Effect of cooling rate and cryoprotectant concentration on intracellular ice formation of small abalone (Haliotis diversicolor) eggs.
The intracellular ice formation (IIF) behavior of Haliotis diversicolor (small abalone) eggs is investigated in this study, in relation to controlling the cooling rate and the concentration of dimethyl sulfoxide (DMSO). The IIF phenomena are monitored under a self-developed thermoelectric cooling (TEC) cryomicroscope system which can achieve accurate temperature control without the use of liquid nitrogen. The accuracy of the isothermal and ramp control is within ±0.5 °C. The IIF results indicate that the IIF of small abalone eggs is well suppressed at cooling rates of 1.5, 3, 7 and 12 °C/min with 2.0, 2.5, 3.0 and 4.0M DMSO in sea water. As 2.0M DMSO in sea water is the minimum concentration that has sufficient IIF suppression, it is selected as the suspension solution for the cryopreservation of small abalone eggs in order to consider the solution's toxicity effect. Moreover, IIF characteristics of the cumulative probability of IIF temperature distribution are shown to be well fitted by the Weibull probabilistic distribution. According to our IIF results and the Weibull distribution parameters, we conclude that cooling at 1.5 °C/min from 20 to -50 °C with 2.0M DMSO in sea water is more feasible than other combinations of cooling rates and DMSO concentrations in our experiments. Applying this protocol and observing the subsequent osmotic activity, 48.8% of small abalone eggs are osmotically active after thawing. In addition, the higher the cooling rate, the less chance of osmotically active eggs. A separate fertility test experiment, with a cryopreservation protocol of 1.5 °C/min cooling rate and 2.0M DMSO in sea water, achieves a hatching rate of 23.7%. This study is the first to characterize the IIF behavior of small abalone eggs in regard to the cooling rate and the DMSO concentration. The Weibull probabilistic model fitting in this study is an approach that can be applied by other researchers for effective cryopreservation variability estimation and analysis.


Melatonin supplementation reduces nighttime blood pressure but does not affect blood pressure reactivity in normotensive adults on a high-sodium diet.
High-sodium diets (HSDs) can cause exaggerated increases in blood pressure (BP) during physiological perturbations that cause sympathetic activation, which is related to cardiovascular risk. Melatonin supplementation has been shown to play a role in BP regulation. Our aim was to examine the effects of melatonin taken during an HSD on 24-h BP and BP reactivity during isometric handgrip (IHG) exercise, postexercise ischemia (PEI), and the cold pressor test (CPT). Twenty-two participants (11 men/11 women, 26.5 ± 3.1 yr, BMI: 24.1 ± 1.8 kg/m2, BP: 111 ± 9/67 ± 7 mmHg) were randomized to a 10-day HSD (6,900 mg sodium/day) that was supplemented with either 10 mg/day of melatonin (HSD + MEL) or placebo (HSD + PL). Twenty-four-hour ambulatory BP monitoring was assessed starting on day 9. Mean arterial pressure (MAP) was quantified during the last 30 s of IHG at 40% of maximal voluntary contraction and CPT, and during 3 min of PEI. Melatonin did not change 24-h MAP (HSD + PL: 83 ± 6 mmHg; HSD + MEL: 82 ± 5 mmHg; P = 0.23) but decreased nighttime peripheral (HSD + PL: 105 ± 10 mmHg; HSD + MEL: 100 ± 10 mmHg; P = 0.01) and central systolic BP (HSD + PL: 97 ± 9 mmHg; HSD + MEL: 93 ± 8 mmHg; P = 0.04) on the HSD compared with the HSD + PL. The absolute and percent change in MAP during IHG was not different between conditions (all P > 0.05). In conclusion, melatonin supplementation did not alter BP reactivity to the perturbations tested on an HSD but may be beneficial in lowering BP in young healthy normotensive adults.NEW & NOTEWORTHY BP reactivity was assessed during isometric handgrip (IHG) exercise, postexercise ischemia (PEI), and the cold pressor test (CPT) after 10 days of a high-sodium diet with and without melatonin supplementation. Melatonin did not alter BP reactivity in healthy normotensive men and women. However, melatonin did decrease nighttime peripheral and central systolic BP, suggesting it may be beneficial in lowering BP even in those with a normal BP.


Mitochondrial DNA displacement loop structure depends on growth state in bovine cells.
One portion of the mitochondrial genome of mammals contains no structural genes. This so-called displacement loop (D-loop) region includes the two major transcriptional promoters and one of the origins of DNA replication. The D-loop region is often found in a novel triplex structure in which a discrete single-stranded DNA segment is hybridized to one strand of the genome displacing the other strand. The significance of this triplex structure and the possible function of the single-stranded D-loop segment have remained obscure. Here we show that the locations of the major 5' termini of D-loops in growing and nongrowing bovine cells differ by 46 nucleotides. The location of bovine D-loop 5' termini is dependent on the cell cycle but is not directly linked to nuclear DNA replication. The nature of D-loop 5' termini in growing cells is altered by inhibitors of cytoplasmic protein synthesis but not by inhibitors of mitochondrial protein synthesis. Changes in D-loop 5' termini correlate with alterations in transcripts from one of the transcriptional promoters. These findings implicate D-loops in the control of bovine mitochondrial gene expression and suggest mechanisms by which this control might by accomplished.


Biodegradable nanoparticles combining cancer cell targeting and anti-angiogenic activity for synergistic chemotherapy in epithelial cancer.
A biodegradable engineered nanoplatform combining anti-angiogenic activity and targeting of cancer cells to improve the anticancer activity of docetaxel (DTX) is here proposed. Indeed, we have developed biodegradable nanoparticles (NPs) of poly(ethylene glycol)-poly(ε-caprolactone), exposing on the surface both folate motifs (Fol) for recognition in cells overexpressing Folate receptor-α (FRα) and the anti-angiogenic hexapeptide aFLT1. NPs showed a size around 100 nm, the exposure of 60% of Fol moieties on the surface, and the ability to entrap DTX and sustain its release with time. NPs were stable in simulated biological fluids and slightly interacted with Fetal Bovine serum, especially in the formulation decorated with Fol and aFLT1. The presence of Fol on NPs did not impair the anti-angiogenic activity of aFLT1, as assessed by in vitro tube formation assay in HUVEC endothelial cells. In both 2D and 3D KB cell cultures in vitro, the cytotoxicity of DTX loaded in NPs was not significantly affected by Fol/aFLT1 double decoration compared to free DTX. Remarkably, NPs distributed differently in 3D multicellular spheroids of FRα-positive KB cancer cells depending on the type of ligand displayed on the surface. In particular, NPs unmodified on the surface were randomly distributed in the spheroid, whereas the presence of Fol promoted the accumulation in the outer rims of the spheroid. Finally, NPs with Fol and aFLT1 gave a uniform distribution throughout the spheroid structure. When tested in zebrafish embryos xenografted with KB cells, NPs displaying Fol/aFLT1 reduced DTX systemic toxicity and inhibited the growth of the tumor mass and associated vasculature synergistically. Overall, nanotechnology offers excellent ground for combining therapeutic concepts in cancer, paving the way to novel multifunctional nanopharmaceuticals decorated with bioactive elements that can significantly improve therapeutic outcomes.


The effect of N-linked glycosylation on the substrate preferences of UDP glucuronosyltransferases.
The presence of potential N-linked glycosylation sites (Asn-X-Ser/Thr) in two forms of UDP glucuronosyltransferase, designated UDPGTr-2 and UDPGTr-4, has been deduced from cDNA sequence data. These forms were glycosylated when synthesized from expression vectors transfected into COS cells and were converted to faster migrating species on SDS polyacrylamide gels when treated with endoglycosidase H. The role of glycosylation was investigated by determining the substrate specificities and stabilities of the glycosylated enzymes and their unglycosylated variants which were synthesized in the presence of tunicamycin. Analysis of the activities towards 13 different aglycones showed that the glycosyl moiety was not essential for catalytic activity and had no effect on the substrate preference of each form. The stabilities of the proteins were not adversely affected by the absence of this posttranslational modification. A possible effect of N-linked oligosaccharides on the catalytic properties of these two forms of UDP glucuronosyltransferase is discussed.


Anomalous electrophoretic behavior of the major potato virus X RNA translation product.
The major potato virus X (PVS) RNA translation product migrates in Laemmli's electrophoresis system as a 210 kDa polypeptide ('p210'). If a Tris-phosphate-SDS buffer system is used instead of a Tris-glycine-SDS one, the mobility of p210 is higher than that of the largest TMV RNA translation product, the 183 kDa protein. It is suggested that anomalous electrophoretic behavior of the largest PVX polypeptide during SDS-electrophoresis is due to its primary structure, namely to the presence of hydrophilic domains.


Magnetic resonance in systems with equivalent spin-1/2 nuclides. Part 2: energy values and spin states.
In an earlier paper (Part 1), featuring group-theoretical analysis, it was shown that the isotropic EPR spectra of free radical (S=1/2) species XL(n), where the n equivalent nuclei also have spin 1/2, have a more complicated form than anticipated from the usual (first-order) oversimplified analysis. The nucleus of X is taken to be spin-less. The latter predicts n+1 lines with intensity ratios given by the coefficients of the binomial expansion; for systems with n=3, the EPR spectrum in fact consists of 6 lines. Analogous considerations hold for NMR spectroscopy of XL(n) non-radicals. For n > or = 3 systems, the degeneracy of the energy levels cannot be completely removed by the Zeeman electronic and nuclear interactions. Explicit solutions for n=3 (analytic, as well as computational) of the spin-hamiltonian for the energies and spin states have been obtained and are given in the present work. Discussion of the underlying theory, invoking exchange degeneracy, is included herein in some detail, focusing on line positions and relative spectral intensities.


