Microevolution of European temperate oaks in response to environmental changes.
This review reconstructs microevolutionary processes that allowed long-lived species as temperate oaks (Quercus petraea and Q. robur) to cope with climate change since the last glacial maximum, by assembling insights from complementary synchronic and allochronic approaches. Paleobotanical and genetic investigations show that oaks migrated at larger velocities than expected, thanks to long-distance rare events and most likely human interferences. Hybridization was a key mechanism accelerating migration and enhancing species succession. Common garden experiments and genome wide association studies demonstrated that diversifying selection across large environmental gradients contributed to rapid local adaptation. Finally the review explores how lessons taken from past evolutionary scenarios may help to predict future responses of oaks to ongoing climate change.


Catecholaminergic Polymorphic Ventricular Tachycardia: A Review of Therapeutic Strategies.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmia provoked by exercise or emotion. Most cases are caused by pathogenic variants in the gene encoding the cardiac ryanodine receptor (RYR2). The options for treating patients with CPVT have increased during the years, and evidence suggests that these have led to lower arrhythmic event rates. In addition, numerous potential new therapies are being investigated. In this review, we summarize the state of knowledge on both established and potential future treatment strategies for patients with CPVT and describe our approach to their management.


CNS involvement in the antisecretory action of [Met5]enkephalinamide on the rat intestine.
The effects of the stable enkephalin, [D-Ala2, Met5]enkephalinamide (DAMA) were examined on basal and stimulated fluid accumulation in intestinal loops of anesthetized Wistar-Furth rats. DAMA (0.1-3.0 micrograms, i.c.v.) dose-dependently increased basal fluid absorption in the medial ileum and decreased jejunal and proximal ileal fluid secretion after 4 h cholera toxin (1 microgram/loop) pretreatment. The antisecretory effects of DAMA were blocked by naltrexone (1 mg/kg s.c.). Thus, the antisecretory effects of opioids may be partially mediated at CNS sites.


Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation.
Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. In contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs.


A quality assurance method that utilizes 3D dosimetry and facilitates clinical interpretation.
To demonstrate a new three-dimensional (3D) quality assurance (QA) method that provides comprehensive dosimetry verification and facilitates evaluation of the clinical significance of QA data acquired in a phantom. Also to apply the method to investigate the dosimetric efficacy of base-of-skull (BOS) intensity-modulated radiotherapy (IMRT) treatment. Two types of IMRT QA verification plans were created for 6 patients who received BOS IMRT. The first plan enabled conventional 2D planar IMRT QA using the Varian portal dosimetry system. The second plan enabled 3D verification using an anthropomorphic head phantom. In the latter, the 3D dose distribution was measured using the DLOS/Presage dosimetry system (DLOS = Duke Large-field-of-view Optical-CT System, Presage Heuris Pharma, Skillman, NJ), which yielded isotropic 2-mm data throughout the treated volume. In a novel step, measured 3D dose distributions were transformed back to the patient's CT to enable calculation of dose-volume histograms (DVH) and dose overlays. Measured and planned patient DVHs were compared to investigate clinical significance. Close agreement between measured and calculated dose distributions was observed for all 6 cases. For gamma criteria of 3%, 2 mm, the mean passing rate for portal dosimetry was 96.8% (range, 92.0%-98.9%), compared to 94.9% (range, 90.1%-98.9%) for 3D. There was no clear correlation between 2D and 3D passing rates. Planned and measured dose distributions were evaluated on the patient's anatomy, using DVH and dose overlays. Minor deviations were detected, and the clinical significance of these are presented and discussed. Two advantages accrue to the methods presented here. First, treatment accuracy is evaluated throughout the whole treated volume, yielding comprehensive verification. Second, the clinical significance of any deviations can be assessed through the generation of DVH curves and dose overlays on the patient's anatomy. The latter step represents an important development that advances the clinical relevance of complex treatment QA.


Design, Synthesis, and Biological Evaluation of (+)-Camphor- and (-)-Fenchone-Based Derivatives as Potent Orthopoxvirus Inhibitors.
In this work, a library of (+)-camphor and (-)-fenchone based N-acylhydrazones, amides, and esters, including para-substituted aromatic/hetaromatic/cyclohexane ring was synthesized, with potent orthopoxvirus inhibitors identified among them. Investigations of the structure-activity relationship revealed the significance of the substituent at the para-position of the aromatic ring. Also, the nature of the linker between a hydrophobic moiety and aromatic ring was clarified. Derivatives with p-Cl, p-Br, p-CF3, and p-NO2 substituted aromatic ring and derivatives with cyclohexane ring showed the highest antiviral activity against vaccinia virus, cowpox, and ectromelia virus. The hydrazone and the amide group were more favourable as a linker for antiviral activity than the ester group. Compounds 3 b and 7 e with high antiviral activity were examined using the time-of-addition assay and molecular docking study. The results revealed the tested compounds to inhibit the late processes of the orthopoxvirus replication cycle and the p37 viral protein to be a possible biological target.


Cross-sectional Pilot Study of Antibiotic Resistance in Propionibacterium Acnes Strains in Indian Acne Patients Using 16S-RNA Polymerase Chain Reaction: A Comparison Among Treatment Modalities Including Antibiotics, Benzoyl Peroxide, and Isotretinoin.
Antibiotic resistance is a worldwide problem in acne patients due to regional prescription practices, patient compliance, and genomic variability in Propionibacterium acnes, though the effect of treatment on the resistance has not been comprehensively analyzed. Our primary objective was to assess the level of antibiotic resistance in the Indian patients and to assess whether there was a difference in the resistance across common treatment groups. A cross-sectional, institutional based study was undertaken and three groups of patients were analyzed, treatment naïve, those on antibiotics and patients on benzoyl peroxide (BPO) and/isotretinoin. The follicular content was sampled and the culture was verified with 16S rRNA polymerase chain reaction, genomic sequencing, and pulsed-field gel electrophoresis. Minimum inhibitory concentration (MIC) assessment was done for erythromycin (ERY), azithromycin (AZI), clindamycin (CL), tetracycline (TET), doxycycline (DOX), minocycline (MINO), and levofloxacin (LEVO). The four groups of patients were compared for any difference in the resistant strains. Of the 52 P. acnes strains isolated (80 patients), high resistance was observed to AZI (100%), ERY (98%), CL (90.4%), DOX (44.2%), and TETs (30.8%). Low resistance was observed to MINO (1.9%) and LEVO (9.6%). Statistical difference was seen in the resistance between CL and TETs; DOX/LEVO and DOX/MINO (P < 0.001). High MIC90 (≥256 μg/ml) was seen with CL, macrolides, and TETs; moreover, low MIC90 was observed to DOX (16 μg/ml), MINO (8 μg/ml), and LEVO (4 μg/ml). Though the treatment group with isotretinoin/BPO had the least number of resistant strains there was no statistical difference in the antibiotic resistance among the various groups of patients. High resistance was seen among the P. acnes strains to macrolides-lincosamides (AZI and CL) while MINO and LEVO resistance was low.


Dendritic arborization patterns of cortical interneurons labeled with the lectin, Vicia villosa, and injected intracellularly with Lucifer yellow in aldehyde-fixed rat slices.
Neurons whose cell bodies had been stained by a lectin, Vicia villosa, which recognizes terminal N-acetylgalactosamine residue, were intracellularly injected with Lucifer yellow (LY), in aldehyde-fixed slices of the parietal cortex of rats. LY was subsequently visualized immunocytochemically. All injected neurons had smooth or only sparsely spiny dendrites and resembled the various forms of gamma-aminobutyric acid-ergic neurons previously described in rat neocortex. In layers II/III, IV and V, most injected neurons were multipolar. In layer VI, most had vertically elongated dendritic fields. Some injected neurons in layer IV had an oval or vertically elongated soma and a bitufted dendritic arborization pattern. There was a gradual increase in the overall dendritic extent in deeper layers of the cortex.


