Microneedle fractional radiofrequency in the treatment of periorbital dark circles.
Periorbital hyperpigmentation (POH) is a common disorder in the patients. Women are more upset with POH in compare to males. Several methods have been used to the POH, with different efficacy and adverse reactions. The aim of the present study is to evaluate the efficacy of microneedle fractional radiofrequency (MRF) in treating POH. So, nine patients with POH and the age range of 25-57 years, were treated by microneedle fractional radiofrequency (MRF). The outcome was evaluated via biometric assessment. The colorimeter was used to assess the skin lightness. Mexameter was used for evaluated the amount of Melanin in the periorbital skin. Cutometer was used for skin elasticity assessment. The skin ultrasound imaging system was utilized to estimate the epidermis and dermis diameter and density. Furthermore, Visioface was applied to assessed the skin color and wrinkles. Also patient's satisfaction and physician's assessment were evaluated. The results displayed that the periorbital skin lightness 32.38% ± 5.67 and elasticity of the R2: 40.29% ± 8.18, R5: 39.03 ± 5.38 and R7: 42.03% ± 14.16 were significantly improved after treatment (p < 0.05). Also the melanin content of the skin was decreased (49.41% ± 9.12). The skin layers were denser in the dermis and also in the epidermis (skin density: 30.21% ± 10.16 and skin thickness: 41.12% ± 13.21) (p < 0.05). The results revealed the decrease in the percent change of the skin color (30.34% ± 9.30) and wrinkle (area: 25.84% ± 6.43 and volume: 30.66% ± 8.12) (p < 0.05). Similarly, the physician and patient's assessment were confirmed the obtained outcomes. In conclusion, the microneedle RF technique is practicable, effective and safe method for periorbital dark circles treatment.


Codon Optimization OnLine (COOL): a web-based multi-objective optimization platform for synthetic gene design.
Codon optimization has been widely used for designing synthetic genes to improve their expression in heterologous host organisms. However, most of the existing codon optimization tools consider a single design criterion and/or implement a rather rigid user interface to yield only one optimal sequence, which may not be the best solution. Hence, we have developed Codon Optimization OnLine (COOL), which is the first web tool that provides the multi-objective codon optimization functionality to aid systematic synthetic gene design. COOL supports a simple and flexible interface for customizing various codon optimization parameters such as codon adaptation index, individual codon usage and codon pairing. In addition, users can visualize and compare the optimal synthetic sequences with respect to various fitness measures. User-defined DNA sequences can also be compared against the COOL optimized sequences to show the extent by which the user's sequences can be further improved. COOL is free to academic and non-commercial users and licensed to others for a fee by the National University of Singapore. Accessible at http://bioinfo.bti.a-star.edu.sg/COOL/ CONTACT: email@example.com Supplementary data are available at Bioinformatics online.


Basic biochemical mechanisms behind the health benefits of polyphenols.
Polyphenols and consequently many flavonoids have several beneficial actions on human health. However, the actual molecular interactions of polyphenols with biological systems remain mostly speculative. This review addresses the potential mechanisms of action that have been so far identified, as well as the feasibility that they could occur in vivo. Those mechanisms include: i) non specific actions, based on chemical features common to most polyphenols, e.g. the presence of a phenol group to scavenge free radicals; and ii) specific mechanisms; based on particular structural and conformational characteristics of select polyphenols and the biological target, e.g. proteins, or defined membrane domains. A better knowledge about the nature and biological consequences of polyphenol interactions with cell components will certainly contribute to develop nutritional and pharmacological strategies oriented to prevent the onset and/or the consequences of human disease.


Polyelectrolyte-functionalized reduced graphene oxide wrapped helical POMOF nanocomposites for bioenzyme-free colorimetric biosensing.
For the sake of effective colorimetric sensing-pattern, a sensitive colorimetric sensor was conceived based on polyoxometalates based metal-organic frameworks (POMOFs) and polydiallyldimethylammonium chloride functionalized reduced graphene oxide (PDDA-rGO) for the first time, in which PDDA as a "glue" molecule turns rGO nanosheets into general platforms for bonding POMOFs nanoparticles. Herein, a new POMOF compound with fascinating helices-on-helices feature, [Ni4(Trz)6(H2O)2][SiW12O40].4H2O (Trz = 1,2,4-triazole) (abbreviated as Ni4SiW12), was synthesized and characterized, then PDDA-rGO sheet as dispersive and conductive material was successfully introduced to Ni4SiW12 fabricating new PDDA-rGO/Ni4SiW12-n nanocomposites, (abbreviated as PMPG-n). The resulting PMPG-n nanocomposites as peroxidase mimetic show excellent catalytic activities under extreme condition (pH value 2.5), attributed to the nature and synergies from POMs, MOFs and PDDA-rGOs. Note that the peroxidase-like activity of PMPG-1 (the mass ratio of Ni4SiW12 to PDDA-rGO is 1:1) exhibits higher sensitivity (1-60 μM), faster response (10 min) and the lowest limit of detection (2.07 μM) among all reported materials to citric acid (CA) to date. This work opens up new application prospects in colorimetric sensing system for food quality control and safety, biotechnology and clinical diagnosis.


Sleep-related habits and preferences in older adults: a pilot study of their range and self-rated importance.
This article explores the sleep-related habits of older persons, as well as the level of importance they assign to these practices. A convenience sample of 58 community-dwelling seniors responded to sleep-related items from the Self-Maintenance Habits and Preferences in Elderly questionnaire. Sleep practices varied greatly across individuals, but did not show much systematic difference between men and women. However, as with many health care issues, women rated them as more important than did men. Knowledge of sleep habits and preferences is important so that it can be taken into account by those responsible for planning care for older adults or for aiding their adaptation to a new setting.


Reflex high-risk human papillomavirus DNA testing (Hybrid Capture 2) of bloody ThinPrep specimens with atypical squamous cells of undetermined significance interpretation: does pretreatment with acetic acid affect test performance?
The current study was conducted to evaluate the efficacy of human papillomavirus (HPV) DNA testing of residual ThinPrep specimens, which were pretreated with acetic acid to optimize cellularity with a special focus on atypical squamous cells of undetermined significance (ASCUS) specimens. A total of 120 ThinPrep gynecologic samples were chosen for a pilot study including cases with a normal or abnormal interpretation and those with or without blood. Each residual specimen was divided into two portions. One portion was treated with glacial acetic acid (GAA) and the other half remained untreated. Both aliquots were tested for high-risk HPV DNA using the Hybrid Capture 2 test. After internal validation, reflex HPV DNA testing was performed on all consecutive 1776 ASCUS specimens including 98 acid-washed bloody specimens in routine practice. Of the 120 specimens with paired aliquots, 117 specimens had concordant HPV DNA test results in the treated and untreated groups with a squared correlation coefficient value of 0.97 and a kappa value of 0.95. Subsequently, in the clinical setting, 43 of 98 (43.9%) acid-washed specimens and 845 of 1676 (50.4%) routine specimens with an ASCUS interpretation tested positive for high-risk HPV DNA. There was no statistically significant difference noted between these two groups with regard to age, percentage HPV DNA positivity, or viral load. The pretreatment of bloody specimens with GAA did not appear to significantly affect high-risk HPV DNA testing in specimens with an ASCUS interpretation.


Xanthogranulomatous cholecystitis in a patient with ulcerative colitis and primary sclerosing cholangitis: A case report.
Chronic gallbladder disease due to xanthogranulomatous cholecystitis is uncommon, and its symptoms are generally vague. While there is no firm evidence to link xanthogranulomatous cholecystitis to primary sclerosing cholangitis or ulcerative colitis. The patient is a 41-year-old male with a history of ulcerative colitis, primary sclerosing cholangitis, and biliary stenting who complained of symptoms of anorexia, jaundice, and pruritus. In the initial ultrasound exam, there was evidence of intrahepatic and extra-hepatic bile duct dilation along with a significant and mass-like circumferential thickening of the gallbladder wall. Magnetic resonance cholangiopancreatography was performed for further evaluation, which indicated increased gallbladder wall thickness, containing multiple T2 hyper-signal nodules while the mucosal layer was intact. There was also a filling defect in the common bile duct's distal portion. These findings matched a xanthogranulomatous cholecystitis diagnosis and a possibly malignant lesion in the distal of the common bile duct. The patient ultimately had a cholecystectomy, and pathology findings confirmed the diagnosis of xanthogranulomatous cholecystitis. Biopsy specimens obtained from the distal of the common bile duct lesion were microscopically identified as intramucosal adenocarcinoma. In patients with a history of primary sclerosing cholangitis who present with nonspecific symptoms suggesting chronic gallbladder disease and radiologic evidence of circumferential gallbladder wall thickening containing intramural nodules and intact mucosa, xanthogranulomatous cholecystitis should be kept in mind.


Demographic factors in the epidemiology of hemophilus influenzae meningitis in young children.
To determine the effect of various demographic factors on the incidence of Hemophilus influenzae, type b meningitis, Rhode Island residents with H. influenzae in 1970-1974 were identified by review of data from the State Department of Health, a private health care research organization, death certificates, and hospital bacteriology laboratories. Of the 108 cases of H. influenzae, 99 (92%) occurred in children under five years of age. The disease incidence among black children under five (103.6/100,000/annum) was significantly (P less than 0.0005) higher than that among white children (23.9/100,000/annum). By eliminating the 29 of 185 census tracts in which the total population was greater than 5% black, disease incidence was studied in a virtually monoracial population. In these white census tracts, in which the population was 99.2% white, the occurrence of H. influenzae was not related to family income, education, number of household members, population density, or rate of hospitalization. These findings confirm the increased incidence of H. influenzae in blacks and indicate that socioeconomic factors do not affect the incidence of the disease in white children.


