Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis.
Mitochondrial complex II is a tumor suppressor comprised of four subunits (SdhA, SdhB, SdhC, and SdhD). Mutations in any of these should disrupt complex II enzymatic activity, yet defects in SdhA produce bioenergetic deficiency while defects in SdhB, SdhC, or SdhD induce tumor formation. The mechanisms underlying these differences are not known. We show that the inhibition of distal subunits of complex II, either pharmacologically or via RNA interference of SdhB, increases normoxic reactive oxygen species (ROS) production, increases hypoxia-inducible factor alpha (HIF-alpha) stabilization in an ROS-dependent manner, and increases growth rates in vitro and in vivo without affecting hypoxia-mediated activation of HIF-alpha. Proximal pharmacologic inhibition or RNA interference of complex II at SdhA, however, does not increase normoxic ROS production or HIF-alpha stabilization and results in decreased growth rates in vitro and in vivo. Furthermore, the enhanced growth rates resulting from SdhB suppression are inhibited by the suppression of HIF-1alpha and/or HIF-2alpha, indicating that the mechanism of SdhB-induced tumor formation relies upon ROS production and subsequent HIF-alpha activation. Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA.


Divergent regulation of the growth-promoting gene IEX-1 by the p53 tumor suppressor and Sp1.
IEX-1, a recently discovered early response gene, regulates cell growth and apoptosis. IEX-1 gene expression is regulated by a variety of factors such as x-irradiation, ultraviolet radiation, steroids, growth factors, and inflammatory stimuli. By systematic examination of the IEX-1 promoter, we show that IEX-1 gene expression is controlled by multiple conserved gene regulatory elements and that IEX-1 is a downstream target of the p53 tumor suppressor and Sp1. In addition, p300, Sox, nuclear factor-kappaB, and AP4 appear to be modulators of IEX-1 gene expression to a lesser degree. We found that there is at least one Sp1 element that functions as an activator and contributes to high basal transcriptional levels of the IEX-1 gene. We demonstrate the presence of a p53 response element that represses IEX-1 promoter activity in HaCaT keratinocytes, indicating that Sp1 and p53 have opposite effects on IEX-1 gene expression. We conclude that IEX-1 expression in cells is regulated by the p53 tumor suppressor and Sp1, thus providing a direct mechanism for control of cell proliferation.


Enhanced gene transfer to pancreatic islets using glucagon-like peptide-1.
The efficient transfer of genes into intact islets is difficult since islets exist as clusters of differentiated cells with little replication potential. Cell proliferation in response to growth factors is known to be accompanied by loosening of cell-to-cell contacts and increasing paracellular permeability. In this study, we investigated whether gene delivery into intact islet cells was facilitated by modulating β-cell proliferation. Isolated rat islets were pretreated with glucagon-like peptide (GLP)-1 or human growth hormone for 24 hours, or with 300 mg/dL of glucose for 48 hours before transduction with a suboptimal dose of recombinant adenoviral vector expressing green fluorescent protein (GFP) and β-galactosidase (multiplicity of infection of 25). Transduction efficiency was assessed by measuring β-galactosidase activity and GFP expression using enzyme-linked immunosorbent assay, flow cytometry, and fluorescence microscopy. The numbers of 7-aminoactinomycin D-positive dead cells and 5-ethynyl-2-deoxyuridine (EdU)-positive proliferating cells were also monitored using flow cytometry and fluorescence microscopy. The transduction efficiency of rat islet cells by a suboptimal dose of viral vector was significantly improved by GLP-1 pretreatment, accompanied by enhanced cell viability and cell proliferation. An increased GFP expression in islet cells after GLP-1 pretreatment was observed among the increased numbers of EdU-positive proliferating cells. Pretreatment of rat islets with GLP-1 enhanced the transduction efficiency of an adenoviral vector, reducing viral dose burden while improving islet cell viability. From a therapeutic standpoint, genetic modification of pancreatic islets combined with GLP-1 pretreatment may be a promising option for ex vivo gene therapy prior to islet transplantation.


Experimentally induced cutaneous leishmaniasis: are L3T4+ T cells that promote parasite growth distinct from those mediating resistance?
A considerable body of evidence from various laboratories indicates that specific T cell responses generated during infection with Leishmania parasites play an important role both in the resolution and progression of cutaneous leishmaniasis. Recent data, summarized in this article, indicate that resolution of lesions and promotion of disease not only result from the activity of functionally distinct parasite-specific L3T4+ T cells but could also be mediated by functionally similar L3T4+ T cells differing only in their fine antigenic specificity. This contention is based on observations which suggests that (a) the induction of T cell tolerance to parasite antigens present during the early phase of infection is beneficial to the host, and (b) the specificity of L3T4+ T cell lines and clones capable of exacerbating the development of lesions is different from that of T cells mediating protection.


Paramedic rhythm interpretation misclassification is associated with poor survival from out-of-hospital cardiac arrest.
Early recognition and rapid defibrillation of shockable rhythms is strongly associated with survival in out of hospital cardiac arrest (OHCA). Little is known about the accuracy of paramedic rhythm interpretation and its impact on survival. We hypothesized that inaccurate paramedic interpretation of initial rhythm would be associated with worse survival. This is a retrospective cohort analysis of prospectively collected OHCA data over a nine-year period within a single, urban, fire-based EMS system that utilizes manual defibrillators equipped with rhythm-filtering technology. We compared paramedic-documented initial rhythm with a reference standard of post-event physician interpretation to estimate sensitivity and specificity of paramedic identification of and shock delivery to shockable rhythms. We assessed the association between misclassification of initial rhythm and neurologically intact survival to hospital discharge using multivariable logistic regression. A total of 863 OHCA cases were available for analysis with 1,756 shocks delivered during 542 (63%) resuscitation attempts. Eleven percent of shocks were delivered to pulseless electrical activity (PEA). Sensitivity and specificity for paramedic initial rhythm interpretation were 176/197 (0.89, 95% CI 0.84-0.93) and 463/504 (0.92, 95% CI 0.89-0.94) respectively. No patient survived to hospital discharge when paramedics misclassified the initial rhythm. Paramedics achieved high sensitivity for shock delivery to shockable rhythms, but with an 11% shock delivery rate to PEA. Misclassification of initial rhythm was associated with poor survival. Technologies that assist in rhythm identification during CPR, rapid shock delivery, and minimal hands-off time may improve outcomes.


Primary Intracranial Extra-Axial Anaplastic Ependymomas.
Ependymomas are usually located in the ventricular system or in the central canal of the spinal cord; intracranial extra-axial ependymomas (IEAEs) are rare. To date, only 17 cases of IEAEs have been reported. We report 2 cases with 3 IEAEs (anaplastic) that were initially misdiagnosed. In Case 1 (47-year-old male), the para-falcine lesion was initially refractory to radiosurgery and gross total resection (GTR) was required due to relentless growth. The lesion had adhered to the falx and was well demarcated from the surrounding cortex. It was then correctly diagnosed as an anaplastic ependymoma on the basis of histopathology, and the patient received radiotherapy. No recurrence was observed after the 53-month follow-up. In Case 2 (30-year-old male), 2 IEAEs underwent staged surgeries and were identified as extra-axial lesions without connection to the ventricular system. Near total resection (NTR) and GTR were achieved in the right temporal and right occipital lesions, respectively, but the patient declined radiotherapy. The residual tumor after NTR regrew rapidly, and aggressive resection was performed followed by radiotherapy. No further recurrence was observed after 28 months. The previous 17 cases were male predominant (76.5%) without correct preoperative diagnoses; no recurrence was observed after total resection in the 9 patients reported in the literature. IEAEs are rare and have a wide spectrum of clinical and radiological phenotypes. Preoperative diagnosis is difficult. Favorable outcomes for IEAEs can be achieved by GTR plus radiotherapy. Multiple IEAEs benefit from tailored staged surgical resection plus radiotherapy.


The Presence of D-Penicillamine during the In Vitro Capacitation of Stallion Spermatozoa Prolongs Hyperactive-Like Motility and Allows for Sperm Selection by Thermotaxis.
Assisted reproductive technologies (ARTs) in the horse still yield suboptimal results in terms of pregnancy rates. One of the reasons for this is the lack of optimal conditions for the sperm capacitation in vitro. This study assesses the use of synthetic human tubal fluid (HTF) supplemented with D-penicillamine (HTF + PEN) for the in vitro capacitation of frozen/thawed stallion spermatozoa by examining capacitation-related events over 180 min of incubation. Besides these events, we explored the in vitro capacity of the spermatozoa to migrate by thermotaxis and give rise to a population of high-quality spermatozoa. We found that HTF induced higher levels of hyperactive-like motility and protein tyrosine phosphorylation (PTP) compared to the use of a medium commonly used in this species (Whitten's). Also, HTF + PEN was able to maintain this hyperactive-like motility, otherwise lost in the absence of PEN, for 180 min, and also allowed for sperm selection by thermotaxis in vitro. Remarkably, the selected fraction was enriched in spermatozoa showing PTP along the whole flagellum and lower levels of DNA fragmentation when compared to the unselected fraction (38% ± 11% vs 4.4% ± 1.1% and 4.2% ± 0.4% vs 11% ± 2% respectively, t-test p < 0.003, n = 6). This procedure of in vitro capacitation of frozen/thawed stallion spermatozoa in HTF + PEN followed by in vitro sperm selection by thermotaxis represents a promising sperm preparation strategy for in vitro fertilization and intracytoplasmic sperm injection in this species.