Characterization of a novel degradation product of 2,2'-dithiobis[N-isoleucylbenzamide], an inhibitor of HIV nucleocapsid protein zinc fingers.
Zinc finger motifs have been found to be important in a variety of protein structures including transcription factors and viral nucleocapsid proteins. Recently, it was demonstrated that various aromatic disulfides effectively remove the metal ion from the zinc finger, resulting in an alteration of tertiary structure in this region of the protein, thereby inhibiting transcription. Among these compounds, 2,2'-dithiobis[N-isoleucylbenzamide] exhibits activity against human immunodeficiency virus (HIV)-type 1 in vitro and has been selected for preclinical development as an anti-HIV agent. Analysis of this agent by reversed-phase high-performance liquid chromatography (HPLC) indicated a significant quantity of two additional compounds. Identifying the parent disulfide was accomplished by scanning eluting peaks with positive ion thermospray ionization (TSP) mass spectrometry (MS). Solution-induced disproportionation of the disulfide into its sulfhydryl monomer was demonstrated by treating the drug with dithiothreitol (DTT) prior to HPLC analysis. TSP-MS analysis of the remaining chromatographic peak suggested a molecular weight of 265, which, with 1H-nuclear magnetic resonance (NMR) data of the isolated material, allowed us to elucidate the chemical structure as N-isoleucyl-benzisothiazolone. Contact with stainless steel, such as that employed in an HPLC system, was found to accelerate degradation of the parent disulfide to the benzisothiazolone.


The effect of pelvic floor muscle training on pelvic floor function and sexuality postpartum. A randomized study including 300 primiparous.
Although pregnancy and childbirth are physiological processes they may be associated with pelvic floor disorders. The aim of this study was to evaluate the influence of pelvic floor muscle training on postpartum pelvic floor and sexual function of primiparous. This is a randomized prospective study including 300 primiparous women. Due to the dropout 200 women were analyzed. Inclusion criteria were the delivery of the first, mature baby, the ability to speak and understand German. The participants were evaluated by clinical examinations and questionnaires after 6 and 12 months postpartum. After 6 months, the women were randomized in two groups. Compared to the control group the intervention groups participated in 45-min pelvic floor muscle training and pelvic floor perception once a week over 6 weeks. The results of the questionnaires showed no significant differences between the groups after 12 months. A significant stronger pelvic floor muscle strength was found for the intervention group after 12 months. The improvement of the pelvic floor and sexual function over the time showed a significant improvement in both groups. Supervised pelvic floor muscle training did not improve both the pelvic floor and the female sexual function in comparison to the control group. After 12 months, the pelvic floor and sexual function improved significant in all women. German Clinical Trials Register (DRKS00024725), retrospectively registrated.


Faeces' odours attract gregarious locust hoppers.
Collective motion is one of the most impressive common features of gregarious locusts: once formed, bands and swarms get moving for long distances. It was shown that visual perception of neighbours plays a key role in maintaining marching behaviour at a local scale. But at a larger scale, mechanisms underlying band cohesion are less understood. It was shown in several field studies that individuals separated from the band were able to get back to the group, even after being separated since a night. In this context, faeces' odours could be a possible indicator of the recent passage of a group. In this study, we tested if nymphs are attracted by faeces' odours and if this effect is modulated by the age of the faeces. To this end, we conducted individual olfactometric behavioural assays of 3rd instar hoppers of desert locust, Schistocerca gregaria, exposed to odours of 1 h-old and 24 h-old faeces. We also used Gas Chromatography-Mass Spectrometry (GC-MS) to identify odours' volatile organic compounds from faeces. The results of behavioural assays indicated a strong attractive effect of faeces, with no preference for one of the two faecal age classes. Nymphs spent significantly more time in the side of the olfactometer where the faeces' odours came from, and 72.7% of tested individuals chose this side first. We filtered and annotated 11 volatile organic compounds present in both fresh and old faeces in GC-MS analyses, including guaiacol and phenol, which are known to cause an aggregative effect on desert locusts. As the attractive effect lasted over 24 h, band's faeces could still have an attractive effect when individuals are separated from the band since one day. In this situation, latecomers individuals would be able to get back to the group by following the traces of their predecessors.


Modelling compound action potentials of peripheral nerves in situ. III. Nerve propagation in the refractory period.
Compound nerve action potentials (CAPs) of sural nerves of healthy persons were measured in the relative refractory period of the fibres. Double stimuli were used with interstimulus intervals ranging from 0.7 to 4.0 msec. The CAP latency increase, its amplitude decrease and its wave shape alterations with decreasing interstimulus interval are discussed, using a model description. Recovery functions for the single fibre action potential in the relative refractory period are defined. These recovery functions, however, cannot sufficiently explain the CAP amplitude diminutions actually measured. Apparently in the relative refractory period an increasing number of fibres ceases to propagate an action potential when the stimulus interval is shortened. This effect, which is caused by subthreshold stimulation, predominantly involves the slower fibres. The usual derivation of refractory period parameters in clinical practice is reviewed.


Solid-state NMR spectroscopy reveals anomer specific transport of galactose in the milk yeast Kluyveromyces lactis.
Genetic evidence indicates that only the β-anomer of galactose is transported to Kluyveromyces lactis cells by galactose/glucose transporter Hgt1p, and that aldose-1-epimerase encoded by GAL10 is a prerequisite for growth on galactose. Minor aldose-1-epimerases other than Gal10p also exist in K. lactis. Using a mutant defective in both aldose-1-epimerases, we show by solid-state nuclear magnetic resonance spectroscopy that only β-anomer is transported in the cell and stays without or with a slow rate of conversion to α-anomer. Signals due to intracellular β-galactose appeared at two positions, both of which were shifted towards higher magnetic fields than that of β-galactose in aqueous solution, suggesting that incorporated galactose binds to cellular components, probably proteins.


Role of Ets2 in cyclic AMP regulation of the human chorionic gonadotropin beta promoter.
Activation of the human chorionic gonadotropin beta (hCGbeta) by the protein kinase A (PKA) pathway has been shown to occur through an activating protein-2 (AP-2)-dependent mechanism. However, in HepG2 cells, which are deficient in AP-2, the PKA catalytic subunit is still able to stimulate the hCGbeta promoter. Ets2 plays a critical role in placental development as revealed by placental abnormalities in Ets2 knockout mice. Transfection of Ets2 into JEG-3 placental cells causes a slight, but reproducible, increase in hCGbeta promoter basal activity. However, cotransfection with the PKA catalytic subunit causes a strong synergistic increase in hCGbeta promoter activity. Ets2 synergistic activation of the hCGbeta promoter is specific for the PKA pathway, as activation of the ras pathway, which also acts through Ets2, does not activate the hCGbeta promoter. c-Jun-mediated repression of hCGbeta is inhibited by Ets2 cotransfection, indicating that protein-protein interactions may be responsible for Ets2 activation of the hCGbeta promoter.


Comparison of follicular fluid and serum anti-Mullerian hormone levels as predictors of the outcome of assisted reproductive treatment.
To compare follicular fluid and serum concentrations of anti-Mullerian hormone (AMH) as predictors of the outcome of assisted reproduction. This observational study enrolled 58 women who were undergoing IVF or ICSI treatment with the long stimulation protocol. Patients diagnosed as having PCOS were excluded. Serum and follicular fluid AMH levels were assessed as predictors of clinical pregnancy. Both the serum and follicular fluid AMH levels were higher in the clinical pregnancy group than in the failed group. A significant correlation was found between the serum and follicular fluid AMH levels, but a discrepancy was observed in some patients with elevated AMH levels in the follicular fluid or serum alone. Assisted reproductive treatment resulted in clinical pregnancy in all of the patients with elevated AMH levels in the follicular fluid (>40pM) or in the serum (>10pM). The ROC-AUC for the combination of follicular and serum AMH was 0.772, which was relatively higher than that for either the serum AMH (AUC: 0.691) or follicular fluid AMH (AUC: 0.688) alone. Elevated AMH levels in either the serum or follicular fluid appeared to be predictive of clinical pregnancy, even if AMH levels in other fluids were low. This is a pilot study with preliminary data that need further confirmation.