Arterial vascularization of the operated stomach: highly selective vagotomy, anterior lesser curve seromyotomy, esophageal replacement by transposed stomach after esophagectomy or circular pharyngolaryngectomy.
The rich vascularisation of the stomach is well known and the remarkable tolerance of the organ to vascular ligatures has been emphasised. However, some clinical observations as well as more and more detailed anatomical studies suggest some modification of this classical concept, especially when operating on the viscus. The aim of this work was to evaluate particularly the importance of parietal ischemia which follows hyperselective vagotomy and the more recent anterior seromyotomy, on the one hand, and the gastrolysis that precedes gastro-esophagoplasty after esophagectomy or circular pharyngolaryngectomy on the other hand. The stomachs of 40 unembalmed adult cadavers were studied by angiography in various ways, according to the operation which was being considered. The findings indicated that hyperselective vagotomy caused an avascular band 2 cm wide along that part of the lesser curve affected by the surgical intervention, and that anterior seromyotomy (allowing for some technical artifacts) caused almost no parietal ischemia, and lastly, that the ischemia from gastro-esophagoplasty varied according to the technique used. Useful conclusions, supported by numerous illustrations, will allow the surgeon to define better the vascular requirements when choosing the procedure to be used, taking account of the clinical situation.


Phylogeny of lymphocyte heterogeneity: the thymus of the channel catfish.
The number of thymocytes (approximately 3 x 10(7)) that were recoverable from fingerling channel catfish remained constant from about 3 to 10 months of age, i.e. from September to April following hatching the previous June. Between 11 and 12 months, i.e. May and June, the thymus dramatically increased in size with 3 x 10(9) thymocytes being recoverable from the tissue of individual fish. The thymus remained enlarged for several months (throughout the summer) but at about 15 months (in September) began to involute such that by 17 months (November) no thymus tissue could be seen macroscopically. This natural involution could be accelerated by subjecting the fish to handling and transport stress. Thymocytes of channel catfish aged 4 to 16 months exhibited reactivity with monoclonal antibodies against peripheral T cells but not B cells. Thymocytes responded to the mitogen Concanavalin A only in the presence of added accessory cells (peripheral blood monocytes) or a monocyte-derived supernatant (presumably containing IL-1) at permissive temperatures (27 degrees C). Thymocytes could also be induced to divide at nonpermissive temperatures (17 degrees C) when incubated in the presence of the following combinations of stimulants, a) the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and the calcium ionophore A23187, b) TPA and ConA, or c) A23187 and ConA. In those cases where TPA or A23187 were used, accessory cells or their products were not needed. Collectively, these results support the notion that channel catfish thymocytes functionally mimic those lymphocytes in the peripheral blood previously designated as T cells.


Medical genomics: The intricate path from genetic variant identification to clinical interpretation.
The field of medical genomics involves translating high throughput genetic methods to the clinic, in order to improve diagnostic efficiency and treatment decision making. Technical questions related to sample enrichment, sequencing methodologies and variant identification and calling algorithms, still need careful investigation in order to validate the analytical step of next generation sequencing techniques for clinical applications. However, the main foreseeable challenge will be interpreting the clinical significance of the variants observed in a given patient, as well as their significance for family members and for other patients. Every step in the variant interpretation process has limitations and difficulties, and its quote of contribution to false positive and false negative results. There is no single piece of evidence enough on its own to make firm conclusions on the pathogenicity and disease causality of a given variant. A plethora of automated analysis software tools is being developed that will enhance efficiency and accuracy. However a risk of misinterpretation could derive from biased biorepository content, facilitated by annotation of variant functional consequences using previous datasets stored in the same or linked repositories. In order to improve variant interpretation and avoid an exponential accumulation of confounding noise in the medical literature, the use of terms in a standard way should be sought and requested when reporting genetic variants and their consequences. Generally, stepwise and linear interpretation processes are likely to overrate some pieces of evidence while underscoring others. Algorithms are needed that allow a multidimensional, parallel analysis of diverse lines of evidence to be carried out by expert teams for specific genes, cellular pathways or disorders.


Identifying the spatiotemporal vulnerability of soils to antimicrobial contamination through land application of animal manure in Minnesota, United States.
Antimicrobials may reach the soil environment from a variety of sources and pathways, including land application of human biosolids and animal manure. Once in soil, antimicrobials can affect the abundance and activity of soil microorganisms and exert selection pressures that enhance the emergence and spread of antimicrobial resistance (AMR). To mitigate the spread of AMR it is important to understand the spatial and temporal interactions between antimicrobials and soil. The goal of this study was to assess the vulnerability of Minnesota (U.S.) soil to contamination with specific antimicrobial compounds at temperatures experienced throughout the year. Soil contamination potential was estimated based upon specific antimicrobial drug binding and permanence, and average monthly temperature. Minnesota soil vulnerability was estimated by incorporating spatially explicit soil contamination potential, land cover type, and livestock density. Assessment of antimicrobials used in livestock production showed that soils are most vulnerable to antimicrobial contamination in southwestern Minnesota, to enrofloxacin, chlortetracycline, and oxytetracycline, and in the months of April and October. While the assessment herein was not based on actual on-farm antimicrobial use data and subsequent excretion of antimicrobial metabolites into the environment, this study provides an overview of the spatial and temporal potential for Minnesota soil to be contaminated by several antimicrobial drugs and demonstrates how specific vulnerability assessments might be conducted for geographic areas with known exposure (e.g., cropland fertilized with livestock manure and/or human biosolids). Such assessments might be used to identify best practices for mitigating antimicrobial exposure to soils and guide additional research to understand the role of environmental antimicrobial contamination in the problem of AMR.


Fat-storing (Ito) cells of rat liver synthesize and secrete apolipoproteins: comparison with hepatocytes.
Fat-storing cells of the liver store most of the vitamin A of the body. Vitamin A is present in a few large fat droplets within the cell. The aim of our study was to investigate apolipoprotein biosynthesis in isolated fat-storing cells from rat liver during the time in culture. Isolated rat hepatocytes were studied for comparison. Proteins were biosynthetically labeled and further identified by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Apoproteins in culture supernatants were identified by density gradient ultracentrifugation and by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of aliquots of the gradient. Rat plasma was processed in the same way and used for comparison. Fat-storing cells synthesized and secreted apoprotein E, apoprotein A-I, apoprotein A-IV, and low amounts of apoprotein C. The synthesis of these proteins increased during the culture time, reaching a maximum at the fifth day after isolation. The proteins were identified mostly as apoproteins of high-density lipoprotein. Hepatocytes synthesized and secreted apoproteins of all classes of lipoproteins. The distribution of high-density lipoprotein apoproteins was similar to that of fat-storing cells but hepatocytes produced larger amounts of the apoproteins.


Yolk sac tumor of the testicle: is retroperitoneal lymph node dissection necessary?
We report our experience with 11 cases of yolk sac tumors, which were treated between 1960 and 1982 at the Hôpital Sainte-Justine and the Montreal Children's Hospital. The role of lymphadenectomy in yolk sac tumors is analyzed critically and put into perspective with the use of serum alpha-fetoprotein. A flow sheet is presented for the management of yolk sac tumors. It seems that the indication for lymphadenectomy in yolk sac tumor should be restricted to patients with persistently elevated serum alpha-fetoprotein after inguinal orchiectomy and chemotherapy.


Turn bane into a boon: Application of invasive plant species to remedy soil cadmium contamination.
Cadmium (Cd) is one of the mostly hazardous soil pollutants and has threatened human health by accumulating in grains of crops. Phytoremediation is a promising technique to remedy soil Cd contamination, but reported Cd hyperaccumulators remain limited. In this study, we explored potential applicability of three invasive plant species (Chromolaena odorata, Bidens pilosa and Praxelis clematidea) to remove soil Cd using greenhouse experiment. Results showed that the three species grew well with Cd treatments compared to the controlled individuals, suggesting that the species had high Cd tolerance by physiological adjustments such as up-regulating the antioxidant enzyme activities. The only exception was that the height of P. clematidea in the 60 mg kg-1 Cd treatment was less than that in the control. Within the tested Cd concentration range, the C. odorata exhibited high bioaccumulation characteristics that meet the recommended standards to identify as a hyperaccumulator (shoot Cd concentration > 100 mg kg-1 with bioconcentration and transfer factors > 1). The other two species had also the shoot bioconcentration factor and transfer factor greater than one, while the shoot Cd concentration was relatively lower. Our results highlight a potential applicability of the invasive species used in this study for remediation of the soil Cd contamination, which turns bane into a boon.


Review on statistical methods for gene network reconstruction using expression data.
Network modeling has proven to be a fundamental tool in analyzing the inner workings of a cell. It has revolutionized our understanding of biological processes and made significant contributions to the discovery of disease biomarkers. Much effort has been devoted to reconstruct various types of biochemical networks using functional genomic datasets generated by high-throughput technologies. This paper discusses statistical methods used to reconstruct gene regulatory networks using gene expression data. In particular, we highlight progress made and challenges yet to be met in the problems involved in estimating gene interactions, inferring causality and modeling temporal changes of regulation behaviors. As rapid advances in technologies have made available diverse, large-scale genomic data, we also survey methods of incorporating all these additional data to achieve better, more accurate inference of gene networks.


Current guidelines and treatment paradigms for nocturnal polyuria: A "NEW" disease state for US physicians, patients and payers.
Nocturia is one of the most bothersome symptoms encountered in urology, and its prevalence rises with age. Causes include both urological and non-urological aetiologies, often in combination. The effects of nocturia on a patient's quality of life can be detrimental. The initial approach to managing this condition includes appropriately classifying nocturia based on the results of a 24-hour bladder diary. Broadly, the categories under which nocturia can be classified include: low nocturnal or global bladder capacity, nocturnal polyuria, global polyuria and mixed.Based on the type of nocturia and possible underlying causes, clinicians can appropriately discuss with patients the treatment plans that may include a combination of behavioural, pharmacologic, and invasive therapy. The available literature on the management of nocturia was reviewed. Findings were incorporated into a practice-based approach for its workup and treatment.


Tuning methyl 4,6-O-benzylidene α-D-glucopyranosides' gelation ability by minor group modifications.
Ten methyl 4,6-O-benzylidene α-D-glucopyranosides were synthesized for the purpose of studying systematically the effect of small group changes at position 4 of the aromatic ring on the ability to gelate organic solvents. The gelation properties are discussed on the basis of small angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) measurements, and scanning electron microscopy (SEM) observations. Sol-gel transition temperatures were determined simultaneously by DSC and temperature-dependent FTIR measurements. The current study emphasizes that carbohydrates furnish not only valuable information about structural requirements for organogelator design, but also for molecular assembly systems in general.