Elevated Mhp462 antibody induced by natural infection but not in vitro culture of Mycoplasma hyopneumoniae.
Mycoplasma hyopneumoniae is the respiratory pathogen of porcine enzootic pneumonia, a chronic respiratory infectious disease that causes substantial pecuniary losses to pig husbandry worldwide. Commercial bacterins only provide incomplete protection and do not prevent the colonization and transmission of M. hyopneumoniae. Identification of new protective antigens is a key imperative for the development of more effective novel vaccine. The objective of this study was to evaluate antibody responses of 27 recombinant proteins in convalescent sera obtained from pigs that were naturally infected with M. hyopneumoniae. Fifteen proteins were identified as serological immunodominant antigens, while 3 proteins were not recognized by any convalescent serum. Moreover, Mhp462, a leucine aminopeptidase, was found to be a discriminative serological immunodominant antigen which reacted with convalescent sera but not with hyperimmune sera. The serological immunodominant proteins were antigenic and were expressed during infection; this suggests that these proteins (especially the discriminative one) are potential candidate antigens for the development of next generation vaccines against M. hyopneumoniae.


Supersensitivity to norepinephrine or dopamine antagonists after knife cuts that produce aphagia and adipsia in rats.
Aphagia and adipsia of equivalent duration were produced by knife cuts along the lateral border of the hypothalamus (PH cuts), or the medial surface of the globus pallidus (MP cuts) in male albino rats. Striatal dopamine (DA) was reduced by 75% in animals with PH cuts but only 50% by MP cuts. Hypothalamic norepinephrine was reduced 25% by PH cuts and was unaffected by MP cuts. Aphagia and adipsia were positively correlated with DA depletions only in rats with PH cuts. Presurgical catecholamine depletions produced by chronic injections of alpha-methyl-p-tyrosine did not alter the duration of aphagia or adipsia resulting from these knife cuts. However, following recovery of ingestive behavior, rats with PH and MP cuts were supersensitive to the anorexic effects of the dopamine-beta-hydroxylase inhibitor, diethyldithiocarbamate. Exaggerated anorexia was also observed after DA blockade by haloperidol or alpha-adrenergic blockade by phenoxybenzamine. The most pronounced effects of catecholamine blockade were observed in rats with PH cuts.


Ultra-light-weight, anti-flammable and water-proof cellulosic aerogels for thermal insulation applications.
Cellulosic aerogels (CNF) are considered naturally available thermal insulating materials as substitutes for conventional polymeric aerogels owing to their extensive sources, low density, low thermal conductivity, sustainability and biodegradability. However, cellulosic aerogels suffer from high flammability and hygroscopicity. In this work, a novel P/N-containing flame retardant (TPMPAT) was synthesized to modify cellulosic aerogels to improve their anti-flammability. TPMPAT/CNF aerogels were further modified by polydimethylsiloxane (PDMS) to enhance the water-proof characteristics. Although the addition of TPMPAT and/or PDMS slightly increased the density and thermal conductivity of the composite aerogels, those values were still comparable to the commercial polymeric aerogels. Compared with pure CNF aerogel, the cellulose aerogel modified by TPMPAT and/or PDMS had higher T-10%, T-50% and Tmax, which indicated that the modified cellulose aerogels have better thermal stability. TPMPAT modification made CNF aerogels highly hydrophilic, while TPMPAT/CNF aerogel modified by PDMS became a highly hydrophobic material with a water contact angle (WCA) of 142°. Pure CNF aerogel burned rapidly after ignition, showing a low limiting oxygen index (LOI) of 23.0% and no UL-94 grade. In contrast, both TPMPAT/CNF-30% and PDMS-TPMPAT/CNF-30% showed self-extinction behaviors with a UL-94 V-0 grade, implying high fire resistance. Combined with high anti-flammability and hydrophobicity, the ultra-light-weight cellulosic aerogels show great potential for thermal insulation applications.


The Duchess of Kingston's Case, the ruling of Lord Mansfield and duty of medical confidentiality in court.
The aim of this article is to demonstrate that the ruling commonly cited as the original precedent(1) for the doctrine that, at common law, medical practitioners' duty of confidentiality to their patients does not apply to court testimony,(2) did not, in fact, establish any such theory. The ruling by Lord Mansfield was made in the context of cross-examination by the Crown of a medical witness in the course of the trial of the Duchess of Kingston (Duchess of Kingston's Case (1776) 20 Howell's State Trials 355; [1775-1802] All ER Rep 623; [1776] 1 Leach 146), and this article will look briefly at: (1) the fascinating life of Elizabeth Chudleigh, the Dowager Duchess of Kingston, and the main events that led to her trial for bigamy; (2) the cross-examination of Caesar Hawkins and the different perceptions of the scope of confidentiality held by 18th century lawyers on the one hand and medical practitioners on the other; (3) Lord Mansfield's ruling that witnesses cannot withhold from the court facts which the law considers to be in the public domain; (4) the subsequent wide interpretation, usually as judicial obiter dicta, of its final paragraph during the 19th century, including early jurisprudential responses to the principle of medical confidentiality; and (5) the influence of John Henry Wigmore's opposition to patients' evidentiary privilege at common law during the twentieth century.


Matrix factorization for the reconstruction of cervical cancer screening histories and prediction of future screening results.
Mass screening programs for cervical cancer prevention in the Nordic countries have strongly reduced cancer incidence and mortality at the population level. An alternative to the current mass screening is a more personalised screening strategy adapting the recommendations to each individual. However, this necessitates reliable risk prediction models accounting for disease dynamics and individual data. Herein we propose a novel matrix factorisation framework to classify females by the time-varying risk of being diagnosed with cervical cancer. We cast the problem as a time-series prediction model where the data from females in the Norwegian screening population are represented as sparse vectors in time and then combined into a single matrix. Using novel temporal regularisation and discrepancy terms for the cervical cancer screening context, we reconstruct complete screening profiles from this scarce matrix and use these to predict the next exam results indicating the risk of cervical cancer. The algorithm is validated on both synthetic and registry screening data by measuring the probability of agreement (PoA) between Kaplan-Meier estimates. In numerical experiments on synthetic data, we demonstrate that the novel regularisation and discrepancy term can improve the data reconstruction ability as well as prediction performance over varying data scarcity. Using a hold-out set of screening data, we compare several numerical models and find that the proposed framework attains the strongest PoA. We observe strong correlations between the empirical survival curves from our method and the hold-out data, and evaluate the ability of our framework to predict the females' next results for up to five years ahead in time using only their current screening histories as input. We have proposed a matrix factorization model for predicting future screening results and evaluated its performance in a female cohort to demonstrate the potential for developing prediction models for more personalized cervical cancer screening.


Lacto- and ganglio-series glycolipids are adhesion receptors for Neisseria gonorrhoeae.
The role of glycolipids as adhesion receptors for Neisseria gonorrhoeae is examined. Serum-resistant isolates, piliated and nonpiliated isogenic variants, as well as gonococci deficient in lipooligosaccharide and protein II, bind specifically to terminal and internal GlcNAc beta 1-3Gal beta 1-4Glc and GalNAc beta 1-4Gal beta 1-4Gcl sequences in lacto- and ganglio-series glycolipids, respectively, as measured by overlaying glycolipid chromatograms with 125I-labeled organisms. The binding activity was not affected by changing the growth conditions of the organism, as the gonococci bound to both classes of glycolipids when grown anaerobically, microaerophilically on agar or in broth, or under iron-limited conditions. The gonococci do not bind to lacto-sylceramide (Gal beta 1-4Glc beta 1-1Cer) derived from lacto-N-triaosylceramide or from asialo-GM2 by treatment with N-acetyl-beta-hexosaminidase, or to other neutral glycolipids tested. Although N. gonorrhoeae bound weakly to some gangliosides on thin-layer chromatograms, including sialylparagloboside and GM1, in solid phase assays the gonococci bound with high avidity to the sequence GalNAc beta 1-4Gal beta 1-4Glc, with moderate avidity to the sequence GlcNAc beta 1-3Gal beta 1-4Glc, and not at all to gangliosides. Interestingly, the 4.8-kDa component of gonococcal lipooligosaccharide, which contains lacto-N-neotetraose (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc), strongly inhibits gonococcal-specific agglutination of human erythrocytes and inhibits the binding of labeled organisms to human paragloboside and lacto-N-triaosylceramide on thin-layer chromatograms. Possibly, this binding specificity explains why gonococci autoagglutinate in vitro.


A dynamic model of transcriptional imprinting derived from the vitellogenesis memory effect.
Transcriptional memory of transient signals can be imprinted on living systems and influence their reactivity to repeated stimulations. Although they are classically ascribed to structural chromatin rearrangements in eukaryotes, such behaviors can also rely on dynamic memory circuits with sustained self-amplification loops. However, these phenomena are either of finite duration, or conversely associated to sustained phenotypic changes. A mechanism is proposed, in which only the responsiveness of the target gene is durably reset at a higher level after primary stimulation, using the celebrated but still puzzling vitellogenesis memory effect. The basic ingredients of this system are: 1), a positive autoregulation of the estrogen receptor α gene; 2), a strongly cooperative action of the estradiol receptor on vitellogenin expression; and 3), a variant isoform of the estradiol receptor with two autonomous transcription-activating modules, one of which is signal-independent and the other, signal-dependent. Realistic quantification supports the possibility of a multistationary situation in which ligand-independent activity is unable by itself to prime the amplification loop, but can click the system over a memory threshold after a primary stimulation. This ratchet transcriptional mechanism can have developmental and ecotoxicological importance and explain lifelong imprinting of past exposures without apparent phenotypic changes before restimulation and without need for persistent chromatin modifications.


Covalent organic frameworks as a novel fiber coating for solid-phase microextraction of volatile benzene homologues.
Covalent organic frameworks (COFs) have attracted great research interest due to their fascinating structures and potential applications in various fields. Here, the COF-SCU1 (SCU for Sichuan University) coated solid-phase microextraction (SPME) fibers were fabricated by coating it on prior functionalized stainless steel wires via a simple physical coating method, and applied to extract some volatile benzene homologues from indoor air samples. The main experimental parameters affecting the extraction efficiency were optimized, including extraction temperature, extraction time, and desorption time. The developed method, which combined the COF-SCU1 coated fiber-based SPME with gas chromatography-mass spectrometric detection, gave large enrichment factors (276-887), low limits of detection (0.03-0.15 ng L-1), and good linearity (0.10-20 ng L-1) for the determination of gaseous benzene homologues from three different indoor air samples. The precision (expressed as the relative standard deviations, RSDs) for six replicate determinations of the analytes at 10 ng L-1 each of the analytes using the same COF-SCU1 coated fiber ranged from 5.8 to 8.9%. The fiber-to-fiber reproducibility for three parallel COF-SCU1 coated fibers varied from 6.9 to 10.7%. The recoveries of the analytes for the method for the spiked indoor air samples with the benzene homologues at the two concentrations of 1 and 10 ng L-1 were in the range of 88.6-101.5% and 87.9-103.4% with the RSDs ranging from 3.9 to 10.3% and 3.4 to 8.5%, respectively. Graphical Abstract The covalent organic frameworks were applied as a novel fiber coating material for the solid-phase microextraction of volatile benzene homologues.


