in October and reaches its nadir in April. The percentage of progressive motile spermatozoa is also dependent on environmental cues. The results support the intuitive idea that recorded data require a proper analysis to be meaningful. In fact, we found that, in the dog, environmental changes appear to affect male gonadal physiology, and this is clear when recorded data are analyzed monthly; in contrast, pooling data into seasonal groups hides monthly environmental variations.


Investigation for Paediatric Cushing's Syndrome Using Twenty-Four-Hour Urinary Free Cortisol Determination.
Paediatric Cushing's syndrome (CS) remains a challenge to diagnose and exclude. We assessed the accuracy of 24-hour urinary free cortisol (UFC) determination in children referred for suspected CS. We conducted a retrospective study of paediatric patients referred to our centre with suspected CS between 1982 and 2014. Of 66 subjects (mean age 12.9 years; range 4.4-16.9), there were 47 cases of CS (29 males), which included Cushing's disease (CD; 39 patients, 25 males), primary pigmented nodular adrenocortical disease (8 patients, 4 males) and 19 'controls' (6 males) in whom the diagnosis of CS was excluded. The subjects had between one and five 24-hour UFC collections analysed by radioimmunoassay, chemiluminescent immunoassay or liquid chromatography-mass spectrometry. The data were normalised, corrected for body surface area (m2) and assessed using receiver operating characteristic analysis and an independent two-tailed t test. The diagnostic accuracy of 24-hour UFC for CS was excellent (area under the curve 0.98, 95% CI 0.946-1.00, sensitivity 89%, specificity 100%). Twenty-four-hour UFC is a reliable and practical investigation with high diagnostic accuracy for paediatric CS. However, further investigations may be required if the UFC is normal but there is a high diagnostic suspicion of CS.


Microalbuminuria among HIV-infected antiretroviral therapy-naive children in the Democratic Republic of Congo.
To determine the prevalence of microalbuminuria and associated factors among Congolese human immunodeficiency virus (HIV)-infected children. This was a cross-sectional study in which 77 HIV-infected antiretroviral therapy-naive children and 89 uninfected controls were enrolled. Microalbuminuria was assessed using the immune-turbidimetry method, and associated factors were studied by logistic regression. The prevalence of microalbuminuria was 18% in the HIV-infected children and 2% in the HIV-uninfected children. No common determinants of proteinuria were significantly associated with microalbuminuria.


Psychological effects of the November 1999 earthquake in Turkey: an epidemiological study.
This study assessed the traumatic stress symptoms and related factors in two towns affected by two earthquakes, which killed 20000 people in 1999 in Turkey. A total of 430 people in selected households were seen 18 months after the earthquake. They were given a self-report questionnaire assessing post-traumatic stress (PTSD) and depressive symptoms, demographics and trauma exposure. The rates of PTSD and depression were higher in the site closer to the epicenter. The traumatic stress symptom checklist scores were predicted by fear during earthquake, loss of friends and neighbours, female gender, lower education and living in rented accomodation. Depression was predicted by study site, death of relatives and past psychiatric illness. These results show that severe earthquakes can cause long-lasting morbidity. Our previous findings that showed a differential prediction for depressive and traumatic stress symptoms after earthquakes are also supported.


The metabolism of deoxyguanosine in mitochondria: relationship of the uptake of deoxyguanosine to the electron transport chain and adenosine triphosphate.
That deoxyguanosine is taken up by isolated rat liver mitochondria has been shown. This report describes the relationship between that uptake and oxidative phosphorylation. By measuring this process in the presence of standard inhibitors of oxidative phosphorylation it was determined that a functional electron transport chain, but not the phosphorylation of ADP, was essential for uptake. ATP analogs adenyl(beta,gamma-methylene)diphosphate and adenylimidodiphosphate blocked uptake, indicating that ATP hydrolysis was required. ADP also proved to be an inhibitor. Exogenous UTP slightly stimulated deoxyguanosine uptake, as did added ATP, but several other nucleotides (dGTP, dATP, UDP, dGDP) were inhibitory. A sulfhydryl group was important for deoxyguanosine uptake and inhibition of uptake by N-ethylmaleimide was protected by both deoxyguanosine and ATP. These data show that deoxyguanosine uptake by mitochondria is a process which is coordinated and, perhaps, regulated by other events which take place in the organelle.