What surgical approach for left-sided eloquent glioblastoma: biopsy, resection under general anesthesia or awake craniotomy?
Neurosurgeons use three main surgical approaches for left-sided glioblastoma (GB) in eloquent areas: biopsy, tumor resection under general anesthesia (GA), and awake craniotomy (AC) with brain mapping for maximal safe resection. We performed a retrospective study of functional and survival outcomes for left-sided eloquent GB, comparing these surgical approaches. We included 87 patients with primary left-sided eloquent GB from two centers, one performing AC and the other biopsy or resection under GA. We assessed Karnofsky performance score (KPS), language and motor deficits one month after surgery, progression-free survival (PFS) and overall survival (OS). The 87 patients had a median PFS of 8.6 months [95% CI: 7.3-11.6] and a median OS of 20.2 months [17-3-24.4], with no significant differences between the three surgical approaches. One month after surgery, functional outcomes for language were similar for all approaches, but motor function was poorer in the biopsy group than in other patients. The proportion of patients with a KPS score > 80 was higher in the resection with AC group than in the other patients at this timepoint. We detected no real benefit of a resection with AC over resection under GA for left-sided eloquent GB in terms of survival or functional outcomes for language. However, given the poorer motor function of biopsy patients, resection with AC should be proposed, when possible, to patients ineligible for surgical resection under GA, to improve functional outcomes and patient autonomy.


Virtual reality exergame in older patients with hypertension: a preliminary study to determine load intensity and blood pressure.
Lifestyle changes and physical activity can make an important contribution to reducing the risk factor for high blood pressure (BP). Whether virtual reality (VR) exergames are also appropriate and make a positive contribution to the reduction of BP has not yet been sufficiently investigated. Therefore, the aim of the study was to gain knowledge of the load intensities to be achieved during a VR exergame and to examine the short-term effects on BP. For the preliminary study, 22 participants with hypertension over the age of 65 years were analyzed. The study took place in a mobile laboratory truck. All participants visited on two occasions. During visit 1, VR strength endurance training (VR-SET) and during visit 2, VR endurance training (VR-ET) was performed. Each VR session lasted approximately 25 min and was of a moderate intensity. Heart rate (HR) was measured across the entire session, as well as BP before and after the VR exergame. The Rating of Perceived Exertion (RPE) and task load using NASA Task Load Index were determined after each VR session. Included in the statistical analysis were the Shapiro-Wilk test, the paired t-test, the Wilcoxon test and ANOVA for repeated measures. During the "main part" (p < .001), at the "end" (p = .002) and for the "maximum HR" (p < .001), significant load differences between both VR sessions could be determined. In addition, significantly more participants in the VR-SET group achieved a moderate load intensity of at least 40% of heart rate reserve (p = .014). Regarding RPE, participants rated their subjectively perceived exertion significantly higher in the VR-SET than in the VR-ET (p = .028). Systolic BP decreased significantly in both VR sessions when compared before VR session and 5 min after VR session (p = .015; p = .003), as well as before VR session and 10 min after VR session (p = .018; p < .001). An individual moderate load intensity of 40% can be reached during VR-SET. In addition, a positive short-term effect of the VR exergame on BP behavior (postexercise hypotension) was observed after both VR sessions. The preliminary results indicate that a VR exergaming could lead to blood pressure lowering effects for older people with hypertension. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00022881, 07/09/2020, https://drks.de/search/de/trial/DRKS00022881 ).


Establishment and characterization of a cell line derived from human colon adenocarcinoma (HuCCL-14).
A continuous human colon carcinoma cell line (HuCCL-14) was established whose cells possess an epithelial-like morphology and are capable of growing in soft agar and on monolayers of normal cells. HuCCL-14 cells yielded high levels of carcinoembryonic antigen, and the analysis of their chromosomal constitution revealed a mode of 70 chromosomes per cell. HuCCL-14 cells produce malignant tumors when injected into nude mice. Preliminary virologic studies indicate the release of RNA particles having a density of 1.15--1.19 g/ml.


Iron Phthalocyanine-Knitted Polymers as Electrocatalysts for the Oxygen Reduction Reaction.
Knitted iron phthalocyanine-based porous polymer networks (K-FePcs) were prepared in a single step using solvent-knitting strategies with commercial iron phthalocyanine as a building monomer. The incorporation of different aryl comonomers (biphenyl and 1,2,4,5-tetraphenylbenzene) to FePc allowed quantitative yields, high porosities, and excellent ORR activity. The reversible Fe(III)/Fe(II) redox potential of FeN4 centers of the knitted polymer networks in N2-saturated electrolyte solution (i.e., ∼0.8 V vs RHE) were shown as good descriptors of their ORR activity. K-FePc2Ph presented the highest amount of FeN4 active sites and an adequate degree of steric hindrance to maintain the isolation between catalytically active sites. Moreover, it displayed comparable current density limits and superior mass activity and half-wave potential (i.e., 0.88 V vs RHE) than those of 20% Pt/C benchmark catalyst, while keeping higher stability toward methanol oxidation. K-FePc2Ph can be an interesting alternative to Pt-based ORR electrocatalysts.


Denervation increases the degradation rate of acetylcholine receptors at end-plates in vivo and in vitro.
We have studied the effect of denervation on the degradation of the existing junctional acetylcholine (ACh) receptors at end-plates in rat muscles. ACh receptors were labelled by injecting animals with iodinated alpha-bungarotoxin (I-alpha BT); 1 day later the left hemidiaphragm was denervated. The degradation of bound I-alpha BT in normal and denervated muscles was examined in organ culture, beginning at various times after denervation in vivo. The original, pre-labelled end-plate ACh receptors are degraded more rapidly after denervation. The rate of degradation begins to increase shortly after the nerve is cut and reaches a maximum value at about 9 days of denervation. Muscles denervated only on transfer to organ culture also show an increase in the degradation rate of bound I-alpha BT with increasing time of denervation (time in culture). In normal diaphragm muscles, the initial rate of degradation of functional ACh receptors, after correcting for non-degradative loss of I-alpha BT, is 0.0018 h-1 (t1/2 = 383 h). The maximal rate at denervated end-plates is 0.0073 h-1 (t1/2 = 94 h). For soleus, sternomastoid, plantaris and intercostal innervated muscles the apparent rate of ACh receptor degradation either in vitro or in vivo ranged from 0.0005 h-1 to 0.002 h-1. The rate of loss of bound I-alpha BT in vivo is more rapid at denervated end-plates than at innervated end-plates. For diaphragm muscles, the rates of I-alpha BT degradation measured in organ culture are able to describe the relative rates of loss of I-alpha BT from innervated and denervated muscles in vivo. At short times after labelling, a fraction (10-20%) of the I-alpha BT bound to innervated muscles is degraded more rapidly than the remaining toxin. The possibility that these I-alpha BT binding sites are degraded at the rate characteristic of extrajunctional receptors on denervated muscle fibres is discussed.


An Erlotinib gold(I) conjugate for combating triple-negative breast cancer.
An Erlotinib triphenylphosphane gold(I) conjugate has been prepared from AuCl(PPh3) and its crystal structure has been established by X-ray diffraction, showing a metallo-helicate formation. IC50 values of the new gold conjugate were calculated towards a panel of human tumor cell lines representative of breast (MCF-7, MDA-MB-231) and colon (HT-29) cancer cells. Overall, the gold conjugate exhibited higher cytotoxic activity than that of Erlotinib against the cancer cells studied. Particularly, the antiproliferative effect of the conjugate demonstrated to be 68-fold higher than Erlotinib in highly metastatic and triple negative MDA-MB-231 cell line. The gold conjugate caused DNA damage, reactive oxygen species (ROS) increase and induced apoptosis. Flow cytometry analysis showed that the conjugate induces significant arrest in S and G2/M phases primarily, whereas Erlotinib, as an inhibitor of epidermal growth factor receptor (EGFR), blocks G1/S transition and increases G1 cell population.


Hepcidin regulates intrarenal iron handling at the distal nephron.
Hepcidin, the key regulatory hormone of iron homeostasis, and iron carriers such as transferrin receptor1 (TFR1), divalent metal transporter1 (DMT1), and ferroportin (FPN) are expressed in kidney. Whether hepcidin plays an intrinsic role in the regulation of renal iron transport is unknown. Here, we analyzed the renal handling of iron in hemochromatosis Hepc(-/-) and Hjv(-/-) mouse models, as well as in phenylhydrazine (PHZ)-treated mice. We found a marked medullary iron deposition in the kidneys of Hepc(-/-) mice, and iron leak in the urine. The kidneys of Hepc(-/-) mice exhibited a concomitant decrease in TFR1 and increase in ferritin and FPN expression. Increased FPN abundance was restricted to the thick ascending limb (TAL). DMT1 protein remained unaffected despite a significant decrease of its mRNA level, suggesting that DMT1 protein is stabilized in the absence of hepcidin. Treatment of kidney sections from Hepc(-/-) mice with hepcidin decreased DMT1 protein, an effect confirmed in renal cell lines where hepcidin markedly decreased (55)Fe transport. In the kidneys of Hjv(-/-) mice exhibiting low hepcidin expression, the iron overload was similar to that in the kidneys of Hepc(-/-) mice. However, in PHZ mice, iron accumulation resulting from hemoglobin leak was detected in the proximal tubule. Thus, kidneys exhibit a tissue-specific handling of iron that depends on the extra iron source. Hepcidin may control the expression of iron transporters to prevent renal iron overload.


Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy.
To show fatigue prevention and quality of life (QOL) improvement from cardiovascular exercise during radiotherapy. Prospective enrollment (n=21), randomized to exercise (n=11) and control groups (n=10), with pre- and post-radiotherapy between- and within-group comparisons. Academic medical center. Localized prostate cancer patients undergoing radiotherapy. The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise. Pre- and post-radiotherapy differences in cardiac fitness, fatigue, depression, functional status, physical, social, and functional well-being, leg strength, and flexibility were examined within and between 2 groups. No significant differences existed between 2 groups at pre-radiotherapy assessment. At post-radiotherapy assessment, the exercise group showed significant within group improvements in: cardiac fitness (P<.001), fatigue (P=.02), Functional Assessment of Cancer Therapy-Prostate (FACT-P) (P=.04), physical well-being (P=.002), social well-being (P=.02), flexibility (P=.006), and leg strength (P=.000). Within the control group, there was a significant increase in fatigue score (P=.004) and a decline in social well-being (P<.05) at post-radiotherapy assessment. Between-group differences at post-radiotherapy assessment were significant in cardiac fitness (P=.006), strength (P=.000), flexibility (P<.01), fatigue (P<.001), FACT-P (P=.006), physical well-being (P<.001), social well-being (P=.002), and functional well-being (P=.04). An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness, flexibility, muscle strength, and overall QOL and prevented fatigue.