Safety and efficiency of chronic ACE inhibition in symptomatic heart failure patients with a systemic right ventricle.
ACE inhibition is an established treatment regimen in patients with congestive heart failure due to left ventricular dysfunction which improves morbidity and mortality. However, little is known about the beneficial effects of ACE inhibition in adult patients after Mustard procedure for transposition of the great arteries with heart failure symptoms. Therefore, we investigated the effects of ACE inhibition in these patients on heart failure symptoms, echocardiographic diameters, NT-proBNP and exercise capacity. In 14 patients (age 25.2 ± 3.5 years), after Mustard procedure for transposition of the great arteries (age at operation 1.1 ± 1.3 years) with heart failure NYHA II (New York Heart Association class), an ACE inhibition was initiated. At baseline and 13.3 ± 4.0 months after treatment with enalapril (10mg twice a day), echocardiography, exercise test and NT-proBNP measurements were performed and compared to an age- and sex-matched control group. Maximum oxygen uptake and echocardiographic parameters did not change significantly in both groups. However, NT-proBNP showed a significant decrease in the treatment group (242 ± 105 vs. 151 ± 93 ng/l, p=0.004), while in the control group a significant increase (120 ± 89 vs. 173 ± 149 ng/l, p<0.05) was observed. Furthermore, ACE inhibitor treatment did not result in a deterioration of heart failure symptoms or renal function. Thus, ACE inhibitor treatment of heart failure symptoms in patients with a systemic right ventricle is safe and reduces NT-proBNP levels significantly as a marker for ventricular overload. Nevertheless, larger scale trials are warranted to show effects on morbidity and mortality in this highly selected patient group.


The cytoplasmic face of cell contact sites.
The cytoplasmic face of cell contact sites comprises large macromolecular assemblies that link transmembrane cell adhesion molecules to the cytoskeleton. These assemblies are dynamic structures that are the targets of regulatory signals that control cell adhesiveness. Recent studies of the biochemistry and structure of the cadherin-catenin complex, vinculin and proteins of the ezrin/radixin/moesin family have begun to reveal the architecture of these assemblies and the mechanisms that are involved in their regulation.


Deciphering the kinetic mechanisms controlling selected plant ADP-glucose pyrophosphorylases.
ADP-Glc pyrophosphorylase (AGPase), a rate-limiting enzyme in starch biosynthesis, is controlled by thermostability and allosteric regulation. Previous studies suggested that redox affects turnover number and heat stability of AGPases. Here, we investigated how allostery and redox state affect kinetic mechanisms of the reduced, heat labile and the oxidized, heat stable potato tuber enzymes; the heat labile maize endosperm enzyme and a chimeric maize/potato heat stable enzyme that lacks the cysteine responsible for redox changes. With 3-PGA, all AGPases followed a Theorell-Chance Bi Bi mechanism with ATP binding first and ADP-Glc releasing last. 3-PGA increases the binding affinity for both substrates with little effect on velocity for the maize and MP isoforms. By contrast, 3-PGA increases the velocity and the affinity for G-1-P for the potato enzymes. Redox state does not affect kcat of the two potato isoforms. Without 3-PGA the oxidized potato enzyme exhibits a rapid equilibrium random Bi Bi mechanism with a dead end ternary complex. This fundamental change from rapid, ordered binding with little buildup of intermediates to a mechanism featuring relatively slow, random binding is unique to the oxidized potato tuber enzyme. Finally, ADP-Glc the physiologically relevant product of this enzyme has complex, isoform-specific effects on catalysis.


Danish obstetricians' personal preference and general attitude to elective cesarean section on maternal request: a nation-wide postal survey.
To assess Danish obstetricians' and gynecologists' personal preference and general attitude towards elective cesarean section on maternal request in uncomplicated single cephalic pregnancies at term. Nation-wide anonymous postal questionnaire. Four hundred and fifty-five obstetricians and gynecologists identified in the records of the Danish Society of Obstetrics and Gynecology from January 2000. Personal preference on the mode of delivery and general attitude towards elective cesarean section on maternal request in an uncomplicated single cephalic pregnancies at term. Of Danish specialists in obstetrics and gynecology, 1.1% would prefer an elective cesarean section in an uncomplicated pregnancy at 37 weeks of gestation with fetal weight estimation of 3.0 kg. This rose to 22.5% when the fetal weight estimation was 4.5 kg at 37 weeks. The main reasons given for preferring abdominal deliveries was the risk to the fetus, risks of perineal injury, and urinary and anal incontinence. Of Danish specialists in obstetrics and gynecology, 37.6% agreed with a woman's right to have an elective cesarean section on maternal request without any medical indication. Obstetricians and gynecologists who had experienced a noninstrumental vaginal delivery themselves or practiced as a private gynecologist only, were less likely to agree with the woman's right to elective cesarean section on maternal request. The vast majority of Danish obstetricians and gynecologists would personally prefer vaginal delivery in uncomplicated pregnancies, but nearly 40% agree with the woman's right to request a cesarean section.


Progress and Promise in Neuroaesthetics.
We review progress and highlight open questions in neuroaesthetics. We argue that computational methods can provide mechanistic insight into how aesthetic judgments are formed, while advocating for deeper collaboration between neuroscientists studying aesthetics and those in the arts and humanities.


A Review on Dietary and Non-Dietary Risk Factors Associated with Gastrointestinal Cancer.
Cancer is a complex disease involving neoplasm of abnormal cells leading to development of tumor cells. Gene mutations result in aberrant gene expression, which is the major cause observed in all the cancers. The GLOBOCAN 2012 reported the highest age-standardized rates for cancer of the colorectum followed by stomach, liver, and esophagus, which are gastrointestinal cancers, and the new cases also followed the same order across the globe. Various risk factors are associated with different types of cancer which can be classified as dietary and non-dietary risk factors. The dietary risk factors include diet, alcohol, and nutrient deficiencies, whereas the non-dietary risk factors of cancers are tobacco, lifestyle choices, certain infections, occupational exposures, and environmental factors. The aim of this review is to focus on the dietary and non-dietary risk factors linked to gastrointestinal cancers, which could be beneficial in clinical decision-making.


Insights into the mechanisms underlying the remediation potential of earthworms in contaminated soil: A critical review of research progress and prospects.
In recent years, soil pollution is a major global concern drawing worldwide attention. Earthworms can resist high concentrations of soil pollutants and play a vital role in removing them effectively. Vermiremediation, using earthworms to remove contaminants from soil or help to degrade non-recyclable chemicals, is proved to be an alternative, low-cost technology for treating contaminated soil. However, knowledge about the mechanisms and framework of the vermiremediation various organic and inorganic contaminants is still limited. Therefore, we reviewed the research progress of effects of soil contaminants on earthworms and potential of earthworm used for remediation soil contaminated with heavy metals, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), pesticides, as well as crude oil. Especially, the possible processes, mechanisms, advantages and limitations, and how to boost the efficiency of vermiremediation are well addressed in this review. Finally, future prospects of vermiremediation soil contamination are listed to promote further studies and application of vermiremediation in contaminated soils.


Understanding the gender gap in advanced practice nursing: A qualitative study.
We aim to explore the perceptions of registered nurses undergoing the advanced practice nurse preparatory programme and of advanced practice nurses towards the recruitment of men into the advanced practice nursing workforce. Given the need to expand and diversify the advanced practice nursing workforce, it is important to recognize the potential implications of gender disparity. It is critical to understand why few males are recruited into the advanced practice nursing preparatory programme and to determine whether gender-related bias is present in the professional development of nurses. We use a descriptive qualitative design. Semi-structured interviews were conducted via Zoom (April to August 2021). Three themes were generated: 'The odds are eventually in the favour of men', 'The APN career-track is unpopular among men', and 'Balancing the gender gap in the APN workforce'. All themes are supported by three subthemes. Although males in nursing enjoy opportunistic advantages in entering the advanced practice nursing workforce, they are not interested in the role and not staying long enough in the nursing profession to become advanced practice nurses. Nurse managers should be more cognizant of the different social stereotypes faced by males and females in nursing. With such awareness, they can be more supportive and less biased in career counselling and job appraisals.


Denosumab for postmenopausal osteoporosis?
Osteoporosis is the most common clinical disorder of bone metabolism, and is characterised by low bone mass and deterioration of the microarchitecture of bone tissue that results in increased bone fragility and susceptibility to bone fracture. In the UK, it is estimated that osteoporosis affects over 3 million people and leads to 230,000 fractures per year. It occurs most commonly in postmenopausal women and prevalence increases markedly with age, from 2% in women at 50 years to more than 25% at 80 years of age. Denosumab (Prolia - Amgen) is a monoclonal antibody that decreases bone resorption. It has been licensed in the EU for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and also for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. Here, we review the role of denosumab in the management of postmenopausal osteoporosis.


Intrinsic esophageal innervation in esophageal atresia without fistula.
Esophageal atresia and tracheo-esophageal fistula (EA + TEF) are often associated with malformations of neural crest origin. Esophageal innervation is also derived from the neural crest and it is abnormal in EA + TEF in which there is motor dysfunction. Our aim was to examine the intrinsic esophageal innervation in children with isolated EA in which different embryogenic mechanisms might be involved. Specimens from the proximal and distal esophageal segments of 6/35 patients who had esophageal replacement for isolated EA between 1965 and 2006 were suitable for the study. They were sectioned and immunostained with anti-neurofilament (NF) and anti-S-100 antibodies. The muscle and neural surfaces on each section were measured with the assistance of image processing software. The surface of the ganglia and the number of neurons per ganglion were determined at high power microscopy. The findings were compared with those of six autopsy specimens from newborns dead of other diseases by means of standard statistical tests and a significance threshold of P < 0.05. Unmatched age/size of babies in isolated EA and control groups precluded comparison of the relative surfaces occupied by neural elements. Patients with pure EA had denser fibrilar network and larger ganglia than controls. The number of neurons/ganglion were similar in both groups although the cells from EA patients were larger. The findings were similar at both esophageal levels studied. In spite of methodologic biases, it seems that intrinsic esophageal fibrilar network is denser and the intramural ganglia larger with larger cells in patients with pure EA than in controls on both esophageal ends of the organ. These neural anomalies are only in part reminiscent of those described in regular EA/TEF but may as well explain esophageal dysfunction in patients with repaired isolated EA.