Pharmaceutical prescribing for children. Part 5. Conscious sedation for dentistry in children.
This is the fifth paper in a series on the prescribing of medicines for children by dentists working in primary dental care. It deals with conscious sedation for children.


Analysis of machining process and thermal conditions during vibration-assisted cortical bone drilling based on generated bone chip morphologies.
When the temperature during bone drilling exceeds the safety threshold, the bone tissue surrounding the drilling site can be irreversibly damaged. To investigate the influence of vibration-assisted drilling (VAD) methods on the temperature increase during bone drilling and the causes for temperature increase, drilling experiments were performed on fresh bovine femur samples. The morphology and granularity distribution of the generated bone chips were innovatively used to directly compare the machining processes and thermal conditions of conventional drilling (CD), low-frequency vibration-assisted drilling (LFVAD), and ultrasonic vibration-assisted drilling (UVAD). The experimental results indicated that LFVAD produced the lowest temperature increase of 31.4°C, whereas UVAD produced the highest temperature increase of 44.1°C with the same drilling parameters. Additionally, the morphologies and granularity distributions of the bone chips significantly differed among these methods. We concluded that the smaller temperature increase in LFVAD was mainly attributed to the improved thermal conditions resulting from the periodic cutting/separation motion and the reliable geometric chip-breaking mechanism. In contrast, the unfavourable thermal conditions of UVAD were caused by the higher applied frequency, which created a significantly larger amount of friction heat. This was the main cause for the highest observed temperature increase, resulting in bone crushing processes that generated additional heat.


Immunotherapy for allergic fungal sinusitis: three years' experience.
Since August 1994, we have treated patients with histologically proven allergic fungal sinusitis with surgery followed by immunotherapy, employing fungal and nonfungal antigens to which hypersensitivity has been demonstrated. Our results continue to be encouraging. Not only have we encountered no indication that fungal immunotherapy has worsened these patients' condition or caused a recurrence of disease, we have confirmed dramatic improvement in these patients compared with the generally accepted course of this disease. Of 11 patients who have received immunotherapy for 1 to 3 years (mean 28 months), none has required regular or frequent treatment with a single brief course of systemic steroids, and only three are receiving topical nasal steroids. No repeat surgeries for recurrent allergic fungal sinusitis have been required in the treatment group. This combination of surgery and immunotherapy has continued to prove beneficial, and we urge others to consider this approach to therapy.


Salivary diagnostics of the novel coronavirus SARS-CoV-2 (COVID-19).
Laboratory testing for the SARS-CoV-2 virus and the consequent respiratory coronavirus disease 2019 (COVID-19) is categorized into methods that detect the viral presence and methods that detect antibodies produced in the host as a response to infection. Methods that detect viral presence into the host excretions measure current infection by SARS-CoV-2, whereas the detection of human antibodies exploited against SARS-CoV-2 evaluates the past exposure to the virus. This review provides a comprehensive overview for the use of saliva as a specimen for the detection of SARS-CoV-2, the methods for the salivary diagnostics utilized till very recently, and the arisen considerations for the diagnosis of COVID-19 disease. The major advantage of using saliva as a specimen for the detection of SARS-CoV-2 is that saliva collection is a non-invasive method which produces no discomfort to the patient and permits the patients to utilize home self-sampling techniques in order to protect health providers from the exposure to the pathogen. There is an urgent need to increase the active research for the detection of SARS-CoV-2 in the saliva because the non-invasive salivary diagnostics may provide a reliable and cost-effective method suitable for the fast and early detection of COVID-19 infection.


Developmental recall lag in learning-disabled children: perceptual deficit or verbal mediation deficiency?
To investigate the development of mediational deficiencies in verbal and nonverbal visual short-term memory of learning-disabled children, the recall task of Atkinson, Hansen, and Bernback was administered to learning-disabled children in two experimental conditions. In Experiment 1 no significant differences on nonverbal short-term memory recall between normal and learning-disabled children were found. Similar recall responses (e.g., middle response bias, primacy effects, and recency effects) were found for both groups. Nonverbal recall was comparable for disabled and normal children as suggested by stimulus content and association scores. Experiment 2 found that while the effects of overt rehearsal on pretrained labels on learning-disabled children's recall was negligible, labels provided superior recall for normal children. Results suggested that learning-disabled children suffer from a verbal mediational deficiency consistent with Flavell's (1970) mediation deficiency hypothesis.


Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients.
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.


Engineering an SspB-mediated degron for novel controllable protein degradation.
Elegant controllable protein degradation tools have great applications in metabolic engineering and synthetic biology designs. SspB-mediated ClpXP proteolysis system is well characterized, and SspB acts as an adaptor tethering ssrA-tagged substrates to the ClpXP protease. This degron was applied in metabolism optimization, but the efficiency was barely satisfactory. Limited high-quality tools are available for controllable protein degradation. By coupling structure-guided modeling and directed evolution, we establish state-of-the-art high-throughput screening strategies for engineering both degradation efficiency and SspB-ssrA binding specificity of this degron. The reliability of our approach is confirmed by functional validation of both SspB and ssrA mutants using fluorescence assays and metabolic engineering of itaconic acid or ferulic acid biosynthesis. Isothermal titration calorimetry analysis and molecular modeling revealed that an appropriate instead of excessively strong interaction between SspB and ssrA benefited degradation efficiency. Mutated SspB-ssrA pairs with 7-22-fold higher binding KD than the wild-type pair led to higher degradation efficiency, revealing the advantage of directed evolution over rational design in degradation efficiency optimization. Furthermore, an artificial SspB-ssrA pair exhibiting low crosstalk of interactions with the wild-type SspB-ssrA pair was also developed. Efforts in this study have demonstrated the plasticity of SspB-ssrA binding pocket for designing high-quality controllable protein degradation tools. The obtained mutated degrons enriched the tool box of metabolic engineering designs.


Effects of cholinesterase inhibitor on brain activation in Alzheimer's patients measured with functional near-infrared spectroscopy.
Neurobiological effects of neuropsychiatric medication can contribute to the understanding of mechanisms of action and to the evaluation of target medication effects. Cholinesterase inhibitors (ChEI) have been used in patients with Alzheimer's disease (AD) for years with only small knowledge about the underlying neurobiological effects. The measurement of brain activation links neurobiological and functional aspects but is challenging in the group of demented patients; here, an alternative method, functional near-infrared spectroscopy (fNIRS), is introduced to measure those medication effects. The current study investigated the influence of ChEI on cortical activation of patients with AD measured using fNIRS during a verbal fluency task (VFT). In this study, 24 probable AD patients were investigated three times using fNIRS: before medication with rivastigmine was given (t0), when the medication was at the target dose after 4 weeks (t1), and after the target dose was kept constant for a further 8 weeks (t2). The results show a concentration increase of oxygenated hemoglobin as measured with fNIRS from t0 to t2 in speech relevant areas and a general decrease in prefrontal areas. Behaviorally, an improvement was found for the VFT used to measure cortical activation during fNIRS. In the neuropsychological test battery, no significant changes were found, yet high effect sizes for the mini mental status examination, immediate and delayed word list recall were found. The results indicate a positive effect of ChEI on cognitive function. The underlying cortical changes can be imaged using fNIRS.


Impact of multiple births on late and moderate prematurity.
Multiple gestations have an increased risk of pregnancy complications compared with singletons. Delay in childbearing and assisted reproductive techniques have remained common reasons for the increase in multiple gestations over the last few decades. Higher rates of both spontaneous and indicated preterm birth in twins and triplets lead to a significant proportion of the moderate preterm birth and late preterm birth rates. The article is a review of the causes of preterm birth and morbidities associated with these pregnancies.


