A two-locus molecular characterization of Paramecium calkinsi.
Paramecium calkinsi (Ciliophora, Protozoa) is a euryhaline species which was first identified in freshwater habitats, but subsequently several strains were also collected from brackish water. It is characterized by clockwise spiral swimming movement and the general morphology of the "bursaria type." The present paper is the first molecular characterization of P. calkinsi strains recently collected in distant regions in Russia using ITS1-5.8S- ITS2-5'LSU rDNA (1100bp) and COI (620bp) mtDNA sequenced gene fragments. For comparison, our molecular analysis includes P. bursaria, exhibiting a similar "bursaria morphotype" as well as species representing the "aurelia type," i.e., P. caudatum, P. multimicronucleatum, P. jenningsi, and P. schewiakoffi, and some species of the P. aurelia species complex (P. primaurelia, P. tetraurelia, P. sexaurelia, and P. tredecaurelia). We also use data from GenBank concerning other species in the genus Paramecium and Tetrahymena (which used as an outgroup). The division of the genus Paramecium into four subgenera (proposed by Fokin et al. 2004) is clearly presented by the trees. There is a clear separation between P. calkinsi strains collected from different regions (races). Consequently, given the molecular distances between them, it seems that these races may represent different syngens within the species.


Synchronous removal of pharmaceutical contaminants and inactivation of pathogenic microorganisms in real hospital wastewater by electro-peroxone process.
Herein, a highly efficient electro-peroxone (E-peroxone) process with graphite felt as ozone diffusion electrode (ODE) was developed for the synchronous removal of pharmaceutical contaminants and inactivation of pathogenic microorganisms in real hospital wastewater. Under optimal conditions, the total organic carbon (TOC) removal rate of real hospital wastewater could reach 93.9%. Importantly, 126 pharmaceutical compounds (antibiotics, antivirals, analgesics, antiepileptics, hormones, and others) were determined in hospital wastewater by using ultra performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). 110 pharmaceutical compounds could be efficiently degraded in E-peroxone system. Concurrently, the microbial community analysis through high-throughput sequencing showed that E-peroxone process exhibited an excellent disinfection effect in real hospital wastewater. Escherichia coli as a bacterial indicator could be completely inactivated in E-peroxone process·H2O2 and hydroxyl radical (OH) were found in E-peroxone system based on the results of chemical probe experiments and electron paramagnetic resonance (EPR) analysis. The in-situ generation of H2O2 from cathodic oxygen reduction in ODE can react with ozone to produce OH, and realize high efficiencies for the elimination of pharmaceutical and sterilization. This work established a green and effective way without extra addition of chemical reagents for high-efficiency treatment of real hospital wastewater.


Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer.
Thyroid nodules are detected in up to 60% of people by ultrasound examination. Most of them are benign nodules requiring only follow up, while about 4% are carcinomas and require surgery. Malignant nodules can be diagnosed by the fine-needle aspiration cytology (FNAC), which however yields an indeterminate result in about 30% of the cases. Testing for RAS mutations has been proposed to refine indeterminate cytology. However, the new entity of non-invasive follicular thyroid neoplasm, considered as having a benign evolution and frequently carrying RAS mutations, is expected to lower the specificity of this mutation. The aggressive behavior of thyroid cancer with RAS mutations, initially reported, has been overturned by the recent finding of the cooperative role of TERT mutations. Although some animal models support the carcinogenic role of RAS mutations in the thyroid, evidence that adenomas harboring these mutations evolve in carcinomas is lacking. Their poor specificity and sensitivity make the clinical impact of RAS mutations on the management of thyroid nodules with indeterminate cytology unsatisfactory. Evidence suggests that RAS mutation-positive benign nodules demand a conservative treatment. To have a clinical impact, RAS mutations in thyroid malignancies need not to be considered alone but rather together with other genetic abnormalities in a more general context.


Mechanism of acute inhalation toxicity of alkanes and aliphatic alcohols.
This study investigated the mechanism of non-specific toxicity of non-reactive volatile organic compounds by using data reported in the literature. Inhalation toxicity data, in terms of LC(50) for alcohols and alkanes in rodents, were examined in relation to their partitioning behaviour in the biological system. Regression analysis of the data showed that, after the elimination of the kinetic influence in the absorption process, lethal toxicity increases linearly with the octanol-air partition coefficient in a homologous series. Comparing this relationship with that for anaesthesia, it could be concluded that lethal toxicity of the test chemical series probably acts on the lipid bilayer plasma membrane through a non-specific biophysical mechanism similar to anaesthesia. The critical concentration hypothesis appears to be valid for lethal toxicity of the test series. It was also shown that toxicity data for the test series by other routes, namely oral, intraperitoneal and intravenous, give a similar toxicity-partition relationship to that by inhalation.


2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 11. Quinolylmethyl analogues with basic substituents conveying specificity.
A series of nine 2,4-diamino-5-[6-( or 7-)quinolylmethyl]pyrimidines has been prepared by condensations of quinolinecarboxaldehydes with beta-anilinopropionitriles, followed by treatment with guanidine. All compounds has basic or methoxy substituents at the 2- or 4-positions of the quinoline ring. All of the 6-quinolylmethyl derivatives were highly inhibitory against Escherichia coli dihydrofolate reductase (DHFR), provided that an 8-substituent was present in the quinoline ring. Those compounds that had basic substituents in the 2-position of the quinoline ring were also highly specific for bacterial dihydrofolate DHFR, relative to a vertebrate counterpart. Protonation on the quinoline ring nitrogen is a possible cause of specificity.


Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer.
There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P450 2D6 (CYP2D6) polymor-phisms. To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes. Eighty-two women were recruited. Seventy-eight completed CYP2D6 genotyping and were categorized into poor, intermediate (IM) and extensive or ultra metabolizer phenotypes. Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent. More than 70% of the women had an IM phenotype, 32% an extensive or ultra metabolizer phenotype, and 0% had a poor metabolizer phenotype. Regardless of genotype, more women opted for aromatase inhibitors. Overall, 80% of women completed 5 years of hormonal therapy. Five women developed recurrence, 3 contralateral breast cancer, 5 died, and 1 was diagnosed with a second primary cancer. Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype, though not statistically significant [P = 0.743, hazard ratio (HR): 1.441, 95% confidence interval (CI): 0.191 to 10.17 and P = 0.798, HR: 1.327, 95%CI: 0.172 to 9.915, respectively]. Women receiving aromatase inhibitors also appeared to have a better, but also nonsignificant, 5-year recurrence-free and overall survival (P = 0.253, HR: 0.368, 95%CI: 0.031 to 0.258 and P = 0.292, HR: 0.252, 95%CI: 0.005 to 4.951, respectively). The IM phenotype was highly prevalent but was not associated with clinical outcome.


Automated quantitative characterisation of retinal vascular leakage and microaneurysms in ultra-widefield fluorescein angiography.
Ultra-widefield fluorescein angiography (UWFA) is an emerging imaging modality used to characterise pathology in the retinal vasculature such as microaneurysms (MAs) and vascular leakage. Despite its potential value for diagnosis and disease surveillance, objective quantitative assessment of retinal pathology by UWFA is currently limited because it requires laborious manual segmentation by trained human graders. In this report, we describe a novel fully automated software platform, which segments MAs and leakage areas in native and dewarped UWFA images with retinal vascular disease. Comparison of the algorithm with human grader-generated gold standards demonstrated significant strong correlations for MA and leakage areas (intraclass correlation coefficient (ICC)=0.78-0.87 and ICC=0.70-0.86, respectively, p=2.1×10-7 to 3.5×10-10 and p=7.8×10-6 to 1.3×10-9, respectively). These results suggest the algorithm performs similarly to human graders in MA and leakage segmentation and may be of significant utility in clinical and research settings.


Highly transparent nonvolatile resistive memory devices from silicon oxide and graphene.
Transparent electronic memory would be useful in integrated transparent electronics. However, achieving such transparency produces limits in material composition, and hence, hinders processing and device performance. Here we present a route to fabricate highly transparent memory using SiO(x) as the active material and indium tin oxide or graphene as the electrodes. The two-terminal, nonvolatile resistive memory can also be configured in crossbar arrays on glass or flexible transparent platforms. The filamentary conduction in silicon channels generated in situ in the SiO(x) maintains the current level as the device size decreases, underscoring their potential for high-density memory applications, and as they are two-terminal based, transitions to three-dimensional memory packages are conceivable. As glass is becoming one of the mainstays of building construction materials, and conductive displays are essential in modern handheld devices, to have increased functionality in form-fitting packages is advantageous.


Understanding pathogenic Burkholderia glumae metabolic and signaling pathways within rice tissues through in vivo transcriptome analyses.
Burkholderia glumae is a causal agent of rice grain and sheath rot. Similar to other phytopathogens, B. glumae adapts well to the host environment and controls its biology to induce diseases in the host plant; however, its molecular mechanisms are not yet fully understood. To gain a better understating of the actual physiological changes that occur in B. glumae during infection, we analyzed B. glumae transcriptome from infected rice tissues using an RNA-seq technique. To accomplish this, we analyzed differentially expressed genes (DEGs) and identified 2653 transcripts that were significantly altered. We then performed KEGG pathway and module enrichment of the DEGs. Interestingly, most genes involved bacterial chemotaxis-mediated motility, ascorbate and trehalose metabolisms, and sugar transporters including l-arabinose and d-xylose were found to be highly enriched. The in vivo transcriptional profiling of pathogenic B. glumae will facilitate elucidation of unknown plant-pathogenic bacteria interactions, as well as the overall infection processes.