Chemotherapy-associated steatohepatitis was concomitant with epicardial adipose tissue volume increasing in breast cancer patients who received neoadjuvant chemotherapy.
To investigate the prevalence of chemotherapy-associated steatohepatitis, quantitate the epicardial adipose tissue (EAT) volume in breast cancer patients, and explore the mediating effect of liver fat content on EAT volume in breast cancer patients who received neoadjuvant chemotherapy (NAC). From October 2018 to April 2020, patients were retrospectively reviewed and divided into breast cancer non-NAC and NAC groups. The prevalence of chemotherapy-associated steatohepatitis was evaluated through quantitative MRI mDIXON-Quant examinations by using defined proton density fat fraction cutoffs of liver fat. The EAT volume was quantified on chest CT by semi-automatic volume analysis software. Bootstrap analysis was used in the breast cancer NAC group to test the significance of the mediating effect of liver fat content on EAT volume. A total of 662 breast cancer patients (non-NAC group: 445 patients; NAC group: 217 patients) were included. The prevalence of chemotherapy-associated steatohepatitis in the NAC group was significantly higher than the prevalence of hepatic steatosis in the non-NAC group (42.8% vs. 33.3%, p < 0.001). EAT volume was measured in 561 of 662 breast cancer patients, and was significantly higher in the NAC group than in the non-NAC group (137.26 ± 53.48 mL vs. 125.14 ± 58.77 mL, p = 0.020). In the breast cancer NAC group, the indirect effect of liver fat content on EAT volume was 2.545 (p < 0.001), and the contribution rate to the effect was 69.1%. EAT volume was significantly higher in the BC-NAC group than in the BC-non-NAC group. • The prevalence of CASH was as high as 42.8% in BC patients. • NAC significantly increased the EAT volume in BC patients. • The liver fat content caused the change of EAT volume through mediating effect.


Familiar unbalanced complex rearrangements involving 13 p-arm: description of two cases.
Copy number variations (CNVs) are largely known today, but their position is rarely established by fluorescence in situ hybridization (FISH) or karyotype analysis. We described two families with copy number gain in which FISH analysis with the specific subtelomeric probe of chromosome 4q and 7q evidenced a third signal at band 13p11.2. Genomic study by array comparative genomic hybridization defined the triple dose segment. In the first case, the duplicate tract is free of known genes, in the second one it contained three expressed genes. The CNV localization on the short arm of an acrocentric chromosome could explain the lack of phenotypic effect, being known the regulatory role of heterochromatin in the position-effect silencing. Furthermore, we would like to underline the importance of using complementary techniques such as FISH and array-CGH to obtain a better definition of genomic rearrangements.


Magnetic resonance spectroscopy in biology and medicine.
Magnetic resonance spectroscopy has developed from a standard tool of the chemist into a very promising modality for clinical and analytical evaluation of human pathophysiology. We present a brief outline of the method and its parameters, as well as a series of examples of its application. Anatomical imaging is also discussed.


The population ecology of the Cinnabar Moth, Tyria jacobaeae L. (Lepidoptera, Arctiidae).
This paper describes the results of a study of the factors determining the abundance and distribution of the Cinnabar Moth in Britain. The main part of the study was on a population of the moth at Weeting Heath in Norfolk. This is an area of sandy heath which is heavily overgrazed by rabbits. Here the moth fluctuates violently in number and periodically it completely defoliates its food plant (ragwort, Senecio jacobaea L.) over large areas. This happened in 1960, 1961, 1967, and 1968.Since 1966, the numbers of the moth have been studied in detail and Life Tables are presented for five years.Adult fecundity varies considerably between years. This is due mainly to fluctuations in adult size resulting from changes in larval density. By comparison adult mortality and dispersal have little effect on fecundity; although there is some evidence to suggest that dispersal is density dependent. Because the number of eggs laid in one generation depends on the size of the previous generation, fecundity tends to be acting as a delayed density dependent factor.Mortality is low during the egg stage, but is high amongst young larvae, due mainly to arthropod predation. As the caterpillars grow they become immune from this predation. They are distasteful to vertebrate predators.A larval parasite, Apanteles popularis, kills many of the fully grown larvae. The highest rates of parasitism have coincided with the lowest densities of the moth, however, so that over the five years it has acted as an inverse density dependent factor.In 1967, the population became so large that the ragwort was completely defoliated, and about 20% of the caterpillars died from starvation. In the following year the population was still large and the ragwort plants were small, owing to the effects of defoliation in the previous year. Food ran out early in the season and about 50% of the larvae starved. Because of the overriding effect of starvation, total larval mortality tends to be density dependent.Mortality is high at, or immediately after, pupation and this is thought to be due primarily to predation by moles (Talpa europaea). Pupal mortality does not appear to be density dependent.The upward growth of the population is limited by food supply. Starvation led to a population crash, so that in 1969 only 62 eggs/150 m2 were laid compared with 17110 and 16493 in the previous two years. The rate of recovery of the population after this crash was dependent upon the rapid recovery of the ragwort plants. Owing to the wet summer in 1968, plant numbers actually increased after defoliation, due to regeneration from root buds. This was in spite of the fact that no seed was produced in the area in either 1967 or 1968.The only factor which appears to buffer the population against extinction in years when food runs out early in the season, is the heterogeneity within the moth and ragwort populations. The earliest individuals manage to obtain sufficient food in those patches of ragwort which survive longest.Large fluctuations in number only occur in some localities. Other populations of the moth persist at low density and never eat out their food supply. Some data are presented from such a population at Monks Wood. This site is on a heavy clay soil, rabbit grazing is less marked than at Weeting, and ragwort occurs only at a low density. The lusher vegetation supports a very large population of arthropod predators and these take a higher percentage of the young caterpillars than was found at Weeting. Pupal survival is also low due probably to waterlogging of the soil. Pupae can withstand considerable desiccation, but excessive moisture soon leads to their death.The distribution of the moth in Britain and its use for the biological control of ragwort are discussed.


Evaluation and management of pediatric rhegmatogenous retinal detachment.
Pediatric rhegmatogenous retinal detachments are rare, accounting for less than ten percent of all rhegmatogenous retinal detachments. While most retinal detachments in the adult population are related to posterior vitreous detachment, pediatric retinal detachment are often related to trauma or an underlying congenital abnormalities or genetic syndrome. The anatomy of pediatric eyes, the often late presentation of the disease, and the high incidence of bilateral pathology in children all pose significant challenges in the management of these patients. We discuss the epidemiology of pediatric rhegmatogenous retinal detachment, review the genetic syndromes associated with a high incidence of retinal detachment, and examine other common causes of retinal detachment in this age group. We then outline an approach to evaluation and management and describe the expected outcomes of repair of retinal detachment in the pediatric population.


Immunohistochemical and in-situ hybridization study of hypoxia inducible factor-1alpha and angiopoietin-1 in a rabbit model of mandibular distraction osteogenesis.
The endogenous release of angiogenic factors in a rabbit mandibular distraction osteogenesis model was investigated. The spatial and temporal expression of hypoxia inducible factor-1alpha (HIF-1alpha) and angiopoietin-1 (Ang-1) was compared at different phases. The lengthened calluses were harvested on post-osteotomy days 13, 20, 34 and 48, and then stained with haematoxylin & eosin. Immunohistochemical (IHC) and in-situ hybridization (ISH) examination of HIF-1alpha and Ang-1 staining was performed. The ossification in the distracted gap was predominantly intramembranous and slightly endochondral. Expression of HIF-1alpha and Ang-1 was mainly detected in the cytoplasm of fibroblast-like cells, osteoblasts and immature osteocytes on day 13 and 20, but declined with bone maturation. HIF-1alpha was also detected in the nuclei of some osteoblasts. These results suggest that the production of HIF-1alpha and Ang-1 in the distracted gap may contribute to new bone formation during gradual distraction of the mandible.


Construction of unique six-coordinated titanium species with an organic amine ligand in titanosilicate and their unprecedented high efficiency for alkene epoxidation.
A novel organic-inorganic layered titanosilicate consisting of Ti-containing MWW-type nanosheets and piperidine ligands was constructed. It exhibited an unprecedented high catalytic activity and recyclability in alkene epoxidation.


Molecular diversity of HLA-DQ. DQ alpha and beta chain isoelectric point differences and their relation to serologically defined HLA-DQ allospecificities.
HLA-DQ molecules were isolated from a panel of HLA-DR-DQ homozygous cell lines, partially of consanguineous origin, derived by the use of monoclonal antibody SPV-L3, and subsequently analyzed by gel electrophoretic techniques. It is demonstrated that both the DQ alpha and beta chain exhibit an extensive isoelectric point polymorphism. Within a panel of 29 B-cell lines tested, at least 5 distinct alpha and 6 distinct DQ beta chain gene products were observed. Of the 30 theoretically possible DQ alpha-beta dimers, only 10 could be identified within the panel: 5 different dimers are associated with the DQw1 allospecificity; HLA-DQw2 and -DQw3 are associated with 2 types of dimers, whereas another DQ alpha-beta combination was expressed by a cell line with a so-called DQ-blank specificity. The relation between the specificities 2B3 and TA10 appeared to be complicated as far as DQ beta chain isoelectric point differences are concerned: monoclonal antibody IIB3 seems to be reactive with four distinct DQ beta chain alleles whereas monoclonal antibody TA10 only reacted with one type of DQ beta chain. These results suggest that the polymorphic DQ alpha and beta chains may both contribute to the definition of the HLA-DQ allospecificity. A particular DQ beta chain was present in two types of HLA-DQw1 molecules, as well as in one type of HLA-DQw2 and -DQw3 (2B3 positive) molecule, and formed dimers with electrophoretic distinct DQ alpha chains. On the other hand, HLA-DQw2 molecules isolated from HLA-DR3-positive cells and one type of HLA-DQw3 (TA10 positive) molecule were found to be constructed of identical alpha chains but appeared to differ in the composition of their DQ beta chain gene products. The implications of these findings will be discussed.


Is it possible to recommend safe drinking levels without increasing per capita consumption? Another aspect of the prevention paradox.
A number of countries have recently embarked on responsible drinking or safe drinking educational campaigns. The object of these campaigns is to discourage people from exceeding levels of alcohol consumption considered compatible with good health. One possible implication of the success of these campaigns is an increase in per capita alcohol consumption. Such increases are usually thought of as inimical to health and therefore present the health educator with a dilemma. Reference is made to Australian data in an examination of this paradox.


Efficacy and safety of Resina Draconis for wound repair in the treatment of diabetic foot ulcer: A systematic review and meta-analysis of randomized controlled trials.
Resina Draconis (RD) is widely used to treat topical skin ulcers. However, its effect on diabetic foot ulcer (DFU) remains unknown. The present meta-analysis aims to evaluate the efficacy and safety of RD for wound healing in DFU treatment. Literature searches were conducted with databases including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure, the Wanfang Database, the Database for Chinese Technical Periodicals, and the China Biology Medicine Disc. Relevant studies were selected based on specified inclusion and exclusion criteria. Software RevMan 5.4 was used for study selection, quality assessment, and data analysis, while the Cochrane Risk of Bias (RoB) 2.0 tool was used to assess RoB. Nine eligible randomized controlled trials (RCTs), involving 679 patients, were included in this review. The results showed that the healing time of the RD group was shorter than that of the control group (P < 0.00001), while the RD group also presented a higher healing rate (P < 0.0001), a higher rate of ulcer area reduction (P = 0.0005), and a higher rate in the patients with a reduced Wagner grade (P = 0.002). Simultaneously, a lower frequency of dressing changes (P < 0.00001) and a shorter length of hospital stays (P < 0.00001) are the characteristics of the RD group as well. The treatment with RD is a safe and effective solution for DFU, and its combination with conventional treatment can improve the healing rate of DFU, reduce healing time, and inhibit further development. However, owing to the limited quality and quantity of included studies, further high-quality research is necessary to support these conclusions.