Exposure to per- and polyfluoroalkyl substances and glycemic control in older US adults with type 2 diabetes mellitus.
Perfluoroalkyl substances (PFAS) have been associated with impaired glucose homeostasis. We aimed to examine associations of serum concentrations of PFAS with poor glycemic control (PGC) in US adults aged ≥65 years with type 2 diabetes mellitus (T2DM). We abstracted data from the 1999 to 2018 NHANES examination. In main analyses, we defined PGC as glycated haemoglobin A1C ≥ 8.0% in adults aged ≥75 years and A1C ≥ 7.0% (in main analyses) or A1C ≥ 7.5% (in sensitivity analyses) in those aged 65-74 years. We considered PFAS detected in >80% of the US population: perfluorodecanoic acid (PFDeA), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS). We estimated the adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of PGC across quartiles of PFAS concentrations using generalized linear mixed models, with the logit link. Of the 4575 adults included, 42.2% were ≥75 years of age and men represented 53.2%. Compared to adults in the bottom quartile, the odds of PGC was lower in the third quartile of PFDeA (aOR = 0.46, 95% CI: 0.29-0.77; P = 0.0026) and PFHxS (aOR = 0.56, 95% CI: 0.32-0.96; P = 0.0368), the second quartile of PFNA (aOR = 0.41, 95% CI: 0.23-0.71), the upper quartile of PFOA (aOR = 0.29, 95% CI: 0.12-0.73; P = 0.0017), and higher in the second quartile of ΣPFAS (aOR = 1.85, 95% CI: 1.16-2.95; P = 0.0102). In sensitivity analyses, likelihood for PGC was higher in the upper quartile of PFNA (aOR = 2.30, 95% CI: 1.25-4.21; P = 0.0071) and PFHxS (aOR = 2.87, 95% CI: 1.56-5.30; P = 0.0007), the second quartile of PFOS (aOR = 2.81, 95% CI: 1.11-7.14; P = 0.0297), PFHxS (aOR = 1.90, 95% CI: 1.09-3.32; P = 0.0240) and ΣPFAS (aOR = 2.29, 95% CI: 1.40-3.77; P = 0.0010). In US adults aged ≥65 years with known T2DM, PGC is more likely to be observed in those with high serum levels of PFNA and PFHxS (independent of sex) and PFDeA (in men), after controlling for confounders.


Neurosurgical anesthesia for a pregnant woman with macroprolactinoma: A case report.
Being required to perform neurosurgery on a pregnant woman is rare, but occasionally unavoidable. In these cases, clinical anesthesiologists are confronted with conflicting information and few evidence-based guidelines. Here, we describe the successful anesthetic management of a 24-week pregnant woman with macroprolactinoma who underwent endonasal transsphenoidal resection of pituitary adenoma. According to the prolactin (PRL) level and magnetic resonance imaging (MRI) results, the patient was diagnosed with macroprolactinoma and kept stable after taking the regular bromocriptine treatment. However, after stopping the drug by herself because of pregnancy, her tumor increased in size and she suffered from vision loss. Surgery was recommended as soon as possible to lessen the compression in the eye. However, the anesthetic management was a considerable risk due to the increased chance of maternal mortality, intrauterine growth restriction, or preterm labor. We held a multidisciplinary meeting before the operation and made a detailed plan for how to proceed. During the operation, our team ensured intensive monitoring, provided adequate oxygen, and achieved haemodynamic stability. Anesthetics like sufentanyl, rocuronium, propofol, and desflurane were carefully chosen in order to ensure the safety of both the mother and fetus. Under the careful and successful anesthetic management, the pregnant woman underwent the surgery smoothly and neither the mother nor baby experienced any pre- or postoperative complications. At the 38th week of gestation, the patient received a cesarean section and the baby had developed normally. Neurosurgeries in pregnancy are sparse, and careful planning with cross-disciplinary specialists was needed in advance of the operation. Moreover, when dealing with such surgeries, we should consider the safety of both the mother and fetus, which is challenging but important.