Implications of sequencing bacterial genomes for pathogenesis and vaccine development.
Improvements in homology search methodology and functional predictions are being complemented by the increase in the volume of sequence data with which comparative analyses can be performed. The experimental methods needed for investigation of gene function and expression in a variety of model systems of infection continue to develop. The identification of surface-exposed microbial structures and their conservation in natural populations of pathogenic species offers prospects for developing novel vaccines. A major challenge is the development of efficient screening methods to select the most promising candidates, such as immunisation with DNA.


Vitamin D and hematinic deficiencies in patients with recurrent aphthous stomatitis.
Recurrent aphthous stomatitis (RAS) represents a dysfunction in focal inflammatory processes. With the emerging anti-inflammatory roles of vitamin D (VD), we wanted to investigate the association between the onset and severity of RAS and serum VD level. Fifty-two RAS cases and sex and age-matched controls were screened for serum iron, B12, folic acid, VD and red cell indices. Variables were compared using independent samples t test and chi square. Binary logistic regression was used to assess the association between the severity of RAS and various hematinic deficiencies. VD was deficient in 53% of the study population with no statistically significant difference between the RAS patients and healthy controls (53.6 versus 51.5 nmol/l, respectively). In comparison with controls, RAS patients had lower means of iron (81.0 versus 89.3 μg/dl), vitamin B12 (368.5 versus 412.7 pg ml) and most of the red cell indices; however, these differences were not statistically significant. No correlations were seen between RAS severity assessed by ulcer diameter, number of ulcers and their frequency and hematinic deficiencies. However, logistic regression showed a significant association between the number of ulcers (single or multiple) and VD deficiency (OR 4.978; 95% CI 1.204-20.576; p value = 0.027), adjusted for age, sex and other hematinics. VD deficiency appears to have a role in aggravating RAS ulcerative episodes, but not their onset. Multiple aphthous ulcers might represent a subcategory of RAS lesions in which VD deficiency plays a role in aggravating the oral ulcerative condition.


Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1.
Early diabetes research is hampered by limited availability, variable quality, and instability of human pancreatic islets in culture. Little is known about the human β cell secretome, and recent studies question translatability of rodent β cell secretory profiles. Here, we verify representativeness of EndoC-βH1, one of the most widely used human β cell lines, as a translational human β cell model based on omics and characterize the EndoC-βH1 secretome. We profiled EndoC-βH1 cells using RNA-seq, data-independent acquisition, and tandem mass tag proteomics of cell lysate. Omics profiles of EndoC-βH1 cells were compared to human β cells and insulinomas. Secretome composition was assessed by data-independent acquisition proteomics. Agreement between EndoC-βH1 cells and primary adult human β cells was ∼90% for global omics profiles as well as for β cell markers, transcription factors, and enzymes. Discrepancies in expression were due to elevated proliferation rate of EndoC-βH1 cells compared to adult β cells. Consistently, similarity was slightly higher with benign nonmetastatic insulinomas. EndoC-βH1 secreted 783 proteins in untreated baseline state and 3135 proteins when stressed with nontargeting control siRNA, including known β cell hormones INS, IAPP, and IGF2. Further, EndoC-βH1 secreted proteins known to generate bioactive peptides such as granins and enzymes required for production of bioactive peptides. EndoC-βH1 secretome contained an unexpectedly high proportion of predicted extracellular vesicle proteins. We believe that secretion of extracellular vesicles and bioactive peptides warrant further investigation with specialized proteomics workflows in future studies.


Toll-like receptor 10-1-6 gene cluster polymorphisms are not associated with benign prostatic hyperplasia in korean population.
Inflammation and infection have been associated with the pathogenesis of benign prostatic hyperplasia (BPH). Toll-like receptors (TLRs) play key roles in the innate immune system and initiate the inflammatory response to foreign pathogens. We investigated the relationship between TLR10-1-6 gene cluster polymorphisms and BPH. We genotyped four promoter single nucleotide polymorphisms (SNPs) (TLR10, rs10004195; TLR1, rs5743557; and TLR6, rs1039560 and rs1039559) by directly sequencing (233 BPH patients and 214 control subjects). SNPStats and Haploview version 4.02 were used to analyze the data. Multiple logistic regression models (log-additive, dominant, and recessive) were performed to determine odds ratios (ORs), 95% confidence intervals (CIs), and P-values. The genotype and allele frequencies of each SNP was not different between the BPH and control groups (P>0.05). Haplotype analysis showed no association between the haplotype in the linkage disequilibrium (LD) block and BPH (P>0.05), although the LD block was constructed. These results indicate that the TLR10-1-6 gene cluster may be not associated with the development of BPH in the Korean population.


Changes in brain amines associated with cancer anorexia.
Analysis of indole amine metabolism within acute (Walker 256 carcinosarcoma) and chronic (methycholanthrene-induced sarcoma) animal models of cancer anorexia demonstrated elevated levels of plasma free tryptophan, whole brain tryptophan, serotonin and 5-hydroxyindoleacetic acid in anorectic tumor-bearing rats. Whole brain levels of catecholamines were not changed within either tumor line. Regional central nervous system determination of tryptophan metabolism in rats bearing Walker 256 tumors revealed elevated tryptophan in the hypothalamus, corpus striatum, mesencephalon, diencephalon, cerebellum and cortex, increased serotonin in the diencephalon and cerebellum and elevated 5-hydroxyindoleacetic acid in the diencephalon, hippocampus, pons-medulla, cerebellum and cortex. Although tryptophan was significantly increased only in the corpus striatum and diencephalon of the more chronic methycholanthrene tumor model, serotonin concentration was elevated in the corpus striatum, diencephalon, hippocampus, pons-medulla, cerebellum and cortex, while levels of 5-hydroxyindoleacetic acid were significantly increased in all these areas as well as in the mesencephalon. Since similar changes in indole activity were not observed in pair-fed control rats, it is concluded that the elevated serotonin and 5-hydroxyindoleacetic acid levels in tumor-bearing rats did not result from undernutrition alone. Assay of regional catecholamines revealed few food-relevant changes, with norepinephrine being elevated in the corpus striatum and decreased in the pons-medulla of tumor-bearing rats. Therefore, these experiments suggest that the increased serotonin metabolism observed in tumor-bearing rats may be involved in the etiology of the anorexia of cancer.


Celecoxib blocks cardiac Kv1.5, Kv4.3 and Kv7.1 (KCNQ1) channels: effects on cardiac action potentials.
Celecoxib is a COX-2 inhibitor that has been related to an increased cardiovascular risk and that exerts several actions on different targets. The aim of this study was to analyze the effects of this drug on human cardiac voltage-gated potassium channels (Kv) involved on cardiac repolarization Kv1.5 (I(Kur)), Kv4.3+KChIP2 (I(to1)) and Kv7.1+KCNE1 (I(Ks)) and to compare with another COX-2 inhibitor, rofecoxib. Currents were recorded in transfected mammalian cells by whole-cell patch-clamp. Celecoxib blocked all the Kv channels analyzed and rofecoxib was always less potent, except on Kv4.3+KChIP2 channels. Kv1.5 block increased in the voltage range of channel activation, decreasing at potentials positive to 0 mV. The drug modified the activation curve of the channels that became biphasic. Block was frequency-dependent, increasing at fastest frequencies. Celecoxib effects were not altered by TEA(out) in R487Y mutant Kv1.5 channels but the kinetics of block were slower and the degree of block was smaller with TEA(in), indicating that celecoxib acts from the cytosolic side. We confirmed the blocking properties of celecoxib on native Kv currents from rat vascular cells, where Kv1.5 are the main contributors (IC(50)≈ 7 μM). Finally, we demonstrate that celecoxib prolongs the action potential duration in mouse cardiac myocytes and shortens it in guinea pig cardiac myocytes, suggesting that Kv block induced by celecoxib may be of clinical relevance.


Newer data on the configuration and variability ranges of body surface maps in a sample of normal subjects.
Quantitative data on the normal variability of body surface maps (BSM) are scarce in the literature. This is one of the reasons why BSM are not yet widely used in clinical practice despite their superior information contents. In this study we determined the average value and variability of a number of parameters derived from BSM in a group of 36 normal adult males, ages 22 to 60. Forty to 60 homogeneous beats were averaged for each subject. This enabled us to extend our study to the low voltage intervals (P,PQ,ST,U) which encompass more than 60% of the entire P-U duration and to contribute new data to controversial issues, such as the presence of two simultaneous maxima during atrial excitation. The following parameters were measured: a) the coordinates of the absolute potential maximum and minimum on the chest surface during the entire cardiac cycle; b) the time course of four voltage-related functions, namely: highest instantaneous potential value on the chest surface, lowest (most negative) potential, highest potential difference, and surface integral of the absolute value of the potential function. In recent studies these parameters were shown to be of considerable value in discriminating normal subjects from different categories of cardiac patients.


An advanced treatment process for 3-high wastewater discharged from crude oil storage tanks.
The wastewater discharged from crude oil storage tanks (WCOST) contains high concentrations of salt and metal iron ions, and high chemical oxygen demand (COD). It belongs to "3-high" wastewater, which is difficult for purification. In this study, WCOST treatments were comparatively investigated via an advanced pretreatment and the traditional coagulation-microfiltration (CMF) processes. After WCOST was purified through the conventional CMF process, fouling occurred in the microfiltration (MF) membrane, which is rather harmful to the following reverse osmosis (RO) membrane unit, and the effluent featured high COD and UV254 values. The analysis confirmed that the MF fouling was due to the oxidation of ferrous ions, and the high COD and UV254 values were mainly attributable to the organic compounds with small molecular sizes, including aromatic-like and fulvic-like compounds. After the pretreatment of the advanced process consisting of aeration, manganese sand filtration, and activated carbon adsorption in combination with CMF process, the removal efficiencies of organic matter and total iron ions reached 97.3% and 99.8%, respectively. All the water indexes of the effluent, after treatment by the advanced multi-unit process, meet well the corresponding standard. The advanced pretreatment process reported herein displayed a great potential for alleviating the MF membrane fouling and enhanced the lifetime of the RO membrane system in the 3-high WCOST treatment.