A study on spleen transient elastography in predicting the degree of esophageal varices and bleeding.
This study aims to investigate the value and determine the accuracy of spleen stiffness in predicting the degree of esophageal varices and bleeding in patients with liver cirrhosis.The age, gender, liver stiffness, spleen stiffness, and gastroscopy results of 124 inpatients or outpatients with liver cirrhosis and healthy volunteers, who underwent both gastroscopy and FibroScan testing in the fasting state, were retrospectively analyzed. According to the gastroscopy results, the patients and healthy volunteers were divided into six groups: varicose bleeding, severe varices, moderate varices, mild varices, no varices, and healthy control group. Then, the receiver operating characteristic curves were drawn, and the corresponding area under each curve was calculated and evaluated to predict the severity of varices based on the relevance of the area and its parameters.The area under the receiver operating characteristic curve of liver stiffness and spleen stiffness for predicting severe and moderate varices in the bleeding group was 0.955 and 0.989, respectively. The cut-off values were 29.6 kPa and 45.5 kPa, respectively. The area under the receiver operating characteristic curve of liver stiffness for predicting varicose bleeding was 0.860 (95% CI: 0.789-0.931). The liver stiffness cut-off value for predicting varicose bleeding was 33.2 kPa, with a specificity and sensitivity of 66.02% and 95.24%, respectively. The area under the receiver operating characteristic curve of spleen stiffness for predicting varicose bleeding was 0.923 (95% CI: 0.875-0.971). A spleen stiffness cut-off value of 55.2 kPa had a sensitivity and specificity of 90.48% and 86.41%, respectively.Spleen stiffness can predict the degree of esophageal varices and bleeding in liver cirrhosis patients, and has good predictive accuracy.


Probing the binding of two 19-nortestosterone derivatives to human serum albumin: insights into the interactions of steroid hormone drugs with functional biomacromolecule.
Norethindrone acetate (NETA) is a fatty acid ester of norethindrone (NET) that can convert to its more active parent compound NET when orally administered. To study the interactions of NETA and NET with human serum albumin (HSA), we applied fluorescence spectroscopy, circular dichroism (CD), and molecular docking. The effects of metal ions on the HSA-NETA/NET system were also explored. Fluorescence data showed that the quenching mechanism of HSA by NETA and NET was consistent with a static model and that the binding constant of NETA was higher than that of NET. Thermodynamic parameters indicated that hydrogen bonds and van der Waals forces were the main forces maintaining the stability of the HSA-NETA/NET complex. Molecular modeling studies revealed that NETA and NET were bound within subdomain IIA of HSA, in accordance with the site probe results. Synchronous fluorescence spectroscopy, CD, and three-dimensional fluorescence spectroscopy further confirmed that the binding of NETA/NET to HSA changed the secondary structure of the protein. All other metal ions, except for Ca(2+) , decreased the K value of the HSA-NETA/NET system with enhancement of the maximum effectiveness of NETA/NET. Three commercially available steroid hormone drugs influenced the binding ability of NETA on HSA to different extents. This study provides novel insights into the interactions between HSA and NETA/NET, as well as a solid foundation for future research on drug pharmacokinetics and pharmacodynamics. Copyright © 2016 John Wiley & Sons, Ltd.


On-Surface Synthesis and Characterization of Triply Fused Porphyrin-Graphene Nanoribbon Hybrids.
On-surface synthesis offers a versatile approach to prepare novel carbon-based nanostructures that cannot be obtained by conventional solution chemistry. Graphene nanoribbons (GNRs) have potential for a variety of applications. A key issue for their application in molecular electronics is in the fine-tuning of their electronic properties through structural modifications, such as heteroatom doping or the incorporation of non-benzenoid rings. In this context, the covalent fusion of GNRs and porphyrins (Pors) is a highly appealing strategy. Herein we present the selective on-surface synthesis of a Por-GNR hybrid, which consists of two Pors connected by a short GNR segment. The atomically precise structure of the Por-GNR hybrid has been characterized by bond-resolved scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc-AFM). The electronic properties have been investigated by scanning tunneling spectroscopy (STS), in combination with DFT calculations, which reveals a low electronic gap of 0.4 eV.


Development and application of reverse transcription droplet digital PCR assay for sensitive detection of apple scar skin viroid during in vitro propagation of apple plantlets.
Apple scar skin viroid (ASSVd), of the genus Apscaviroid, causes serious pome fruit diseases, such as apple scar skin, dapple apple, pear rusty skin, pear fruit crinkle, and pear dimple fruit. This study aimed at establishing a sensitive and accurate method for quantification of ASSVd in apple leaves and plantlets using a reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) assay. The specificity was analyzed using other apple viruses, and the negative amplification of the cross-reaction assay demonstrated the high specificity of RT-ddPCR. The detection limit of ASSVd by RT-ddPCR was 1.75 × 102 copies/μL (0.14 concentration), and the sensitivity was ten-fold higher than that of RT-qPCR. Similarly, positive detection in apple plantlet samples by RT-ddPCR was higher than that by RT-qPCR. The RT-ddPCR assay represents a promising alternative for accurate quantitative detection and diagnosis of ASSVd infection in ASSVd-free certification programs.


Fast-Response, Highly Air-Stable, and Water-Resistant Organic Photodetectors Based on a Single-Crystal Pt Complex.
Organic semiconductors demonstrate several advantages over conventional inorganic materials for novel electronic and optoelectronic applications, including molecularly tunable properties, flexibility, low-cost, and facile device integration. However, before organic semiconductors can be used for the next-generation devices, such as ultrafast photodetectors (PDs), it is necessary to develop new materials that feature both high mobility and ambient stability. Toward this goal, a highly stable PD based on the organic single crystal [PtBr2 (5,5'-bis(CF3 CH2 OCH2 )-2,2'-bpy)] (or "Pt complex (1o)") is demonstrated as the active semiconductor channel-a material that features a lamellar molecular structure and high-quality, intraligand charge transfer. Benefitting from its unique crystal structure, the Pt-complex (1o) device exhibits a field-effect mobility of ≈0.45 cm2 V-1 s-1 without loss of significant performance under ambient conditions even after 40 days without encapsulation, as well as immersion in distilled water for a period of 24 h. Furthermore, the device features a maximum photoresponsivity of 1 × 103 A W-1 , a detectivity of 1.1 × 1012 cm Hz1/2 W-1 , and a record fast response/recovery time of 80/90 µs, which has never been previously achieved in other organic PDs. These findings strongly support and promote the use of the single-crystal Pt complex (1o) in next-generation organic optoelectronic devices.


Reference values for B cell subpopulations from infancy to adulthood.
The composition of the peripheral blood lymphocyte compartment underlies developmental changes during ontogeny. Recently, several new B cell populations have been characterized which were suggested to develop in an age-dependent manner. However, age-dependent reference values for distinct B cell populations have rarely been reported. Therefore, we have characterized developmental changes in peripheral B cell populations from infancy to adulthood in order to define age-dependent reference values. Using a flow cytometric approach we analysed the frequencies as well as the absolute counts of naive, switched and non-switched memory B cells, CD27-negative memory B cells, transitional B cells as well as CD21(low) CD38(low) B cells from neonates up to the age of 50 years. Most of the B cell subsets showed age-dependent developmental changes: while the peripheral B cell pool during infancy is characterized predominantly by transitional and naive B cells, the fraction of switched and non-switched memory B cells increases gradually with age. CD21(low) CD38(low) B cells as well as plasmablasts do not exhibit developmental changes. In summary, we could demonstrate particular changes in the peripheral blood B cell compartment during ontogeny. This study provides reference values of different B cell subpopulations offering comparability for studies addressing disturbed peripheral B cell development in immunodeficiency, autoimmunity or B cell reconstitution following cell-depleting therapies.


[Immunopathology of the small intestine].
The gastrointestinal tract is the site of exciting immunological interactions between the epithelium and the mucosa-associated lymphoid tissue, leading to the immune response to food and microbial antigens in the digestive lumen. The objective of this review is to present the main dysimmune pathologies of the digestive tract leading to an enteropathy. As examples, we describe celiac and non-celiac enteropathies to clarify a florid diagnostic framework, by identifying a spectrum of elementary lesions, which must be confronted with the clinico biological context of the patient to orient the diagnosis. The microscopic lesions observed are most often non-specific and may be encountered in several diagnostic settings. Moreover, it is a set of elementary lesions in each clinical context that will orient the diagnostic framework. Celiac disease is the main etiology of enteropathy with villous atrophy, its diagnosis is multidisciplinary and there are many differential diagnoses. We will discuss celiac disease lymphomatous complications as enteropathy associated T-cell lymphoma including refractory sprue type 2. We will then present the non-celiac enteropathies. Among these, enteropathies of unknown etiology may be associated with a primary immune deficiency that may be reflected by florid lymphoid hyperplasia of the gastrointestinal tract and/or be associated with an infectious etiology that should also be constantly sought. Finally, we will discuss of induced enteropathy by new immunomodulatory treatments.


Outbreaks by Klebsiella oxytoca in neonatal intensive care units: Analysis of an outbreak in a tertiary hospital and systematic review.
Klebsiella oxytoca can cause nosocomial infections, affecting vulnerable newborns. There are few studies describing nosocomial outbreaks in the neonatal intensive care units (NICU). In this study, a systematic review of the literature was carried out to know the main characteristics of these outbreaks and the evolution of one is described. We conducted a systematic review in the Medline database up to July 2022, and present a descriptive study of an outbreak with 21 episodes in the NICU of a tertiary hospital, between September 2021 and January 2022. 9 articles met the inclusion criteria. The duration of outbreaks was found to be variable, of which 4 (44.4%) lasted for a year or more. Colonization (69%) was more frequent than infections (31%) and the mortality rate was 22.4%. In studies describing sources, the most frequent was the environmental origin (57.1%). In our outbreak there were 15 colonizations and 6 infections. The infections were mild conjunctivitis without sequelae. Molecular typing analysis made it possible to detect 4 different clusters. There is an important variability in the evolution and results of the published outbreaks, highlighting a greater number of colonized, use of PFGE (pulsed-field gel electrophoresis) techniques for molecular typing and implementation of control measures. Finally, we describe an outbreak in which 21 neonates were affected with mild infections, resolved without sequelae and whose control measures were effective.