Removal of the herbicide 2,4-dichlorophenoxyacetate from water to zinc-aluminium-chloride layered double hydroxides.
Batch sorption studies were conducted to investigate the potential of [Zn-Al-Cl] layered double hydroxides (LDHs) for the removal of the herbicide 2,4-dichlorophenoxyacetate (2,4-D) from contaminated aqueous solutions. Experiments were performed at different pH values, initial pesticide concentration, solid/pesticide ratio and anion exchange capacity of LDHs. The LDH samples evaluated had very high retention capacity for 2,4-D whose removal was a rapid process, as a quasi-equilibrium state was reached after 1-h reaction time. The adsorption can be described by Langmuir-type isotherms, with an average affinity constant of 12.5 L mmol(-1). At initial 2,4-D concentrations between 0.08 and 4 m molL(-1), the solids removed up to 98% of the pesticide. Physicochemical characterization of the LDH solids, both fresh and after removal of 2,4-D, by X-ray diffraction, infrared spectroscopy and thermogravimetry, indicates that the retention of 2,4-D is done by adsorption on the surface of the solid for low 2,4-D concentrations. However, a combination of surface adsorption and interlayer ion exchange takes place when the 2,4-D concentration is high.


Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II.
Calcium entry through voltage-activated Ca2+ channels is important in regulating many cellular functions. Activation of these channels in many cell types results in feedback regulation of channel activity. Mechanisms linking Ca2+ channel activity with its downregulation have been described, but little is known of the events responsible for the enhancement of Ca2+ current that in many cells follows Ca2+ channel activation and an increase in cytoplasmic Ca2+ concentration. Here we investigate how this positive feedback is achieved in single smooth muscle cells. We find that in these cells voltage-activated calcium current is persistently but reversibly enhanced after periods of activation. This persistent enhancement of the Ca2+ current is mediated by activation of calmodulin-dependent protein kinase II because it is blocked when either the rise in cytoplasmic Ca2+ is inhibited or activation of calmodulin-dependent protein kinase II is prevented by specific peptide inhibitors of calcium-calmodulin or calmodulin-dependent protein kinase II itself. This mechanism may be important in different forms of Ca2+ current potentiation, such as those that depend on prior Ca2+ channel activation or are a result of agonist-induced release of Ca2+ from internal stores.


Pharmaceutical Production of Anti-tumor and Immune-potentiating Enterococcus faecalis-2001 β-glucans: Enhanced Activity of Macrophage and Lymphocytes in Tumor-implanted Mice.
Enterococcus faecalis 2001 is a probiotic lactic acid bacterium and has been used as a biological response modifier (BRM). From physiological limitation of bacterial preservation in storage and safety, the live E. faecalis 2001 has been heat-treated and the BRM components containing high level of β-glucan, named EF-2001, were prepared. The heat-treated EF-2001 has been examined for the antioxidative potential for radical scavenging and anti-tumor activities as well as immune-enhancing response in mice. Lymphocyte versus polymorphonuclear leukocyte ratio was increased in mice upon treatment with EF-2001. The number of lymphocytes was increased in the EF-2001-treated group. In the mice bearing two different Ehrlich solid and Sarcoma-180 carcinomas, the treatment with EF-2001 resulted in anti-tumor action. Tumor-suppressive capacity upon treatment with EF-2001 was significantly increased compared to normal controls. During the time interval administration of 5 weeks between the priming and secondary administration of EF-2001, the expression and production levels of TNF-α were also observed in the EF- 2001-administered mice. Additionally, anti-tumor activity examined with the intravenous administration of EF 2001 with a 34 times interval was also observed, as the growth of Sarcoma180 cells was clearly inhibited by the EF-2001. From the results, it was suggested that the immune response is enhanced due to antioxidative activity caused by the EF-2001 and anti-tumor activity by NK cells and TNF-α.


Comparative pneumotoxicity of cyclopentadienyl manganese tricarbonyl and methylcyclopentadienyl manganese tricarbonyl.
The acute pneumotoxic effects of cyclopentadienyl manganese tricarbonyl (CMT) and methylcyclopentadienyl manganese tricarbonyl (MMT) were compared to delineate the role of the methyl side chain in the toxicity of these organomanganese compounds and to further our understanding of the mechanisms by which these compounds act. Specifically, lung manganese (Mn) burdens and the pneumotoxic response, as measured by bronchoalveolar lavage parameters, were determined in male Sprague-Dawley rats 24 hr after sc administration of 0.5, 1.0, or 2.5 mg Mn/kg as CMT or MMT. The pneumotoxic response to either compound was characterized by large increases in lavage albumin and protein content with smaller increases in lactate dehydrogenase levels. CMT was approximately twice as potent as MMT. This difference in potency may be due to methyl side chain oxidation, a metabolic detoxification pathway unavailable to CMT. Lung Mn content was significantly elevated after treatment with either CMT or MMT. Heptane extraction studies revealed that Mn was accumulated in a nonlipid soluble form, suggesting the accumulation of metabolites rather than heptane soluble parent MMT or CMT. A strong correlation between pulmonary Mn content and toxicity was observed, suggesting a causal relationship between the accumulation of CMT or MMT metabolites and toxicity. Piperonyl butoxide diminished both the pneumotoxicity and Mn accumulation resulting from CMT or MMT, suggesting both phenomena are due to monooxygenase metabolites. Pulmonary nonprotein sulfhydryl (NPSH) levels were increased twofold 24 hr after administration of either CMT or MMT. Depletion of NPSH was not observed 1.5 or 6 hr after administration. The mechanisms of this response are unclear but may be due to the metabolism of CMT or MMT to unstable compounds which release inorganic Mn within pulmonary cells.


Kimura's Disease: A Rare Cause of Parotid Swelling.
Kimura's disease also known as subcutaneous angioblastic lymphoid hyperplasia with peripheral eosinophilia is a rare clinicopathological entity. It is a chronic granulomatous disease of unknown etiology. The clinical presentation varies from subcutaneous swellings of the head and neck region with regional lymphadenopathy with salivary gland involvement to systemic manifestations like nephrotic syndrome. The clinical features are mild, rarely life threatening. The present article is a case report of Kimura's disease presenting as multiple swellings at the left temporal region, left parotid and bilateral post auricular region. Though the lesion is benign, the cosmetic disfigurement caused by the swellings was of significant concern to our patient. MRI Scan was suggestive of a parotid swelling extending into the temporal and post auricular region of the left side. Surgical modality of treatment was adopted- Superficial Parotidectomy with excision of subcutaneous swellings. Histopathological examination confirmed the diagnosis of Kimura's disease. The mode of presentation as multiple large swellings with the involvement of the parotid gland created a diagnostic dilemma, hence this article intends to consider Kimura's disease as a rare but possible cause of a parotid swelling.


Role of IgG fractions with high isoelectric points in the thymol turbidity test in syphilis. Evidence for an increase in basic IgG in early syphilis.
It is demonstrated that IgG fractions with isoelectric points above 7.6, isolated from pooled syphilitic sera, are able to elevate the thymol turbidity. The effect increases with increasing isoelectric points of the isolated fraction. IgG from individual syphilitic patients exerts a stronger effect on the thymol turbidity than normal IgG. It is concluded that elevated amounts of these basic immunoglobulins are present in the sera of syphilitic subjects.


Manual Annotation of Time in Bed Using Free-Living Recordings of Accelerometry Data.
With the emergence of machine learning for the classification of sleep and other human behaviors from accelerometer data, the need for correctly annotated data is higher than ever. We present and evaluate a novel method for the manual annotation of in-bed periods in accelerometer data using the open-source software Audacity®, and we compare the method to the EEG-based sleep monitoring device Zmachine® Insight+ and self-reported sleep diaries. For evaluating the manual annotation method, we calculated the inter- and intra-rater agreement and agreement with Zmachine and sleep diaries using interclass correlation coefficients and Bland-Altman analysis. Our results showed excellent inter- and intra-rater agreement and excellent agreement with Zmachine and sleep diaries. The Bland-Altman limits of agreement were generally around ±30 min for the comparison between the manual annotation and the Zmachine timestamps for the in-bed period. Moreover, the mean bias was minuscule. We conclude that the manual annotation method presented is a viable option for annotating in-bed periods in accelerometer data, which will further qualify datasets without labeling or sleep records.