Longitudinal impedance variability in patients with chronically implanted DBS devices.
Deep brain stimulation (DBS) is an effective therapy for advanced movement disorders, but its optimal use is still controversial. One factor that could play a role in the proper delivery of therapeutic stimulation by current DBS devices is the variability of the impedance at the interface between the electrode surface and surrounding tissue. To analyze variability and trends in the impedance of chronically-implanted DBS electrodes in subjects with movement disorders. We reviewed impedance values from medical records of DBS patients at an academic tertiary-care movement disorders center. The standard deviation of data recorded within individual subjects and single contacts were used as measures of longitudinal impedance variability. A generalized linear mixed model (GLMM) determined if a number of effects had significant influences on impedance. We analyzed 2863 impedance measurements from 94 subjects. Median variability, for subjects with follow-up from 6 months to 5 years (n = 77), was 194 Ω for individual subjects and 141 Ω for individual contacts, with a range spanning from 18 to over 600 Ω. The GLMM, incorporating all subjects (n = 94), identified time, electrical activity, implanted target, contact position on the electrode and side of implantation as significant predictors of impedance. Age and disease duration at surgery, gender or ethnicity were not significant predictors. Our analysis suggests that a significant amount of impedance variability can be expected in chronically implanted DBS electrodes and indicates a number of factors with possible predictive value. Further studies are needed to link impedance characteristics to clinical outcomes.


Serum contains a macromolecular effector promoting the synthesis of nerve growth factor (NGF) in L cells.
Addition of serum to the culture medium of murine L cells increased both the cellular level of NGF mRNA and the secretion of mature factor. Stimulation of NGF production by the serum was dose-dependent and appeared mediated by some specific factor(s). After gel filtration chromatography of serum, most of the biological activity formed a major peak with an apparent MW of about 160 kDa. This promoting factor was sensitive to heat at neutral pH, but resisted after heating at pH4. An activity inducing NGF synthesis, and displaying a comparable thermal sensitivity was also detected in Cohn fraction IV of human or bovine plasma.


The role of some risk factors of exposure to malaria in determining the outcome of the immunofluorescent antibody test in an urban population.
Data obtained previously were analysed to assess the relative importance of variables which relate to the risk of exposure to malaria in explaining the level of indirect fluorescent antibody (IFAT) reactions observed among the urban study population. In the analysis specific activities, notably travelling out of the main towns, season when out of the main towns, length of period since having been out of the main towns, and history of having had malaria in the last year, were of help in predicting the level of IFAT reaction. Sensitivity and specificity values of history of malaria, history of having been out of the main towns, and serological results were higher in older people in both periods and were highest in the March-April 1985 survey period.


Massive pulmonary haemorrhage due to leptospirosis.
A young man with leptospirosis developed massive pulmonary haemorrhage. This was remarkable both in its severity and in its occurrence early in the clinical course - before the onset or presence of jaundice, renal failure or of a serological diagnosis. It occurred in the absence of a coagulopathy or thrombocytopenia and presumably was a consequence of the capillary fragility characteristic of the disease - perhaps precipitated in this instance by mechanical ventilation.


The bacteriological ecosystem of the skin of children in an African tropical envirovment (Tanzania).
Using a standardized method for sampling, the aerobic microbial flora of the skin of ninety-five children in Dar es Salaam, Tanzania, was studied qualitatively and quantitatively. The subjects comprised three groups; group A, thirty-seven normal infants (below the age of 1 year); group B, twenty-nine infants with various bacterial skin lesions; and group C, twenty-nine nursery school children between 4-5 and 7 years. The following observations were made: (I) The quantitative results indicated; (a) great variation between individuals, which was more marked among the females; (b) lower bacterial counts in infants than in older children; (c) counts were not affected by the presence of infection or state of cleanliness; (d) there were some differences between females and males and between different ethnic groups. (2) Qualitatively, the types of organisms isolated were similar to those reported elsewhere. There were differences in carrier rates of many organisms but these were most striking with Staphylococcus aureus and Staph. albus. It is concluded that there are great differences in carrier rates between persons in a tropical African environment and those studied elsewhere. These difference may be due to environmental, geographical or ethnic factors. Such observations call for more studies in this area to establish the normal flora.


Invasive aspergillosis in 2002: an update.
Despite significant advances in the management of immunosuppressed patients, invasive aspergillosis remains an important life-threatening complication. In the past two decades, the incidence of invasive aspergillosis in this population has continued to increase. Factors that predispose patients to develop invasive aspergillosis include prolonged granulocytopenia, the development of graft-versus-host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and the prolonged impairment of host defenses associated with diseases such as chronic granulomatous disease. Environmental factors also play a key part in the pathogenesis of this infection, and therefore, infection control measures play a critical role in reducing exposure of patients to Aspergillus. New exciting developments in the early diagnosis of invasive aspergillosis and the acceleration of antifungal drug discovery offer promise for the future.