Meet the authors: Laura Hsieh, Muryam Gourdet, and Geeta Narlikar.
We talk to co-first authors Laura Hsieh and Muryam Gourdet, and professor Geeta Narlikar, about their academic journeys, juggling motherhood and lab work during the pandemic, their paper, "A hexasome is the preferred substrate for the INO80 chromatin remodeling complex, allowing versatility of function," and the importance of remaining open-minded and unafraid to challenge the field.


Tuberculous tenosynovitis of the Flexor Tendons of the hand and wrist: A case report and mini-review.
Tuberculous tenosynovitis of hand and wrist is a rare disease but it is found sometimes, especially in TB-endemic areas. The clinical presentation is not specific, however, most patients present with painless swelling at the wrist and hand with limited range of motion, and nerve compression symptoms have been reported. The diagnosis of this conditions can be made from histopathology. Antituberculosis drugs are the mainstay treatment while surgery is controversial. We present the case of an 83-year-old Thai woman with no history of exposure to tuberculosis. She presented with swelling and mild pain at her right wrist and the fifth finger of her right hand for 3 months. Ultrasonography revealed tenosynovitis in the right hand and wrist. Mycobacterium tuberculosis was confirmed with tissue diagnosis after an open biopsy. 2-months regimens containing Isoniazid, Rifampicin, Pyrazinamide and Ethambutol/6-months of isoniazid and rifampicin treatment was successful without complications. We follower her up for 1 year, at which time she had returned to do normal daily activities. Her final DASH score was 10.8. Tuberculous tenosynovitis is rare, but still occasionally encountered, especially in TB-endemic areas. The challenge is that this condition is difficult to diagnose due to its clinically insidious onset and the presentation is not obviously specific. Laboratory analysis, imaging (MRI, ultrasonography) and microbiology are useful to help reach a diagnosis, but finally confirmation is from histopathology. The treatment mainstay is medical, but surgery may be required if conservative treatment fails or in late stages of the disease.


Influence of sex hormone antagonists on the anticonvulsant action of conventional antiepileptic drugs against amygdala-kindled seizures in male and female rats.
The effects of three gonadal steroid antihormones, tamoxifen (TXF, an estrogen antagonist), cyproterone acetate (CYP, an antiandrogen) and mifepristone (MIF, a progesterone antagonist) alone or combined with conventional antiepileptics were evaluated in amygdala-kindled seizures in male and female rats. None of the three antihormones used in this study affected any seizure parameter. TXF (50 mg/kg) and CYP (50 mg/kg), when combined with carbamazepine, or phenobarbital applied at their subprotective doses of 15 mg/kg, resulted in significant reductions of the seizure and afterdischarge durations, both in male and female rats. Additionally, the combination of carbamazepine and CYP markedly increased the afterdischarge threshold in fully-kindled rats of both genders. The interaction between antihormones and carbamazepine, or phenobarbital, was not reversed by respective sex steroid hormones (estradiol, testosterone). However, the TXF- and CYP-induced anticonvulsant effects in combinations with carbamazepine were attenuated by bicuculline, N-methyl-D-aspartate (NMDA) and aminophylline. Kainic acid and strychnine remained ineffective in this respect. The effect of a combination of TXF with phenobarbital was reversed by bicuculline and NMDA and that of CYP with phenobarbital-by bicuculline and aminophylline. Neither TXF nor CYP altered the free plasma concentrations of carbamazepine or phenobarbital, so a pharmacokinetic interaction is not probable. The combined treatment of the two antihormones with antiepileptic drugs did not affect motor performance, and did not result in significant long-term memory deficits. Our data confirm the hypothesis that sex hormone antagonist-mediated events may play some role in seizure processes in the central nervous system and can modulate the protective activity of some conventional antiepileptic drugs against kindled seizures.


Ocular explosion after peribulbar anesthesia.
We report 3 cases of globe rupture after peribulbar anesthesia. We discuss the predisposing factors, presenting features, and visual outcome after this complication. Globe explosion is a severe complication of inadvertent intraocular injection during peribulbar anesthesia. Visual outcome after vitrectomy is generally poor; however, cases that do not develop a retinal detachment may achieve good results.


Effects of Exogenous Dietary Advanced Glycation End Products on the Cross-Talk Mechanisms Linking Microbiota to Metabolic Inflammation.
Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD, n = 15) and AGE-enriched diet (AGE-D, n = 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased Nε-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements.


The effect of hospitalization on oral anticoagulation control: a population-based study.
For patients taking oral anticoagulants (OAC), the proportion of time spent in the therapeutic range is strongly associated with bleeding and thromboembolic risk. Previous studies examining OAC control may not generalize because the patient population was select or INR capture was incomplete. Measure OAC control for an entire population of elderly people and determine patient factors associated with OAC control. People in Eastern Ontario without valve replacement aged 65 years or greater who were treated with warfarin between 1 September 1999 and 1 September 2000. Retrospective cohort study using population-based administrative databases. OAC control was measured as the proportion of days in therapeutic range (PDTR), defined as the number days with the INR between 2 and 3 divided by total number of days observation. Linear interpolation was used to determine INR levels between measures. Negative binomial regression was used to identify patient factors independently associated with PDTR. We also determined which factors were associated with proportion of days with a critically low (<1.5) or critically high (>/=5) INR. 7179 people were followed for a total of 3238 years. 15% of people were hospitalized during the study. Overall, PDTR was 59.2% (95% CI 59.1%-59.2%). Independent of all other significant factors, hospitalization was associated with a 15% decrease in the PDTR 15% (rate ratio 0.85, 95% CI 0.83-0.87). Hospitalization was also independently associated with greater proportion of time with a critically low INR (rate ratio 1.68, 95% CI 1.51-1.88) and a critically high INR (1.70, 95% CI 1.38-2.08). Elderly people in eastern Ontario taking warfarin were therapeutic 59.2% of the time. Independent of other patient factors, patients who are hospitalized have the greatest risk of poor anticoagulation control. Control for anticoagulated patients who get hospitalized should be reviewed to determine if and how it could be improved.


[Use of an automated venous occlusion plethysmograph for late postoperative studies on the arterial blood flow of the leg after use of the external iliac artery for retrograde perfusion].
The authors report on a new segment plethysmograph by help of which quick and completely automatic measuring of top flow is possible in high quality. The device is present as model for laboratory use and has proven good in practice. It was used, e.g., for the control of arterial blood supply in legs of patients who years ago were perfused via an external iliac artery during open heart surgery. Corresponding with the clinical findings, also by plethysmography no statistically significant differences of blood flow values were found in the legs with perfused or non-injured arteries.


Hair cortisol concentration associates with insomnia and stress symptoms in breast cancer survivors.
Stress, depressive symptoms and sleep quality are important and modifiable determinant of health and their association with hair cortisol concentrations (HCC) in breast cancer survivors has not been evaluated. We selected a random sample of 65 participants (mean age 57.9 years old, range 44-75 years) recruited from local patients' associations of breast cancer survivors. Each provided a hair sample at enrollment and basic clinical data and psychological evaluation regarding self-perceived stress (PSS-scale), depressive (GDS scale) and insomnia symptoms (Athens scale). We observed a direct and significant (p = 0.001) association between HCC and stress-levels. Depressive symptoms associated significantly (p < 0.01) with stress levels but not with HCC. There were also a significant and direct correlation between hair cortisol concentration and totals core of insomnia symptoms (p = 0.002), and the subdimension of sleep difficulty symptoms (p = 0.002), and with daytime sleepiness symptoms (p = 0.016). Further investigations into the association between stress and insomnia and changes in HCC in breast cancer survivors are warranted in order to validate this biomarker for diagnosis of psychological alterations and to tailor the effects of interventions aimed to reduced stress and improve sleep quality in these women.


[The effect of subsocial behaviour of the seed-sucking bugsOncopeltus fasciatus dall. andDysdercus fasciatus sign. on their nutrition].
The quantitative uptake of food of isolated individuals or groups ofOncopeltus fasciatus andDysdercus fasciatus has been investigated comparatively. In groups of both species (2-4 members) the feeding activity and the volume of food ingested is increased. The subsocial behaviour is found to have more influence on unattractive food than on optimal one. The subsocial behaviour ofD. fasciatus andO. fasciatus exhibits intraspecific differences. The function and importance of the watery saliva is discussed emphasizing the functional relation of subsocial behaviour and economy of salivation of these seed-sucking species.


A case of double pylorus.
Doubling of the pyloric channel is one of the rare anomalies of the intestinal tract. There have been 23 cases of double pylorus that we have been able to find in the literature. As the etiologic aspects of double pylorus the majorities of the cases were thought to be acquired lesions from ulcer disease except three cases. We present a case of double pylorus which seems to be acquired lesion, with a review of the literature.


Phylogeny of the filamentous bacterium Eikelboom Type 1851, and design and application of a 16S rRNA targeted oligonucleotide probe for its fluorescence in situ identification in activated sludge.
Micromanipulation was used to obtain an isolate (BEN 52) of Eikelboom Type 1851 from a bulking activated sludge plant. Its 16S rDNA sequence reveals its closest relative is 'Roseiflexus castenholzii', a member of the phylum 'Chloroflexi', class 'Chloroflexi', previously called the green non-sulfur bacteria. The 16S rRNA targeted oligonucleotide probe designed for fluorescence in situ hybridisation against this sequence successfully identified filamentous bacteria with the morphological features of Type 1851 in activated sludge samples from plants in several countries and different operational configurations.