Identification of surfactins and iturins produced by potent fungal antagonist, Bacillus subtilis K1 isolated from aerial roots of banyan (Ficus benghalensis) tree using mass spectrometry.
The banyan endophyte, Bacillus subtilis K1, produces a complex mixture of lipopeptides exhibiting potent antifungal activity. These lipopeptides were purified by high-performance liquid chromatography and analyzed using MALDI-TOF-MS as well as liquid chromatography coupled with ESI-MS. A heterogenous mixture of lipopeptides belonging to three different families of cyclic lipopeptides, viz., fengycins, iturins and surfactins, was detected in the cell-free extracellular extract of B. subtilis K1. The detailed mass spectrometric characterization revealed the presence of four variants of iturin A and three variants of iturin C varying in the β-amino fatty acid chain length from C13 to C17. The MS/MS of monovalent alkali metal ion adducts (Na and K) of iturin suggested the Glu4 as a binding site for metal ion. The LC-ESI-MS/MS analysis of surfactins enabled the identification of seven surfactin variants with the variations in Val/Ile/Leu at position 4 and C13-C17 β-hydroxy fatty acids. This study demonstrates the application of tandem mass spectrometry in identification of closely related lipopeptides from a heterogenous mixture obtained from a natural source. Furthermore, this is the first report of an endophytic bacillus strain co-producing so many variants of surfactins and iturins.


Expression of MBP-HCV NS1/E2 fusion protein in E. coli and detection of anti-NS1/E2 antibody in type C chronic liver disease.
To characterize the putative NS1/E2 (non-structural protein 1/envelope 2) domain of HCV (hepatitis C virus), we expressed the hydrophilic three-quarters of this domain in a form of MBP (maltose binding protein) fusions in Escherichia coli. When we checked the positive frequency of antibody to this fusion protein, 17% of patients with type C chronic liver disease had this antibody. However, they were all positive for HCV-RNA in sera. These results suggest that the appearance of anti-NS1/E2 antibody does not serve as evidence of viral clearance.


A biomass-derived porous carbon-based nanocomposite for voltammetric determination of quercetin.
Porous carbon was prepared from wheat flour by alkali treatment and carbonization. The resulting biomass-derived porous carbon (BPC) was employed to prepare a Pt-Au-BPC nanocomposite by a hydrothermal method. The material was then placed on the surface of a carbon ionic liquid electrode (CILE). The Pt-Au-BPC was characterized by SEM, XPS, and the modified CILE by electrochemical methods. They revealed a porous structure, a large specific surface with high conductivity. Pt-Au-BPC/CILE was applied to the sensitive determination of quercetin. Electrochemical response was studied by cyclic voltammetry and differential pulse voltammetry (DPV). Under optimized experimental conditions, the oxidation peak current (measured at 0.48 V vs. Ag/AgCl by DPV) increases linearly in the 0.15 to 6.0 μM and in the 10.0 to 25.0 μM quercetin concentration range. The detection limit is 50.0 nM (at 3σ). The Pt-Au-BPC/CILE was applied to the direct determination of quercetin in ginkgo tablets sample and gave satisfactory results. Graphical abstract A Pt-Au-BPC nanocomposite modified carbon ionic liquid electrode was applied to differential pulse voltammetric determination of quercetin. BPC: biomass-derived porous carbon.


An essential component of the Magnet journey: fostering an environment for evidence-based practice and nursing research.
Creating, advancing, and sustaining a practice environment grounded in evidence-based practice and nursing research is essential to achieving Magnet status. The purpose of this article is 2-fold. First, to describe a model for the integration of evidence-based practice. Second, to illustrate how a community hospital used this model as a framework for the integration of evidence-based practice and nursing research as part of its journey toward achieving Magnet status.


Interfacial thiol-isocyanate reactions for functional nanocarriers: a facile route towards tunable morphologies and hydrophilic payload encapsulation.
Functional nanocarriers were synthesized using an in situ inverse miniemulsion polymerization employing thiol-isocyanate reactions at the droplet interface to encapsulate hydrophilic payloads. The morphology of the nanocarriers is conveniently tunable by varying the reaction conditions and the dispersions are easily transferable to the aqueous phase.


Muscle ultrasonography: a diagnostic tool for amyotrophic lateral sclerosis.
In a prospective study we tested whether muscle ultrasonography can differentiate between amyotrophic lateral sclerosis (ALS) and mimics. Furthermore, we assessed the ability of ultrasonography to identify subclinical lower motor neuron involvement. In 59 patients, suspected for adult onset motor neuron disease, ultrasound scans were made of 12 different muscle groups. Echo intensity was determined and each muscle was screened for fasciculations. Ultrasonography was considered diagnostic for ALS when echo intensity was 1.5 SD above normal in at least two muscles and fasciculations were present in at least four muscles. Ultrasonography differentiated between ALS and mimics with 96% sensitivity and 84% specificity. In the 27 ALS patients, ultrasonography detected 15 regions with lower motor neuron involvement that were negative using either clinical examination or needle EMG. Muscle ultrasound can differentiate between amyotrophic lateral sclerosis and mimics with high sensitivity and specificity, and is a sensitive tool to screen for regional lower motor neuron involvement. Muscle ultrasonography is a promising tool in the diagnostic work up of ALS.


Phase I dose-finding and pharmacokinetic trial of irinotecan (CPT-11) administered every two weeks.
This trial was performed to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of irinotecan (CPT-11) when administered on a once-every-2-week schedule. CPT-11 was administered to successive cohorts of patients at progressively increasing starting doses ranging from 125 to 350 mg/m2. The MTD and DLTs were determined both for CPT-11 alone and for CPT-11 followed by filgrastim (G-CSF). Plasma samples were obtained during the first 24 hours after initial dosing to determine the total concentrations (lactone + carboxylate forms) of CPT-11; of the active metabolite SN-38; and of SN-38 glucuronide (SN-38G). Neutropenic fever was the DLT for CPT-11 at the 300 mg/m2 dose level. When G-CSF was added, dose escalation beyond 350 mg/m2 could not be achieved due to grade 2-3 toxicities that prevented on-time retreatment with CPT-11. Severe, late diarrhea was uncommon on this schedule. Peak plasma concentrations of SN-38 and SN-38G were approximately 2.5% and 4.2% of the corresponding peak plasma concentration for CPT-II, respectively The harmonic mean terminal half-lives for CPT-11, SN-38, and SN-38G were 7.1 hours, 13.4 hours, and 12.7 hours, respectively. No predictive correlation was observed between CPT-11 or SN-38 peak concentration or AUC and first-cycle diarrhea, neutropenia, nausea, or vomiting. Across the range of doses studied, mean CPT-11 clearance was 14.0 +/- 4.0 l/h/m2 and volume of distribution was 146 +/- 45.9 l/m2. When administered every two weeks, the recommended phase II starting dose of CPT-11 is 250 mg/m2 when given alone and 300 mg/m2 when supported by G-CSF. This every-two-week regimen offers a tolerable and active alternative to weekly or every-three-week single-agent CPT-11 therapy.


Antibodies to nucleic acids in systemic lupus erythematosus and rheumatoid arthritis patients and their relatives.
Sera of systemic lupus erythematosus (SLE) patients contain antibodies to double-stranded and single-stranded DNA while antibodies found in rheumatoid arthritis sera are specific mainly to single-stranded DNA. Anti-RNA antibodies in the both cases are directed against double-stranded RNA and belong to the IgM class while anti-DNA antibodies are IgG. Genetic variance analysis based on family correlations suggests that the synthesis of antibodies to DNA is subject to different modes of gene regulations in systemic lupus erythematosus and rheumatoid arthritis patients. In the case of SLE, a high degree of genetic determination is demonstrated, due mainly to the X-chromosomal component of the general phenotypic variance. The failures in the immunoregulation system that are responsible for anti-RNA antibody production are rather similar in the two groups of patients and involve a combination of environmental and autosomal factors.