Intraperitoneal chromophore injections delay early-onset and rapid retinal cone degeneration in a mouse model of Leber congenital amaurosis.
Highly expressed in the retinal pigment epithelium (RPE), the RPE-specific 65-kDa (RPE65) enzyme is indispensable to generate 11-cis-retinal (11cRAL), a chromophore for rhodopsin and cone photopigments. RPE65 deficiency can lead to Leber congenital amaurosis type 2 (LCA2), in which the isomerization of photobleached all-trans-retinal into photosensitive 11cRAL is blocked, ultimately causing severe retinal dysfunction and degeneration. The related mouse models, which are constructed through gene knockout or caused by spontaneous mutations, morphologically present with early-onset and rapid retinal cone cells degeneration, including loss of short-wavelength-sensitive cone opsins (S-opsins) and mislocalization of medium-wavelength-sensitive cone opsins (M-opsins). Studies have shown that routine Rpe65 gene replacement therapy, mediated by an adeno-associated virus (AAV) vector, can restore RPE65 protein. However, AAV transfection and Rpe65 transgene expression require at least one to two weeks, and the treatment cannot fully block the early-onset cone degeneration. To determine the feasibility of delaying cone degeneration before gene therapy, we investigated the impact of 11cRAL treatment in an early-age LCA2 retinal degeneration 12 (rd12) mouse model. Similar to human patients, the mouse model carries a spontaneous mutation in the Rpe65 gene, which results in disrupted endogenous 11cRAL regeneration. We found that RPE65 deficiency did not notably affect rodent retinal vessels. Under red light illumination, the rd12 mice were intraperitoneally injected with exogenous 11cRAL from postnatal day (P) 14 to P21. Three days after the last injection, a notable recovery of retinal function was observed using scotopic and photopic electroretinograms. Using optical coherence tomography and histological analyses of the deficient retinas, we found changes in the thickness of the photoreceptor outer segment (OS); this change could be rescued by early 11cRAL treatment. In addition, the treatment notably preserved M- and S-opsins, both of which maintained appropriate localization inside cone cells, as shown by the wild-type mice. In contrast, the age-matched untreated rd12 mice were characterized by retinal S-opsin loss and M-opsin mislocalization from the photoreceptor OS to the inner segment, outer nuclear layer, or outer plexiform layer. Notably, 11cRAL treatment could not maintain retinal function for a long time. Ten days after the last injection, the rod and M-cone electroretinograms significantly decreased, and S-cone responses almost extinguished. Our findings suggest that early 11cRAL treatment is useful for restoring retinal function and rescuing morphology in the rd12 mouse model, and the early-onset and rapid cone degeneration can be delayed before gene therapy.


Protective effect of adult children's education on parental survival in China: Gender differences and underlying mechanisms.
This study investigates whether adult children's education has a protective effect on parental survival, using data from all waves (2010-2018) of the China Family Panel Studies. We exploited the exogenous temporal and geographical variations in the enforcement of the 1986 compulsory schooling laws in China to construct an instrumental variable (IV) for adult children's education. The IV estimates indicated that the law-induced higher education of adult children led to sizeable improvements in the likelihood of paternal survival, although it had no significant effect on maternal survival. The protective effect on paternal survival was mainly driven by better-educated daughters, while sons' education had only a modest positive effect on maternal survival. Further evidence suggested that such heterogeneity by the gender of adult children might mainly come through more informal caregiving from better-educated daughters to older fathers with a limited role played by financial support from adult children.


Differentiation of isomeric hydroxypyridine N-oxides using metal complexation and electrospray ionization mass spectrometry.
Differentiation between two isomers of hydroxypyridine N-oxide according to the metal cation adducts generated by electrospray ionization (ESI) was investigated for different metal cations, namely Mg(II), Al(III), Ca(II), Sc(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), besides the diatomic cation VO(IV). Protonated molecules of the isomeric hydroxypyridine N-oxides as well as the singly/doubly charged adducts formed from neutral or deprotonated ligands and a doubly/triply charged cation were produced in the gas phase using ESI, recording mass spectra with different metal ions for each isomer. While complex formation was successful for 2-hydroxypyridine N-oxide with trivalent ions, in the case of 3-hydroxypyridine N-oxide, only peaks related to the protonated molecule were present. On the other hand, divalent cations formed specific species for each isomer, giving characteristic spectra in every case. Hence, differentiation was possible irrespective of the metal cation utilized. In addition, quantum chemical calculations at the B3LYP/6-31+G(d,p) level of theory were performed in order to gain insight into the different complexation of calcium(II) with the isomers of hydroxypyridine N-oxide. The relative stability in the gas phase of the neutral complexes of calcium made up of two ligands, as well as the singly charged and doubly charged complexes, was investigated. The results of these calculations improved the understanding of the differences observed in the mass spectra obtained for each isomer.


The role of yoga in inflammatory markers.
Yoga is an ancient system for integrating the mind, body, and spirit. In the hatha yoga ashtanga tradition (the eight limb Patanjali Yoga), three of the limbs are meditation, breathwork (pranayama) and physical postures (asana), which are widely practised in yoga classes. The benefits of yoga for mental and physical health are rooted in the practice's origins: in yoga, stress is said to be the root of all diseases. The established fields of psychoneuroimmunology and immunopsychiatry study the interplay between the immune system and mood or mental states. This mini-review has shifted the emphasis from research that focuses on yoga's benefits for stress, the most commonly studied outcome of yoga research, to a summary of the research on the effects of yoga practices on the immune system. The current literature bears strong evidence for the benefits of yoga on the levels of circulating cortisol and classical inflammatory markers, such as C-reactive protein (CRP) and cytokines such as interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ). The evidence for other less studied markers, telomerase activity, β-endorphins, Immunoglobulin A (IgA) and brain-derived neurotrophic factor (BDNF) is also growing. This mini-review centres around the interplay between yoga and these markers in stress management and depression, vascular and immune function in the older population, cardiovascular and metabolic diseases, auto-immune diseases, breast cancer and pregnancy. Overall, the literature examined reveals the novelty of this field of research and sheds light on methodological challenges; however, it uncovers the potential for yoga to be used as adjuvant therapy in conditions with an inflammatory component.


Chloroplast DNA sequence from a miocene Magnolia species.
DNA has been successfully extracted from several samples of preserved tissue, the oldest so far reported originating from a 13,000-year-old ground sloth. Both severe damage to the preserved DNA, primarily due to oxidation of the pyrimidines, has prevented the acquisition of sequence data from ancient samples except in a few cases. We report here the extraction of DNA from fossil leaf samples from the Miocene Clarkia deposit (17-20 Myr old), the amplification of an 820-base pair (bp) DNA fragment from the chloroplast gene rbcL from a fossil of the genus Magnolia, and its subsequent sequencing. The sequence was verified by comparison with published and unpublished rbcL sequences. These results extend our ability to analyse ancient DNA and may open new avenues into problems in palaeobotany, biogeography, and in the calibration of mutation rates.


Effect of polyestradiol on lecithin: cholesterol acyltransferase in male and female rats.
The effects of two doses of polyestradiol phosphate of lecithin: cholesterol acyltransferase activity and on liver and plasma cholesterol levels have been studied on female and male rats. Both treatments increased the hepatic content of esterified cholesterol, but the LCAT activity expressed as a percentage of cholesterol esterification was unaltered. The progress of esterification was not affected by the administration of the hormone. The LCAT activity in terms of the initial rate of esterification was decreased by the high dose of estradiol. This decrease was associated with a reduction of free plasma cholesterol level, as there is a significant positive correlation between these two parameters. The findings suggest that the increased esterified cholesterol in liver of estradiol-treated rats ins not mediated by an alteration in the LCAT activity.


TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype.
Somatic gene mutations are key determinants of outcome in patients with myelodysplastic syndromes (MDS) and secondary AML (sAML). In particular, patients with TP53 mutations represent a distinct molecular cohort with uniformly poor prognosis. The precise pathogenetic mechanisms underlying these inferior outcomes have not been delineated. In this study, we characterized the immunological features of the malignant clone and alterations in the immune microenvironment in patients with TP53-mutant and wild-type MDS or sAML. Notably, PDL1 expression is significantly increased in hematopoietic stem cells of patients with TP53 mutations, which is associated with MYC upregulation and marked downregulation of MYC's negative regulator miR-34a, a p53 transcription target. Notably, patients with TP53 mutations display significantly reduced numbers of bone marrow-infiltrating OX40+ cytotoxic T cells and helper T cells, as well as decreased ICOS+ and 4-1BB+ natural killer cells. Further, highly immunosuppressive regulatory T cells (Tregs) (ie, ICOShigh/PD-1-) and myeloid-derived suppressor cells (PD-1low) are expanded in cases with TP53 mutations. Finally, a higher proportion of bone marrow-infiltrating ICOShigh/PD-1- Treg cells is a highly significant independent predictor of overall survival. We conclude that the microenvironment of TP53 mutant MDS and sAML has an immune-privileged, evasive phenotype that may be a primary driver of poor outcomes and submit that immunomodulatory therapeutic strategies may offer a benefit for this molecularly defined subpopulation.


Effects of different small HSPB members on contractile dysfunction and structural changes in a Drosophila melanogaster model for Atrial Fibrillation.
The most common clinical tachycardia, Atrial Fibrillation (AF), is a progressive disease, caused by cardiomyocyte remodeling, which finally results in contractile dysfunction and AF persistence. Recently, we identified a protective role of heat shock proteins (HSPs), especially the small HSPB1 member, against tachycardia remodeling in experimental AF models. Our understanding of tachycardia remodeling and anti-remodeling drugs is currently hampered by the lack of suitable (genetic) manipulatable in vivo models for rapid screening of key targets in remodeling. We hypothesized that Drosophila melanogaster can be exploited to study tachycardia remodeling and protective effects of HSPs by drug treatments or by utilizing genetically manipulated small HSP-overexpressing strains. Tachypacing of Drosophila pupae resulted in gradual and significant cardiomyocyte remodeling, demonstrated by reduced contraction rate, increase in arrhythmic episodes and reduction in heart wall shortening, compared to normal paced pupae. Heat shock, or pre-treatment with HSP-inducers GGA and BGP-15, resulted in endogenous HSP overexpression and protection against tachycardia remodeling. DmHSP23 overexpressing Drosophilas were protected against tachycardia remodeling, in contrast to overexpression of other small HSPs (DmHSP27, DmHSP67Bc, DmCG4461, DmCG7409, and DmCG14207). (Ultra)structural evaluation of the tachypaced heart wall revealed loss of sarcomeres and mitochondrial damage which were absent in tachypaced DmHSP23 overexpressing Drosophila. In addition, tachypacing induced a significant increase in calpain activity, which was prevented in tachypaced Drosophila overexpressing DmHSP23. Tachypacing of Drosophila resulted in cardiomyocyte remodeling, which was prevented by general HSP-inducing treatments and overexpression of a single small HSP, DmHSP23. Thus, tachypaced D. melanogaster can be used as an in vivo model system for rapid identification of novel targets to combat AF associated cardiomyocyte remodeling.