Occurrence of Trichophyton vanbreuseghemii in Hungary.
The occurrence of Trichophyton vanbreuseghemii in Hungary is reported. The micromorphological characteristics of the species are discussed.


Orbital hybridisation effects in B2 phase Cr doped Co2MnAl.
We investigate here the magnetic, transport, local structural and electronic properties of Co2Mn1-xCrxAl (x= 0, 0.05, 0.1 and 0.2). Our results show that all the compounds stabilise in B2 phase and are ferromagnets. The results reveal disorder at the structural and magnetic levels. X-ray absorption near edge structure (XANES) analysis reveal signature of antisite disorder between Mn and Al atoms with equal ratio. The electronic structure calculations suggest enhancement in the half metallicity, localisation of electrons at the Fermi level and an increment in density of states with doping. The combined results of electronic structure calculations and XANES studies suggest transfer of electrons to the Co site. The results of high temperature resistivity measurements suggest the conduction electrons are undergoing transition from delocalisation to weak localisation to activated behaviour with Cr doping. The extended x-ray absorption spectroscopic analysis shows that the local structure around Mn atom is different from the global structure as obtained from the x-ray diffraction results. The behaviour of the edge region is in line with the trend as obtained from the compositional analysis. We observe link between the hybridisation of 3dlike states at the Mn, Cr sites with that at the Co site and the transport properties. This could help in understanding the unusual decrement in the lattice parameter with doping. These results reveal the role of local structure in understanding the physical properties of such systems.


Acute interstitial nephritis manifesting as a persistent nephogram.
We report a case of a 61-year-old woman who presented to the emergency department with high inflammatory parameters and acute renal failure. Marked enlarged kidneys with persistent nephrogram were found on contrast-enhanced computed tomography . Renal biopsy showed acute interstitial nephritis. Acute interstitial nephritis must be included in the differential diagnosis in patients presenting with a persistent nephrogram.


Decitabine activates specific caspases downstream of p73 in myeloid leukemia.
The demethylating effect of 5-aza-2' deoxycytidine (decitabine, DAC) has been well characterized. The molecular events downstream of methylation inhibition are less well known. Here, DAC was shown to induce apoptosis in acute myeloid leukemia (AML) cells (p53 mutant and wild type) but not in epithelial or normal peripheral blood mononuclear cells. Apoptosis was characterized by activation of the mitochondrial but not the receptor death pathway, as demonstrated by the release of cytochrome c and loss of mitochondrial membrane potential. Western blotting and enzyme assays showed that caspase-3, but not caspase-6 or caspase-8, were activated. Decitabine induced expression of the cell cycle inhibitor p21, arresting AML cell lines in G1 of the cell cycle. Expression of p21 was induced irrespective of the methylation status of its promoter, mediated instead via reexpression of the tumor suppressor p73, an upstream regulator of p21. The promoter of p73 was hypermethylated in AML cell lines in vitro and in primary AML cells ex vivo but not in DAC-resistant epithelial cells. In conclusion, DAC acts on leukemic myeloid cells via caspase activation, which may be dependent on demethylation of the hypermethylated p73 promoter and consequent reexpression of p73.


Transient neonatal hyperthyrotropinemia: a factitious syndrome due to the presence of heterophilic antibodies in the plasma of infants and their mothers.
In a national screening program for neonatal hypothyroidism, our criterion for diagnosis is a plasma TSH value exceeding 40 microunits/ml on the fifth day of life. Excluding cases with obvious thyroid abnormalities, we identified a group of 14 neonates with unexplained plasma TSH elevation out of 10,261 screened. The mothers of these infants also exhibited high plasma TSH immunoreactivity; both mother and child in these instances were clinically euthyroid. The material responsible for this TSH immunoreactivity had the following characteristics. After parturition, it disappears from circulation within 2 months in the infants and within 4-6 months in the mother, its apparent molecular weight approximated 150,000 daltons, and its affinity for protein A-Sepharose and its binding properties suggested that the material was an immunoglobulin. Binding is observed typically for heterologous immunoglobulin and human TSH. The heterophilic character of these immunoglobulins explains their interference in many RIA systems, including the TSH RIA commonly used in neonatal screening programs for hypothyroidism.


Addition of the Sartorius Tendon Improves Biomechanics of a Four-Strand Hamstring Anterior Cruciate Ligament Autograft.
The purpose of this study was to quantify and compare the biomechanical properties and change in graft size when adding the sartorius tendon as a fifth strand to a four-strand ST-G hamstring autograft. Additionally, the sartorius tendon was tested individually to quantify its independent biomechanical properties. Four-strand and five-strand hamstring tendon grafts were harvested from matched cadaveric knees (mean age: 81.6 ± 9.8). These matched grafts were biomechanically tested using a MTS servohydraulic test system at a rate of testing representative of physiologic tears. The mean diameter, cross-sectional area, and ultimate load to failure were quantified and compared with a one-sided, paired Student's t-test. A P < .05 was considered statistically significant. The mean diameter of the five-strand graft was significantly larger than the four-strand graft (9.30 ± .84 mm vs 8.10 ± .42 mm; P = .002). The average ultimate load to failure of the five-strand graft was 65.3% higher than the four-strand graft (2984.05 ± 1085.11 N vs. 1805.03 ± 557.69 N; P = .009) and added 14.8% to the diameter of the four strand ST-G autograft. The addition of the sartorius tendon to a four-strand hamstring autograft significantly increased ultimate load to failure by 65%, graft cross-sectional area by 32%, and graft diameter by 15% compared to a traditional four-strand ST-G autograft. This information can be helpful to surgeons who wish to improve the strength of a four-strand ST-G autograft and for undersized grafts as an alternative to allograft supplementation. The addition of the sartorius to the four-strand ST-G hamstring autograft significantly increases the ultimate load to failure and overall graft diameter, which can be particularly helpful in undersized autografts as an alternative to allograft supplementation.


Dermoscopic Features of Actinic Cheilitis and Other Common Inflammatory Cheilitis: A Multicentric Retrospective Observational Study by the International Dermoscopy Society.
Clinical differentiation between different cheilitis variants may be difficult. Application of mucoscopy, in addition to clinical background, could provide additional diagnostic clues facilitating initial patient management. To determine mucoscopic clues differentiating actinic cheilitis from the main forms of inflammatory cheilitis, including eczematous cheilitis, discoid lupus erythematosus, and lichen planus of the lips. This was a retrospective, multicenter study being a part of an ongoing project "Mucoscopy - an upcoming tool for oral mucosal disorders" under the aegis of the International Dermoscopy Society. Cases included in the current study were collected via an online call published on the IDS website (www.dermoscopy-ids.org) between January 2019 and December 2020. Whitish-red background was found in actinic cheilitis as well as in cheilitis due to discoid lupus erythematous and lichen planus. Polymorphous vessels were more likely to be seen in actinic cheilitis compared to other causes of cheilitis. White scales, ulceration, and blood spots predominated in actinic cheilitis and lichen planus, whereas yellowish scales typified eczematous and discoid lupus erythematous cheilitis. Radiating white lines although most common in lichen planus patients were also seen in actinic cheilitis. Despite differences in the frequency of mucoscopic structures, we have not found pathognomonic features allowing for differentiation between analyzed variants of cheilitis.


Identification of predictive factors interacting with heart rate reduction for potential beneficial clinical outcomes in chronic heart failure: A systematic literature review and meta-analysis.
There is an absence of clinical evidence on what factors modify the effect of heart rate (HR)-reducing treatment on mortality and morbidity in symptomatic heart failure patients with reduced ejection fraction (HFrEF). We performed a Bayesian meta-analysis and meta-regression to identify predictive factors that interact with HR-reducing therapy. A systematic review was performed to identify randomized placebo-controlled trials that enrolled symptomatic HFrEF patients. The primary objective was to evaluate how different predictive factors modify the efficacy of HR-reducing therapy on clinical outcomes. Secondary objectives included the evaluation of subgroups stratified by a HR reduction threshold of 10 bpm. Data from 20 studies were synthesized and HR-reducing therapy was responsible for 16.7 %, 16.4 %, and 21.1 % risk reductions in all-cause mortality, cardiovascular (CV)-related mortality, and rehospitalization due to worsening HF (WHF), respectively. Empirical Bayes meta-regression showed that type 2 diabetes mellitus (T2DM) significantly modified the efficacy of HR-reducing therapy on all-cause mortality (slope = 0.012 in log risk ratio (RR) per 1 %-unit [95 % credible interval (CrI) 0.004, 0.021]) and CV-related mortality (0.01 in log RR per 1 %-unit [95 % CrI 0.0003, 0.0200]). There were insufficient studies to perform a meta-regression when stratifying by a HR reduction threshold of 10 bpm; however, when including all studies, we observed a significant effect modification for rehospitalization due to WHF (p = 0.004). This meta-analysis focused on the central tenet of HR-reducing therapy and revealed that T2DM is a predictor of HR-reducing treatment effect on all-cause mortality and CV-related mortality in HFrEF patients.


In vitro indeterminate teleost myogenesis appears to be dependent on Pax3.
The zebrafish (Danio rerio) has been used extensively as a model system for developmental studies but, unlike most teleost fish, it grows in a determinate-like manner. A close relative, the giant danio (Devario cf. aequipinnatus), grows indeterminately, displaying both hyperplasia and hypertrophy of skeletal myofibers as an adult. To better understand adult muscle hyperplasia, a postlarval/postnatal process that closely resembles secondary myogenesis during development, we characterized the expression of Pax3/7, c-Met, syndecan-4, Myf5, MyoD1, myogenin, and myostatin during in vitro myogenesis, a technique that allows for the complete progression of myogenic precursor cells to myotubes. Pax7 appears to be expressed only in newly activated MPCs while Pax3 is expressed through most of the myogenic program, as are c-Met and syndecan-4. MyoD1 appears important in all stages of myogenesis, while Myf5 is likely expressed at low to background levels, and myogenin expression is enriched in myotubes. Myostatin, like MyoD1, appears to be ubiquitous at all stages. This is the first comprehensive report of key myogenic factor expression patterns in an indeterminate teleost, one that strongly suggests that Pax3 and/or Myf5 may be involved in the regulation of this paradigm. Further, it validates this species as a model organism for studying adult myogenesis in vitro, especially mechanisms underlying nascent myofiber recruitment.