Affinity chromatography on 2',5'-ADP-Sepharose 4B for purification of malic enzyme from crustacean muscle.
Shrimp abdomenal muscle NADP-dependent malic enzyme (E.C.220.127.116.11) was purified about 1500-fold to a specific activity of 48 units (mumol/min)/mg at 30 degrees C with good quantitative recovery in three chromatographic steps, including affinity chromatography on 2',5'-ADP-Sepharose 4B, a "substrate activation" method using malate substrate plus manganese chloride. In addition to the malate-manganese chloride substrate pair, succinate or glutamate plus manganese chloride or magnesium chloride could be used in this "substrate activation" method for crustacean NADP-malic enzyme purification on 2',5'-ADP-Sepharose 4B. Affinity chromatography alone purified malic enzyme almost 43 fold, and the overall method resulted in homogeneous enzyme since polyacrylamide gel electrophoresis of the native purified enzyme revealed only a single band staining for protein and enzyme activity.


Radiomics models for preoperative prediction of the histopathological grade of hepatocellular carcinoma: A systematic review and radiomics quality score assessment.
To systematically review the efficacy of radiomics models derived from computed tomography (CT) or magnetic resonance imaging (MRI) in preoperative prediction of the histopathological grade of hepatocellular carcinoma (HCC). Systematic literature search was performed at databases of PubMed, Web of Science, Embase, and Cochrane Library up to 30 December 2022. Studies that developed a radiomics model using preoperative CT/MRI for predicting the histopathological grade of HCC were regarded as eligible. A pre-defined table was used to extract the data related to study and patient characteristics, characteristics of radiomics modelling workflow, and the model performance metrics. Radiomics quality score and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were applied for research quality evaluation. Eleven eligible studies were included in this review, consisting of 2245 patients (range 53-494, median 165). No studies were prospectively designed and only two studies had an external test cohort. Half of the studies (five) used CT images and the other half MRI. The median number of extracted radiomics features was 328 (range: 40-1688), which was reduced to 11 (range: 1-50) after feature selection. The commonly used classifiers were logistic regression and support vector machine (both 4/11). When evaluated on the two external test cohorts, the area under the curve of the radiomics models was 0.70 and 0.77. The median radiomics quality score was 10 (range 2-13), corresponding to 28% (range 6-36%) of the full scale. Most studies showed an unclear risk of bias as evaluated by QUADAS-2. Radiomics models based on preoperative CT or MRI have the potential to be used as an imaging biomarker for prediction of HCC histopathological grade. However, improved research and reporting quality is required to ensure sufficient reliability and reproducibility prior to implementation into clinical practice.


Screen-based sedentary behaviors but not total sedentary time are associated with anxiety among college students.
The purpose of the study was to investigate the associations of device-measured total sedentary time and screen-based sedentary time with anxiety in college students. Three hundred and twenty-one college students (mean age = 19.72 ± 1.18, 55.8% females) were recruited from Shanghai, China. Total sedentary time was objectively measured using accelerometry, while screen-based sedentary time was self-reported. Anxiety symptom was evaluated using the Self-Rating Anxiety Scale. Linear regression modeling was used to assess the associations of total sedentary time and screen-based sedentary time with anxiety symptom. Accelerometer-assessed total sedentary time was not associated with anxiety symptom. Prolonged sedentary time on TV and movie viewing (>2 h on weekdays) and social media using (>2 h on weekdays and weekend) were associated with a higher level of anxiety. However, time on video gaming and recreational reading was not associated with anxiety symptom. The findings indicated that screen-based sedentary behaviors but not total sedentary time were associated with anxiety symptom among college students. The associations of screen-based sedentary behaviors with anxiety symptom varied by the types of screen time.


Properties of an anti-idiotype antiserum: demonstration of cross-reacting mitogenic determinants on bone marrow plasmacytoma cells.
An antiserum against a monoclonal protein of IgG/kappa type from a patient S. was produced by immunization of guinea pigs. Idiospecificity of the antiserum (anti-Id AS) was tested by immunoprecipitation and hemagglutination inhibition. About 70% mononuclear cells prepared from the bone marrow (BM) aspirate of this patient stained positive when the antiserum was used in an indirect immunofluorescence (IF) procedure detecting surface membrane structures. Commercial antisera specific for gamma, kappa and lambda immunoglobulin (Ig) chains stained only 5-17% of the cells. With mu chain and delta chain specific antisera no reactivity could be observed. The presence of idiotype cross-reacting determinants (Id-CR-D), that is idiotypes not associated with Ig isotypes could be also demonstrated by a significant increase of 3H-thymidine incorporation of the BM cells in the presence of the anti-Id AS. Phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A had no effect. In a cell sorting experiment using affinity gel chromatography it could be shown that the anti-Id AS preferentially binds to proplasmacytes. Cells of this type were enriched two-fold over plasma cells in the eluate. The analysis of peripheral blood lymphocytes (PBL) from the patient revealed about 40% positive cells without correlation to a certain subpopulation. Administration of prednisolone to the patient resulted in a significant reduction of the Id positive cells within two days. In conclusion it appears that our antiserum detects cells of an individual tumour clone within PBL and BM-cells. By the stimulating effect of the anti-Id AS a proliferative potential of plasmacytoma cells could be defined which may work also 'in vivo'. Thus, Id-CR-D may operate as a tumour growth receptor.


Solution state NMR structure and dynamics of KpOmpA, a 210 residue transmembrane domain possessing a high potential for immunological applications.
The three-dimensional structure of the outer membrane protein A from Klebsiella pneumoniae transmembrane domain was determined by NMR.This protein induces specific humoral and cytotoxic responses, and is a potent carrier protein. This is one of the largest integral membrane proteins(210 residues) for which nearly complete resonance assignment, including side chains, has been achieved so far. The methodology rested on the use of 900 MHz 3D and 4D TROSY experiments recorded on a uniformly 15N,13C,2H-labeled sample and on a perdeuterated methyl protonated sample. The structure was refined from 920 experimental constraints, giving an ensemble of 20 best structures with an r.m.s. deviation of 0.54 A for the main chain atoms in the core eight-stranded beta-barrel. The protein dynamics was assessed, in a residue-specific manner, by 1H-15N NOEs (pico- to nanosecond timescale), exchange broadening (millisecond to second) and 1H-2H chemical exchange (hour-weeks).


Patients' and Healthcare Professionals' Perspectives on Better Use of Patient-Reported Outcome Measures in Head and Neck Cancer.
Patients with head and neck cancer (HNC) are often highly affected by disease and treatment, resulting in impaired physical functioning and quality of life. Therefore, evaluation of patients' psychosocial and functional outcomes can be facilitated by patient-reported outcome measures (PROMs). By providing the patients' own perspectives, PROMs are crucial to improving patient-centered care. This study aimed to improve understanding of the perceived value of PROMs in HNC care and how to optimize their clinical value based on patients' and multidisciplinary healthcare professionals' (HCPs) perspectives. Population-based surveys among patients with HNC through their patient association and among HCPs nationwide through the Dutch Head and Neck Audit. A total of 54 patients and 40 multidisciplinary HCPs from all 14 nationwide HNC centers (100%) responded. For patients, the most important element of patient-reported outcome collection systems was including a call to action for those with worse-than-average scores (28%), whereas clinicians found discussing scores during clinical visits the most important (39%). Although 16% of clinicians found short completion time the most important element, none of the patients selected completion time as most important. Additionally, 17% of patients stated completion time was not an issue, provided clinicians would use the outcomes for clinical purposes. Although patients and clinicians acknowledged the value of patient-reported outcomes, patients would like to be more involved in the clinical implications of their outcomes. Enhancing patients' involvement by a call to action and providing feedback on their scores during outpatient clinic visits may improve the clinical value of PROMs.