Reverse-transcriptase polymerase chain reaction to detect extracellular mRNAs.
The presence of extracellular nucleic acids has been reported in serum/plasma from cancer and diabetes patients that may help in disease diagnosis. Taking insulin-producing cells as examples here, RT-PCR was used to investigate a correlation between the presence and amounts of extracellular mRNA(s) and cell mass and/or function. RT-PCR was performed on a range of mRNAs, including Pdx1, Npy, Egr1, Pld1, Chgb, InsI, InsII, and Actb in biological triplicate analyses.Reproducible amplification of these mRNAs from MIN6, MIN6 B1, and Vero-PPI cells and their CM suggests that beta cells transcribe and release these mRNAs into their environment. mRNAs secreted from insulin-producing cells into their extracellular environment may have potential as extracellular biomarkers for assessing beta cell mass and function.


Characteristics of injured children attending the emergency department: patients potentially in need of rehabilitation.
To provide an epidemiological overview of the characteristics of injured children and to compare hospitalized and nonhospitalized injured children to identify predictors of hospitalization and, with that, possible predictors of disablement. Retrospective analysis of data obtained from a computerized trauma registration system and medical records. Department of Traumatology, University Hospital Groningen, the Netherlands. Children (0-19 years) injured in 1996 and 1997 (n = 5,057). The majority of children were injured in home and leisure accidents (53%) and sustained minor injuries. Only 55 (1%) children were severely injured (Injury Severity Score (ISS) > or = 16). Overall, 512 (10%) patients required hospitalization, 19 children were referred to a rehabilitation centre, and 24 children died due to their injuries. The majority of these patients were injured in traffic. Compared with the group of nonhospitalized patients, the group of hospitalized patients consisted of more males and traffic victims, were more severely injured and sustained more head/neck, spine, and thorax and abdomen injuries. Nonhospitalized patients incurred proportionally more upper and lower extremity injuries. The ISS, the body region of most severe injury, and injury cause (traffic accidents) were significant predictors of hospitalization. Young traffic victims, severely injured children in terms of high ISS scores, and children with injuries affecting the head/neck/face or thorax/abdomen carry the highest risk of hospitalization.


Thrombin activatable fibrinolysis inhibitor in preeclampsia and gestational hypertension throughout the gestation.
To clarify the role of TAFI in hypertensive disorders in pregnancy, 22 subjects, including 10 with pre-eclampsia (PE) and 12 with gestational hypertension were examined for the levels of TAFI and thrombin-antithrombin (TAT) complex. Thirty normal pregnant women served as controls. ELISA was employed for the detection. The results showed that the TAFI antigen levels in normal pregnancy group, gestational hypertension group and PE group were (85.35+/-24.69)%, (99.65+/-18.27)%, (110.12+/-23.36)%; (97.06+/-21.40)%, (114.08+/-27.76)%, (125.49+/-24.70)%; (106.6+/-19.21)%, (129.2+/-25.07)%, (139.1+/-30.12)%, in the 1st, 2nd and 3rd trimester respectively. No significant differences were found between the normal pregnancy group and gestational hypertension group but significant difference existed between normal pregnancy group and PE group in each trimester (P<0.05). TAT complexes were significantly higher in patients with PE than that in controls (P<0.05), but no correlation was found between TAT and TAFI. It is concluded that TAFI may contributed to the impairment of fibrinolysis in the patients with PE and may serves as a sensitive indicator for PE, but it may not help in the diagnosis of the gestational hypertension.


Cholecalcin (28-kDa CaBP) in the rat cochlea. Development in normal and hypothyroid animals. An immunocytochemical study.
The distribution of cholecalcin (28-kDa calcium-binding protein) in the cochlea of developing rats was followed by immunocytochemistry. In normal animals, the protein first appeared in utero in the cells of Kölliker's organ, a structure involved in the secretion of the tectorial membrane. The inner hair cells, followed by the outer hair cells, then became immunoreactive from the base of the cochlea to the apex. Their cuticular plate, the anchoring structure for stereocilia, was particularly labeled. The cells of Kölliker's organ lost their immunoreactivity after the first postnatal week, the time when they lose their secretory activity. During the same period, when the tunnel of Corti and the space of Nuel open, labeling appeared in the supporting cells. The neurons of the spiral ganglion were stained from the second postnatal week and the fibers of the cochlear nerve after the end of the first month. No difference was induced by thyroid deficiency until the second postnatal week. Thereafter, Kölliker's organ did not transform and its cholecalcin immunoreactivity persisted, together with the secretory activity. As a result, the tectorial membrane was greatly distorted and the mechanical properties of the organ of Corti were dramatically impaired. The supporting cells were labeled although the tunnel of Corti and the space of Nuel did not open. Staining of the spiral ganglion neurons was delayed. All the nervous structures of the cochlea were, however, stained at the end of the first postnatal month, as in normal animals, despite the irreversible complete deafness. Cholecalcin is thus present during development of the cochlea in both non-neuronal and neuronal structures, and is probably involved in very different processes in various types of cells.


Dynamic studies on the mobility of trace elements in soil and sediment samples influenced by dumping of residues of the flood in the Mulde River region in 2002.
In the analysis of soil samples, batch sequential extraction procedures are traditionally used for the fractionation of trace elements to access their mobility and potential risk for the contamination of groundwater. In the present work a continuous-flow technique has been used that enables not only the fast and efficient leaching of trace elements but as well as time-resolved studies on the mobilization of arsenic and selected heavy metals in different forms to be made. Rotating coiled columns (RCC) earlier used mainly in countercurrent chromatography have been successfully applied to the dynamic leaching of heavy metals from soils contaminated by flooding sludge's. The sample was retained in a PTFE rotating column as the stationary phase whereas aqueous solutions were continuously pumped through. The contents of elements were determined by on-line coupling of RCC and inductively coupled plasma atomic emission spectrometry (ICP-AES). This enables real-time data on the leaching process to be obtained. Dynamic and traditional batch procedures were compared. It has been shown that the aqueous elution under centrifugal forced conditions is much more effective for the mobilization of heavy metals. Hence, the dynamic leaching is characterized by a substantially more intensive interaction between solid and water and is besides substantially more time-saving than the conventional batch procedure. The RCC procedure was also employed for preliminary leaching studies with a simulated "acid rain". In comparison with the water leaching, the mobilization of heavy metals and arsenic from soil samples with employment of simulated acid rain as eluent was less effective.


Doxorubicin-loaded functionalized selenium nanoparticles for enhanced antitumor efficacy in cervical carcinoma therapy.
Development of novel tumor-targeted drug vehicles for cancer therapy is very important and has become one of major topics for designing nanoscale chemotherapeutics delivery systems. In the present study, selenium nanoparticles (SeNPs) was decorated with hyaluronic acid (HA) to prepare HA-SeNPs nanoparticles which were used to load doxorubicin (DOX) to fabricate tumor-targeted functionalized selenium nanoparticles HA-Se@DOX. In vitro and in vivo antitumor activities of HA-Se@DOX in human cervical carcinoma treatment were investigated. HA-Se@DOX showed selective cellular uptakes between cervical cancer HeLa cells and human umbilical vein endothelial cells (HUVEC). In vitro release result indicated that DOX was released from HA-SeNPs faster in acidic environment in comparison with normal physiological environment and 76.9% DOX was released in pH 5.4 during initial 30 h. HA-Se@DOX showed high activity to inhibit HeLa cell proliferation and triggered HeLa cell apoptosis via activating Bcl-2 signaling pathway. In vivo antitumor study showed that HA-Se@DOX inhibited tumor growth through suppressing cancer cells proliferation and inducing cancer cells apoptosis. Interestingly, HA-Se@DOX exhibited stronger anticancer activity than free DOX and Se@DOX in vitro and in vivo. Additionally, HA-Se@DOX did not cause damage to major organs at the used dose. HA-Se@DOX is a promising antitumor agent for human cervical carcinoma treatment and this research provides a novel therapeutic strategy for cancer therapy.


Phase Control and In Situ Passivation of Quasi-2D Metal Halide Perovskites for Spectrally Stable Blue Light-Emitting Diodes.
The fabrication of efficient and spectrally stable pure-blue perovskite light-emitting diodes (LEDs) has been elusive and remains of great interest. Herein, we incorporate diammonium salts into quasi-2D perovskite precursors for phase control of multiple quantum well structures to yield tunable and efficient emission in the blue region. With detailed characterizations and computational studies, we show that in situ passivation by the diammonium salts effectively modifies the surface energies of quasi-2D phases and inhibits the growth of low-band gap quasi-2D and 3D phases. Such phase control and in situ passivation could afford blue light-emitting perovskite thin films with high photoluminescence quantum efficiencies of, for instance, 75% for the emission peak at 471 nm. Using this perovskite thin film as an emitting layer, spectrally stable pure-blue LEDs with an emission peak at 474 nm and a full width at half-maximum of 26 nm could be fabricated to exhibit a brightness of 290 cd m-2 at 8 V and an external quantum efficiency of 2.17%.


Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors.
Supernumerary ring or giant rod marker chromosomes are a characteristic of well-differentiated liposarcomas (WDLPS) and atypical lipomas (ALP) and are often observed as the sole cytogenetic abnormality, but are rare in lipomas. Using a combination of different methods, we extensively investigated the structure and composition of rings and giant rods in a series of 17 WDLPS-ALP samples and three intra- or intermuscular lipomas (IMLP), revealing a unique combination of particular features strikingly related to these tumors. Although the rings and rods displayed in vitro and in vivo stability, the presence of alpha-satellites could not be detected on these supernumerary structures. Comparative genomic hybridization analysis, in combination with fluorescence in situ hybridization, identified the chromosomal regions contributing to the formation of these chromosomes: in WDLPS-ALP, all carried amplifications of 12q 14-15 and the MDM2 gene, with variable other noncontiguous regions. In the three IMLP, the rings consistently carried amplifications of 12q15-21 and 1q21, but increased copies of MDM2 were found in only one case. Other genes located more proximal in 12q14-15 were amplified in several WDLPS-ALP, but showed a normal copy number in IMLP. Furthermore, the immunohistochemical expression of the MDM2 protein was detected in most (12/14) WDLPS-ALP, in 1-30% of the cells, but never in IMLP. These supernumerary chromosomes represent a peculiar kind of amplification structure, midway between double minute chromosomes and homogeneously staining regions, but the mechanisms underlying the formation of these structures remain obscure.