[Heart and lungs : cardinal symptom dyspnea].
Dyspnea is one of the major clinical symptoms which patients report to general practitioners, internists, cardiologists and hospitals. In this review article we discuss the evidence of medical history, laboratory procedures and diagnostic investigations to approach patients with acute or chronic dyspnea and try to structure this complex symptom dyspnea to reach the etiology of the underlying disease.


Reduction of NrF2 as coadjuvant during the development of persistent periapical lesions.
Persistent periapical lesions (PPL) are the result of pulpar necrosis induced by bacterial infection resulting in bone degradation and culminating with the loss of dental piece. Pathological changes in the peripapice are associated with the presence of free radicals. The transcription factor Nrf2 is the main regulator of the endogenous antioxidant response against oxidative stress and has been implicated in the regulation of osteoclastogenesis.The aim is to determine the oxidative condition in samples from patients with Persistent Periapical Injuries as a detonating factor of tissue damage. An observational, descriptive, cross-sectional study was carried out in samples with PPL (cases) and samples by removal of third molars (controls) obtained in the clinic of the specialty in endodontics, University of Guadalajara. Samples were submitted to histological staining with Hematoxylin-Eosin, lipoperoxide analysis, Superoxide Dismutase (SOD), Glutathione-Peroxidase (GPx) and Catalase (CAT) activities were determined by immunoenzymatic assays and NrF2 by Western Blot analysis. Samples from PPL patients histologically showed an increased presence of lymphocytes, plasma cells, and eosinophils, as well as a decrease in extracellular matrix proteins and fibroblast cells. There was a rise in lipid peroxidation, GPx and SOD activities, but an important decline (36%) in Catalase activity was observed (p<0.005); finally, NrF2-protein was diminished at 10.41%. All comparisons were between cases vs controls. The alterations in antioxidants endogenous NrF2-controlled are related to osseous destruction in patients with PPL.


Piriformospora indica requires kaurene synthase activity for successful plant colonization.
Ent-kaurene (KS) synthases and ent-kaurene-like (KSL) synthases are involved in the biosynthesis of phytoalexins and/or gibberellins which play a role in plant immunity and development. The relationship between expression of five synthase genes (HvKSL1, HvKS2, HvKS4, HvKS5, HvKSL4) and plant colonization by the endophytic fungus Piriformospora indica was assessed in barley (Hordeum vulgare). The KS gene family is differently up-regulated at 1, 3 and 7 day after P. indica inoculation. By comparison, the HvKSL4 gene expression pattern is more significantly affected by UV irradiation and P. indica colonization. The characterizations of two silencing lines (HvKSL1-RNAi, HvKSL4-RNAi) also were analyzed. HvKSL1-RNAi and HvKSL4-RNAi lines in the first generation lead to less dark green leaves and slower plant development. Further, reduced spikelet fertility in progenies of RNAi plants heterozygous for HvKSL1 were observed, but not for HvKSL4. T2 generation of HvKSL1-RNAi line showed semi-dwarf phenotype while the wild type phenotype could be restored by applying GA3. Silencing of HvKSL4 and HvKSL1 resulted in reduced colonization by P. indica especially in the HvKSL1-RNAi line. These results probably suggest the presence of two ent-KS synthase in barley, one (HvKSL1) that participates in the biosynthesis of GAs and another (HvKSL4) that is involved in the biosynthesis of phytoalexins.


Heparin Modulates the Main Properties of the Central Nervous System in Experimental Post-Traumatic Stress Disorder: A New Concept of the Mechanisms of Pathogenesis and Treatment.
Elevated plus-maze test was used to reveal the role of excitation and inhibition mechanisms in the CNS in the organization of the behavior of male Wistar rats under normal conditions and during modeling experimental post-traumatic stress disorder (with or without administration of low doses of high-molecular-weight heparin). The data about insufficiency in the system of excitation mechanisms and pronounced excess in the system of inhibition mechanisms in post-traumatic stress disorder are prioritized. Heparin seems to be a promising and effective preparation to cope with extreme psychotraumatic abnormalities in CNS.


Groundwater quality assessment and its vulnerability to pollution: a study of district Nowshera, Khyber Pakhtunkhwa, Pakistan.
Groundwater is the drinking water source for the majority of rural settlements of district Nowshera, Khyber Pakhtunkhwa, Pakistan. The study aimed to analyze the groundwater quality and its vulnerability to pollution and to develop its spatial distribution mapping. For this purpose, forty-eight groundwater samples were collected from dug wells, tube wells, and hand pumps of sixteen villages and analyzed for physicochemical parameters. The XY coordinates of the sample's sources were marked by Magellan Triton 1500 handheld global positioning system (GPS). The results were compared with WHO and Pak-EPA guidelines. The results of the majority of selected parameters were found within the WHO and Pak-EPA guidelines; however, in certain areas the concentration of total dissolved solids (TDS), chlorides (Cl-), and alkalinity were higher than the guideline limits. Based on cumulative water quality the excellent water quality prevails over an area of 376 km2 (21% of district area), good water quality 726 km2 (42%), poor 424 km2 (24%), very poor 116 km2 (6%), and unfit for drinking 84 km2 (4%). The water of the Nizampur and Rashaki areas were categorized unfit for drinking. The groundwater quality of nearly one-half of the district varies from poor to very poor, and the soil type and vadose zone sediment/material was found the key reason for groundwater contamination. Based on the infiltration capacity of vadose zone material, the study area was divided into four water pollution vulnerable zones. The low vulnerable zone covers an area of 104 km2, moderate 862 km2, high 667 km2, and very high 93 km2. The most important factor which determines the vulnerability of the groundwater to contamination is the vadose zone material/sediment which in turn determines the soil infiltration capacity. The generated groundwater susceptibility and water quality maps provide critical information for identifying optimal locations for supply wells.


A combined theoretical treatment of T(1)-->S(0) intersystem crossing and intramolecular vibrational redistribution in thiophosgene.
We combine our two recent theoretical approaches for electronic relaxation T(1)-->S(0) and vibrational relaxation processes in thiophosgene (SCCl(2)) to provide a more detailed picture of the intersystem crossing (ISC) and phosphorescence from the first triplet T(1). Our analysis shows that ISC is not a true irreversible decay and should lead to violent phosphorescence quantum beats that could be observed experimentally.


Soft tissue infections from fish spike wounds: normal commensal bacteria are more common than marine pathogens.
A fish spike injury can be sustained by anyone handling fish; during fishing, meal preparation or in retail. Case reports of fish spikes inoculating victims with virulent marine-specific pathogens and causing systemic illness led us to question whether empirical treatment of these injuries with amoxicillin and clavulanic acid is adequate. This 2-year prospective observational study was conducted at Middlemore Hospital, Auckland, New Zealand. Wound swabs and tissue samples belonging to patients presenting to the Department of Plastic and Reconstructive Surgery with an upper limb fish spike injury were sent to the laboratory (n = 60). A series of stains and cultures were performed to look specifically for marine bacteria not typically isolated in other soft tissue injuries. Patient demographic data and injury details were collected. Of the patients with adequate microbiology samples, 12% (6/50) grew clinically relevant bacteria resistant to amoxicillin and clavulanic acid. These included methicillin-resistant Staphylococcus aureus (8%, 4/50), Enterobacter cloacae (2%, 1/50) and an anaerobic sporing bacillus (2%, 1/50). Only one patient grew a true marine-specific bacteria, Photobacterium damselae, which was susceptible to amoxicillin and clavulanic acid. The authors concluded that amoxicillin and clavulanic acid is an adequate first-line antibiotic for fish spike injuries but that flucloxacillin may be more appropriate given most bacteria were from patients' own skin flora. The authors suggest that clinicians consider the presence of resistant marine-specific bacteria in cases where there is sepsis or inadequate response to initial therapy.


Auto- and iso-antigens of human spermatozoa detected by immunoblotting with human sera after SDS-PAGE.
A sodium dodecylsulphate-polyacrylamide gel electrophoretic system for analysis of the proteins of human spermatozoa was established. Subsequent immunoblotting of the gels with human sera gave a reproducible immunolabelling of distinctive polypeptide bands. To identify auto- and isoantigens, 28 well-characterized sera from the WHO Reference Bank for Reproductive Immunology (1977, Acta Pathol. Microbiol. Scand. Sect. C, Suppl. 252) containing agglutinating and complement fixating antibodies (9 female (F) and 19 male (M) and 30 normal sera (14 F and 16 M) were analysed with reference to binding of IgG. Three spermatozoal antigens with Mr values in reduced state of 120,000 (6), 41,000 (6) and 32,000 (15) were found to be specifically correlated to the agglutinating activity of the reactive sea. (The number of these are given in parentheses). Furthermore, IgG from 2 and 3 of the normal sera and 14 and 17 of the agglutinating sera reacted with 78 and 64 kDA polypeptide, respectively. Identical binding patterns of IgG to spermatozoal polypeptides were obtained with IgG from male and female sera. The IgG-binding could not be correlated to the modes of spermatozoal agglutination. In a similar analysis of the IgM binding antigens of 21 agglutinating and 12 normal sera no differences in binding between the sera were found, except for a specific reaction to a 78 kDa antigen for 5 of the agglutinating sera.


The condition medium of mesenchymal stem cells promotes proliferation, adhesion and neuronal differentiation of retinal progenitor cells.
Retinal progenitor cell is a promising candidate in the treatment of retinal pigmentosa diseases. The limiting factors of stem cell transplantation are the proliferation and differentiation capacities of hRPCs, which may be governed by culture conditions. Previous studies have proved that the secretome of human Umbilical Cord Mesenchymal stem cells (hUCMSCs) and human Adipose derived stem cells (hADSCs), including more active cytokines and neurotrophic factors, have the paracrine potential of enhancing proliferation and differentiation in several cell types. The aim of this study was to investigate whether hRPCs could effectively proliferate, adhere and differentiate towards specific retinal cell types by treating with the condition medium (CM) of hUCMSCs (hUCMSCCM) or hADSCs (hADSCCM). Here, we show that hUCMSCCM or hADSCCM enhances the proliferation rate of the S and G2 phase cells, with an upregulation of Ki67 expression. Moreover, the upregulation expression of NF, Recoverin and Rhodopsin indicates that specialized retinal cells including ganglion cells and photoreceptors are favored over hRPCs differentiation due to hUCMSCCM or hADSCCM. Under FBS induced differentiation conditions, hRPCs treated with hUCMSCCM or hADSCCM increase the expression of retinal neuron and photoreceptor specific markers. These results suggest that hUCMSCCM and hADSCCM can stimulate the hRPC proliferation, promote its adherence and support hRPC neuronal and photoreceptor differentiation. These findings may provide a new strategy to improve the viability of hRPCs and photoreceptor differentiation capacities.