The structure of the capsular polysaccharide of Klebsiella K-type 31.
The structure of the Klebsiella K31 capsular polysaccharide has been elucidated by periodate oxidation, methylation analysis, characterization of oligosaccharides obtained by partial, acid hydrolysis, and proton magnetic resonance. The polymer consists of pentasaccharide repeating-units having the following structure (1).


Duffy blood group and hemoglobin variants.
Data on a sample of 809 Afro-Americans indicated that there is no association between Duffy null (a-,b-) blood type and sickle cell trait. The results further rule out close linkage as an alternative hypothesis to explain the reported association between these loci in areas where falciparum and vivax malaria are endemic and indicate that, even if the two loci are independent or loosely linked, direct evidence of the selection favoring AS Fy-Fy- individuals must come from populations where mixed malaria infections occur. Stratification, as an explanation for the reported association, is also discussed.


Retracted: Picture Fuzzy Einstein Hybrid-Weighted Aggregation Operator and Its Application to Multicriteria Group Decision Making.
[This retracts the article DOI: 10.1155/2022/6925670.].


An interspecies correlation model to predict acute dermal toxicity of plant protection products to terrestrial life stages of amphibians using fish acute toxicity and bioconcentration data.
This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD50) from standard acute toxicity values (96-h LC50) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates.


The property of contingent negative variation (CNV) in psychiatric patients: schizophrenia and neurosis.
The CNV parameters (amplitude and morphology) and the relationship between CNV parameters and performances (motor response time) were studied on schizophrenics (15 subjects), neurotics (15 subjects) and normal controls (30 subjects divided into 2 groups) in order to clarify the property of CNV in psychiatric patients. Also, the relationship between CNV and personality traits was investigated in neurotics. Since it has been known that age, sex and psychoactive drugs influence the CNV genesis in normal subjects, the control group method was used for these factors in this study. The results obtained were as follows: 1) Mean amplitudes of CNV's for schizophrenics and neurotics in each session of control, nonresponse and recovery tended to be lower than those for normal controls. Significant differences were found between schizophrenics and normal controls. 2) Correlations between CNV amplitude and response time in schizophrenics tended to be positive, while normal controls showed significantly high negative correlations. These findings were discussed from the viewpoint of the arousal theory of CNV genesis. 3) For the neurotic patients, the personality variables appeared to influence CNV amplitude. 4) Type B-CNV was most frequently seen in all sessions for normal controls. Schizophrenics and neurotics tended to show the increment of type P-CNV in nonresponse sessions without a motor response. 5) "Field Dependency" type-CNV was not found in psychiatric patients. This result did not correspond with the data reported by other investigators. 6) Type III- and type IV-prolonged CNV's appeared almost especially in schizophrenics although type II-CNV was observed in all groups. The mechanism of genesis of the prolonged CNV's was discussed.


Polyethylene glycol versus vegetable oil based bisacodyl suppositories to initiate side-lying bowel care: a clinical trial in persons with spinal cord injury.
Neurogenic bowel dysfunction resulting from spinal cord injury (SCI) frequently requires bowel care (BC) with stimulant suppositories for initiation of effective defecation. The excessive time required for BC and bowel complications have limited quality of life after SCI. To test the hypothesis that: the time required for bowel care with bisacodyl suppositories can be reduced by substituting a polyethylene glycol base (PGB) for the traditional hydrogenated vegetable oil base (HVB) in the suppository. Inpatient SCI medicine unit. Fourteen persons with SCI with chronic stable paralysis from upper motor neuron SCI for greater than one year with a stable HVB bisacodyl suppository initiated BC. Crossover Controlled. Subjects received HVB bisacodyl suppositories for six sequential BC sessions and then were crossed over to PGB bisacodyl suppositories for six more BCs. BC event times were utilized to derive BC intervals: suppository insertion to first flatus= Time to flatus, first flatus until the beginning of stool flow = Flatus to stool flow, begin stool flow until end stool flow = Defecation period, end stool flow until end of clean up = Clean up, and suppository insertion until end clean up = Total bowel care time. The data included two groups of BC sessions: HVB (n = 84) and PGB (n = 81). Mean times in minutes and P values from t tests for paired samples yielded: Time to flatus: (HVB 31, PGB 12.8 P < 0.002), Defecation period: (HVB 58, PGB 32, P < 0.0005), Clean up: (HVB 1.9, PGB 3.2 P = 0.165), Total bowel care time: (HVB 102, PGB 51.2 P < 0.0005). This analysis suggests that PGB based bisacodyl suppositories may stimulate reflex defecation sooner and shorten the Total BC Time as compared with HVB bisacodyl suppositories.


A novel and reproducible release mechanism for a drug-delivery system in the gastrointestinal tract.
To establish a reliable, reproducible and accurate release of the drug in the gastrointestinal tract, a novel release mechanism for a controllable drug-delivery system has been investigated. The release mechanism, consisting of a one-way valve for drug release, a drug chamber, two axially magnetized cylindrical permanent magnets and a multi-layer solenoid coil, is hosted in the capsule-shaped shell with diameter 11 mm and length 30 mm. To actuate the coil piston, the two static magnetic fields produced by the two magnets are aligned along the same axis, having the same magnitude, but opposite directions. Based on the principle of the electromagnetic force and the Bernoulli equation, the actuating force can be expressed as a function of the coil stroke and the excitation current, which was modeled and experimentally verified. Thus the actuating force can be controlled by adjusting the activated period and intensity of the coil, resulting in the reproducible release with different doses and mean rates. Then, a prototype of the drug-delivery system has been developed, which consists of a drug-delivery capsule, a radio frequency transmission module, an interface circuit, and an instruction setting and triggering platform. All the drug release parameters, including the release mode, times, dose and mean flow rate, can be set by the platform. The experiment verifies that the drug-delivery capsule can deliver a predetermined dose with different flow rates and dip angles of the capsule. The relative error of the releasing dose becomes larger with increasing releasing rate and decreasing releasing dose.


Acute Pain Management Protocols in Pediatric Intensive Care Units.
Pediatric pain has historically been difficult to assess and even more difficult to treat. It is encouraging that there is current research regarding pain control in pediatric patients that provide evidence for treating pediatric pain. Patients in a pediatric intensive care setting demonstrate a great deal of patient variability with regard to patient diagnosis, age, developmental level, weight, and amount of pain control needed. The use of an evidence-based protocol for pediatric pain control can decrease variability in pain control and decrease potential adverse effects such as respiratory depression, constipation, withdrawal, delirium, and developmental delays while allowing for patient variability.


Older adults' outdoor walking and the built environment: does income matter?
Our aim was to examine the association between Street Smart Walk Score® and self-reported outdoor walking among older Canadians, and to determine whether socioeconomic status modifies this association. We linked objective walkability data with cross-sectional survey data from the Canadian Community Health Survey Healthy-Aging 2008-2009 Cycle for a sample of 1309 British Columbians aged ≥ 65 years. We examined associations between Street Smart Walk Score and meeting physical activity guidelines (≥150 min of moderate to vigorous activity/week) through self-reported outdoor walking using multivariable logistic regression, and tested for significant interactions with household income. A ten point higher Street Smart Walk Score was associated with a 17 % higher odds of meeting physical activity guidelines through walking outside (95 % CI: 1.07,1.27). In addition, older adults living in neighbourhoods categorised as Walker's Paradise were over three times more likely to meet guidelines than those living in Car-dependent/Very car dependent neighbourhoods. We found no evidence that household income moderated the effect of Walk Score on walking outside. Neighbourhood design may be one avenue whereby physical activity levels of older people can be enhanced through outdoor walking, with benefit across socioeconomic strata.


Dementia Care at a Glance Jenkins Catharine Ginesi Laura and Keenan Bernie Dementia Care at a Glance 176pp £26.99 Wiley-Blackwell 9781118859988 1118859987 [Formula: see text].
This book adds to Wiley's critically acclaimed 'at a glance' series with an overview of dementia care for all grades of healthcare providers, including healthcare assistants.


Comparison of characteristics of 18F-fluorodeoxyglucose and 18F-fluorothymidine PET during staging of esophageal squamous cell carcinoma.
The aim of this study was to compare the characteristics derived from fluorine-18 fluorodeoxyglucose (F-FDG) and fluorine-18 fluorothymidine (F-FLT) PET quantitatively and to assess their capacities during staging of esophageal squamous cell carcinoma (ESCC). Thirty-six patients with a diagnosis of ESCC who underwent both F-FDG and F-FLT PET were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, and texture features were determined. Considering histopathologic examination as the gold standard, the performance of the extracted indices during staging of ESCC was assessed using the Kruskal-Wallis test and the Mann-Whitney test. Considering the F-FDG PET images, the SUVmax, SUVmean, length (LEN), and eccentricity (EC) were significant during staging of American Joint Committee on Cancer (AJCC) and TNM (P<0.01), whereas for the F-FLT image, the SUVmax, LEN, and EC were significant during staging of AJCC and TNM (P<0.01). The characteristics of F-FDG and F-FLT PET for the classification of ESCC stage were significantly different. F-FDG image-derived characteristics including image textural features, SUV, and shape feature allow for better stratification of AJCC and TNM than F-FLT PET in ESCC patients.