Immunocytochemical localization of human papilloma virus and cytomorphologic correlation in smears and biopsies of cervical flat condylomata.
The cytomorphologic features in cervical biopsies and smears associated with human papilloma virus antigen (Ag) expression as demonstrated by immunoperoxidase staining techniques are presented. There was good concordance between cytology and biopsy results with respect to immunoperoxidase staining for human papilloma virus Ag. Cytomorphologic scoring of low-grade lesions (cervical intraepithelial neoplasias, grades O and I) showed atypical mitoses, macronucleated koilocytes, superficial cell keratohyaline granules, and multinucleation to be more frequent in Ag+ biopsy specimens. Chronic inflammation was more evident in Ag- biopsy specimens (P less than 0.05). Parakeratosis was more frequent in Ag+ cytologic specimens. Koilocytosis was not a reliable indicator of Ag expression in either preparation. Human papilloma virus (HPV) Ag testing by immunoperoxidase techniques appears to be a useful adjunct for screening low-grade atypias of the cervix.


Synthetic Protein Switches: Theoretical and Experimental Considerations.
Synthetic protein switches with tailored response functions are finding increasing applications as tools in basic research and biotechnology. With a number of successful design strategies emerging, the construction of synthetic protein switches still frequently necessitates an integrated approach that combines detailed biochemical and biophysical characterization in combination with high-throughput screening to construct tailored synthetic protein switches. This is increasingly complemented by computational strategies that aim to reduce the need for costly empirical optimization and thus facilitate the protein design process. Successful computational design approaches range from analyzing phylogenetic data to infer useful structural, biophysical, and biochemical information to modeling the structure and function of proteins ab initio. The following chapter provides an overview over the theoretical considerations and experimental approaches that have been successful applied in the construction of synthetic protein switches.


Reconstruction of the epispadiac penis in adolescents.
Now that reconstructive surgery has taken the exstrophy and epispadias patient beyond the stage of merely saving life and even preserving bladder function, it is essential that proper attention is paid to the penis. Careful surgery in early life may well give a good cosmetic appearance during the important years of schooling. It may also produce a penis with a satisfactory angle of erection for sexual intercourse. In those patients who are not so fortunate in infancy or who were born before the era of modern reconstructive surgery, careful assessment must be made at an appropriate time as the patient goes through puberty. The commonest erectile deformity found in epispadias in adult life is tight dorsal chordee. Surgical correction is required. In some patients, adequate correction will be achieved by clearance of superficial pericorporeal scar tissue, possibly aided by Nesbit's procedure. For the remainder, formal correction of the chordee is required. This is best done by the insertion of a gusset of dura or other material to lengthen the concave side of the curve.


Unfractionated heparin reduces hepcidin levels in critically ill patients.
A strong anti-hepcidin activity has been observed in heparins. Mean hepcidin levels were significantly reduced compared to baseline, following the first day of unfractionated heparin administration in critically patients. Heparin displayed a strong independent negative association with hepcidin. These results may lead to future treatment methods of forms of anaemia characterised by hepcidin excess, common among the critically ill.


(Anthracen-9-ylmeth-yl)benzyl-ammonium chloride.
In the title compound, C(22)H(20)N(+)·Cl(-), the anthracene system makes a dihedral angle of 72.65 (4)° with the benzene ring. The C-N-C-C torsion angles in the chain connecting the benzene ring and anthracene system are 52.24 (15) and -170.73 (11)°. The crystal structure is stabilized by inter-molecular N-H⋯Cl and C-H⋯Cl hydrogen bonds, which link the mol-ecules into tetra-mers about inversion centers.


Prospective evaluation of the point-of-care use of a rapid antigenic SARS-CoV-2 immunochromatographic test in a paediatric emergency department.
This study aimed to evaluate the immunochromatographic coronavirus disease 2019 (COVID-19) speed antigen test (BioSpeedia, France) as an antigen point-of-care test (AgPOCT) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the paediatric emergency department of the University Hospital of Saint-Etienne in France. Between 15 January and 28 May, 2021, children presenting with respiratory symptoms compatible with COVID-19 infection (symptomatic group) or those requiring hospitalization for any reason (asymptomatic group) were included prospectively and received a nasopharyngeal aspiration to carry out both AgPOCT and quantitative reverse transcription (RT) PCR (RT-qPCR) tests, with the latter being used as the reference standard, for the diagnosis of SARS-CoV-2 infection. Among the 1009 enrolled children, we obtained a result from both techniques for 990: 33 (3.3%) tested positive with AgPOCT and 46 (4.6%) with RT-qPCR. The overall sensitivity and specificity of the AgPOCT were 69.6% (95% confidence interval (CI), 54.3-82.3) and 99.9% (95% CI, 99.4-100), respectively, compared with the RT-qPCR. Sensitivity increased to 82.9% (95% CI, 66.4-93.4) in symptomatic children. The mean cycle threshold value was significantly lower in positive samples for AgPOCT than in negative samples in the overall population and in both the symptomatic and asymptomatic groups. The use of the COVID-19 speed antigen test at the bedside in the emergency department has satisfactory performance for diagnosing SARS-CoV-2 infection in symptomatic children.


A mathematical approach to the analysis of diversity in antibody gene families.
In this article, we develop a mathematical approach for the analysis of diversity in antibody gene families. This approach is arrived at by examing two general questions about protein populations: (1) What is a relative measure of the diversity exhibited by one protein family when compared with a second? (2) What is the probability that two protein populations were derived from a single common population? These quantitative approaches permit a variety of precise evolutionary, genetic, and developmental questions to be asked of antibody gene families. Using this methodology, we demonstrate that the diversity in mouse K-immunoglobulin chains is considerably greater than in their human K counterparts. We also show that the variable (Vl) regions of light chains associated with IgG and IgA immunoglobulins in the mouse appear to have been derived from a common population of Vl genes. This approach also can be used to analyse sequence data from other informational multigene families.


Nontrivial nonradiating all-dielectric anapole.
Dynamic anapole is a promising element for future nonradiating devices, such as cloaked sources and sensors, quantum emitters, and especially the sources for observing dynamic Aharonov-Bohm effect. However, the anapole response can be damped by the Joule losses. In this paper we theoretically propose and experimentally demonstrate a novel type of active all-dielectric source, which is in some sense, realizes the elementary anapole of Afanasiev, and study its radiative/nonradiative regimes in the microwave range.


A putative SOS repair gene (dinF-like) in a hyperthermophilic archaeon.
The hyperthermophilic archaeon, Pyrococcus (strain IFREMER AL585), contains an ORF that encodes a polypeptide with a high similarity to the Escherichia coli dinF (DNA damage-inducible) gene product. The conservation of this protein between Archaea and Bacteria suggests that a SOS repair system might operate in Archaea.


Pediatric Walking Speed Normal Reference Values in a Local Population.
This study's aim was to develop a local walking speed norm using the 10-m walk test (10MWT) for 5- to 17-year-old children and youth who are developing typically. Healthy child and adolescent participants were recruited from schools in one rural Alaska school district. The 10MWT was performed using a 2 repetitions per speed protocol. Outcome measures were average time for the normal and fast-speed trials, separated by age and gender. Average walking speed was established in this group of children and youth who are developing typically by age and gender. Local walking speed norms for 5- to 17-year-olds can be accurately obtained by examining students in a rural school district.


Effect of glucose, maltose, soluble starch, and CO2 on the growth of the hyperthermophilic archaeon Pyrococcus furiosus.
The hyperthermophilic archaeon Pyrococcus furiosus was cultivated in batch and continuous fermentations on different carbon substrates. The cultivation of P furiosus on soluble starch as the only carbon source resulted in cell densities three times higher than in cultivations on maltose, 1.06 x 10(10) cells/ml compared to 3.4 x 10(9) cells/ml. The yield coefficient, Y(x/y) = 0.12 g/g, and the growth rate, mu = 0.33 h(-1), were almost equal on soluble starch and on maltose, but on glucose no growth could be detected. An inhibitory effect of glucose, when added to other carbon substrates, also could not be found. Isobutyric and isovaleric acid were detected as novel metabolites produced by P. furiosus. Inhibitory effects of these acids, as well as of the well-known products acetic acid, propionic acid, and alanine, could be precluded. Concentrations of 10% CO2 in the gas supply respective to the exhaust gas enhanced the growth of P furiosus significantly. The maximum cell number was two orders of magnitude higher than was observed with pure nitrogen. Further increase of the CO2 concentration up to 100% had no significant effect on the growth of P. furiosus.


Use it or lose it: how neurogenesis keeps the brain fit for learning.
The presence of new neurons in the adult hippocampus indicates that this structure incorporates new neurons into its circuitry and uses them for some function related to learning and/or related thought processes. Their generation depends on a variety of factors ranging from age to aerobic exercise to sexual behavior to alcohol consumption. However, most of the cells will die unless the animal engages in some kind of effortful learning experience when the cells are about one week of age. If learning does occur, the new cells become incorporated into brain circuits used for learning. In turn, some processes of learning and mental activity appear to depend on their presence. In this review, we discuss the now rather extensive literature showing that new neurons are kept alive by effortful learning, a process that involves concentration in the present moment of experience over some extended period of time. As these thought processes occur, endogenous patterns of rhythmic electrophysiological activity engage the new cells with cell networks that already exist in the hippocampus and at efferent locations. Concurrent and synchronous activity provides a mechanism whereby the new neurons become integrated with the other neurons. This integration allows the present experience to become integrated with memories from the recent past in order to learn and predict when events will occur in the near future. In this way, neurogenesis and learning interact to maintain a fit brain.