Allergic contact dermatitis to radiotherapy dye.
Allergic contact dermatitis to resorcin in Castellani's paint used to mark radiotherapy ports is reported.


Pregnant patients requiring appendectomy: comparison between open and laparoscopic approaches in NY State.
Even though acute appendicitis is the most common general surgical condition encountered during pregnancy, the preferred approach to appendectomy in pregnant patients remains controversial. Current guidelines support laparoscopic appendectomy as the treatment of choice for pregnant women with appendicitis, regardless of trimester. However, recent published data suggests that the laparoscopic approach contributes to higher rates of fetal demise. Our study aims to compare laparoscopic and open appendectomy in pregnancy at a statewide population level. ICD-9 codes were used to extract 1006 pregnant patients undergoing appendectomy between 2005 and 2014 from the NY Statewide Planning and Research Cooperative System (SPARCS) database. Surgical outcomes (any complications, 30-day readmission rate, length of stay (LOS)) and obstetrical outcomes (antepartum hemorrhage, preterm delivery, cesarean section, sepsis, chorioamnionitis) were compared between open and laparoscopic appendectomy. Multivariable generalized linear regression models were used to compare different outcomes between two surgical approaches after adjusting for possible confounders. The laparoscopic cohort (n = 547, 54.4%) had significantly shorter LOS than the open group (median ± IQR: 2.00 ± 2.00 days versus 3.00 ± 2.00 days, p value < 0.0001, ratio = 0.789, 95% CI 0.727-0.856). Patients with complicated appendicitis had longer LOS than those with simple appendicitis (p value < 0.0001, ratio = 1.660, 95% CI 1.501-1.835). Obstetrical outcomes (p value = 0.097, OR 1.254, 95% CI 0.961-1.638), 30-day non-delivery readmission (p value = 0.762, OR 1.117, 95% CI 0.538-2.319), and any complications (p value = 0.753, OR 0.924, 95% CI 0.564-1.517) were not statistically significant between the laparoscopic versus open appendectomy groups. Three cases of fetal demise occurred, all within the laparoscopic appendectomy group. The laparoscopic approach resulted in a shorter LOS. Although fetal demise only occurred in the laparoscopic group, these results were not significant (p value = 0.255). Our large population-based study further supports current guidelines that laparoscopic appendectomy may offer benefits over open surgery for pregnant patients in any trimester due to reduced time in the hospital and fetal and maternal outcomes comparable to open appendectomy.


Humoral immunity at the brain borders in homeostasis.
The meninges encase the brain and spinal cord and house a variety of immune cells, including developing and mature B cells, and antibody-secreting plasma cells. In homeostasis, these cells localize around the dural venous sinuses, providing a defense 'zone' to protect the brain and spinal cord from blood-borne pathogens. Dural plasma cells predominantly secrete IgA antibodies, and some originate from the gastrointestinal tract, with the number and antibody isotype shaped by the gut microbiome. For developing B cells arriving from the adjacent bone marrow, the dura provides a site to tolerize against central nervous system antigens. In this review, we will discuss our current understanding of meningeal humoral immunity in homeostasis.


"When night falls": Violence against women and its repercussions on children and adolescents.
Violence against women is a profound global injustice. It is a major obstacle to fulfilling the human rights of women and their children. Confined to their aggressors, women exposed to this violence have even greater difficulty in accessing support networks and care services. Furthermore, the economic impact of the pandemic, which disproportionately affected women, created additional barriers. In reality, however, femicide is forgotten, underestimated, and poorly prosecuted throughout the world. In this context, more than 100 children witnessed a murder or were at home when it took place. This form of indirect violence is vicarious, in which children are left out, anonymous, and invisible. The trauma generated potentiates mentalization difficulties, emotional dependence, and instability in future relationships, caused by pain and psychological suffering.


Utility of Skin Grafting and Tissue Expansion in Penile Reconstruction for the Exstrophy-Epispadias Complex.
To describe the use of additional tissue recruited for coverage after penile lengthening in male exstrophy-epispadias complex patients using either local skin from tissue expansion (TE) or extragenital skin with a skin graft (SG) and report their respective outcomes. An institutionally approved database of exstrophy-epispadias complex patients was retrospectively reviewed for male patients who received penile reconstruction. This included a penile lengthening procedure and the subsequent use of TE and/or a full thickness skin graft to provide cutaneous coverage of gained corporal length. A total of 50 patients (mean age 18.1 years) underwent penile reconstruction. TE was used in 27 patients, SG in 19, and 4 received a combination of TE and SG. The mean number of previous penile operations was 2.7 for patients that received TE and 3.1 for SG. A successful outcome from primary reconstruction was achieved in 35 patients (70%) and overall successful reconstruction was achieved by 48 patients (96%). TE and SG are useful techniques in providing soft tissue coverage following penile lengthening. TE is the preferred technique for primary reconstruction in a lengthening procedure. When genital skin is not expandable or coverage from TE is insufficient after lengthening, extragenital skin (SG) is recruited.


The new concept of bariatric surgery in China--reevaluation of surgical indications and criteria of therapeutic effect of laparoscopy for treatment of obesity.
The etiology of morbid obesity is multifactorial and is related to inheritance, physiology, metabolism, sociocultural, behavioral, and psychological factors. In China, the incidence of obesity is increasing with the improvement of the standard of living each year. The USA is known as the nation that has a high prevalence of overweight and obese individuals, as indicated from the Nutrition and Health Status report. Obesity in China is a growing phenomenon that cannot be ignored. In this paper, we review the relatively new concept of bariatric surgery in China.


Prevalence and progression of rheumatic heart disease: a global systematic review and meta-analysis of population-based echocardiographic studies.
This systematic review and meta-analysis aimed to provide a contemporaneous estimate of the global burden of rheumatic heart disease (RHD) from echocardiographic population-based studies. We searched multiple databases between January 01, 1996 and October 17, 2017. Random-effect meta-analysis was used to pool data. We included 82 studies (1,090,792 participant) reporting data on the prevalence of RHD and 9 studies on the evolution of RHD lesions. The pooled prevalence of RHD was 26.1‰ (95%CI 19.2-33.1) and 11.3‰ (95%CI 7.2-16.2) for studies which used the World Heart Federation (WHF) and World Health Organization (WHO) criteria, respectively. The prevalence of RHD varied inversely with the level of a country's income, was lower with the WHO criteria compared to the WHF criteria, and was lowest in South East Asia. Definite RHD progressed in 7.5% (95% CI 1.5-17.6) of the cases, while 60.7% (95% CI 42.4-77.5) of cases remained stable over the course of follow-up. The proportion of cases borderline RHD who progressed to definite RHD was 11.3% (95% CI 6.9-16.5). The prevalence of RHD across WHO regions remains high. The highest prevalence of RHD was noted among studies which used the WHF diagnostic criteria. Definite RHD tends to progress or remain stable over time.


A monoclonal antibody directed against a synthetic peptide reacts with a cell surface rabbit class I MHC molecule.
Monoclonal antibodies were prepared against synthetic peptides synthetized on the basis of nucleotide sequence from cDNA and genomic clones encoding a class I antigen expressed by the rabbit RL-5 cell line. Using a peptide corresponding to positions 61-73 of the N domain, we were able to obtain an hybridoma producing monoclonal antibody which recognized the peptide as well as the native class I antigen. This hybridoma, designated anti-61, reacted with cell surface molecules on RL-5 cells and on human HeLa cells transfected with the 19-1 gene encoding RL-5 class I antigen. No reactivity with HeLa cells prior to transfection could be detected by radioimmunoassay or by fluorescent activated cell sorter analyses, although these cells were strongly positive in both assays with anti-human class I reagents. Antibody reaction to positive cells could be inhibited by the homologous peptide but not by unrelated peptides. Anti-61 antibody precipitated a 41,000 mol. wt molecule from RL-5 cells with an N-terminal amino acid sequence corresponding to the RL-5 class I antigen.


Stromal reprogramming: A target for tumor therapy.
Cancer associated fibroblasts (CAFs) as the dominant, long-lived and highly plastic cells within the tumor microenvironment (TME) with multi-faceted roles that are endowed with tumor aggressive features. They can instruct and shape the stroma of tumor into being a highly qualified bed for cellular recruitment, differentiation and plasticity in the host tissue or secondary organ/s. In this Review, we have a discussion over CAF reprogramming as a general concept, inducers and outcomes, pursued by suggesting potential strategies to combat this key promoter of tumor.


Comparative study on the efficacy and safety of alteplase and urokinase in the treatment of acute cerebral infarction.
Acute cerebral infarction (ACI) is a common cerebrovascular disease in clinical practice. The present study aims to investigate the efficacy and safety of alteplase and urokinase in treating ACI. A total of 96 patients with ACI, who were treated with alteplase and urokinase, were selected as the main subjects. Among these patients, 45 patients with ultra-early acute cerebral infarction, who received intravenous thrombolysis with RT-PA (alteplase), were included in the treatment group, while 51 patients with acute cerebral infarction, who were treated with urokinase in the same time period, were included in the control group. The National Institute of Health Stroke Scale (NIHSS) scores were significantly lower in the treatment group and control group (P< 0.05) at two hours, seven days and 14 days after thrombolysis, when compared to those before thrombolysis. The bleeding rate was significantly lower in the control group, when compared to the treatment group (P< 0.05). The intravenous thrombolysis with urokinase or alteplase in the ultra-early stage of acute cerebral infarction can reduce the neurological injury symptoms and effectively improve the prognosis of patients with stroke. Urokinase is lower in risk of bleeding, but better in safety, when compared to alteplase.