Coronary artery disease and body mass index: What is the relationship?
Nowadays, obesity is considered an independent risk factor for the development of cardiovascular diseases (CVD), which has been presented as an important cause of worldwide morbidity and mortality, especially coronary artery disease (CAD). The objective of the study was to verify the association between body mass index (BMI) and severity of CAD, its risk factors and surgical and percutaneous treatment in patients hospitalized in cardiological units. An ambispective, cross-sectional study was performed with patients older than 18 years attended by nutrition in the cardiology units, who underwent coronary angiography. The severity of CAD was categorized into two distinct classifications (CAD Class I and II), considering the presence of CAD as lesions ≥50% and ≥70%. The nutritional status of the patient was established based on BMI according to the World Health Organization (WHO) for the total sample and group of adults, and according to the Pan American Health Organization (PAHO) for the elderly. Age, gender, presence of associated comorbidities, history of smoking, and performed procedures were collected in patients' records. For statistical analysis Kruskal Wallis and Chi-square tests were used, and Hodges-Lehmann estimate was used for the median. Comparisons and associations were considered significant when p < 0.05. A total of 703 patients were included, of which 495 had arterial lesions ≥70% and 513 patients' lesions ≥50%. The average age was 61 years, women were older (63 vs 61; p = 0.008), had a higher BMI (28.16 kg/m2 vs 26.68 kg/m2, p = 0.001) and were more likely to have diabetes mellitus (DM) (p < 0.001), dyslipidemia (DSLP) (p < 0.001), and hypertension (HTN) (p = 0.001). The majority of the sample consisted of men, who more often underwent percutaneous coronary intervention (PCI) (53,9% vs 39%, p < 0.001), and were more likely to present more severe CAD (p < 0.001 and p = 0.003). In patients diagnosed with CAD the increase in BMI was positively associated with the presence of DM (p < 0.001), DSLP (p < 0.001) and HTN (p < 0.001), and negatively with age (p = 0.007). Patients with obesity III, were diagnosed with CAD, in average, 11 years earlier than patients with normal BMI (p = 0.05). Therefore, the higher the BMI, the lower the age at the moment of the examination in the total sample, and in the group of elderly, and this association was not found in adults. There was no significant association of BMI with the severity of CAD, or with PCI and coronary artery bypass grafting (CABG). The greater severity of CAD was positively associated with the presence of DM (p = 0.012 and p = 0.001), HTN (p = 0.033 and p = 0.003) and older age (p = 0.005 and p = 0.015). Patients who underwent CABG had a higher incidence of and HTN (p = 0.003), DM (p = 0.006), whereas patients who had PCI had a lower incidence of HTN (p = 0.021) and DM (p = 0.004). Obesity was showed to be as an independent risk factor for the early incidence of CAD, which is strongly associated with the presence of comorbidities such as DM, HTN and DSLP. The greater severity of CAD and coronary interventions were associated with the presence of risk factors for CAD.


Primary health care service use among women who have recently left an abusive partner: income and racialization, unmet need, fits of services, and health.
Primary health care (PHC) can improve the health of women who have experienced intimate partner violence; yet, access to and fit of PHC services may be shaped by income and racialization. We examined whether income and racialization were associated with differences in PHC service use, unmet needs, fit with needs, and mental and physical health in a sample of 286 women who had separated from an abusive partner. Mothers, unemployed women, and those with lower incomes used more PHC services and reported a poorer fit of services. Poorer fit of services was related to poorer mental and physical health.


Spin State Energetics of VGe n -/0 (n = 5-7) Clusters and New Assignments of the Anion Photoelectron Spectra.
The geometrical structures, electron leading configurations, and relative energies of the low-lying states of VGe n -/0 (n = 5-7) clusters have been investigated with density functional theory and CASSCF/CASPT2 method. The pure GGA BP86 functional gave almost the same relative energy order for the low-lying states as the CASPT2 method. At the BP86 and CASPT2 levels, the ground states of VGe n -/0 (n = 5-7) clusters were proposed to be the 1 A1 and 2 A1 of A-VGe5 -/0 , 3 A″ and 2 A″, 2 A' (2 E2 ) of A-VGe6 -/0 , and 1 A' and 2 A' of A-VGe7 -/0 isomers. The adiabatic and vertical detachment energies (ADEs and VDEs) of the detachments of one electron from several orbitals of the anionic ground states were reported at the CASPT2 level. The calculated ADEs and VDEs corresponded well with the experimental values as observed in the 266 nm anion photoelectron spectra. © 2018 Wiley Periodicals, Inc.


Schisandra chinensis bee pollen's chemical profiles and protective effect against H2O2-induced apoptosis in H9c2 cardiomyocytes.
Schisandra chinensis (Turcz.) Baill bee pollen extract (SCBPE) is often used as a functional food in China due to its good antioxidant property. However, its chemical compositions and effects on H9c2 cardiomyocytes against H2O2-induced cell injury still lacks of reports thus far. This study aimed to characterize the main components of SCBPE and investigate its protective effects against H2O2-induced H9c2 cardiomyocyte injury. The main components of SCBPE were analyzed via ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF MS/MS). The three main nucleosides in SCBPE were quantitatively analyzed via ultraperformance liquid chromatography-diode array detection. Furthermore, the potential mechanism by which SCBPE exerts protective effects against H2O2-induced H9c2 cardiomyocyte injury was explored for the first time via cell survival rate measurements; cell morphological observation; myocardial superoxide dismutase (SOD) activity and malondialdehyde (MDA) and glutathione (GSH) level determination; flow cytometry; and quantitative polymerase chain reaction. Two carbohydrates, three nucleosides, and nine quinic acid nitrogen-containing derivatives in SCBPE were identified or tentatively characterized via UPLC-QTOF MS/MS. The nine quinic acid nitrogen-containing derivatives were first reported in bee pollen. The contents of uridine, guanosine, and adenosine were 2.4945 ± 0.0185, 0.1896 ± 0.0049, and 1.8418 ± 0.0157 μg/mg, respectively. Results of in vitro experiments showed that cell survival rate, myocardial SOD activity, and GSH level significantly increased and myocardial MDA level significantly decreased in SCBPE groups compared with those in H2O2 group. Cell morphology in SCBPE groups also markedly improved compared with that in H2O2 group. Results indicated that SCBPE protected H9c2 cardiomyocytes from H2O2-induced apoptosis by downregulating the mRNA expressions of Bax, cytochrome C, and caspase-3 and upregulating the Bcl-2 mRNA expression. This study is the first to report that SCBPE could protect against oxidative stress injury and apoptosis in H2O2-injured H9c2 cells. Results indicated that the nucleosides and quinic acid nitrogen-containing derivatives could be the main substances that exert protective effects against H2O2-induced H9c2 cardiomyocyte injury.


Bipolar Fusionless Versus Standard Fusion Surgery in Neuromuscular Scoliosis: A Two-center Comparative Study.
Nonrandomized controlled cohort. To compare early results between bipolar fusionless construct (BFC) and single posterior fusion (SPF) surgery in neuromuscular scoliosis (NMS). Surgical treatments for NMS have traditionally been characterized by high complication rates. A mini-invasive BFC was developed to reduce these risks while maintaining adequate curve reduction. There is, however, a current lack of studies comparing clinical and radiologic perioperative outcomes between both techniques. All patients surgically treated for NMS with to-pelvis construct between 2011 and 2021 at 2 centers were included and divided into 2 groups according to the surgical technique (BFC or SPF). Gender, age, main deformity region, etiology, preoperative and postoperative main curve magnitude and pelvic obliquity, surgery time, estimated blood loss and transfusion rates, length of hospital stay, the magnitude of main curve and pelvic obliquity correction, and early complications were compared. Quantitative data were compared through ANOVA or Mann-Whitney test. Analysis of qualitative outcomes was performed through Fisher exact test and logistic regressions. Kruskal-Wallis test was used to compare complications between groups. Eighty-nine NMS patients were included: 48 in the SPF group and 41 in the BFC group. Surgery time (203 vs. 241 min), rate (32 vs. 52%) and severity of complications, unplanned returns to the operating room (15 vs. 39%), estimated blood loss (179 vs. 364 cc), and transfusion rates (27 vs. 73%) were lower in the BFC group ( P <0.05). There were no significant differences in age, maturity stage, preoperative curve magnitude, preoperative pelvic obliquity and postoperative curve, and pelvic obliquity correction between groups. BFC may be a safer and less invasive option for NMS surgical treatment, resulting in similar curve corrections while significantly decreasing the number and severity of complications as well as intraoperative blood loss when compared with SPF. Level -lll.


Amikacin therapy for gram-negative septicemia.
Amikacin was administered to 18 patients with gram-negative septicemia. Ten of the patients had blood culture isolates highly resistant to gentamicin; six of these patients had persistent bacteremia while receiving gentamicin alone or in combination with other agents. Fourteen of the 18 patients were cured with amikacin therapy and adjunctive measures. Nine of the 10 patients with gentamicin-resistant pathogens were cured. The occurrence of nephrotoxicity in four patients with elevated amikacin serum levels and serious underlying disease indicates the desirability of monitoring serum amikacin levels. Minor ototoxicity occurred in two patients and was associated with prolonged therapy and high serum amikacin levels. Amikacin is a highly effective agent for treating patients with gram-negative bacteremia; it is the agent of choice in the therapy of patients with suspected or documented gram-negative bacteremia caused by pathogens resistant to gentamicin and susceptible to amikacin.


The influence of diet and feeding state on FMRFamide-related peptides in the gut of Locusta migratoria L.
Gut tissues of 2-week post-ecdysis female Locusta migratoria L. were assayed for FMRFamide-like immunoreactivity (FLI) during various feeding states using both radioimmunoassay and immunohistochemistry. The feeding states investigated were: (a) 48- and 24-h starved; (b) 5-, 30-, or 60-min post-feeding initiation; and (c) a diet of wheat grass, carrots, or apples. We determined: (1) the feeding state of a locust influences FLI in all gut tissues; (2) variations in diet appear to influence FLI in all gut tissues; (3) more than one FMRFamide-related peptide (FaRP) responds to differences in diet and state of starvation in the gut tissues; and (4) the protein poor diets (carrot and apple), in conjunction with the assertion that protein to carbohydrate ratio in the diet is the key component for nutrient balancing, suggests that FaRPs may play a role in maintaining balanced nutrient content in the locust.