[Experience on Guepar-hinge-prosthesis (author's transl)].
Total replacement of the knee joint by the G.U.E.P.A.R. hinge prosthesis has been performed in 72 patients suffering from severe gonarthrosis combined with ligamentous instability. Follow-up examination over a period of 1/2-5 years were made in 65 cases considering pre- and postoperative findings (pain, range of motion, ability to walk). This paper reports on problems of joint replacement surgery especially on details of operative technique to restore free gliding of the patella and muscular force as well. The G.U.E.P.A.R hinge posthesis has given good or excellent results in the great majority of cases.


A technique for chronic intermittent bile collection from the rat.
A technique is described for inserting into the bile duct, a re-entrant cannula with a sampling arm to allow intermittent collections of bile from unanaesthetised, minimally restrained rats, for a period of 30 days or more. The flow rate of bile (5.38+/-0-25 cm3/h/kg) was higher than that previously reported when using simple or re-entrant cannulas. This higher flow rate may be a result of allowing a minimum of 10 days post-operative recovery period before starting collection of bile and of avoiding anaesthesia and other stresses at the time of collection.


Author Correction: Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Deep Learning for Voice Gender Identification: Proof-of-concept for Gender-Affirming Voice Care.
The need for gender-affirming voice care has been increasing in the transgender population in the last decade. Currently, objective treatment outcome measurements are lacking to assess the success of these interventions. This study uses neural network models to predict binary gender from short audio samples of "male" and "female" voices. This preliminary work is a proof-of-concept for further work to develop an AI-assisted treatment outcome measure for gender-affirming voice care. Retrospective cohort study. Two hundred seventy-eight voices from male and female speakers from the Perceptual Voice Qualities Database were used to train a deep neural network to classify voices as male or female. Each audio sample was mapped to the frequency domain using Mel spectrograms. To optimize model performance, we performed 10-fold cross validation of the entire dataset. The dataset was split into 80% training, 10% validation, and 10% test. Overall accuracy of 92% was obtained, both when considering the accuracy per spectrum and per patient metric. The accuracy of the model was higher for recognizing female voices (F1 score of 0.94) compared to male voices (F1 score of 0.87). This proof of concept study shows promising performance for further development of an AI-assisted tool to provide objective treatment outcome measurements for gender affirming voice care. 3 Laryngoscope, 131:E1611-E1615, 2021.


Carba-Sugar Analogs of Glucosamine-6-Phosphate: New Activators for the glmS Riboswitch.
Riboswitches are 5'-untranslated mRNA regions mostly found in bacteria. They are promising drug targets to overcome emerging bacterial resistance against commonly used antibiotics. The glmS riboswitch is unique among the family of riboswitches as it is a ribozyme that undergoes self-cleavage upon binding to glucosamine-6-phosphate (GlcN6P). Previously, we showed that carba glucosamine-6-phosphate (carba-GlcN6P) induces self-cleavage of the riboswitch with a potency similar to that of GlcN6P. Here, we report a synthetic approach to a new class of carba-GlcN6P derivatives with an alkoxy substituent in the carba position. Key features of the synthesis are a ring closing metathesis followed by a hydroboration. The strategy gives access to libraries of carba-GlcN6P derivatives. Ribozyme cleavage assays unraveled new activators for the glmS riboswitch from Listeria monocytogenes and Clostridium difficile.