[Successful combination treatment for psoriasis with phototherapy and low-dose cytokines: A spontaneous, retrospective observational clinical study].
Psoriasis is a chronic, inflammatory autoimmune skin disease that affects 1-3% of the world's population. Most patients with psoriasis have plaque psoriasis or psoriasis vulgaris, characterized by thickened erythematous scaly plaques and presenting in a variety of forms with distinct characteristics. Psoriasis is associated with a decreased quality of life as well as with severe comorbidities. The aim of this spontaneous, retrospective observational clinical study was to evaluate the pharmacological activity of advanced treatment based on the use of UVA-1 laser therapy with or without the co-administration of low dose cytokines [interleukin (IL)-4, IL-10] and anti-IL-1 antibodies in patients affected by psoriasis vulgaris. In this study the efficacy of UVA-1 phototherapy and, in parallel, the decisive (statistically relevant) boosting activity of low-dose cytokines in ameliorating the Psoriasis Area Severity Index (PASI) score were assessed. These results show the effectiveness of combined use of phototherapy and low-dose cytokines therapy, highlighting the fundamental role of anti-inflammatory cytokines (IL-4, IL-10, anti-IL-1 antibodies) in the treatment of psoriasis vulgaris. Further studies are necessary to confirm these preliminary data.


The significant role of Carbapenems-resistant Acinetobacter Baumannii in mortality rate of patients with COVID-19.
Background: Infections caused by Acinetobacter baumannii, especially carbapenem-resistant (CR) strains, pose important challenges in patients with COVID-19 infection. Therefore, in the present study, we investigated co-infection and antimicrobial resistance patterns, as well as the role of A. baumannii in the outcome of patients with COVID-19. Materials and methods: Between February 2019 and January 2021, 141 patients with A. baumannii infections were detected from seven different hospitals (A to G) in Arak, Iran, and the antibacterial susceptibility pattern of these isolates was evaluated using disk diffusion and E-test methods. Forty-seven of these patients were co-infected with COVID-19. During the study, the data about the clinical course, demographic data, and the role of A. baumannii infections in the mortality rate of COVID-19 patients were collected. Results: Hospitals A and B reported the most patients, with 53 (38%) and 47 (33%), respectively. Additionally, most cases (105 cases, 75%) were reported from surgical and general ICUs. Mechanical ventilators were detected as predisposing factors in 95 (67%) patients, and infection was detected in 20% of patients on the 10th day after intubation. All of the A. baumannii isolates were resistant to different classes of antibiotics, such as carbapenems. Notably, 33% (47 patients) were also positive for COVID-19, and 68% (32 patients) died due to the infection. Statistical analysis showed a significant role of A. baumannii co-infection in the mortality rate of COVID-19 patients (p-value 0.05). Conclusion: co-infection with A. baumannii is one of the most important challenges in COVID-19 patients. Our results showed that all isolated bacteria were CR and significantly increased mortality rates in COVID-19 patients.


Patterns of upper limb muscle activation in children with unilateral spastic cerebral palsy: Variability and detection of deviations.
The aim of this study was two-fold: (1) to quantify the variability of upper limb electromyographic patterns during elbow movements in typically developing children and children with unilateral spastic cerebral palsy, and to compare different amplitude normalization methods; (2) to develop a method using this variability to detect (a) deviations in the patterns of a child with unilateral spastic cerebral palsy from the average patterns of typically developing children, and (b) changes after treatment to reduce muscle activation. Twelve typically developing children ([6.7-15.9yo]; mean 11.0 SD 3.0yo) and six children with unilateral spastic cerebral palsy ([7.9-17.4yo]; mean 12.4 SD 4.0yo) attended two sessions during which they performed elbow extension-flexion and pronation-supination movements. Surface electromyography of the biceps, triceps, brachioradialis, pronator teres, pronator quadratus, and brachialis muscles was recorded. The Likelihood method was used to estimate the inter-trial, inter-session, and inter-subject variability of the electromyography patterns for each time point in the movement cycle. Deviations in muscle patterns from the patterns of typically developing children and changes following treatment were evaluated in a case study of a child with cerebral palsy. Normalization of electromyographic amplitude by the mean peak yielded the lowest variability. The variability data were then used in the case study. This method detected higher levels of activation in specific muscles compared with typically developing children, and a reduction in muscle activation after botulinum toxin A injections. Upper limb surface electromyography pattern analysis can be used for clinical applications in children with cerebral palsy.


Interspecific variation in desiccation survival time of Aedes (Stegomyia) mosquito eggs is correlated with habitat and egg size.
Survival times of eggs under three humidity conditions (42%, 68%, 88% RH) were investigated among Aedes (Stegomyia) mosquitoes from temperate and tropical zones (5 species and 20 geographical strains). This subgenus tends to occupy small aquatic sites as larvae, where desiccation resistance of eggs is necessary during habitat drought. Interspecific comparison showed that the egg survival time was correlated with egg volume and dryness of source locality, and probably with habitat. Aedes aegypti is associated most with arid climate and human-disturbed habitats - its large eggs survived the longest periods at all humidities. Aedes albopictus ranges from tropics to temperate zones and inhabits both disturbed and forest habitats - its eggs were less desiccation-resistant than A. aegypti eggs. The survival times for forest species eggs (A. riversi, A. galloisi, A. flavopictus) were variable at high humidities but at the lowest humidity were consistently shorter than for eggs of A. aegypti and A. albopictus.


Inhibition of acetylcholinesterase modulates the autoregulation of cerebral blood flow and attenuates ischemic brain metabolism in hypertensive rats.
We designed the present study to examine whether or not the inhibition of acetylcholinesterase modulates cerebral microcirculation in hypotension and improves brain metabolism in ischemia induced by bilateral carotid artery occlusion in hypertensive rats. Blood flow to the parietal cortex was determined by the H2 clearance method. Lactate, pyruvate, and ATP were estimated by enzymatic methods. Acetylcholinesterase inhibitor (AChEI, ENA-713), at 0.05, 0.1, or 0.5 mg/kg, was intravenously injected 10 min before either hemorrhagic hypotension or cerebral ischemia. The levels of acetylcholine in the control were 29.3 +/- 8.1 (mean +/- SD) and 39.5 +/- 8.1 pmol/mg in the cortex and hippocampus, respectively, and they were significantly decreased by 15-19% after 60 min of ischemia in the vehicle-treated rats. AChEI preserved the levels to 93-98% of the control (p < 0.05 versus vehicle). The lower limit of autoregulation was 74 +/- 9% of the resting values. The administration of AChEI helped preserve blood flow and lowered the limit to 64 +/- 6% (p < 0.05 versus control). After 60 min of ischemia, lactate increased 6.5-fold and ATP decreased to 64% of the control value. The administration of AChEI dose-dependently reduced the lactate level 1.9- to 3.9-fold and well preserved the ATP level to 94-97% of the control. The inhibition of acetylcholinesterase activity may preserve cerebral autoregulation during hypotension and protect cerebral metabolism against ischemic insult.


An inter-method comparison of four Human Reliability Assessment models.
This paper presents a comparison of four common Human Reliability Assessment (HRA) models through a scoping literature review and sensitivity analysis. The scoping literature review identified 72 relevant studies which formed the basis of the comparison. Studies reported the four selected models have similarities in terms of the sector of origin, applied sectors, output calculation, and a lack of clear guidelines on Performance Influencing Factors (PIFs) selection and risk level allocation. The studied models have differences in the number and type of PIF inputs and Human Error Probability (HEP) calculation procedures. The One Factor At a Time (OFAT) and "combined" sensitivity analysis were conducted to examine the HRA models' responses to systematic risk level changes when each of 8 matching PIFs were systematically set to "high" and then "low" levels individually and simultaneously. The OFAT analysis showed coefficients of variation (CV) in HEP varying from 9% for skills/training up to 94% for work procedure when the PIFs are assigned to a "low" risk level individually. The combined analysis showed the median HEP value close to 97% and 1% when PIFs are assigned to" high" and "low" risk levels respectively. Although the selected HRA models were reported to be validated in high-risk domains there was no study found that validated these models in low-risk domains such as manual order picking, or manual assembly lines. The HRA models examined here are disconnected from specific system design elements which can inhibit design improvement efforts. The study outcome suggests the need for clear guidelines for PIFs selection and risk level allocation. Future research should address both the connection of error assessment to the design of the system and the features of new HRA models that affect its reliability and validity in a variety of industrial contexts.


Thermoregulatory effects of intraventricularly injected dopamine in the goat.
Dopamine (DA) was injected in the third brain ventricle of goats and the thermoregulatory effects were studied under different ambient conditions. The effects depended on dose, ambient conditions and cannula used. In the cold, there was a drop in body temperature, sometimes accompanied by suppression of shivering and by vasodilatation. Both temperature decrease and suppression of shivering were dose-dependent but there was no relation between magnitude of temperature drop and occurrence of shivering suppression. In a thermoneutral environment, there was either a slight vasoconstriction or hypothermia, occasionally accompanied by induction of panting. In the heat, either hypothermia or hyperthermia was observed. Hypothermia was accompanied by an increase in panting. Hyperthermia only occurred when the animals became excited as a result of the injection of DA. It is concluded that DA acts by stimulating the thermoregulatory pathway from heat sensors to heat loss effectors at a locus similar to that for 5-hydroxytryptamine in the thermoregulation model of Bligh et al. (1971).