Molecular characterization and functional analysis of two phospholipid hydroperoxide isoforms from Larimichthys crocea under Vibrio parahaemolyticus challenge.
Glutathione peroxidases family is a key role in the antioxidant system in oxybiotic organisms for cell redox homeostasis. One of their members, phospholipid hydroperoxide glutathione peroxidase (GPx4) have unique monomeric structure and can directly react with complex lipid and membrane-bound peroxides under the presence of glutathione(GSH). In this paper, two complete GPx4 cDNAs (designated as LcGPx4a and LcGPx4b) from Larimichthys crocea are identified by rapid amplification of cDNA ends. The cDNA of LcGPx4a was consisted of a 5'-untranslated region (UTR) of 258 bp, a 3'-UTR of 330 bp, and an open reading frame (ORF) of 561 bp encoding 186 amino acid (aa) polypeptides. And the full-length sequence of LcGPx4b was 1164 bp with a 5'-UTR of 34 bp, a 3'-UTR of 551 bp and an ORF of 576 bp encoding a polypeptide of 191 aa residues with a predicted signal peptide of 15 aa. The characteristic selenocysteine insertion (SECIS) sequence was detected in the 3'UTR of the two sequences with 78 bp in length. The conserved active site of selenocysteine (Sec) encoded by TGA was also identified and formed a tetrad functional structure with glutamine, tryptophan, and asparagine in LcGPx4a and LcGPx4b. Two signature site motifs ("LRILAFPSNQFGNQEPG" and "LRILGFPCNQFGGQEPG") were both conserved in the deduced amino acid of LcGPx4a and LcGPx4b. The genomic structure analysis revealed that the two sequences both had 7 exons and 6 introns, and the Sec opal codon and SECIS element were located at the third and seventh exons, respectively. LcGPx4a and LcGPx4b both have a wide distribution in 9 tissues with various relative expression levels and a highest expression pattern in the liver. Under Vibrio parahaemolyticus challenge, their relative expression levels were altered in the liver, spleen, kidney, and head kidney but with different magnitudes and response time. LcGPx4a and LcGPx4b showed a significantly up-regulated trend in the spleen during experimental period. Above results suggested that LcGPx4a and LcGPx4b were two conserved immune molecules and might play a role in the immune response of fish with a tissue-depemdent manners.


Differences in Size Between Unruptured and Ruptured Saccular Intracranial Aneurysms by Location.
It is generally accepted that larger saccular intracranial aneurysms are at greater risk to rupture. We investigated whether aneurysm location influences the effect of aneurysm size on the propensity of rupture. We reviewed patient and aneurysm characteristics in a consecutive series of patients with unruptured and ruptured aneurysms presenting to our institution between 2006 and 2018. Differences between unruptured and ruptured aneurysms at different locations were subsequently investigated. A total of 766 aneurysms in 568 patients were included, with 355 and 411 unruptured and ruptured aneurysms, respectively. There were significant differences in the distribution of aneurysm location between unruptured and ruptured aneurysms (P < 0.001). The most common locations of unruptured aneurysms were the middle cerebral artery (MCA) (27.6%) and paraclinoid internal carotid artery (ICA) (25.4%), whereas the most common locations of ruptured aneurysms were the anterior communicating artery (ACOM) (34.8%) and posterior communicating artery (17.8%). Ruptured aneurysms were larger than unruptured aneurysms at all locations except at the ACOM, where there was no difference in size between unruptured and ruptured aneurysms (5.4 vs. 5.8 mm, respectively; P = 0.40). Ruptured ACOM aneurysms were also smaller than ruptured aneurysms of the paraclinoid ICA (5.8 vs. 10.3 mm; P < 0.001), MCA (5.8 vs. 8.0 mm; P = 0.021), and basilar apex (5.8 vs. 10.5 mm; P < 0.001), respectively. We observed no difference in size between unruptured and ruptured ACOM aneurysms, possibly suggesting a greater susceptibility for ACOM aneurysms to rupture at smaller sizes.


Retrieval of Entrapped Catheter-Mounted Axial Flow Pump From Mitral Subvalvular Apparatus Using a Snare Catheter.
Axial-flow ventricular assist devices are being increasingly used to support hemodynamically compromised patients undergoing percutaneous coronary intervention. Periprocedural valvular complications have been recognized in a few case reports. We present a unique case of entanglement of the Impella within he mitral subvalvular apparatus, retrieved successfully using a snare under fluoroscopic guidance. (Level of Difficulty: Advanced.).


Progress in 3-D treatment planning for photon beam therapy.
The purpose of this report is to study the feasibility of improving dose distributions using non-coplanar photon beams from a linear accelerator. Non-coplanar beams may enter the patient in any arbitrary configuration. This type of treatment technique requires a three-dimensional (3-D) planning system. Clinical examples are used to illustrate the general problems in 3-D treatment planning, and the potential improvement over coplanar beam treatments. Features of a treatment planning system for 3-D planning are discussed.


Breast cancer imaging with radiolabelled peptide from complementarity-determining region of antitumour antibody.
Specific tumour imaging with radiolabelled monoclonal antibodies has been extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasation, catabolism by the reticuloendothelial system, and non-specific uptake of macromolecules such as antibodies. We have tried to overcome some of the problems associated with monoclonal antibodies while retaining their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-chain complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity against the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin, detected by the parent antibody. The peptide was radiolabelled with technetium-99m and injected intravenously to image malignant lesions in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shortly after administration of alpha M2, and was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful imaging was achieved in 14 of 15 primary tumour sites and all of eight local recurrences. Five of six metastases in the opposite breast, eight of 15 metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph nodes were imaged. Metastatic sites in the lungs, mediastinum, chest wall, and liver were poorly visualised because of background cardiac blood pool. alpha M2 detected small lesions ( < 2 cm) as efficiently as larger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observed. Specific tumour targeting with the radiolabelled anticancer peptide alpha M2 offers new opportunities for breast cancer imaging and possibly therapy.


The influence of alcohol on the outcome of automated static perimetry.
It is well known that perimetric findings fluctuate within a single examination. There is additional fluctuation between perimetric examinations. The cause of this fluctuation is not yet fully understood, but such things as changes in attention, patient cooperation, or drugs have been discussed. To study such possible factors, we carried out perimetry on subjects who had consumed alcohol and who had not. The results indicate that alcohol, at a blood concentration of approximately 0.08%, barely influences the results of static automated perimetry. Differential light sensitivity remained unchanged by alcohol at all eccentricities tested. A decrease in the ability to cooperate was manifested by a significant higher score of false-positives in catch trials. There was also a tendency toward an increase in false-negative responses in catch trials, an increase in the number of stimuli presentations required, and higher short-term fluctuation. Lack of the influence of alcohol on the differential light threshold does not necessarily mean that alcohol has no influence on visual function. It indicates, however, that differential light sensitivity, as measured with the automated perimeter Octopus, is not influenced by moderate alcohol ingestion.


Motorcyclist rear brake simple perception-response times in rear-end collision situations.
The purpose of this study was to determine the baseline motorcycle riders' perception-response times (PRTs) in an expected object braking task and to determine the significant difference between PRTs of older and younger riders. Fifty-nine participants sat on their motorcycles in exactly the same way as they would when riding and then they awaited activation of the taillights of the passenger car (parked) in front of them. PRTs of the motorcyclists were transcribed from the camcorder when the riders hit the brakes as quickly as possible following the activation of the car's brake lights. Results of PRT were calculated by taking the average of both male and female older and younger riders. The study demonstrates that the mean and standard deviation of the motorcycle baseline PRTs are 0.44 and 0.11 s, respectively. Riders' age and gender were not found to be significant variables for PRT. The mean of baseline perception-reaction time of motorcycle riders is smaller than that of passenger car drivers. If traffic facilities are designed based on passenger car drivers' simple perception-reaction times where drivers are generally more alert (for example, in traffic signal design), they can provide the required PRT for motorcyclists. This suggests that the utilization of more powerful brake lights on motorcycles could be highly effective for preventing rear-end motorcycle collisions.


Investigating the chemical profile of Rheum lhasaense and its main ingredient of piceatannol-3'-O-β-D-glucopyranoside on ameliorating cognitive impairment.
Rheum lhasaense A. J. Li et P. K. Hsiao, a stout herb plant from the Polygonaceae, is a typical Tibetan folk herb with heat-clearing and detoxifying effects, but does not have the typical laxative effect compared with other rhubarb plants. Nevertheless, its chemical composition and pharmacological activities still lack in-depth research. The present study endeavored to analyze the possible phytochemical constituents in R. lhasaense and explore the main compound piceatannol-3'-O-β-D-glucopyranoside (PG) effect on cognitive impairment and its underlying mechanism. The chemical profile of R. lhasaense discovered 46 compounds, including 27 stilbenoids and 13 gallotannins using UPLC-Q-TOF-MS/MS. The UPLC determined the contents of 6 main stilbenoids, among which the content of PG was the highest, up to 61.06 mg/g. Moreover, behavioral tests showed that PG (40 mg/kg and 160 mg/kg) administration markedly ameliorated memory impairments of scopolamine-induced mice. Biochemical parameters showed that PG treatment alleviated the levels of Ach, AchE, and inflammatory factors while elevating the levels of antioxidants in mice. In addition, network pharmacology was performed to reveal PG exert an mild cognitive impairment effect by participating in neurodegenerative disease pathways, proliferation and apoptosis-, and inflammation-related pathways. Eventually, the results of molecular docking and the qRT-PCR revealed that PG down-regulated the mRNA expressions of MMP3, MMP9 and BACE1 in cognitive impairment mice brain tissue. In conclusion, our results demonstrated that PG mitigated scopolamine-induced cognitive dysfunction in mice by targeting the BACE1-MMP3/9 pathway, and PG might be a promising mild AD drug candidate.


Nasopharyngeal electrodes in temporal lobe epilepsy: A reappraisal of their diagnostic utility.
To compare electroencephalography (EEG) recordings with nasopharyngeal electrodes (NPEs) plus anterior temporal electrodes (ATEs) (NPE recordings) and those with only ATEs (non-NPE recordings) for the detection of interictal epileptiform discharges (IEDs) in patients with suspected temporal lobe epilepsy (TLE). We retrospectively analyzed the initial EEGs of 229 patients that were recorded simultaneously with ATEs and NPEs in addition to the electrodes of the 10-20 system of electrode placement. Two data sets of NPE and non-NPE recordings were reviewed independently by three interpreters with differing degrees of experience. Discordant findings in the interpretation among the three interpreters were resolved by a consensus to yield final results. IEDs were detected in 76.4% of patients with NPE recordings compared to 55.5% with non-NPE recordings (p < 0.01). Bilateral independent IEDs were found in 26.2% and 11.4% of EEGs with NPE and non-NPE recordings (p < 0.01). The degree of agreement for the detection of IEDs among the three interpreters was higher with the NPE than with non-NPE recordings (κappa score, 0.70 vs. 0.54). The increased diagnostic yield of NPE recordings for the detection of IEDs was particularly prominent in patients with mesial and non-lesional TLEs. EEG recordings using NPEs are useful to improve the sensitivity and level of agreement among interpreters for the detection of IEDs in patients with TLE. NPE recordings may be recommended in routine EEGs for the evaluation of patients with suspected TLE.