Effect of composition ratio on the thermal and physical properties of semicrystalline PLA/PHB-HHx composites.
In this study, composites of semicrystalline, biodegradable polylactide (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHB-HHx) were prepared by direct melt compounding. The physical and thermal properties of the composites were investigated as a function of the composition ratio. Differential scanning calorimetry analysis indicated that PLA and PHB-HHx formed immiscible composites over the observed range of composition. The crystallization of PLA was gradually suppressed by increasing proportions of PHB-HHx. Dynamic mechanical analysis results confirmed that the innate ductility of PHB-HHX and its inhibiting effect on PLA crystallization improved the stiffness of the composite compared to those of neat PLA. The infrared spectra of the immiscible PLA/PHB-HHx composites at two crystallization temperatures (30 °C, 130 °C) were obtained and presented. At 30 °C, PHB-HHx existed as crystalline domains in the PLA matrix, while, amorphous phase of molten PHB-HHx was diffused within the crystalline phase of PLA at 130 °C. The interaction between PHB-HHX and PLA could not be elucidated from the temperature data. Mechanical tests showed that the addition of PHB-HHx improves ductility of PLA/PHB-HHx composite. Morphological analysis revealed that small proportions of PHB-HHx exhibited less tendency to aggregate, which resulted in greater plastic deformation and improved toughness. From this study, PLA blended with small portions of PHB-HHx may further expand the use of bio-friendly resources in a variety of applications such as flexible films, food packaging and something like that.


SHIPing news: a new way to keep your weight down.
Almost always, obesity is an obligate prerequisite for the development of type 2 diabetes mellitus. Loss of a well-known lipid phosphatase appears to prevent insulin-resistant diabetes in mice by removal of a positive regulator of adiposity.


Different Categorizations of Women's Sexual Orientation Reveal Unique Health Outcomes in a Nationally Representative U.S. Sample.
Sexual minority women (i.e., women minoritized for their sexualities) are identified as high risk for mental health and substance use problems; however, there is no consensus on the criteria by which women are categorized as sexual minority. Though there is some evidence suggesting that certain subgroups of women are at higher risk than others based on sexual orientation, different categorization schemes for sexual orientation have yet to be compared within the same sample. Using data from the National Epidemiologic Survey of Alcohol and Related Conditions-III (N = 19,528), we examined how multiple categorization schemes (i.e., identity, behavior, recency of sexual behavior) for categorizing women who have sex with women (WSW) yield different estimates of prevalence of mental health and substance use issues. We used chi-square and logistic regression to analyze the link between sexual orientation categorization schemes and health, categorizing by 1) self-identification only, 2) behavior only, and 3) the combination of self-identification and behavior (recent vs. past). We discovered high prevalence rates of health problems among heterosexual-identified WSW who reported no recent sexual activity with women (i.e., previously had sex with women but not within the past 12 months); this category of women comprised 35% of all WSW. Step by step, we found more detailed information about these women's experiences by moving to the complex categorization scheme (the combination of self-identification and behavior). Heterosexual-identified women who have had sex with women in their past (though not recently) presented as a large group with high prevalence rates of substance use and mental disorders. These women remain invisible to researchers who categorize sexual orientation only by sexual identity or by behavior and ignore the role of behavior change over time-imprecisely categorizing such women as heterosexual or as women who have sex with men. They thus are underserved by health research and represent a significant population for further study and intervention.


Transcriptome analysis of Euwallacea interjectus reveals differentially expressed unigenes related to developmental stages and egg laying.
Euwallacea interjectus (Curculionidae: Scolytinae) is an ambrosia beetle species in its early stages of research. Therefore, studying the related molecular mechanism associated with the development and egg laid is essential. Transcriptome sequencing was used in this study to compare the gene expression of the beetles at different developmental stages and female adults before and after oviposition. A total of 40,047 annotated unigenes were obtained. There were 4225 differentially expressed unigenes (DEUs) from larva to prepupa stage, 3651 DEUs between prepupa and pupa, 1675 DEUs generated from pupa to adult, and 4762 DEUs between females before and after oviposition. The most significant pathway differences between different development stages and before and after oviposition were selected through functional annotation of DEUs between different stages. Among them, there were many pathways related to protein metabolism including: neuroactive ligand-receptor interaction, endoplasmic reticulum and RNA transport. This study provides valuable information on the molecular regulation mechanism of development and the egg laid of E. interjectus.


A new semisynthetic 1-O-acetyl-6-O-lauroylbritannilactone induces apoptosis of human laryngocarcinoma cells through p53-dependent pathway.
Initiation of apoptosis is an important event for chemoprevention and chemotherapy of cancer. Naturally derived products had drawn growing attention as lead compounds for anticancer drug discovery. ABL-L, a semisynthetic analogue of natural sesquiterpenoid 1-O-acetylbritannilactone (ABL) isolated from Inula britannica, showed stronger suppression against three solid tumor cell lines with 4-10 fold improvement than ABL. However, its molecular mechanism of cell death induction has still not been determined. The present study evaluated the anticancer efficacy of ABL-L and its biological activities mechanism on human laryngocarcinoma cells HEp-2 in vitro. We found that ABL-L-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest. Typical apoptotic morphological and biochemical features were also observed in treated cells. Furthermore, the levels of the anti-apoptotic Bcl-2, pro-caspase 3/8/9 and poly(ADP-ribose) polymerase PARP decreased, and the level of pro-apoptotic Bax increased. Involvement of the caspase-mediated apoptosis was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. In addition, ABL-L induced a tumor suppressor p53 and its target genes expression p21, fas, noxa and puma. The results of p53 knockdown suggest that caspase-mediated apoptosis induced by ABL-L was in p53-dependent pathway on HEp-2 cells. Our data indicate that the cytotoxicity of the novel semisynthetic analogue ABL-L involved G1 cell cycle arrest and apoptosis via a p53-dependent, caspase-mediated pathway on human laryngocarcinoma cells.


The effect of open vs closed-book testing conditions upon performance on a multiple-choice examination in pediatrics.
This study compared the performance of medical students and practicing pediatricians taking a graduate-level examination in pediatrics under open-book vs closed-book conditions. Students performed significantly better under open-book conditions, but there was no significant difference for the practitioner group.


[Transports and hospitalizations avoided thanks to teleconsultations for elderly patients living in nursing homes].
The care of elderly people living in nursing homes is a medical public health issue. The objective of this study is to evaluate the number of hospitalizations and transports avoided thanks to teleconsultations and to evaluate the therapeutic and follow up consequences of these teleconsultations. A retrospective descriptive study of cardiology and neuropsychogeriatric teleconsultations was performed in three nursing home participating in the TokTokDoc Mobile Polyclinic project between September 1st, 2020 and February 28, 2021. We included 77 patients who had a total of 120 teleconsultations. Sixty-seven transports (55.8%) and 12 hospitalizations (10%) were avoided. Therapeutic optimization was achieved in 38 cases (40%). Complex medical assessments were carried out in the same way as a face-to-face consultation. Telemedicine is a relevant tool for improving the healthcare circuit care of residents, by avoiding medical transport and hospitalizations. These preliminary results also show the feasibility of teleconsultations in cardiology and neuropsychogeriatrics despite the medical complexity of these two specialties.


Absence of NC14A Domain of COLXVII/BP180 in Mice Results in IL-17‒Associated Skin Inflammation.
The deletion of exon 18 from Col17a1 in transgenic ΔNC14A mice results in the absence of the NC14A domain. NC14A corresponds to the human NC16A domain, the immunodominant epitope in bullous pemphigoid. Before the age of 1 year, 84% of ΔNC14A mice have developed severe itch and skin erosion. Further characterization of mice with mutated CoLXVII (Bp180) revealed acanthosis; subepidermal blistering; and inflammatory cell infiltrates, especially neutrophils, eosinophils, and mast cells in the lesional skin. Direct immunofluorescence analysis detected linear complement C3, IgG, and/or IgA deposition in the dermo‒epidermal junction of symptomatic ΔNC14A mice. Elevated gene expression of IL-17‒associated cytokines was detected in the lesional skin. An increased proportion of dendritic cells, myeloid-derived suppressor cells, and NK cells and a decrease of T cells were found in both the spleen and lymph nodes of symptomatic ΔNC14A mice. The proportions of B cells and regulatory T cells were increased in lymph nodes. An 8-week treatment with an anti‒IL-17A decreased the expression of Il6, Il23a, and Cxcl1 in the nonlesional skin. Our results suggest that the absence of the NC14A domain of CoLXVII in mice causes an autoimmune response against the cutaneous basement membrane and manifests as an IL-17‒associated inflammation in the skin.


Prescription of potentially inappropriate medication in Korean older adults based on 2012 Beers Criteria: a cross-sectional population based study.
A high number of elderly people with multiple comorbidities are exposed to the risk of polypharmacy and prescription of potentially inappropriate medication (PIM). The purpose of this study was to determine the prevalence and patterns of PIM prescription in Korean older adults according to the 2012 Beers Criteria. A retrospective study was conducted using data from the Korean Health Insurance Review and Assessment (KHIRA) database of outpatient prescription claims collected from January 1, 2009 to December 31, 2011. A total of 523,811 elderly subjects aged 65 years and older were included in the study, and several covariates related to the prescription of PIMs were obtained from the KHIRA database. These covariates were analyzed using Student's t test and the chi-square test; furthermore, multivariate logistic regression analysis was used to evaluate the risk factors associated with the prescription of PIMs. A total of 80.96 % subjects were prescribed at least one PIM independent of their diagnosis or condition according to the 2012 Beers Criteria. The most commonly prescribed medication class was first-generation antihistamines with anticholinergic properties (52.33 %). Pain medications (43.04 %) and benzodiazepines (42.53 %) were next in line. When considering subjects' diagnoses or conditions, subjects diagnosed with central nervous system conditions were most often prescribed PIMs. Female sex, severity of comorbidities, and polypharmacy were significant risk factors for PIM prescriptions. This study confirmed that PIM prescription is common among elderly Koreans. A clinical decision support system should be developed to decrease the prevalence of PIM prescriptions.