Electromembrane extraction of peptides.
Rapid extraction of eight different peptides using electromembrane extraction (EME) was demonstrated for the first time. During an extraction time of 5 min, the model peptides migrated from a 500 microL aqueous acidic sample solution, through a thin supported liquid membrane (SLM) of an organic liquid sustained in the pores in the wall of a porous hollow fiber, and into a 25 microL aqueous acidic acceptor solution present inside the lumen of the hollow fiber. The driving force of the extraction was a 50 V potential sustained across the SLM, with the positive electrode in the sample and the negative electrode in the acceptor solution. The nature and the composition of the SLM were highly important for the EME process, and a mixture of 1-octanol and 15% di(2-ethylhexyl) phosphate was found to work properly. Using 1mM HCl as background electrolyte in the sample and 100 mM HCl in the acceptor solution, and agitation at 1050 rpm, enrichment up to 11 times was achieved. Recoveries were found to be dependent on the structure of the peptide, indicating that the polarity and the number of ionized groups were important parameters affecting the extraction efficiency. The experimental findings suggested that electromembrane extraction of peptides is possible and may be a valuable tool for future extraction of peptides.


Shoulder surgery in beach chair position causing perioperative stroke: Four cases and a review of the literature.
Perioperative stroke is a rare, but serious complication in shoulder-arthroscopy or arthroplasty. Recent literature suggests the beach chair position, widely used during shoulder surgery, might induce severe perioperative hypotension, and with this cerebral desaturation and ultimately perioperative stroke. In this article we report four cases of perioperative stroke in shoulder surgery. In all cases, patients underwent brief periods of hypotension, which might have caused perioperative stroke. Based on an analysis in our hospital, we think the prevalence of perioperative stroke during shoulder surgery is higher than reported. Surgeons should be aware of this risk when using the beach chair position.


DISC1-kendrin interaction is involved in centrosomal microtubule network formation.
Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation segregating with schizophrenia, bipolar disorder and other major mental illnesses in a Scottish family. We previously identified 446-533 amino acids of DISC1 as the kendrin-binding region by means of a directed yeast two-hybrid interaction assay and showed that the DISC1-kendrin interaction is indispensable for the centrosomal localization of DISC1. In this study, to confirm the DISC1-kendrin interaction, we examined the interaction between deletion mutants of DISC1 and kendrin. Then, we demonstrated that the carboxy-terminus of DISC1 is indispensable for the interaction with kendrin. Furthermore, the immunocytochemistry revealed that the carboxy-terminus of DISC1 is also required for the centrosomal targeting of DISC1. Overexpression of the DISC1-binding region of kendrin or the DISC1 deletion mutant lacking the kendrin-binding region impairs the microtubule organization. These findings suggest that the DISC1-kendrin interaction plays a key role in the microtubule dynamics.


[Technique for intracavitary radiotherapy using an iridium 192 wire ("umbrella") in the treatment of adenocarcinoma of the body of the uterus (author's transl)].
The description of an intrauterine device for the application of local radiotherapy in non-radioactive preparation. The device consists of polyethylene tubes froming two perpendicular loops joined and fixed and their topmost point by ligature. A traction wire is used to open these loops, therby obtaining a cuboid target-volume from four radioactive lines. Dosimetry for this technique (known as "umbrella") may be obtained using a computerised programme.


Multi-class analysis of 46 antimicrobial drug residues in pond water using UHPLC-Orbitrap-HRMS and application to freshwater ponds in Flanders, Belgium.
Increasing anthropogenic pressure and agricultural pollution raises concerns regarding antimicrobial resistance and biodiversity loss in aquatic environments. In order to protect and restore water resources and biodiversity, antimicrobial drug residues should be monitored in all aquatic environments including pond water. Consequently, the objective of this research was to develop and validate a novel multi-residue method for the simultaneous quantification of 46 targeted human and veterinary antimicrobial drugs in pond water. A suitable extraction method based on solid-phase extraction (SPE) was developed, assisted by a fractional factorial design. A broad polarity range of compounds was covered (log P from -4.05 to 4.38), including major representatives of the following classes: sulfonamides, tetracyclines, quinolones, macrolides, lincosamides, nitrofurans, penicillins, cephalosporins, diaminopyrimidines, pleuromutilins and phenicols. All analytes were separated using ultra-high performance liquid chromatography (UHPLC) and detected in full-scan by Orbitrap high resolution mass spectrometry (Orbitrap-HRMS). Good linearity was obtained for all compounds with R2 ≥ 0.993 and goodness-of-fit coefficient (g) ≤ 11.56%. Method detection limits ranged from 10 to 50 ng L-1 and method quantification limits were 50 ng L-1 for all compounds. Acceptable values were obtained for within-day and between-day apparent recoveries (i.e. between 50 and 120%), precision (< 30% and < 45%) and measurement uncertainty (< 50%). Targeted analysis of 18 freshwater ponds throughout Flanders was performed to demonstrate the applicability of the newly developed UHPLC-HRMS method. Overall, 20 antimicrobial drugs were detected with highest concentrations observed for tetracyclines and their transformation products ranging between 51 and 248 ng L-1. Finally, suspect screening was performed suggesting the presence of 14 additional pharmaceuticals including 3 antimicrobial degradation products (e.g. apo-oxytetracycline, amoxicillin penicilloic acid and penilloic acid) and 11 pesticides.


The resistance to waterlogging of three Eucalyptus species : Effect of waterlogging and an ethylene-releasing growth substance on E. robusta, E. grandis and E. saligna.
Seedlings of Ecalyptus grandis W. Hill ex Maiden were found to be more resistant to waterlogging than those of Eucalyptus robusta Sm. and seedlings of both species were more resistant than those of Eucalyptus saligna Sm. Resistance depended on the stress avoidance mechanism of adventitious root formation. The ethylene-releasing growth substance 2-chloroethylphosphonic acid (ethephon) applied to non-flooded plants was used as a tool to study the role of ethylene in the response of plants to waterlogging. Plant height and total dry weight decreased linearly with plant ethylene content. There was no difference between the species in their response to ethephon.


Involvement of 5-HT1B/1D receptors in the inflammatory response and oxidative stress in intestinal ischemia/reperfusion in rats.
Acute mesenteric ischemia (AMI) is caused by an abrupt cessation of blood flow to the small intestine. Reperfusion is the return of blood flow to the ischemic bowel. Intestinal ischemia/reperfusion (I/R) leads to the formation of reactive oxygen species, local inflammatory response, and may lead to the patient's death. Pre-treatment of the intestinal may reduce the high mortality associated with AMI. 5-Hydroxytryptamine 1B (5-HT1B) and 5-HT1D receptors have anti-inflammatory and neuroprotective effects in different experimental studies. We aimed to investigate the potential involvement of these receptors in intestinal I/R injury. Firstly, we assessed the expression and localization of 5-HT1B and 5-HT1D receptors in the enteric nervous system using an immunofluorescence-based method. Intestinal I/R in rats was induced by 30 min occlusion of superior mesenteric artery and reperfusion for 2 h. Rats were randomly divided in different control and I/R groups (n = 6) receiving either vehicle, sumatriptan (5-HT1B/1D receptors agonist; 0.1 mg/kg), GR127,935 (5-HT1B/1D receptors antagonist; 0.1 mg/kg) and combination of sumatriptan (0.1 mg/kg) + GR127,935 (0.1 mg/kg) before determination of biochemical and histological parameters. In the enteric nervous system, 5-HT1B and 5-HT1D receptors were expressed 17% and 11.5%, respectively. Pre-treatment with sumatriptan decreased 5-hydroxytryptamine (5HT) level by 53%, and significantly decreased calcitonin gene-related peptide (CGRP) levels, lipid pereoxidation, neutrophil infiltration, and level of pro-inflammatory markers in the serum. Histopathologic studies also showed a remarkable decrease in intestinal tissue injury. These findings suggest that sumatriptan may inhibit intestinal injury induced by I/R through modulating the inflammatory response by activation of 5-HT1B/1D receptors.


Gaps in care following first time seizure in an underserved region: A retrospective analysis.
This study investigated the characteristics of patients presenting with the first-time seizure (FTS) and whether neurology follow-up occurred in a medically underserved area. A retrospective study of adults with a FTS discharged from the Emergency Department (ED) at Loma Linda University between January 1, 2017 and December 31, 2018 was performed. The primary outcome was days from the ED visit to the first neurology visit. Secondary outcomes included repeat ED visits, percentage of patients who had specialty assessment in one year, type of neurologist seen, and percentage lost to follow-up. Of the 1327 patients screened, 753 encounters met criteria for manual review, and after exclusion criteria were applied, 66 unique encounters were eligible. Only 30% of FTS patients followed up with a neurologist. The median duration for neurology follow-up was 92 days (range=5-1180). After initial ED visit, 20% of follow-up patients were diagnosed with epilepsy within 189 days, and 20% of patients re-presented to the ED with recurrent seizures while awaiting their initial neurology appointment. Reasons for lack of follow-up included: referral issues, missed appointments, and shortage of available neurologists. This study highlights the significant treatment gap that a first-time seizure clinic (FTSC) could fill in underserved communities. FTSC may reduce the morbidity and mortality associated with untreated recurrent seizures.


Detection of coronary artery disease in diabetic patients.
Coronary artery disease may be difficult to detect in diabetic patients. This study was designed to determine the specificity and sensitivity of three noninvasive tests. Accordingly, the results of 48-h ambulatory electrocardiogram (ECG) monitoring, maximal ECG exercise test, and intravenous dipyridamole myocardial thallium scintigraphy were compared in 59 middle-aged diabetic patients who were consecutively selected for suspected coronary artery disease. All patients also underwent coronary angiography, which was performed regardless of the results of the non-invasive tests. Twenty patients (34%) had significant coronary lesions, i.e. stenosis equal to or greater than 70%, and 16 of these 20 patients (80%) had double or triple vessel disease. Sensitivity and specificity were, respectively, 25% and 88% for ambulatory ECG monitoring, 75% and 77% for the exercise test and 80% and 87% for thallium myocardial scintigraphy. This observation strongly supports the use of non-invasive tests for the detection of coronary artery disease in those diabetic patients at high risk of such disease. As the exercise test is cheaper and more widely available than thallium myocardial scintigraphy it should be used as a first line examination. Dipyridamole myocardial scintigraphy may provide an alternative solution for those patients who cannot perform maximal exercise, or with atypical clinical presentation.