Re-Evaluating the Effect of Preoperative Tranexamic Acid on Blood Loss and Field Quality During Rhinoplasty: A Randomized Double-Blinded Controlled Trial.
Nowadays, minimizing the surgical complications of rhinoplasty has gained more importance. Results from previous trials show that Tranexamic acid (TXA) reduces intraoperative bleeding, one of the major complicating factors during rhinoplasty. To contribute to previous evidence by re-evaluating the efficacy of TXA, specifically in reducing intraoperative blood loss and increasing surgical field quality in rhinoplasty. A randomized placebo-controlled trial was conducted (IRCT20111219008458N2). The outcomes included total intraoperative blood loss, measured by the total volume of fluid collected by suction and gauzes, subtracted by volume of used irrigation fluids, and the quality of surgical field, measured by surgeon's satisfaction on a 5-point Likert scale. Demographics, blood coagulation measures, and clinical data were also collected and were held as covariates in analysis. After blinding, randomization, and group allocations, the intervention group received TXA 10mg/kg and the placebo group normal saline in equal volumes. Data of a total of 80 patients were gathered and analyzed. The total intraoperative blood loss was insignificantly lower (mean difference [95% CI]: - 3.6 ( - 19.19, 11.99), P = 0.65) and surgeon's satisfaction was insignificantly higher (mean difference [95% CI]: 0.18 ( - 0.11, 0.46), P = 0.22) in TXA group. Results were confirmed by multivariable analysis. In contrast to most of the previous studies, this study showed only a statistically insignificant decrease in total intraoperative blood loss in patients receiving TXA compared to placebo. Further studies are required to more precisely estimate the efficacy of TXA in reducing blood loss during rhinoplasty. LEVEL I, RANDOMIZED CONTROLLED TRIAL.: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


What types of degenerative lumbar pathologies respond to nerve root injection? A retrospective review of six hundred and forty one cases.
Peri-radicular injection is a widely used procedure for treating lumbar radicular pain, but it remains unclear what types of lumbar pathologies respond well to this treatment. We aimed to investigate the efficacy of peri-radicular injection for degenerative lumbar disorders and to determine what types of pathologies respond well to this treatment. We reviewed the records of 641 consecutive patients who underwent peri-radicular injection for degenerative lumbar pathologies with mean follow-up of 23.4 months. The pathologies included herniated disc in 286 patients, spinal stenosis in 141, degenerative spondylolisthesis in 136, failed back surgery in 24, isthmic spondylolisthesis in 22, degenerative scoliosis in 18, and foraminal stenosis in 14. Outcome measure was whether or not surgery is avoided by using peri-radicular injection. The rate of obviating surgery was determined in each pathology. Peri-radicular injection obviated surgeries in 331 patients (51.7%). There were no complications related to the procedure, including neurological deterioration, infection, and haematoma. The rate of obviating surgery was 42.0% in disc herniation, 52.9% in degenerative spondylolisthesis, 67.4% in spinal stenosis, 54.5% in isthmic spondylolisthesis, 57.1% in foraminal stenosis, 61.1% in degenerative scoliosis and 54.1% in failed back surgery. Poor outcomes were observed in herniated disc with spinal stenosis (17.9% success), foraminal disc herniation (33.3%), recurrent disc herniation (18.2%) and failed back surgery with instability (33.3%). This study demonstrated that 51.7% of patients with degenerative lumbar pathologies were successfully treated by peri-radicular injection. Efficacy was limited in cases of herniated disc with spinal stenosis, foraminal disc herniation, recurrent disc herniation and failed back surgery with instability.


Segmentation and quantification of infarction without contrast agents via spatiotemporal generative adversarial learning.
Accurate and simultaneous segmentation and full quantification (all indices are required in a clinical assessment) of the myocardial infarction (MI) area are crucial for early diagnosis and surgical planning. Current clinical methods remain subject to potential high-risk, nonreproducibility and time-consumption issues. In this study, a deep spatiotemporal adversarial network (DSTGAN) is proposed as a contrast-free, stable and automatic clinical tool to simultaneously segment and quantify MIs directly from the cine MR image. The DSTGAN is implemented using a conditional generative model, which conditions the distributions of the objective cine MR image to directly optimize the generalized error of the mapping between the input and the output. The method consists of the following: (1) A multi-level and multi-scale spatiotemporal variation encoder learns a coarse to fine hierarchical feature to effectively encode the MI-specific morphological and kinematic abnormality structures, which vary for different spatial locations and time periods. (2) The top-down and cross-task generators learn the shared representations between segmentation and quantification to use the commonalities and differences between the two related tasks and enhance the generator preference. (3) Three inter-/intra-tasks to label the relatedness discriminators are iteratively imposed on the encoder and generator to detect and correct the inconsistencies in the label relatedness between and within tasks via adversarial learning. Our proposed method yields a pixel classification accuracy of 96.98%, and the mean absolute error of the MI centroid is 0.96 mm from 165 clinical subjects. These results indicate the potential of our proposed method in aiding standardized MI assessments.


Societal burden of stroke rehabilitation: Costs and health outcomes after admission to stroke rehabilitation.
To estimate societal costs and changes in health-related quality of life in stroke patients, up to one year after start of medical specialist rehabilitation. Observational. Consecutive patients who received medical specialist rehabilitation in the Stroke Cohort Outcomes of REhabilitation (SCORE) study. Participants completed questionnaires on health-related quality of life (EuroQol EQ-5D-3L), absenteeism, out-of-pocket costs and healthcare use at start and end of rehabilitation and 6 and 12 months after start. Clinical characteristics and rehabilitation costs were extracted from the medical and financial records, respectively. From 2014 to 2016 a total of 313 stroke patients completed the study. Mean age was 59 (standard deviation (SD) 12) years, 185 (59%) were male, and 244 (78%) inpatients. Mean costs for inpatient and outpatient rehabilitation were US$70,601 and US$27,473, respectively. For inpatients, utility (an expression of quality of life) increased significantly between baseline and 6 months (EQ-5D-3L 0.66-0.73, p = 0.01; visual analogue scale 0.77-0.82, p < 0.001) and between baseline and 12 months (visual analogue scale 0.77-0.81, p < 0.001). One-year societal costs from after the start of rehabilitation in stroke patients were considerable. Future research should also include costs prior to rehabilitation. For inpatients, health-related quality of life, expressed in terms of utility, improved significantly over time.


Cholesterol feeding to rats does not modulate the expression of binding sites for HDL on liver membranes.
The binding of HDL, Apo-E-free, was studied in rats fed a cholesterol rich diet for 2, 4 and 7 days. Plasma cholesterol increased up to 16-fold (from 55 to 900 mg/dl); liver cholesterol was also raised, from 0.5 to 16 mg/g of tissue. The HDL binding to membrane preparations was not affected while the binding of beta VLDL was reduced to about 50% of the controls. These data show, therefore, that liver binding sites for HDL are refractory to regulation by dietary cholesterol.


[Corneal lesions in ichthyosis (author's transl)].
The authors report about observations they made in two sisters. One sister showed a fibroid degeneration of the cornea, the other a band-shaped keratopathy respectively, together with an ichthyosis and an alopecia as a result of capillary fractures due to pili torti. An autosomal recessive hereditary transmission could be determined. The cutaneous lesion is either an ichthyosis vulgaris, the hereditary transmission of which could not yet be confirmed, or it is a transition form of ichthyosis vulgaris and congenita.


Synergistic anticonvulsant effect of valproic acid and ethosuximide on pentylenetetrazole-induced epileptic phenomena in rats.
The possible synergistic effect of valproic acid and ethosuximide in combination on pentylenetetrazole-induced epilepsy was investigated in rats. Valproic acid and ethosuximide administered intraperitoneally both showed dose-dependent anti-epileptic activity towards pentylenetetrazole-induced myoclonias and tonic-clonic seizures. The valproic acid-ethosuximide combination had a synergistic pharmacological effect. Against myoclonias combined valproic acid-ethosuximide produced a non-significant decrease in the effective dose of both drugs compared with treatment with either drug alone. In the case of tonic-clonic seizures the protective effect against the seizures was significantly increased by combined treatment compared with treatment with either drug alone. Neither plasma concentrations nor any other pharmacokinetic parameters were significantly changed when the same doses of valproic acid and ethosuximide were given, singly or in combination.


Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation.
Postconditioning (PostC) modifies the early post-ischemic pH, redox environment, and activity of enzymes. We hypothesized that early acidosis in PostC may affect superoxide dismutase (SOD) and catalase (CAT) activities, may reduce 3-nitrotyrosine (3-NT) protein levels, and may increase S-nitrosylated (SNO) protein levels, thus deploying its protective effects. To verify this hypothesis, we studied the early (7(th) min) and late (120(th) min) phases of reperfusion (a) endogenous SOD and CAT activities and (b) 3-NT protein levels and SNO protein levels. Isolated rat hearts underwent 30-min ischemia/120-min reperfusion (I/R) or PostC (5 cycles of 10-s I/R at the beginning of 120-min reperfusion) either with or without exogenous CAT or SOD infused during the initial 3 min of reperfusion. The effects of early reperfusion with acid buffer (AB, pH 6.8) on endogenous antioxidant enzymes were also tested. Pressure, infarct size, and lactate dehydrogenase release were also measured. At the 7(th) min, PostC induced a significant decrease in SOD activity with no major change both in Mn and Cu/Zn SOD levels and in CAT activity and level. PostC also reduced 3-NT and increased SNO levels. Exogenous SOD, but not CAT, abolished PostC cardioprotection. In late reperfusion (120-min), I/R increased SOD activity but decreased CAT activity and Cu/Zn SOD levels; these effects were reversed by PostC; 3-NT was not affected, but SNO was increased by PostC. AB reproduced PostC effects on antioxidant enzymes. The conclusions are as follows: PostC downregulates endogenous SOD and preserves CAT activity, thus increasing SNO and reducing 3-NT levels. These effects are triggered by early post-ischemic acidosis. Yet acidosis-induced SOD downregulation may limit denitrosylation, thus contributing to PostC triggering. Hence, exogenous SOD, but not CAT, interferes with PostC triggering. Prolonged SOD downregulation and SNO increase may contribute to PostC and AB beneficial effects.