MFGE8/Integrin β3 pathway alleviates apoptosis and inflammation in early brain injury after subarachnoid hemorrhage in rats.
Milk fat globule-epidermal growth factor-factor 8(MFGE8)/Integrin β3 pathway was reported to be involved in reducing oxidative stress and early brain injury after subarachnoid hemorrhage (SAH). In the present study, the potential effects of MFGE8 and its receptor Integrin β3 in the inhibition of apoptosis and neuroinflammation in early brain injury after SAH were investigated. Ninety-five (95) male Sprague-Dawley rats were used. The SAH model was induced by endovascular perforation. Recombinant human MFGE8 (rhMFGE8), MFGE8 small interfering RNA (siRNA) and Integrin β3 siRNA were injected intracerebroventricularly. SAH grade, neurologic scores, Western blots and immunofluorescence were employed to study the mechanisms of MFGE8 and its receptor Integrin β3, as well as neurological outcome. SAH induced significant neuronal apoptosis and inflammation and exhibited neurological dysfunction in rats. Knockdown endogenous MFGE8 with siRNA significantly increased the protein levels of cleaved caspase 3 and IL-1β, accompanied with more neurological deficits. rhMFGE8 significantly reduced neural cell death in cortex, decreased cleaved caspase 3 and IL-1β expressions, and improved neurological functions 24h after SAH. The anti-apoptosis and anti-inflammation effects of rhMFGE8 were abolished by Integrin β3 siRNA. MFGE8 could alleviate neurologic damage in early brain injury after SAH via anti-inflammation and anti-apoptosis effects. MFGE8 may serve as a promising therapeutic target for future management of SAH patients.


Research on key acoustic characteristics of soundscapes of the classical Chinese gardens.
Soundscapes have played an important role in the design and building of classical Chinese gardens. In Chinese classical poetry, biophonies such as bird calls, and geophonies such as wind, are the preferable sound sources. Although these major sound sources have been categorized and summarized by scholars extensively, little research has been conducted to analyze the physical characteristics and preference matrix of these preferred sound sources. Moreover, the perceived loudness of sound in classical Chinese gardens has received more attention from scholars than acoustic frequency. In this study, we selected 12 sound sources that are most typically present in classical Chinese gardens based on extensive literature research on Chinese classical poetry, and acquired respective audio samples from the BBC's library of Sound Effects. Through the spectrogram analyses, pitch detection algorithm and LSTM audio classification methods, the sound sources were classified into discrete sound sources with pitch variation and continuous sound sources with spectral characteristics of white noise or pink noise. The reasoning behind the preference for these two types of sound sources was then discussed from physical and mental healing perspectives, which aims to help provide perspectives on the associated implications in the planning of urban green spaces.


Ovarian ultrasound assessment in normal children, idiopathic precocious puberty, and during low dose pulsatile gonadotrophin releasing hormone treatment of hypogonadotrophic hypogonadism.
Ultrasound assessment of ovarian volume, follicular size, and uterine growth was undertaken in 40 normal premenarcheal girls aged 6 months to 14 years. Ovarian follicles were detected from 6 months of age and increased in size and number, so that after the age of 8.5 years there was a progressive increase in the incidence of 'megalocystic' appearance. Eight girls with idiopathic precocious puberty had large megalocystic ovaries which regressed on treatment with gonadotrophin releasing hormone analogue. These findings contrasted with those seen in two prepubertal patients with hypogonadotrophic hypogonadism in whom the natural sequence of ovarian development was greatly accelerated by pulsatile administration of native gonadotrophin releasing hormone.


Clinical value of serum calcium in elderly patients with sepsis.
To explore the clinical value of serum calcium (Ca) in elderly patients with sepsis. The clinical data and laboratory data of elderly patients with sepsis (n = 165) and elderly population for physical examination (n = 67) in a tertiary hospital from January 2020 to November 2020 were collected. We analyzed serum Ca levels in sepsis and septic shock firstly, and then continued to investigate them in the survival group and the death group. Meanwhile, we also assessed the correlation between serum Ca and PCT. The serum Ca levels of the elderly patients with sepsis were lower than that of the control group (median 1.98 vs 2.31 mmol/L, P < 0.001), and the more severe the sepsis, the lower the serum Ca levels. Sepsis patients with decreased serum Ca had higher shock rate and mortality. There was a negative correlation between serum Ca and PCT (r = -0.2957, P < 0.001). Serum Ca has a certain value for the early recognition of elderly patients with sepsis and the judgment of the severity of the disease.