Horizontal transmission of Parathelohania anophelis to the copepod, Microcyclops varicans, and the mosquito, Anopheles quadrimaculatus.
The copepod Microcyclops varicans was infected with Parathelohania anophelis by unincleate meiospores from a field-collected fourth instar Anopheles quadrimaculatus larva. Large numbers of unincleate, pyriform spores developed in the copepod. These spores were fed to early instar A. quadrimaculatus larvae, infecting both males and females, resulting in the production of cylindrical, binucleate spores in the adult. These spores were responsible for vertical transmission, through the eggs, to the larvae. The original spore type collected from the field was found in the male progeny from the infected females. Another P. anophelis-infected mosquito colony was established by feeding spores from a single, field-collected, infected copepod to A. quadrimaculatus larvae. The microsporidium was continuously maintained by vertical transmission in newly established infected colonies.


Three-dimensional modelling of blur property for conventional optical microscopes.
Intensity diffusion caused by optical diffraction limits the imaging resolution of conventional optical microscopes, therefore modelling and measuring the intensity transmission and distribution property of the light sources is a significant research topic in system development and pattern recognition. However, the complicated wave propagation process in optical imaging makes it difficult to provide a direct, analytical and simple mathematical model to measure the relationship between the blur degree and various camera parameters. In this study, an improved intensity transmission and distribution calculation method for conventional optical microscopes was proposed; furthermore, a simple mathematical relation between the blur degree and camera parameters was achieved based on the proposed method. First, the light intensity distribution and propagation characteristics of a conventional optical microscope were modeled based on the property of the Fresnel circular hole diffraction combined with the practical optical parameters. Second, by analyzing the property of intensity distribution and blurring imaging, a quantitative simplified mathematical relationship between the blur degree and camera parameters in optical microscope imaging was obtained, and the three-dimensional (3D) blur property in the optical imaging process was analyzed under different conditions. Third, the connection between diffractive optics and geometric optics was obtained by summarizing and generalizing the 3D blur property curve of each monochromatic light source. Finally, the proposed method was verified through a series of simulations and experiments.


Barriers that influence eating behaviors in adolescents.
Adolescence is a time of rapid growth and development with biologic, psychological, and emotional changes occurring simultaneously. We conducted a critical review of the literature to analyze key topics in the study of adolescents' eating behaviors and to identify barriers to healthy eating experienced by adolescents. The literature documents that nutritional deficits and poor eating established during adolescence have long-term health, growth, and developmental consequences. Gaps in the literature are identified and recommendations for future studies are proposed.


A 24-Year-Old Woman With Cough, Arthralgia, and Skin Ulcerations.
A 24-year-old Senegalese woman without remarkable history except anemia and iron deficiency related to excessive menstrual bleeding and sickle cell trait was admitted to our internal medicine department with 4-month fever, weight loss (-13 kg), dyspnea for limited efforts, intermittent productive cough, and bilateral metacarpophalangeal (MCP) and interphalangeal arthralgia. She was born and lived in France. She traveled previously to Senegal in 2015. She had no history of tobacco, alcohol, or drug use nor proximity with animals. She was taking no medication.


Patient's assessment and prediction of recovery after stroke: a roadmap for clinicians.
In neurorehabilitation clinical practice, assessment is usually more oriented to evaluate patient's present status, than to plan interventions according to predicted outcomes. Therefore, we conducted an extensive review of current prognostic models available in the literature for recovery prediction of many functions and constructs, after stroke. We reported results in the form of a practical guide for clinicians, with the aim of promoting the culture of early clinical assessment for patient stratification, according to expected outcome. To define a roadmap for clinicians, a stepwise sequence of five actions has been developed, from collecting information of past medical history to the adoption of validated prediction tools. Furthermore, a clinically-oriented organization of available prediction tools for recovery after stroke have been proposed for motor, language, physiological and independency functions. Finally, biomarkers and online resources with prognostic value have been reviewed, to give the most updated state of the art on prediction tools after stroke. Clinical assessment should be directed both towards the objective evaluation of the present health status, and to the prediction of expected recovery. The use of specific outcome measures with predictive value is recommended to help clinicians with the definition of sound therapeutic goals.


Leishmania braziliensis isolated from disseminated leishmaniasis patients downmodulate neutrophil function.
The polymorphism observed in Leishmania braziliensis is associated with different clinical forms of leishmaniasis. Neutrophils (PMNs) participate in the pathogenesis of leishmania infection, and here, we evaluate neutrophil function after infection with isolates of L. braziliensis from cutaneous leishmaniasis (CL) or disseminated leishmaniasis (DL) patients. Neutrophils from 30 healthy subjects (HS) were infected with isolates of L. (V.) braziliensis obtained from three CL and three DL patients. They were infected at the ratio of 3:1 parasites per neutrophil, and leishmania uptake was evaluated by microscopy. The neutrophil activation markers and oxidative burst by expression of dihidrorhodamine (DHR) were evaluated by flow cytometry and cytokine production by ELISA. The frequency of infected cells and the number of amastigotes were higher in neutrophils infected with CL isolates compared to DL isolates (P < 0.05). The DHR and CD66b expression after infection with DL isolate was lower than with CL isolates. There was no difference regarding chemokine production. The L. (V.) braziliensis isolates of DL induced lower respiratory burst and neutrophils activation markers compared with CL isolates which may contribute to parasite survival and dissemination in DL patients.


Hospital at Home: another piece of the armoury against COVID-19.
Hospital at Home (@Home) services bring the ward to the patient, providing acute care in the home. The @Home team adapted to support the care of patients with COVID-19 in the community who would otherwise have required hospitalisation. An evidence-based guideline and treatment bundle (dexamethasone, oxygen, intravenous fluids and thromboprophylaxis) for managing severe COVID-19 was developed. Data were retrospectively extracted from notes of patients with COVID-19 admitted between 16 December 2020 to 14 February 2021, and service users contacted for feedback. One-hundred and twenty-five adults with COVID-19 were treated by @Home; 42 severe (34%) and 83 non-severe (66%) infections; average length of stay was 7 days (interquartile range 4-8). Eight-hundred and seventy-five hospital-occupied bed days were saved. Service users emphasised the importance of being with loved ones and the value of respecting peoples' wishes to be at home. @Home gave people with COVID-19 a choice of active treatment at home, thereby extending available healthcare capacity beyond the acute hospital setting.


A low-cost, high-quality method for remote recording of presentations.
The purpose of this article was to develop a low-cost method for high-quality remote capturing and recording of multimedia presentations. The method for making high-quality digital recordings of presentations by using the mix of freely available software presented in this article offers great potential for institutions on a budget as well as others seeking viable alternatives to current methods of presentation recording.


Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy.
To determine the effect of long-term intermittent cyclic etidronate treatment on spinal bone density and vertebral fracture rates. Postmenopausal osteoporotic women (n = 423) were randomized initially into a 2-year, double-blind, multicenter study; it was extended to a third year of blinded treatment followed by open-label treatment: 357 patients continued treatment in Year 3 (305 receiving blinded therapy and 52 receiving calcium supplementation) and 277 in Year 4. During Years 1 through 3, patients received double-blind treatment with phosphate (1.0 g) or placebo twice daily for 3 days, etidronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) daily for the remainder of each 91-day treatment cycle. During Year 4, open-label intermittent cyclic etidronate therapy (without preceding phosphate) was administered to all patients. Spinal bone density and vertebral fracture rates were the main outcome measures. During Year 3, etidronate therapy maintained the significant increases in spinal bone mineral density of the first 2 years. Over the 3-year period, proximal femur bone density increased in etidronate-treated patients. Etidronate therapy for 3 years significantly decreased the vertebral fracture rate in patients at higher risk for fracture (low spinal bone density and three or more vertebral fractures at study entry), as compared with nonetidronate treatment (228 versus 412 fractures per 1,000 patient-years, respectively; p < 0.05). After 1 year of open-label treatment, patients previously treated with etidronate maintained bone mass, and vertebral fracture rates in all groups were lower than in any other study period. There were no apparent serious adverse effects. Three years of intermittent cyclic etidronate therapy produced significant increases in spinal and hip bone density, with a significant reduction in vertebral fracture rates in patients at higher fracture risk. Maintenance of bone mass and low fracture rate were observed when etidronate was continued for an additional year.


Virulence factors and antimicrobial resistance in Staphylococcus aureus isolated from bovine mastitis in Brazil.
This study aimed to evaluate virulence factors and genetic markers of antimicrobial resistance in 400 Staphylococcus aureus strains isolated from bovine mastitis in four Brazilian states, as well as to assess the association between these characteristics and field information. Virulence factors and drug resistance genes were identified by PCR screening. Biofilm-forming and hemolytic phenotype were detected using Congo red Tryptic Soy Broth and defibrinated sheep blood agar, respectively. Of all isolates, 83.5% were biofilm-forming and 98.5% strains exhibited biofilm gene icaAD, and a significant association between phenotype and genotype for biofilm was observed (P = 0.0005). Hemolysin genes were observed in 82.85% (hla+hlb+), 16.5% (hla+) and 0.75% (hlb+) isolates, whereas the hemolytic phenotype exhibited was complete and incomplete hemolysis in 64.25%, complete in 28.25%, incomplete in 4.75%, and negative in 2.75% of the strains. Virulence factors genes luk, seb, sec, sed, and tst were observed in 3.5%, 0.5%, 1%, 0.25%, and 0.74% isolates, respectively. The gene blaZ was detected in 82.03% of penicillin-resistant isolates, whereas tetK and aac(6')-Ie-aph(2')-Ia were observed in 33.87% and 45.15% of the tetracycline and aminoglycosides-resistant isolates, respectively. Fluoroquinolone resistance gene mepA was detected for the first time in S. aureus from bovine mastitis. Resistance genes tetM (3.22%), tetL (1.61%), ermA (14.29%), ermB (14.29%), ermC (33.3%), ermT (9.52%), ermY (4.76%), msrA (9.52%), and mphC (9.52%) were also detected among resistant isolates. No association between virulence factors or antimicrobial-resistant genes and year of isolation, geographic origin, or antimicrobial resistance profile was observed. Our results showed that S. aureus strains isolated from bovine mastitis in the four Brazilian states sampled are mainly biofilm-forming and hemolytic, whereas virulence genes associated with enterotoxins, luk and tst, were less frequently observed. Moreover, a wide variety of resistance genes that confer resistance to almost all classes of antimicrobial agents approved for use in animals and humans were found. Overall, the data point to a great pathogenic potential of S. aureus associated with bovine mastitis and to the non-negligible risks to public health of staphylococcal infections from animal origin.