Primary Prevention of Prescription Drug Misuse Among Culturally and Linguistically Diverse Suburban Communities.
Comprehensive strategies for prescription drug misuse must reach culturally and linguistically diverse suburban populations to effectively combat the ongoing opioid epidemic. The purpose of this study was to conduct a community needs assessment and inform the development and implementation of culturally appropriate primary prevention strategies for community-based interventions, specifically related to medication disposal practices. Three data collection techniques were utilized: key informant interviews (n = 4), intercept surveys (n = 71), and focus group discussions (n = 8; 61 participants). To accommodate linguistically diverse subpopulations, surveys and focus groups were available in English, Spanish, Arabic, Russian, and Hindi. Participants were overwhelmingly female (survey: 70%/FGD: 84%), ethnic minorities (survey: 61%/FGD: 66%), and, on average, middle-aged [survey: 52 years (SD: 19)/FGD: 54 (15)]. Approximately one in three survey respondents (30%) had heard of drug-take back events, and one in ten (10%) had participated. Non-English speakers were less likely to both perceive a community problem with prescription drugs (β = - .35; p < .001) and be aware of take-back opportunities (β = - .23; p = .038). Focus group participants expressed confusion about appropriate medication disposal methods, identifying potential sources of conflicting information. Recent media coverage and political events have heightened stigma towards non-English speaking and non-native peoples, increasing their fear of law enforcement and other perceived threats. To encourage community engagement in take-back events, we identified multiple ways, such as multilingual materials and marketing campaigns, which may help marginalized suburban subpopulations feel less threatened and more included in prescription drug misuse prevention activities.


Review article: Population screening for colorectal cancer.
Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.


Portulaca oleracea seeds' extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats.
Acrylamide (ACR) is a widespread industrial and food contaminant that garnered considerable attention for its carcinogenic, neurotoxic, and reproductive toxic effects. The antioxidant effects of Portulaca oleracea seeds extract (POS) and its fertility-enhancing effects were inspiring to evaluate the protective potential and pinpoint the mechanisms and molecular targets of the UPLC-MS fingerprinted POS extract on ACR-induced testicular toxicity in rats. Male Wistar rats were divided into 6 equal groups of negative control, ACR model (10 mg/kg b.wt.), POS at doses of (200 and 400 mg/kg b.wt.) and POS-treated ACR groups. All treatments were given by oral dosing every day for 60 days. Administration of POS extract reversed the ACR-induced epididymides weight loss with improved semen quality and count, ameliorated the ACR-decreased testicular lesion scoring, testicular oxidative stress, testicular degeneration, Leydig cell apoptosis and the dysregulated PCNA and Caspase-3 expression in a dose-dependent manner. It upregulated the declined level of serum testosterone and the expression of steroidogenic genes such as CYP11A1 and 17β3-HSD with an obvious histologic improvement of the testes with re-establishment of the normal spermatogenic series, Sertoli and Leydig cells. The supplementation with POS extract may provide a potential protective effect for ACR-induced testicular dysfunction which is mediated by its antioxidant, antiapoptotic and steroidogenic modulatory effects.


Impact of the revised FIGO/WHO system on the management of patients with gestational trophoblastic neoplasia.
To study the effect of a change in disease scoring systems on the management of patients with gestational trophoblastic neoplasia (GTN) in our supra-regional treatment centre. We reviewed disease characteristics and treatment outcomes in 632 GTN patients managed at our centre from 1973 to 2006. Two disease scoring systems were used sequentially, the Sheffield modification of the Charing Cross Scoring System (SCCSS) before 2000, and the revised FIGO/modified WHO system (FIGO 2000) thereafter. Using the SCCSS 573 (90.7%) patients were classified as low risk (LR) and 59 (9.3%) as high risk (HR). With FIGO 2000, 587 (92.9%) were LR and 45 (7.1%) HR. For LR patients, the complete response (CR) to first line single agent chemotherapy was 77% before 2000 and 61.6% from 2000 to 2006. For HR patients, the CR rates with first line chemotherapy were 79.5% and 75% respectively. The higher threshold for assigning a patient as HR using FIGO 2000 had an impact on the success of treatment; only 7/19 patients (37%) who were scored 6 by FIGO 2000, and thus treated as LR with methotrexate/folinic acid, achieved a CR. In our experience, the revised FIGO/modified WHO scoring system has down scored some patients who would have been considered as high risk with the previous scoring system. A trend to lower CR with first line chemotherapy and an increase in the need for second line chemotherapy was seen.


The living-tissue microscope: the importance of studying stem cells in their natural, undisturbed microenvironment.
Advances in stem cell research highlight the importance of analysing multicellular interactions in vivo before modelling them in cell culture systems. Gain-of-function assays such as transplantation are useful, but are not equivalent to studying cells in their natural, undisturbed microenvironment.


Targeting GRP78 suppresses oncogenic KRAS protein expression and reduces viability of cancer cells bearing various KRAS mutations.
KRAS is the most commonly mutated oncogene in human cancers with limited therapeutic options, thus there is a critical need to identify novel targets and inhibiting agents. The 78-kDa glucose-regulated protein GRP78, which is upregulated in KRAS cancers, is an essential chaperone and the master regulator of the unfolded protein response (UPR). Following up on our recent discoveries that GRP78 haploinsufficiency suppresses both KRASG12D-driven pancreatic and lung tumorigenesis, we seek to determine the underlying mechanisms. Here, we report that knockdown of GRP78 via siRNA reduced oncogenic KRAS protein level in human lung, colon, and pancreatic cancer cells bearing various KRAS mutations. This effect was at the post-transcriptional level and is independent of proteasomal degradation or autophagy. Moreover, targeting GRP78 via small molecule inhibitors such as HA15 and YUM70 with anti-cancer activities while sparing normal cells significantly suppressed oncogenic KRAS expression in vitro and in vivo, associating with onset of apoptosis and loss of viability in cancer cells bearing various KRAS mutations. Collectively, our studies reveal that GRP78 is a previously unidentified regulator of oncogenic KRAS expression, and, as such, augments the other anti-cancer activities of GRP78 small molecule inhibitors to potentially achieve general, long-term suppression of mutant KRAS-driven tumorigenesis.


Process optimization and mechanism for removal of high-concentration chlorine from municipal solid waste incineration fly ash washing wastewater by Friedel's salt.
Waterwashing is an important pretreatment method for the reuse of municipal solid waste incineration (MSWI) fly ash. However, the presence of high levels of chlorides and small amounts of sulfides in the waterwashing solution makes it difficult to treat and reuse. Therefore, in this study, a calcium sulfate- Friedel's salt precipitation method was used to dechlorinate and desulfurize in the MSWI fly ash washing solution. This paper mainly focused on the chloride removal, and the effects of factors such as reagent ratios, temperature, and reaction time on chloride removal rate and the two-stage dechlorination and desulfurization process were optimized. The experimental results indicated that when the ratio in the first stage was n(Ca):n(Al):n(Cl) = 3:1.5:1, and in the second stage, n(Ca):n(Al):n(Cl) = 8:4:1, a chloride removal rate of up to 90.5% and a sulfide removal rate of over 99.88% could be obtained. The deposited particles were analyzed by using FE-SEM, XRD, and FTIR to investigate their size, morphology, phase composition, and functional groups. The study revealed that excessively high or low reagent ratios could reduce the interlayer spacing of Friedel's salt. Additionally, high temperatures led to the decomposition of Friedel's salt, and the dechlorination efficiency was affected.


Pro-poor policies and improvements in maternal health outcomes in India.
Since 2005, India has experienced an impressive 77% reduction in maternal mortality compared to the global average of 43%. What explains this impressive performance in terms of reduction in maternal mortality and improvement in maternal health outcomes? This paper evaluates the effect of household wealth status on maternal mortality in India, and also separates out the performance of the Empowered Action Group (EAG) states and the Southern states of India. The results are discussed in the light of various pro-poor programmes and policies designed to reduce maternal mortality and the existing supply side gaps in the healthcare system of India. Using multiple sources of data, this study aims to understand the trends in maternal mortality (1997-2017) between EAG and non EAG states in India and explore various household, economic and policy factors that may explain reduction in maternal mortality and improvement in maternal health outcomes in India. This study triangulates data from different rounds of Sample Registration Systems to assess the trend in maternal mortality in India. It further analysed the National Family Health Surveys (NFHS). NFHS-4, 2015-16 has gathered information on maternal mortality and pregnancy-related deaths from 601,509 households. Using logistic regression, we estimate the association of various socio-economic variables on maternal deaths in the various states of India. On an average, wealth status of the households did not have a statistically significant association with maternal mortality in India. However, our disaggregate analysis reveals, the gains in terms of maternal mortality have been unevenly distributed. Although the rich-poor gap in maternal mortality has reduced in EAG states such as Bihar, Odisha, Assam, Rajasthan, the maternal mortality has remained above the national average for many of these states. The EAG states also experience supply side shortfalls in terms of availability of PHC and PHC doctors; and availability of specialist doctors. The novel contribution of the present paper is that the association of household wealth status and place of residence with maternal mortality is statistically not significant implying financial barriers to access maternal health services have been minimised. This result, and India's impressive performance with respect to maternal health outcomes, can be attributed to the various pro-poor policies and cash incentive schemes successfully launched in recent years. Community-level involvement with pivotal role played by community health workers has been one of the major reasons for the success of many ongoing policies. Policy makers need to prioritise the underperforming states and socio-economic groups within the states by addressing both demand-side and supply-side measures simultaneously mediated by contextual factors.