Plasma ferritin, premature rupture of membranes, and pregnancy outcome.
The objective of this study was to determine whether plasma ferritin levels predict maternal or neonatal outcomes in women with preterm rupture of membranes at <32 weeks' gestation. Plasma from 223 women with premature rupture of membranes at <32 weeks' gestation who had participated in a randomized antibiotic trial were analyzed for ferritin at random assignment and at delivery, and the results were compared with the development of clinical chorioamnionitis, latency until delivery, neonatal sepsis, and a composite adverse neonatal outcome variable. The mean plasma ferritin level rose from 19.2 +/- 29.1 microgram/L on admission to 38.3 +/- 54.3 microgram/L at delivery, with a mean latency of 9.3 +/- 14.6 days. Plasma ferritin levels were significantly higher at both times in mothers whose infants acquired sepsis than in those whose infants did not, especially at delivery (68.5 +/- 96.3 microgram/L vs 32.5 +/- 40.5 microgram/L, P =.01), and neonatal sepsis was 2 to 3 times more common among women with plasma ferritin levels above the median than among those with levels below the median. Among women with premature rupture of membranes at <32 weeks' gestation, plasma ferritin levels were significantly associated with neonatal sepsis. These data suggest that higher plasma ferritin levels may serve as a marker of infection among women with premature rupture of membranes; however, the clinical utility of plasma ferritin levels in predicting neonatal outcome appears limited.


Use of steel slag as a granular material: volume expansion prediction and usability criteria.
The theoretical equation for predicting volume expansion of steel slag is deduced based on both chemical reaction and physical changes of free lime in steel slag during the hydration process. Laboratory volume expansion testing is conducted to compare the results with the theoretical volume expansion. It is proved that they correlated well. It is furthermore experimentally proved that certain volume expansion of steel slag can be absorbed internally by the void volume in bulk steel slag under external surcharge weight making the apparent volume expansion equal zero. The minimum (lowest) absorbable void volume is approximately 7.5%, which is unrelated to the free lime content. A usability criterion is then developed based on the volume expansion of steel slag (%) and the minimum percentage of the volume that can take the volume expansion of steel slag (%). Eventually the criterion (relationship) is established based on the free lime content, the specific gravity and bulk relative gravity of a specific steel slag sample. The criteria can be used as guidance and specification for the use of steel slag and other expansion-prone nonferrous slags, copper, nickel for instance as a granular material in highway construction.


A behavioral perspective on insomnia treatment.
The major behavioral treatments of insomnia--progressive relaxation, biofeedback, cognitive approaches, stimulus control instructions, chronotherapy, and sleep restriction therapy--are described. The basis of these interventions are conceptualized as issuing from the interdependence of sleep and wakefulness, the temporal organization of sleep-wake processes, cognitive effects on arousal, the role of perpetuating factors in chronic insomnia, and conditioning. A pilot study of the conditioning of rapid sleep onset with the aid of a hypnotic provides a preliminary demonstration of the application of conditioning to the pharmacotherapy of sleep. It is predicted that the commonly accepted view of sleep latency as solely reflecting physiological sleep tendency, will require modification to include the effects of conditioning. The current pattern of hypnotic usage, an issue of widespread concern, is subjected to a behavioral analysis based on a new model of conditioned tolerance. The intermittent administration of placebo within a hypnotic regimen is predicted to be especially beneficial in sustaining hypnotic efficacy.


Surgical site infection in skin surgery-An observational study.
Surgical site infection (SSI) has a significant impact on patients' morbidity and aesthetic results. To identify risk factors for SSI in dermatologic surgery. This prospective, single-centre, observational study was performed between August 2020 and May 2021. Patients that presented for dermatologic surgery were included and monitored for the occurrence of SSI. For statistical analysis, we used a mixed effects logistic regression model. Overall, 767 patients with 1272 surgical wounds were included in the analysis. The incidence of SSI was 6.1%. Significant risk factors for wound infection were defect size over 10cm2 (OR 3.64, 95% confidence interval [CI] 1.80-7.35), surgery of cutaneous malignancy (OR 2.96, CI 1.41-6.24), postoperative bleeding (OR 4.63, CI 1.58-13.53), delayed defect closure by local skin flap (OR 2.67, CI 1.13-6.34) and localisation of surgery to the ear (OR 7.75, CI 2.07-28.99). Wound localisation in the lower extremities showed a trend towards significance (OR 3.16, CI 0.90-11.09). Patient-related factors, such as gender, age, diabetes, or immunosuppression, did not show a statistically significant association with postoperative infection. Large defects, surgery of cutaneous malignancy, postoperative bleeding, and delayed flap closure increase the risk for SSI. High-risk locations are the ears and lower extremities.