Hitting moving targets: a dissociation between the use of the target's speed and direction of motion.
Previous work has indicated that people do not use their judgment of a target's speed to determine where to hit it. Instead, they use their judgment of the target's changing position and an expected speed (based on the speed of previous targets). In the present study we investigate whether people also ignore the target's apparent direction of motion, and use the target's changing position and an expected direction of motion instead. Subjects hit targets that moved in slightly different directions across a screen. Sometimes the targets disappeared after 150 ms, long before the subjects could reach the screen. This prevented subjects from using the target's changing position to adjust their movements, making it possible to evaluate whether subjects were relying on the perceived or an expected (average) direction to guide their movements. The background moved perpendicular to the average direction of motion in some trials. This influences the target's perceived direction of motion while leaving its perceived position unaffected. When the background was stationary, subjects hit disappearing targets along their trajectory, just as they hit ones that remained visible. Moving the background affected the direction in which subjects started to move their hand, in accordance with the illusory change in direction of target motion. If the target disappeared, this resulted in a hit that was systematically off the target's trajectory. If the target remained visible, subjects corrected their initial error. Presumably they did so on the basis of information about the target's changing position, because if the target disappeared they did not correct the error. We conclude that people do use the target's perceived direction of motion to determine where to hit it. Thus the perceived direction of motion is treated differently than the perceived speed. This suggests that the motion of an object is not broken down into speed components in different directions, but that speed and direction are perceived and used separately.


The Associations Between Sleep and Externalizing and Internalizing Problems in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Empirical Findings, Clinical Implications, and Future Research Directions.
Sleep problems are common in youth with attention-deficit/hyperactivity disorder (ADHD). Externalizing and internalizing problems contribute to dysfunction in youth with ADHD and are amplified by disrupted sleep. This objective of this article is to synthesize empirical studies that examined the associations between sleep and internalizing or externalizing problems in individuals with ADHD. The main findings are that sleep problems precede, predict, and significantly contribute to the manifestation of internalizing and externalizing behavior problems among children and adolescents with ADHD. Clinicians should assess sleep and integrate sleep interventions into the management of youth with ADHD.


The administration of rhBmal1 reduces sleep deprivation-induced anxiety and cognitive impairment in mice.
In mammals, circadian rhythms control metabolism, immunological response and reproductive processes. Bmal1 (brain and muscle Arnt-like protein-1) is a key element in the regulation of circadian rhythms. This investigation explores the pathophysiological effects of sleep deprivation in a mouse model as well as the potential underlying mechanisms. A mouse sleep deprivation model was constructed using a modified multi-platform water environment method. The anxiety-like behaviours of mice were assessed by the open field test and elevated plus maze, and the cognitive function of mice was tested by the nest-building test. The expression levels of targeted genes were determined by Western blotting assay and RT-qPCR assay. We found that sleep deprivation profoundly enhanced anxiety levels and impaired cognitive function in mice. Sleep deprivation also reduced the expression levels of Bmal1 and BDNF (brain-derived neurotrophic factor) and increased oxidative stress in the hippocampus of mice. The intraperitoneal injection of human recombinant rhBmal1 protein alleviated sleep deprivation-induced anxiety and cognitive impairment, restored Bmal1 and BDNF levels, and reduced oxidative stress in the hippocampus of mice. rhBmal1 treatment might serve as a potential therapy for mitigating sleep deprivation-related unfavourable symptoms.


A plasma image-spectrum fusion correction strategy for improving spectral stability based on radiation model in laser induced breakdown spectroscopy.
Spectral fluctuation is one of the main obstacles affecting the further development of LIBS, and it is also the current research hotspot and difficulty. To meet the requirements of industrial monitoring, a novel method named plasma image-spectrum fusion laser induced breakdown spectroscopy (PISF-LIBS) was proposed to correct the spectral fluctuation and improve the quantitative accuracy. In this method, by systematically analyzing the spectral radiation model, six main factors affecting the spectral stability were obtained. Further, the standard spectrum in the ideal plasma state which is not affected by these six factors was calculated, and the deviation from the actual spectrum was obtained. According to the above analysis, the calculated deviation was mainly affected by these six factors and can be estimated through them. Therefore, this study creatively proposed to use the effective information in the plasma images and spectra to indirectly characterize the deviation, so as to realize the correction of spectral fluctuation. To verify the wide applicability of PISF-LIBS in experimental conditions, the LIBS spectra of aluminum alloy obtained under four different experimental conditions were used. After PISF-LIBS correction, the R2 increased to more than 0.974, and the RMSE, MAPE and RSD of the prediction set decreased by 44.789%, 47.854% and 51.687% on average. To further verify the wide applicability of PISF-LIBS in experimental samples, alloy steel samples and pressed samples were also used. For alloy steel samples, after PISF-LIBS correction, the R2 increased to more than 0.996, and the RMSE, MAPE and RSD of the prediction set decreased by 48.337%, 52.856% and 25.819% evenly. For pressed samples, the R2 increased over 0.992, and the RMSE, MAPE and RSD of the prediction set decreased by 61.493%, 61.080% and 39.945% averagely. The experimental results prove the effectiveness and wide applicability of PISF-LIBS in spectral fluctuation correction.


Medial frontal epilepsy: histological, histochemical, and ultrastructural study. Preliminary observations.
The authors have studied the histological, histochemical, and ultrastructural aspects of eight corticectomies of epileptogenic foci in the medial surfaces of frontal lobes. In all cases they were able to see more gliosis and fewer neurons than normal. The shape and number of dendritic spines were thought to be normal with the Golgi-Cox method. The histochemical study showed an increment of activity of Glucose-6-Phosphatase, Glucose-6-Phosphatedehydrogenase, adenosintriphosphatase, and acid phosphatase. The electron microscope showed, in every case, a variety of changes, among which the authors can point to perivascular lipid accumulation, and an increase of lipofuscin bodies in the cytoplasm of pyramidal cells.


Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation.
Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium. The homogenous layer of adherent cells exhibited a typical fibroblast-like morphology, a large expansive potential, and cell cycle characteristics including a subset of quiescent cells. In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic, osteogenic and chondrogenic lineages. Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells, which uniformly expressed CD29, CD44, CD73, CD105, CD166, laminin, fibronectin and vimentin while being negative for expression of CD31, CD34, CD45 and alpha-smooth muscle actin. Most importantly, immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-I), but they did not express MHC-II molecules. Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli. This strongly implies that they may have potential application in allograft transplantation. Since placenta and UCB are homogeneous, the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.


Atypical haemolytic uremic syndrome with refractory multiorgan involvement and heterozygous CFHR1/CFHR3 gene deletion.
We present this challenging case report of Atypical Haemolytic Uremic Syndrome (aHUS) presenting with multi-organ involvement in a patient and heterozygous CFHR1/CFHR3 gene variant, which was refractory to initial eculizumab therapy. A forty-three year old female presented with aHUS and had heterozygous disease-associated deletions in the complement genes CFHR1/CFHR3. She had progressive kidney failure and severe extra-renal manifestations including cardiomyopathy and haemorrhagic cystitis; as well as pulmonary, gastrointestinal and neurological involvement. The initial kidney biopsy revealed thrombotic microangiopathy (TMA) changes involving all glomeruli. Clinical improvement was initially seen during eculizumab initiation with suppressed CH50 level, but a new rhinovirus/enterovirus upper respiratory tract infection triggered further severe multi-organ disease activity. The extra-renal manifestations stabilised, then ultimately improved after a period of eculizumab dose intensification. However, the impact on dose intensification on this improvement is unclear. Despite the extra-renal clinical improvement, she ultimately progressed to end-stage kidney disease (ESKD), commencing peritoneal dialysis for three years before undergoing a successful uncomplicated cadaveric kidney transplant without prophylactic eculizumab. Two years after transplant, she has excellent transplant graft function without any further disease recurrence. This case highlights the concept of extra-renal manifestations in aHUS initially resistant to eculizumab, which potentially responded to dose intensification. Whilst organ injuries are potentially reversible with timely targeted treatment, it appears that the kidneys are most vulnerable to injury.


Mismatch between shape changes and ecological shifts during the post-settlement growth of the surgeonfish, Acanthurus triostegus.
Many coral reef fishes undergo habitat and diet shifts during ontogeny. However, studies focusing on the physiological and morphological adaptations that may prepare them for these transitions are relatively scarce. Here, we explored the body shape variation related to ontogenetic shifts in the ecology of the surgeonfish Acanthurus triostegus (Acanthuridae) from new settler to adult stages at Moorea Island (French Polynesia). Specifically, we tested the relationship between diet and habitat shifts and changes in overall body shape during the ontogeny of A. triostegus using a combination of geometric morphometric methods, stomach contents and stable isotope analysis. After reef settlement, stable isotope composition of carbon and nitrogen revealed a change from a zooplanktivorous to a benthic algae diet. The large amount of algae (> 75% of stomach contents) found in the digestive tract of small juveniles (25-30 mm SL) suggested the diet shift is rapid. The post-settlement growth of A. triostegus is highly allometric. The allometric shape changes mainly concern cephalic and pectoral regions. The head becomes shorter and more ventrally oriented during growth. Morphological changes are directly related to the diet shift given that a small mouth ventrally oriented is particularly suited for grazing activities at the adult stage. The pectoral fin is more anteriorely and vertically positioned and its basis is larger in adults than in juveniles. This shape variation had implications for swimming performance, manoeuvrability, turning ability and is related to habitat shift. Acanthurus triostegus achieves its main transformation of body shape to an adult-like form at size of 35-40 mm SL. Most of the shape changes occurred after the reef colonization but before the transition between juvenile habitat (fringing reef) and adult habitat (barrier reef). A large amount of allometric variation was observed after diet shift from zooplankton to benthic algae. Diet shift could act as an environmental factor favouring or inducing morphological changes. On the other hand, the main shape changes have to be achieved before the recruitment to adult populations and start negotiating the biophysical challenges of locomotion and feeding in wave- and current-swept outer reef habitat.


Calcium levulinate medication. A pitfall in the diagnosis of organic acidurias.
Five children, who received calcium levulinate (calcium 4-oxopentanoate) intravenously in pharmacological doses excreted in the following 24-h period both 4-oxopentanoic acid (3.5--11.0 mg/24 h) and 4-hydroxypentanoic acid (4.5--10.4 mg/24 h). Attention is drawn to the fact that in gas chromatographic-mass spectrometric systems these compounds closely resemble the two acids found in children with beta-ketothiolase deficiency.


Intensive care of the patient after abdominal surgery.
After surgical correction of the underlying abdominal disorder, careful postoperative care is the most important factor resulting in increased survival rates. Intensive care of the postoperative patient can be done practically and economically.