The effects of intrinsic apoptosis on cystogenesis in PKD1-deficient ADPKD pig model.
Apoptosis is a form of cell death that plays a critical role in the maintenance of tissue homeostasis involving the development and elimination of unwanted cells. Dysregulation of apoptosis appears to be associated in the pathogenesis of many human diseases. Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disease and is mainly caused by mutations in PKD1. Previous studies proved that increased cell death occurred in ADPKD patients and animal models. However, the role of apoptosis in kidney cystogenesis is not clear. In current study, due to the high similarities between human and pig, PKD1-deficient (PKD1+/-) pigs and PKD1-knockdown (PKD1KD) pig kidney epithelial cells were used to investigate the mechanisms of apoptosis in driving cystogenesis. In PKD1+/- pigs, increased intrinsic and extrinsic apoptosis were found at ages of 1 month and 3 months, whereas the autophagy and pyroptosis were not altered. Meanwhile, the intrinsic apoptosis was activated along with untouched extrinsic apoptosis in PKD1KD pig kidney cells. Thus, the intrinsic apoptosis played important roles in cystogenesis. This work provides detail analysis of the roles of different cell death types during cystogenesis in ADPKD pig model. The results suggested a potential new strategy for the diagnosis and treatment of ADPKD by targeting intrinsic apoptosis.


Strongly carinate species of Alpheopsis Coutière, 1897 of the tropical Atlantic and eastern Pacific, with redescription of A. trigona (Rathbun, 1901) and description of three new species (Malacostraca: Decapoda: Alpheidae).
The present study deals with four species of the alpheid shrimp genus Alpheopsis Coutière, 1897 characterised by the presence of at least one strong carina on the dorsal surface of the carapace. Alpheopsis trigona (Rathbun, 1901) is redescribed based on the holotype from Puerto Rico and additional material from US Virgin Islands and Florida. Two new species closely related to A. trigona, viz. A. paratrigona sp. nov. and A. gotrina sp. nov., are described, the first based on material from several localities in the tropical western Atlantic, and the second from the Pacific coast of Panama and Colombia. The three species together form a distinctive transisthmian clade within Alpheopsis, the A. trigona species complex, characterised by the presence of several strong longitudinal carinae on the carapace and very distinctive colour pattern. A more distantly related species, A. aristoteles sp. nov., characterised by the presence of only one strong mid-dorsal carina in the anterior region of the carapace, is described based on material from São Tomé Island in the tropical eastern Atlantic.


Energy compensation in enterally fed children.
Limited exposure to solid food in early childhood may affect the development of appetite regulation. We used formal satiation studies to assess energy compensation in children who have been artificially fed. Subjects were 11 children, median age 4.5 years (range 1-10) who were formerly (n=4) or currently (n=5) mainly tube fed or supplement fed (n=2), with a range of surgical or neurodevelopmental problems. On 2 separate days a high-energy preload (HEP) and low-energy preload (LEP) drink were given followed by a multi-item test lunch. A compensation index (COMPX) score was derived as follows: COMPX (%)=[(Meal(lep)-Meal(hep))/(Preload(hep)-Preload(lep))]× 100. The median (range) COMPX of the participants was 70% (-73% to 178%). The 8 boys tended to compensate more (median 99%) than the 3 girls (30%; P Mann-Whitney=0.1), but there was no clear association of compensation with age. Although a small preliminary study, this suggests that children who have been artificially fed demonstrate energy compensation comparable to that of normally fed children.


The coagulation of insect hemolymph.
In contrast to both vertebrates and non-insect arthropods, little is known about the coagulation of hemolymph (hemostasis) in insects. We discuss the integration of the hemostatic response with other branches of the insect immune system. We also describe the present stage in the characterization of both soluble and cellular factors that contribute to hemostasis in insects. The factors of the well-characterized clotting cascades of vertebrates, primitive chelicerates and crustaceans are used to assess the implications of sequencing the whole Drosophila genome for searching candidate genes involved in hemostasis. Some striking similarities between blood clotting in vertebrates and the reaction of insect cells involved in hemolymph coagulation have implications for a phylogenetic comparison of hemostasis between divergent animal classes.


Advances in DNA damage response inhibitors in colorectal cancer therapy.
One potential cause of cancer is genomic instability that arises in normal cells due to years of DNA damage in the body. The clinical application of radiotherapy and cytotoxic drugs to treat cancer is based on the principle of damaging the DNA of cancer cells. However, the benefits of these treatments also have negative effects on normal tissue. While there have been notable advancements in molecular-driven therapy and immunotherapy for colorectal cancer (CRC), a considerable portion of patients with advanced CRC do not experience any benefits from these treatments, leading to a poor prognosis. In recent years, targeted therapy aimed at suppressing the DNA damage response (DDR) in cancer cells has emerged as a potential treatment option for CRC patients, offering them more choices for treatment. Currently, the integration of DDR and clinical intervention remains in the exploratory phase. This review primarily elucidates the fundamental principles of DDR inhibitors, provides an overview of their current clinical application status in CRC, and discusses the advancements as well as limitations observed in relevant studies.


Schizophrenia spectrum and attention-deficit/hyperactivity disorder symptoms in autism spectrum disorder and controls.
This study compared the differential severity of specific symptoms of schizophrenia spectrum disorder (SSD) in children with autism spectrum disorder (ASD) and child psychiatry outpatient referrals (controls). Each group was further subdivided into subgroups with and without co-occurring attention-deficit/hyperactivity disorder (ADHD). Children with ASD (n = 147) and controls (n = 335) were evaluated with parent and teacher versions of a psychometrically established DSM-IV-referenced rating scale. The two ASD groups (with and without ADHD) had a larger number of more severe SSD symptoms than their respective control groups (with and without ADHD), extending the observation of an association between ASD and SSD to subgroups with and without co-occurring ADHD. The ASD groups exhibited more severe schizoid personality symptoms than controls, but findings for schizophrenia symptoms were mixed. The ASD + ADHD group generally had more severe disorganized thought, disorganized behavior, and negative schizophrenia symptoms than controls (with and without ADHD); nevertheless, findings varied according to ADHD status (present versus absent), individual symptom (symptom specificity), and informant (informant specificity). Ratings of hallucinations and delusions indicated mild severity and few group differences. Negative symptoms such as inappropriate emotional reactions evidenced considerable group divergence. Findings provide additional support for an interrelation between ASD and SSD symptoms and the differential influence of neurobehavioral syndromes on co-occurring symptom severity, underscore the multidimensionality of SSD in children with ASD, and suggest how symptom phenotypes may contribute to a better understanding of the etiology, nosology, and possibly clinical management.


A watertight construct in arthroscopic rotator cuff repair.
It is unknown which type of rotator cuff repair technique best isolates the healing zone interface from the synovial fluid environment. The purpose of this study was to determine the leakage area and pattern onto the rotator cuff footprint after 3 different rotator cuff repairs. Six fresh frozen cadaveric glenohumeral joints in each of 3 groups were injected with gelatin to a pressure of 103 mm Hg (∼2 psi) after 1 of 3 different rotator cuff repairs of a supraspinatus tear: (1) single-row repair (SR), (2) knotless transosseous equivalent repair (KTE), and (3) traditional transosseous equivalent repair (TTE), which uses medial tied knots. Specimens were cycled in external rotation and abduction and were cooled to allow the gelatin to solidify. The supraspinatus was dissected off the footprint and photographs were taken. Scion Image (Frederick, MD, USA) was used to quantify the area. The average area of leakage was 1.09 cm(2) for the SR and 1.15 cm(2) for the KTE. The TTE did not demonstrate any leakage. The pattern of leakage for the KTE was medial and central on the footprint, whereas the SR demonstrated leakage up to the tied knots. The difference in the area of leakage in the SR and KTE compared with the TTE was statistically significant. There was no difference in area of leakage between the SR and KTE. A transosseous equivalent repair technique best prevents leakage onto the rotator cuff footprint compared with single-row and knotless repairs.


Vascular actions of octreotide in the portal hypertensive rat.
1. We have investigated the actions of the somatostatin analogue octreotide in the portal hypertensive Wistar rat in vivo and in rat small mesenteric artery and aorta in vitro. 2. In small mesenteric artery, octreotide (0.1-0.3 microM) failed to produce any direct contraction, nor did it affect contractions to noradrenaline (NA, 10 microM) or endothelium-dependent relaxations to acetylcholine. 3. In rat aorta, octreotide (0.3 microM) and somatostatin (1 microM) failed to affect contractions to NA (1 microM), or concentration-contractile response curves to NA. 4. In rat vas deferens, octreotide and somatostatin significantly reduced contractile responses to electrical stimulation with pD2 values (-log IC50) of 8.19 +/- 0.10 (n = 4) and 8.16 +/- 0.26 (n = 4), respectively. Hence, the lack of effect of these agents in aorta or mesenteric artery was not due to lack of efficacy or inappropriate choice of concentration. 5. In the anaesthetized portal hypertensive rat, intravenous injection of octreotide (1-100 microg kg[-1]) did not significantly affect systemic blood pressure, nor did it affect mesenteric vascular conductance as measured by laser doppler flow probes. However, octreotide (100 microg kg[-1]) significantly reduced vascular conductance to 74.2 +/- 7.7% of control (n = 6) in porto-systemic shunt vessels as measured by laser doppler flow probes. 6. Phenylephrine (1 microg kg[-1]) significantly raised blood pressure and significantly decreased vascular conductance in both mesenteric (66.6 +/- 3.7% of control) and porto-systemic shunt vessels (58.7 +/- 10.0% of control). 7. It was concluded that octreotide has selective effects on porto-systemic shunt vessles in vivo in the portal hypertensive rat.


Optimizing Donor Chimerism Threshold for Next-Generation Sequencing Monitoring of Measurable Residual Disease Post-Allogeneic Stem Cell Transplantation for Myeloid Neoplasms.
Next-generation sequencing (NGS) is used to monitor genetically measurable residual disease (gMRD) following allogeneic stem cell transplantation (aSCT). It is unknown whether an upper limit of chimerism exists such that gMRD NGS testing can be safely forgone. We reviewed 61 patients with acute myeloid leukemia and 24 patients with myelodysplastic syndrome who had at least 1 NGS panel before and after aSCT between 2016 and 2020. Donor chimerism was quantified. Logistic regression characterized which factors predicted gMRD. Receiver operating characteristic (ROC) curves were used to determine the optimal chimerism threshold for which gMRD would not be detected. Data from an additional 22 patients with follow-up NGS testing in 2022 were also analyzed to validate our proposed threshold. A: s expected, donor chimerism was a significant predictor of gMRD (odds ratio, .38; 95% confidence interval, .10 to .62; P = .02). Age, sex, conditioning regimen, presence of a related donor, and diagnosis were not associated with gMRD. A chimerism threshold of 92.5% optimized sensitivity (97.7%) and specificity (95.4%) such that values >92.5% strongly predicted the absence of gMRD (area under the ROC curve [AUC], .986). The validation cohort demonstrated similarly strong predictive capability (AUC, .974) with appropriate sensitivity (100%) and specificity (90.9%). NGS monitoring of gMRD is redundant at chimerism values greater than a more conservative threshold of 92.5% after aSCT.