Impact of Personal Protective Equipment on Surgical Performance During the COVID-19 Pandemic.
The Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has exposed surgeons to hazardous working conditions, imposing the need for personal protective equipment (PPE) use during surgery. The use of such equipment may affect their non-technical skills, augment fatigue, and affect performance. This study aimed to assess the surgeons' perceptions of the impact of wearing PPE during emergency surgery throughout the pandemic. An international cooperation group conducted an anonymous online survey among surgeons from over 30 countries, to assess perceptions about the impact of PPE use on non-technical skills, overall comfort, decision making, and surgical performance during emergency surgery on COVID-19 patients. Responses to the survey (134) were received from surgeons based on 26 countries. The vast majority (72%) were males. More than half of the respondents (54%) felt that their surgical performance was hampered with PPE. Visual impairment was reported by 63%, whereas 54% had communication impediments. Less than half (48%) felt protected with the use of PPE, and the same proportion perceived that the use of such equipment influenced their decision making. Decreased overall comfort was cited by 66%, and 82% experienced increased surgical fatigue. Surgeons perceived impediment for both visibility and communication, and other non-technical skills while using PPE on emergency surgery in COVID-19 patients. Their perceived lack of protection and comfort and increased fatigue may have inhibited their optimal surgical performance. More attention should be placed in the design of more user-friendly equipment, given the possibility of a second wave of the pandemic.


Examining the reliability and validity of a self-regulated learning strategy scale for undergraduate nursing students and effective factors of self-regulated learning strategies.
Self-regulated learning in higher education has increasingly attracted attention in recent years. This study involved a survey of nursing students using an originally developed tool called the Self-regulated Learning Strategy Scale for Undergraduate Nursing Students (SRLSS-NS). We aimed to elucidate factors relating to the promotion of self-regulated learning while confirming the reliability and validity of the novel scale. A cross-sectional survey design was adopted. School of Health Science, Faculty of Medicine. Participants included first- to fourth-year undergraduate nursing students. Descriptive statistics were used to ascertain participant characteristics. We confirmed the criterion-related validity of the survey through exploratory factor analysis and Pearson's product-moment coefficient with external criteria. Reliability was calculated using Cronbach's α coefficient. To examine stability, we confirmed the correlation between the first and second surveys. Multiple regression analysis was performed using the SRLSS-NS score as the objective variable and basic attributes/individual factors, learning-related factors, and cognitive factors as explanatory variables. The statistical significance level was defined as 5 %. The scale consisted of 12 items related to three factors-construct validity, internal consistency, and stability-which were confirmed. Regarding factors related to the SRLS of undergraduate nursing students, the SRLSS-NS score was greater for items such as, "I feel that university education gives me confidence in learning" (β = 0.255, p < 0.001), "I like/find interest in things I am learning" (β = 0.228, p < 0.001), "I feel that university education teaches me how to learn" (β = 0.198, p = 0.003), and "Self-esteem as a professional" (β = 0.143, p = 0.023). As more efforts are made to improve undergraduate nursing students' SRLS, the importance of education for increasing confidence, promoting intrinsic motivation, teaching learning methods, and fostering occupational identity is emphasized.


Effects of dietary glycerol inclusion on growth performance, carcass and meat quality characteristics, glycogen content, and meat volatile compounds in Korean cattle steers.
We have tested our hypothesis that inclusion of purified glycerol as a replacer of portions of dried distillers grain with solubles (DDGS) would affect growth performance, rumen fermentation and blood parameters, carcass and sensory traits, reducing sugar and glycogen contents, and volatile compound profiles in longissimus thoracis (LT) in Korean cattle steers. A total of 20 Korean cattle steers (27.0±0.2 months old; 647±10.5 kg body weight [BW]) were assigned to a conventional control group or a glycerol group (3.17% purified glycerol addition as a replacement for DDGS and molasses). The steers were individually allowed to receive the experimental concentrate at the daily amount of 1.5% of their individual BW and a total 1.0 of kg/d of rice straw twice daily. The feeding trial was conducted for a period of 20 weeks. Glycerol supplementation (GS) increased (p = 0.001) concentrate intake. However, GS did not affect (p>0.05) average daily gain, feed efficiency, and ruminal volatile fatty acid concentrations. GS tended to increase (p≤0.10) serum glucose concentrations at the 16th and 20th weeks. GS decreased (p = 0.001) LT pH. GS did not affect (p>0.05) carcass traits and the chemical or physicochemical compositions, reducing sugar or glycogen contents, sensory traits, and most of volatile compounds in the LT. The inclusion of purified glycerol as a replacement for DDGS in the finishing diet did not affect growth performance, rumen fermentation parameters, and carcass quality in Korean cattle. The purified glycerol could be used as a substitute for other energy sources such as DDGS in beef cattle, depending on the price.


Inhibition of spermiation in the Syrian hamster using dibutyryl cyclic-AMP.
Young adult male Syrian hamsters were given intraperitoneal injections of 50 mg dibutyryl cyclic AMP twice daily for a period of three days. On the fourth day the animals were sacrificed and their testes were processed for light and electron microscopy. The results indicate that the mature spermatozoa were retained within the seminiferous epithelium after the stage in the seminiferous cycle in which spermiation normally occurs. The unreleased spermatozoa were ultrastructurally normal. Typical Sertoli-spermatid junctional specializations remained associated with the retained spermatozoa. These findings indicate that normally spermiation is initiated by the disappearance of the junctional specializations. In addition, the present results demonstrate that spermiation can be controlled.


Medullomyoblastoma. A histologic, immunohistochemical, and ultrastructural study.
The light and electron microscopic features of a medullomyoblastoma arising in the cerebellar vermis of a 3-year-old boy are described. Differentiation along both glial and neuronal lines was present in the medulloblastoma component of the tumor. Astrocytic differentiation was confirmed by the observation of compact bundles of 8 to 10 nm glial filaments in cellular processes on ultrastructural examination, and by positive immunostaining for glial fibrillary acidic protein (GFAP). Neuroblastic differentiation was suggested by the demonstration of axon-like processes on silver impregnation, and ultrastructurally by the observation of microtubules, dense-core and clear vesicles, and rare synapse-like structures within cytoplasmic processes. The presence of both primitive and well-differentiated striated muscle fibers in the tumor was confirmed by the demonstration of thick and thin myofilaments and Z bands on electron microscopy, and by positive immunostaining for myoglobin. These findings clearly establish the presence of both neuroectodermal and rhabdomyoblastic components in this neoplasm, and thus set it apart from the pure rhabdomyosarcomas, which may also occur in the cerebellar vermis in children. This case also illustrates the usefulness of electron microscopy and immunohistochemistry in the diagnosis and histogenetic evaluation of primitive or poorly differentiated small cell tumors of the central nervous system.


Immunization of Solid Organ Transplant Candidates and Recipients: A 2022 Update.
Immunizations are a relatively safe and cost-effective intervention to prevent morbidity and mortality associated with vaccine preventable infection (VPIs). As such, immunizations are a critical part of the care of pre and posttransplant patients and should be prioritized. New tools are needed to continue to disseminate and implement the most up-to-date vaccine recommendations for the SOT population. These tools will help both primary care providers and multi-disciplinary transplant team members taking care of transplant patients to stay abreast of evidence-based best practices regarding the immunization of the SOT patient.


Metabolic engineering of Escherichia coli for high-level production of violaxanthin.
Xanthophylls are a large class of carotenoids that are found in a variety of organisms and play particularly important roles in the light-harvesting and photoprotection processes of plants and algae. Violaxanthin is an important plant-derived xanthophyll with wide potential applications in medicines, foods, and cosmetics because of its antioxidant activity and bright yellow color. To date, however, violaxanthins have not been produced using metabolically engineered microbes on a commercial scale. Metabolic engineering for microbial production of violaxanthin is hindered by inefficient synthesis pathway in the heterologous host. We systematically optimized the carotenoid chassis and improved the functional expression of key enzymes of violaxanthin biosynthesis in Escherichia coli. Co-overexpression of crtY (encoding lycopene β-cyclase), crtZ (encoding β-carotene 3-hydroxylase), and ZEP (encoding zeaxanthin epoxidase) had a notable impact on their functions, resulting in the accumulation of intermediate products, specifically lycopene and β-carotene. A chassis strain that did not accumulate the intermediate was optimized by several approaches. A promoter library was used to optimize the expression of crtY and crtZ. The resulting strain DZ12 produced zeaxanthin without intermediates. The expression of ZEP was further systematically optimized by using DZ12 as the chassis host. By using a low copy number plasmid and a modified dithiol/disulfide system, and by co-expressing a full electron transport chain, we generated a strain producing violaxanthin at about 25.28 ± 3.94 mg/g dry cell weight with decreased byproduct accumulation. We developed an efficient metabolically engineered Escherichia coli strain capable of producing a large amount of violaxanthin. This is the first report of a metabolically engineered microbial platform that could be used for the commercial production of violaxanthin.


Evaluation of the usefulness of the indocyanine green clearance test for chemotherapy-associated liver injury in patients with colorectal cancer liver metastasis.
The indocyanine green (ICG) clearance test is reported to be useful for the preoperative evaluation of hepatic functional reserve. However, the ICG clearance test has not been sufficiently investigated in patients with colorectal liver metastasis after chemotherapy. The aim of the present study was to evaluate whether the ICG clearance test is a useful parameter for the preoperative detection of chemotherapy-associated liver injury. Ninety-four patients undergoing liver resection for colorectal liver metastasis after chemotherapy were studied. The medical records for each case were retrospectively reviewed. They underwent pathological assessment to clarify the degree of histopathological liver injury of the nontumoral liver parenchyma. In addition, the correlation between the pathological score and the ICG retention rate at 15 min (ICG-R15) was analyzed. Sinusoidal injury was observed in the 31 of 94 patients. Steatohepatitis was observed in the 40 of 94 patients. There was no strong correlation between the preoperative ICG-R15 value and the sinusoidal pathological score (r = 0.117, P = 0.261). There was no strong correlation between the ICG-R15 and the nonalcoholic fatty liver disease activity score (r = 0.215, P = 0.037). It was difficult to predict the degree of chemotherapy-associated liver injury by the preoperative ICG-R15 value. It is necessary to estimate the hepatic functional reserve based on a combination of several clinical indicators without relying on the ICG test, in order to perform a safe radical liver resection.