Achilles heel of environmental risk from recycling of sludge to soil as amendment: A summary in recent ten years (2007-2016).
Recycling sludge as a soil amendment has both positive and negative effects because of its enrichment in both nutrients and contaminants. So far, the negative effect has to be extensively investigated that the severities of different types of contaminants also remain unclear. The environmental behavior and risk of organic contaminant and pharmaceuticals, heavy metal and salt as well as pathogenic microorganisms brought by sludge amendment are summarized and discussed here. Organic contaminants and pharmaceuticals are typically found at low concentrations in sludge, the risks from sludge-amended soil decrease over time owing to its biodegradability. On the other hand, application of sludge generally increases soil salinity, which may cause physiological damage to plants grown in sludge-amended soil. In some extent, this negative effect can be alleviated by means of dilution; however, greater attention should be paid to long term increasing possible risk of eutrophication. Heavy metal (particularly of mobile heavy metals, such as Cd) with high concentrations in sludge and soil receiving considerable sludge can cause its incremental abundance in soil and crop contamination, further posing risks to humans, but most cases showed that there remained not excessive in heavy metal caused by sludge amendment. It is worth noting that increasing soil organic matter content may reduce transfer of heavy metal from soil to crops, but not restrict its uptake by crops at all. Combined literature together, it is summarized that heavy metal becomes a relatively severe bottleneck in recycling of sludge as soil amendment due to its non-biodegradability and potential damage to health by adventuring contamination from agricultural products. Particular attention should therefore be paid to long term monitoring the change of heavy metals concentration in sludge amended soil.


Diaphragmatic hernias in the horse: a review of the literature and an analysis of six additional cases.
Eighteen cases of equine diaphragmatic hernia were reviewed. Most of the cases were of long duration, with an additional factor precipitating acute abdominal crisis. History and physical examination were of little diagnostic significance. Radiography, if available, and exploratory laparotomy were the most useful diagnostic procedures. The prognosis for successful surgical repair and recovery was poor.


Herbal medicine Shakuyaku-kanzo-to reduces paclitaxel-induced painful peripheral neuropathy in mice.
Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors such as breast, ovarian and lung cancer. However, it sometimes induces moderate to severe muscle pain, and impairs the patients' quality of life. An appropriate method for relieving this pain is not well established. Shakuyaku-kanzo-to, a herbal medicine, is known to relieve menstrual pain, muscle spasm, and muscle pain, and its effectiveness is expected. To ascertain the effectiveness of Shakuyaku-kanzo-to on paclitaxel-induced pain, we investigated the effects of Shakuyaku-kanzo-to and its constituent herbal medicines in a mouse model. Seven-week-old male ddY mice were used. To make a mouse model of paclitaxel-induced pain, different single, intraperitoneally injected doses of this drug were tested in various groups of mice, and the optimal dose was determined. To estimate the effects of Shakuyaku-kanzo-to, the constituent herbal medicines Shakuyaku and Kanzo, and loxoprofen sodium as a non-steroidal anti-inflammatory drug on paclitaxel-induced pain, mechanical allodynia and hyperalgesia of the hind paw were assessed. Paclitaxel administered at a dose of 10mg/kg or more produced allodynia and hyperalgesia; the time courses were similar to those of pain after paclitaxel administration in cancer patients. Shakuyaku-kanzo-to significantly relieved the allodynia and hyperalgesia induced by paclitaxel (10mg/kg). Shakuyaku and Kanzo inhibited the allodynia and hyperalgesia to some extent, but not significantly, while loxoprofen sodium was without effects. A single administration of paclitaxel (10mg/kg) produced allodynia and hyperalgesia in mice, suggesting that it could be used as an animal model resembling the painful conditions observed in humans medicated with this drug. Using this model, Shakuyaku-kanzo-to was shown to relieve paclitaxel-induced painful peripheral neuropathy.


Effects of intracerebroventricular administration of ovine corticotropin-releasing factor (CRF 1-41) on passive avoidance behaviour: lack of influence on monoamine contents of limbic brain areas.
The effects of intracerebroventricular administration of synthetic ovine corticotropin-releasing factor (CRF 1-41) have been investigated on the retention of passive avoidance behaviour, and on the dopamine, norepinephrine and serotonin contents of the hypothalamus, mesencephalon, amygdala, septum and striatum, as well as on the plasma corticosterone levels of hypophysectomized and sham-operated rats. Treatment with CRF 1-41 20 min before the first retention test, 24 hours after the learning trial, significantly facilitated the passive avoidance behaviour of hypophysectomized animals in a dose-dependent manner. No effect was found in sham-operated rats. No significant effects of a wide dose range of intracerebroventricularly injected CRF on the monoamine contents of limbic brain structures were detected. However, the same doses of CRF 1-41 increased the plasma corticosterone level in sham-operated rats. The data suggest that the release of CRF from neurons in the limbic system does not alter the monoamine contents in this system, although this peptide facilitates the retention of the passive avoidance behaviour of hypophysectomized rats.


Virus-mediated decrease of LKB1 activity in the mPFC diminishes stress-induced depressive-like behaviors in mice.
As a highly prevalent neuropsychiatric disorder worldwide, the pathophysiology of depression is not yet fully understood and based on multiple factors among which chronic stress is critical. Numerous previous studies have shown the role of central mammalian target of rapamycin complex 1 (mTORC1) signaling in depression. However, so far it remains elusive by which way chronic stress down-regulates the activity of central mTORC1. Liver kinase b1 (LKB1) has been demonstrated to regulate the activity of the mTORC1 signaling cascade by phosphorylating AMP activated protein kinase (AMPK). Here, this study aimed to explore whether LKB1 participates in depression by regulating the downstream AMPK-mTORC1 signaling, and various methods including mouse models of depression, western blotting and immunofluorescence were used together. Our results showed that chronic stress significantly enhanced the expression of both phosphorylated LKB1 and total LKB1 in the medial prefrontal cortex (mPFC) but not the hippocampus. Furthermore, genetic knockdown of LKB1 in the mPFC fully reversed not only the depressive-like behaviors induced by chronic stress in mice but also the effects of chronic stress on the activity of AMPK and the mTORC1 system. Taken together, this study preliminarily suggests that LKB1 in the mPFC could be a feasible target for antidepressants. This study also provides support for the potential use of LKB1 inhibition strategies against the chronic stress-related neuropsychiatric disorders.


Fertility-sparing management for endometrial cancer: review of the literature.
Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered. We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020. Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%. Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.


Niizalactams A-C, Multicyclic Macrolactams Isolated from Combined Culture of Streptomyces with Mycolic Acid-Containing Bacterium.
A terrestrial bacterium, Streptomyces sp. NZ-6, produced niizalactams A-C (1-3), unprecedented di- and tricyclic macrolactams, by coculturing with the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596. Their complete structures, including absolute configurations, were elucidated on the basis of spectroscopic data and chemical derivatization. Their unique skeletons are proposed to be biosynthesized from a common 26-membered macrolactam intermediate by SN2 cyclization or an intramolecular Diels-Alder reaction.


Dermatophytosis of children in Kuwait: a prospective survey.
Tinea capitis in children is widely reported, whereas there have been only isolated reports on involvement of sites other than the scalp. The purpose of this study was to examine the epidemiological features and treatment responses of dermatophytosis of children in Kuwait. Epidemiological features and the treatment responses of 202 consecutive children with dermatophytosis were studied. The 202 children constituted 44% of the total dermatophytic infections seen during a period of 1 year. Tinea capitis was the most commonly encountered infection (78%), followed by tinea corporis, tinea faciei, tinea cruris and manus, respectively. Microsporum canis was the most prevalent species (96%) in this region. A history of pets at home could be elicited in 52% of the cases. A familial occurrence of similar infections was seen in 56% of the patients. In patients with tinea capitis, addition of topical clotrimazole or ketoconazole to oral griseofulvin produced better therapeutic results compared to griseofulvin alone or in combination with selenium sulfide shampoo. Tinea capitis is the most common dermatophytic infection in children. Thirty percent of the children may have dermatophytosis at sites other than the scalp. A combination of topical clotrimazole or ketoconazole with oral griseofulvin is superior to griseofulvin alone or in combination with selenium sulfide shampoo in the treatment of tinea capitis.


Limitations of the transmitted photonic spin Hall effect through layered structure.
In this paper, we show theoretically that the spin-dependent transverse shift of the transmitted photonic spin Hall effect (SHE) through layered structure cannot exceed half of the incident beam waist. Exact conditions for obtaining the upper limit of the transmitted SHE are clarified in detail. In addition, different from the popular view in many investigations, we find that there is no positive correlation between the spin-dependent transverse displacement and the ratio between the Fresnel transmission coefficients (tp, ts). In contrast, the optimal transmission ratio is determined by the incident angle and the beam waist. Moreover, two conventional transmission structures are selected and studied in detail. The characteristics of the transverse displacements obtained are in very good agreement with our theoretical conclusions. These findings provide a deeper insight into the photonic spin Hall phenomena and offer a guide for future related research.


Tumor mutational burden is not predictive of cytotoxic chemotherapy response.
High tumor mutational burden (TMB) predicts checkpoint blockade responsiveness, although the association with outcomes may be nuanced in certain tissue contexts. The correlation between TMB and cytotoxic chemotherapy sensitivity is unknown. This study evaluated the relationship between TMB and outcome in patients with solid tumors receiving cytotoxic chemotherapy. University of California San Diego patients who received cytotoxic chemotherapy within one year after biopsy for TMB evaluation were included in a retrospective analysis. Physician notes and imaging reports in the electronic medical record were reviewed to determine clinical benefit and progression-free survival (PFS). Among 1526 patients with TMB availability, there were 294 eligible patients who received chemotherapy. There were no significant differences in TMB between those with stable disease ≥6 months/partial response/complete response versus others (t-test, p = .22). There were no significant differences in PFS for patients with TMB <10 vs. TMB ≥10 mutations/Mb (log-rank test, median and 95% CI: 6.0 (4.8-7.4) vs. 5.4 (4.3-6.6) months; p = .21). Nor were there significant differences in PFS for patients with a TMB <10 vs. TMB ≥10 mutations/mb for breast (p = .07), lung (p = .47), or gastrointestinal cancer (p = .53). In summary, TMB was not predictive of stable disease ≥6 months/partial response/complete response or PFS in patients receiving cytotoxic chemotherapy. NCT02478931.