Vardenafil reverses erectile dysfunction induced by paroxetine in rats.
Selective serotonin reuptake inhibitors (SSRIs) are associated with a high incidence of impotence. Paroxetine is an extensively used SSRI that has been shown to impair erectile function in patients, to induce erectile dysfunction and to inhibit nitric oxide synthase (NOS) activity and NO production in animal models. NO is a key mediator of penile erection. Vardenafil is a type 5 phosphodiesterase inhibitor that potentiates NO-mediated responses in isolated trabecular smooth muscle and penile erection in men in clinical trials. The aim of this study was to evaluate the effects of vardenafil on the impairment of erectile responses produced by paroxetine in the rat model. Application of cavernosal nerve electrical stimulation (CNES) produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor N(G)-nitro-L-arginine (0.3 mg/kg) and potentiated by vardenafil (0.3 mg/kg). Acute paroxetine treatment (10 mg/kg) significantly reduced ICP-responses to CNES. This inhibition was completely reversed by vardenafil (0.3 mg/kg) administration. The results show that the erectile dysfunction induced by paroxetine in rats can be effectively treated with vardenafil, suggesting that the use of this compound could be a reasonable therapeutic approach to treating erectile dysfunction associated with SSRI administration.


High-density lipoprotein cholesterol and brain aging amongst rural-dwelling older adults: a population-based magnetic resonance imaging study.
Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural-dwelling older adults. This population-based cross-sectional study included 184 rural-dwelling adults (age ≥ 65 years, 39.1% women) in Shandong, China. In 2014-2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models. Of the 184 participants, 47 were defined with MCI. Low high-density lipoprotein cholesterol (HDL-C; <1.55 vs. ≥1.55 mmol/l) was significantly associated with reduced volumes of total white matter (multi-adjusted β = -9.77, 95% confidence interval -19.48-0.06) and hippocampus (-0.23, -0.46-0.01), a lower MMSE score (-1.49, -2.67-0.31) and a higher likelihood of MCI (multi-adjusted odds ratio 3.21, 95% confidence interval 1.42-7.29). The mediation effects of structural brain measures on the associations between a low level of HDL-C and MMSE score or MCI were not statistically significant (p > 0.05). This study suggests that low HDL-C may be involved in structural brain aging and cognitive dysfunction amongst rural-dwelling older adults in China, but the association of low HDL-C with cognitive aging phenotypes appears not to be mediated by brain structure.


Modelling for the proposed roll-out of the '111' service in Wales: a case study.
NHS Direct Wales provides a single point of access where members of the public can telephone and seek medical support and/or advice. The service is provided for all the Health Boards in Wales by a single virtual call centre run from a main location in Swansea with 2 satellite locations. Patients in Wales can also access a local General Practitioner service during the evenings and at weekends, by phoning their Out of Hours service. The introduction of a '111' service is intended to combine these two operations on a pan-Wales basis using the existing NHS Direct Wales call centre and staff, with the existing Health Board Out of Hours 'hubs'. The merger of the two services is intended to improve the overall performance of both services. This paper focuses on the planned introduction of '111' in Cwm Taf and Hywel Dda University Health Boards. The purpose of the case study was to support the merger of the two telephony systems from both an organisational and service delivery perspective, by developing a Discrete Event Simulation to model the impact on service levels and staffing. In particular, to examine the percentage increase / decrease in the staffing requirements needed under partial or full integration of the two services. The results from the scenario analysis highlight that extra staffing resources would be required in certain groups (nurses and call handlers) whilst savings could be achieved in others, provided that there wasn't an increase in call volume after implementation of the new service.


Spirulina enhances the viability of Lactobacillus rhamnosus E/N after freeze-drying in a protective medium of sucrose and lactulose.
Response surface methodology (RSM) was used to optimize a protective medium for enhancing the viability of Lactobacillus rhamnosus E/N cells during lyophilization. Spirulina, sucrose and lactulose were selected, on the basis of a Plackett-Burman factorial design, as important protectants having the following protective effects on cell viability: 102.025, 36.885 and -34.42, respectively. A full-factorial central composite design was applied to determine optimal levels of three used agents. The optimal protective medium composition was determined to be: Spirulina 1.304% (w/v), lactulose 5.48% (w/v), and sucrose 13.04% (w/v) (Polish Patent P-393189). The predictive value of cell viability in this medium was 89.619%, and experimental viability obtained during freeze-drying was 87.5%. In this study, Spirulina was used for the first time as the protective agent in freeze-drying medium, significantly increasing lactobacilli viability and giving synbiotic character of the final product.


Assessment of perioperative total blood loss during total ankle arthroplasty.
Although many authors have discussed total blood loss after arthroplasty of the knee, hip, and shoulder, reports on perioperative blood loss after total ankle arthroplasty (TAA) are rare. The purpose of this study was to assess total blood loss after TAA and to identify correlated factors. A total of 103 cases (99 patients) of TAA for end-stage ankle osteoarthritis were enrolled in this study. Perioperative total blood loss was divided into intraoperative and postoperative blood loss. The patient-related variables evaluated for total blood loss were age, sex, body mass index, American Society of Anesthesiologists Classification score, comorbidities, history of previous ankle surgery, preoperative use of anticoagulants, platelet count and prothrombin time/international normalized ratio. Operation-related variables including type of anesthesia, operation time, TAA implant, and procedures performed in addition to TAA (if any) were evaluated to analyze correlations with total blood loss. In addition, the rate of transfusions after surgery was identified, and risk factors for transfusion were statistically analyzed. The total blood loss was mean 795.5±351.1mL, which included 462.2±248.5mL of intraoperative blood loss and 333.2±228.6mL of postoperative blood loss. Sex, TAA implant, and additional bony procedures performed along with TAA were significantly correlated with total blood loss (p=0.039, 0.024, 0.024, respectively) but the other variables were not significant (p>0.05). Transfusions were administered for 4 cases (3.8%) but no risk factors for transfusion could be identified. The total blood loss after TAA was 795.5mL and the rate of transfusions was 3.8%. This study demonstrated that male sex, use of TAA implants with a larger cutting surface, and bony procedures performed in addition to TAA were associated with an increase in total blood loss after TAA. The findings of this study will help surgeons to better predict blood loss and make optimal surgical plans accordingly. Level IV, retrospective case series.


Postprandial distribution of apolipoproteins C-II and C-III in normal subjects and patients with mild hypertriglyceridemia: comparison of meals containing corn oil and medium-chain triglyceride oil.
Five healthy male subjects and five patients with mild hypertriglyceridemia were studied following the administration of 800-kcal liquid meals containing 40% of energy from fat, 40% from carbohydrate, and 20% from protein. On the first day of the study, the fat source was corn oil (long-chain triglyceride), whereas medium-chain triglyceride (MCT) oil was used the second day. Meals were infused into the duodenum using a peristaltic pump. Plasma samples, obtained at hourly intervals for 8 hours, were analyzed for glucose, cholesterol, triglyceride, and apolipoproteins C-II and C-III. The distribution of apoC-II and apoC-III between ultracentrifugally-separated triglyceride-rich lipoproteins (TRL) and high-density lipoproteins (HDL) was also evaluated. The patient group had significantly elevated fasting levels of triglyceride, apoC-II and apoC-III, as well as much greater lipemic response to the meal containing corn oil. In both groups, TRL apoC-II and apoC-III levels were positively correlated with the triglyceride level as it increased following the corn oil meal. These correlations were also observed in the normal subjects when the MCT oil meal was administered, even though changes in plasma triglycerides were minimal. In normal subjects, whole plasma levels of apoC-II and apoC-III decreased significantly following the meal containing corn oil, whereas no net changes occurred following the MCT oil meal. In hypertriglyceridemic subjects, small decreases in plasma apoC-II and apoC-III levels occurred after both meals, although the changes in apoC-II were not statistically significant. The tendency for decreased plasma apoC levels following alimentary lipemia confirms previous reports, and provides further data to support the concept that some apoC is cleared from plasma in association with TRL remnants. The finding that mildly hypertriglyceridemic subjects responded similarly to both conventional fat and MCT may indicate that their rates of remnant clearance were similar following the two meals.


High diagnostic accuracy for lymph node metastasis of oral squamous cell carcinoma using PET/CT with a silicon photomultiplier.
The higher sensitivity of the new-generation positron emission tomography/computed tomography (PET/CT) with silicon photomultiplier (SiPM) may increase false-positive rates in detecting metastatic lymph nodes (LNs). This study aimed to clarify the usefulness of the SiPM PET scanner in diagnosing LN metastasis of oral squamous cell carcinoma (SCC). We retrospectively reviewed consecutive F-18 fluorodeoxyglucose PET/CT images of 39 SCC patients using SiPM PET and 31 SCC patients using non-SiPM PET. We measured the maximum standardized uptake value (SUVmax) of the LNs on PET images and maximum short-axis diameter on transverse CT images. The sensitivity and specificity of SiPM PET were 86.2% and 95.6%, respectively (cut-off SUVmax, 4.6). The area under the curve (AUC) of SiPM PET (0.977; 95% confidence interval [CI], 0.958-0.995) was significantly higher than that of non-SiPM PET (0.825; 95% CI 0.717-0.934) (P < 0.01). In a size-limited analysis of diameter, the AUC of SiPM PET (≥ 0.96 for all diameters) was significantly higher than that of non-SiPM PET (tended to decrease as the LN diameter decreased) for the diagnosis of LN metastasis by SUVmax. SiPM PET had higher diagnostic accuracy for LN metastasis of oral SCC than non-SiPM PET, even for small LN metastasis without increasing false-positives.