Steroid 5alpha-reductase type 1 immunolocalized in the rat peripheral nervous system and paraganglia.
Steroid 5alpha-reductase is an enzyme that converts a number of steroids with a C-4, 5 double bond and C-3 ketone to 5alpha-reduced metabolites. This enzyme has been suggested to play a role in brain development and myelination in the rat nervous system. In the present study, we examined the cellular and subcellular localization of the enzyme immunocytochemically in the rat peripheral nervous system and paraganglia using a polyclonal antibody against rat 5alpha-reductase type 1. Light and electron microscopical studies localized 5alpha-reductase in the Schwann cells of myelinated and unmyelinated nerve fibres, the satellite cells of the ganglia, the enteric glial cells and the supporting/sustentacular cells of the paraganglia. In the myelinated nerve fibres, immunoreactivity was observed in the outer loops, the nodes of Ranvier and the Schmidt-Lanterman incisures. Subcellularly, the immunoreactivity was localized in the cytoplasm of various glial cells. No immunoreactivity was observed in the myelin membrane, the axon or the neuronal perikaryon. These findings suggest that 5alpha-reductase is widely distributed in glial cells, and that, in addition to myelination, 5alpha-reduced steroids play a role in some glial functions in the peripheral nervous system.


Glutathione alterations in rat liver after acute and subacute oral administration of paracetamol.
1. The effect on hepatic glutathione was studied in rats pretreated orally with various dosages of paracetamol (acetaminophen) for varying time intervals. 2. Paracetamol caused a dose-dependent depletion of hepatic glutathione, the maximum depletion occurring 3 h after acute dosing, the levels returning to normal by 12 h after low doses (0-1 or 0-25 g/kg, p.o.) and by 72 h after the highest doses (1 g/kg, p.o.). 3. Before returning to normal, the liver glutathione levels became significantly greater than the control values (35-40%) at 24 and 48 h in 0-5 and 1 g/kg paracetamol-treated rats, respectively, suggesting thereby a 'glutathione rebound action' of paracetamol-pretreatment. 4. In contrast with the acutely treated rats, the liver glutathione content remained unchanged when 0-5 g/kg paracetamol was administered twice daily for 7 consecutive days. 5. Fasting caused a significant reduction in hepatic glutathione, the glutathione stores were replenished within 6 h after feeding. 6. The results suggest that the hepatic glutathione levels are reversibly depleted by single large doses of paracetamol, while the glutathione depletory effect appears to decrease after the repeated administration of this hepatotoxic agent.


Genetic divergence and reproductive barriers among morphologically heterogeneous sympatric clones of Eunotia bilunaris sensu lato (Bacillariophyta).
The study of reproductive isolation between populations, combined with estimates of genetic divergence, provides important insights into mechanisms of speciation. In this study, sixteen morphologically heterogeneous sympatric clones of Eunotia bilunaris sensu lato (Bacillariophyta) were brought into culture to study their phylogenetic relationships and pre- and postzygotic reproductive barriers. An ITS rDNA phylogeny was congruent with morphology and divided the clones into three groups ('slender', 'robust' and 'labile'), pointing to the presence of several species in E. bilunaris. Whereas most strains had a heterothallic mating system, four 'labile' clones displayed apomictic behaviour. A further 'labile' clone had a heterothallic mating behaviour, however, suggesting a very recent origin for apomixis. Despite high sequence divergence, hybridization occurred between clones belonging to different groups, but was 20-400 times less frequent than in intra-group matings. F1 hybrids had an intermediate morphology and were almost completely sterile; gamete formation was generally arrested in the early stages of meiosis I. The ITS divergence of 11.5-12.3% between the 'robust' and 'slender' clones seems to represent an upper limit of divergence in which cell pairing, gamete formation and auxosporulation are still possible but heavily reduced, and where hybrid sterility has already evolved.


How Midwestern College students protected their families in the first year of COVID-19.
College students routinely visit their families due to geographic proximity and their financial dependence. Consequently, the potential of transmitting COVID-19 from campus to their families' homes is consequential. Family members are key sources of support for one another in nearly all matters but there is little research uncovering the mechanisms by which families have protected each other in the pandemic. Through an exploratory qualitative study, we examined the perspectives of a diverse, randomly sampled, group of students from a Midwestern University (pseudonym), in a college town, to identify COVID-19 prevention practices with their family members. We interviewed 33 students between the end of December 2020 and mid-April 2021 and conducted a thematic analysis through an iterative process. Students navigated major differences in opinions and undertook significant actions in attempts to protect their family members from COVID-19 exposure. Students' actions were rooted in the greater good of public health; prosocial behavior was on display. Larger public health initiatives could target the broader population by involving students as messengers.


Highly efficient patterning technique for silver nanowire electrodes by electrospray deposition and its application to self-powered triboelectric tactile sensor.
A patterned transparent electrode is a crucial component of state-of-the-art wearable devices and optoelectronic devices. However, most of the patterning methods using silver nanowires (AgNWs), which is one of the outstanding candidate materials for the transparent electrode, wasted a large amount of unused AgNWs during the patterning process. Here, we report a highly efficient patterning of AgNWs using electrospray deposition with grounded electrolyte solution (EDGE). During electrospray deposition, a patterned electrolyte solution collector attracted AgNWs by strong electrostatic attraction and selectively deposited them only on the patterned collector, minimizing AgNW deposited elsewhere. The enhanced patterning efficiency was verified through a comparison between the EDGE and conventional process by numerical simulation and experimental validation. As a result, despite the same electrospray deposition conditions for both cases except for the existence of the electrolyte solution collector, the coverage ratio of AgNWs fabricated by the EDGE process was at least six times higher than that of AgNWs produced by the conventional process. Furthermore, the EDGE process provided high design flexibility in terms of not only the material of the substrate, including a polymer and a ceramic but also the shape of the substrate, including a 2D flat and 3D curved surface. As an application of the EDGE process, a self-powered touch sensor exploiting the triboelectric effect was demonstrated. Thus, the EDGE process would be utilized in further application in wearable or implantable devices in the field of biomedicine, intelligent robots, and human-machine interface.


Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.
Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.


Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells.
Together with peptides, T lymphocytes respond to hydrophobic molecules, mostly lipids, presented by the non-classical CD1 family (CD1a-e). These molecules have evolved complex and diverse binding grooves in order to survey different cellular compartments for self and exogenous antigens, which are then presented for recognition to T-cell receptors (TCRs) on the surface of T cells. In particular, most CD1d-presented antigens are recognized by a population of lymphocytes denominated natural killer T (NKT) cells, characterized by a strong immunomodulatory potential. Among NKT cells, two major subsets (type I and type II NKT cells) have been described, based on their TCR repertoire and antigen specificity. Here we review recent structural and biochemical studies that have shed light on the molecular details of CD1d-mediated antigen recognition by type I and II NKT cells, which are in many aspects distinct from what has been observed for peptide major histocompatibility complex-reactive TCRs.


Quantum dots increased fat storage in intestine of Caenorhabditis elegans by influencing molecular basis for fatty acid metabolism.
Caenorhabditis elegans is a useful model animal for fat storage study. In nematodes, CdTe quantum dots (QDs) induced an increase in fat storage in intestine that is partially due to prolonged defecation cycle length, and not attributed to altered feeding or cadmium ion released from CdTe QDs. Moreover, CdTe QDs altered the molecular basis of both synthesis and degradation of fatty acid; however, CdTe QDs did not influence that of degradation of phospholipids. CdTe QDs increased expression of fasn-1 and pod-2 genes encoding enzymes required for fatty acid synthesis, and decreased expression of acs-2 and ech-1 genes encoding enzymes required for fatty acid β-oxidation. The altered molecular basis of fatty acid synthesis or degradation by CdTe QDs acted in intestine to regulate fat storage. Our study highlights the potential of CdTe QDs in influencing lipid metabolism in certain organs or tissues in animals.


Prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma.
To assess the prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma (NPC). From January 1987 to December 1994, 197 untreated NPC patients were examined by CT scan before treatment. The parapharyngeal space was separated into pre-styloid and post-styloid compartments on axial images by the styloid process. Potentially significant parameters were analyzed by both univariate and multivariate methods using SPSS 8.0 software. The actual survival, disease-free survival, and local failure-free rates were affected by the presence of parapharyngeal space involvement (p = 0.0115, p = 0.0035, p = 0.0367, respectively). The 5-year actual survival, disease-free survival, and the local failure-free rates in the patients without parapharyngeal space disease, or with pre-styloid and post-styloid compartment involvement were 87.9%, 88.0%, 96.9% and 75.0%, 71.2%, 93.7% and 60.5%, 57.7%, 86.8%, respectively. Parapharyngeal space involvement correlated well with lymphadenopathy and advanced N disease. Distant metastasis is more likely in the presence of obvious post-styloid compartment involvement (p = 0.0153). Age is a strong prognostic factor for survival. Parapharyngeal tumor involvement has significant predictive value. The parapharyngeal space involvement affects local tumor failure, regional tumor failure, and distant metastasis. Its survival rate is low


Catheter ablation in adult congenital heart disease on uninterrupted oral anticoagulation: Is it safe? Data from a large single-center study.
Catheter ablation in adult congenital heart disease (ACHD) patients is a critical treatment strategy for complex arrhythmias including atrial fibrillation (AF) and atrial tachycardia (AT). In addition to vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) are increasingly used in this patient population. The purpose of this study was to assess the safety of catheter ablation in ACHD patients on uninterrupted oral anticoagulation with VKA or DOAC, examining thromboembolic, bleeding, and vascular access complications. Retrospective analysis of 234 ACHD patients with simple (n = 83), moderate (n = 66), or complex (n = 85) CHD (mean age 46 years) undergoing 368 ablation procedures on uninterrupted oral anticoagulation with VKA (45.4%) or DOAC (54.6%) was undertaken. Arrhythmias were AF in 97, right AT in 181, left AT in 65, or a combination of AF and AT in 25. No thromboembolic complications occurred. Major complications occurred in 4 patients (1.1%; 1 VKA, 3 DOAC), including retroperitoneal hematoma in 2 and arteriovenous (AV) fistula requiring surgical treatment in 2. Minor bleeding or vascular access complications occurred in 46 cases (12.5%), including hematomas >5 cm in 26, AV fistulas (not requiring surgical intervention) in 13, and pseudoaneurysms in 7 (thrombin injection in 3/7). Overall, no significant difference was found between DOAC (14.9%) and VKA groups (12.0%; P = .411). Catheter ablation in ACHD patients on uninterrupted oral anticoagulation with VKA or DOAC is feasible and safe. No thromboembolic events occurred, and major bleeding or vascular access complications were rare. No significant differences regarding minor bleeding or vascular access complications between patients on DOAC or VKA were found.


Act like a warrior to defeat medication counselling barriers: A cross sectional study.
In the previous literature, patients' perceptions of medication consultation provided by pharmacists was found to poor, depending upon various factors, which may lead to poor compliance with medication instructions and, therefore, poor health outcomes. In the Kingdom of Saudi Arabia (KSA), this specific area has been overlooked to date, so this study aims to examine patients' perceptions of medication counselling and the factors that influence their likelihood of participating in medication counselling as well as determine the predictors of patients' likelihood to take part in medication counselling delivered by pharmacists in KSA. A cross-sectional survey was conducted involving people over 18 years of age, who had purchased or collected medicine for their own use from community and/or hospital pharmacies within the past two years and who lived in Saudi Arabia. The data were analysed using IBM SPSS Statistics version 24. Descriptive statistics were applied to each item as well as linear regression and Pearson's correlation. Five hundred and eleven participants (male (n = 101), female (n = 410), the majority of whom were aged 18-24-years-old) were included. Almost an equal number of participants had accessed either community (CP) (n = 228: 45%) or hospital pharmacies (HP) (n = 283: 55%) within the past two years in regards to their condition and/or medication. The perceived susceptibility construct had weak positive correlations with all of the constructs being measured (r < 0.3). Perceived barriers had a weak negative relationship with likelihood (r < 0.3), which means that, as the perceived barriers increase, the perceived benefits and future likelihood to participate in medication counselling decrease. Linear regression analysis found that age (β = -0.06; P =˃0.05), gender (β = 0.14; P =˃0.05), education level (β = -0.01; P =˃0.05) and type of pharmacies accessed (β = -0.05; P =˃0.05) were non-significant predictors of the participants' likelihood of participating in medication counselling. In order to improve the medication consultation provided by pharmacists and, therefore, enhance the patients' experience and care, it is important to understand the public's views, concerns and demands regarding medication consultation, in order to provide the proper interventions and serve as a platform for developing a plan of action for good pharmacy practice.


High diversity of the emerging pathogen Acinetobacter baumannii and other Acinetobacter spp. in raw manure, biogas plants digestates, and rural and urban wastewater treatment plants with system specific antimicrobial resistance profiles.
Carbapenem-resistant Acinetobacter baumannii causing immense treatment problems in hospitals. There is still a knowledge gap on the abundance and stability of acquired resistances and the diversity of resistant Acinetobacter in the environment. The aim of the study was to investigate the diversity and antimicrobial resistances of Acinetobacter spp. released from livestock and human wastewater into the environment. Raw and digested manure of small scale on farm biogas plants as well as untreated and treated wastewater and sewage sludge of rural and urban wastewater treatment plants (WWTPs) were studied comparatively. A total of 132 Acinetobacter isolates were phylogenetically identified (16S rRNA gene and rpoB sequence analyses) and 14 different phylotypes were detected. Fiftytwo isolates represented A. baumannii which were cultured from raw and digested manure of different biogas plants, and most stages of the rural WWTP (no hospital wastewater receiving) and the two studied urban WWTPs receiving veterinarian and human hospital wastewater. Multi-locus sequence typing (Pasteur_MLST) identified 23 novel and 12 known STs of A. baumannii. Most novel STs (18/23) were cultured from livestock samples and the rural WWTP. A. baumannii isolates from livestock and the rural WWTP were susceptible to carbapenems, colistin, ciprofloxacin, ceftazidime, and piperacillin. In contrast, A. baumannii isolates from the two urban WWTPs showed clinical linkage with respect to MLST and were multi-drug resistant (MDR). The presence of viable A. baumannii in digested manure and sewage sludge confirmed the survival of the strict aerobic bacteria during anoxic conditions. The study indicated the spread of diverse Acinetobacter from anthropogenic sources into the environment with a strong linkage of clinial associated MDR A. baumannii strains to the inflow of hospital wastewater to WWTPs. A more frequent detection of Acinetobacter in sewage sludge than effluent waters indicated that particle-attachment of Acinetobacter must be considered by the risk assessment of these bacteria.


BIPCO: ultrasound feature points based on phase congruency detector and binary pattern descriptor.
Detection of feature points in medical ultrasound (US) images is the starting point of many clinical tasks, such as segmentation of lesions in pathological areas, estimation of organ deformation, and multimodality image fusion. However, obtaining a reliable feature point localization is a complex task even for an expert radiologist due to the US image characteristics: strong presence of noise, insidious artifacts, and low contrast. In this work, we describe a feature detector based on phase congruency (PhC) combined with a binary pattern descriptor. We introduce a feature detector specifically designed for US images and based on PhC analysis. We also introduce a descriptor based on local binary pattern (LBP) operator to improve and simplify the matching between feature points extracted from different images. LBP is not applied directly to the intensity values; instead, it is applied to the PhC output obtained during the detection step to improve robustness to intensity transformation, and the rejection of noise. We tested the proposed approach compared to state-of- the-art methods applied to real US images subject to realistic synthetic transformations. The results of the proposed method, in terms of accuracy and precision, outperform the state-of-the-art approaches that are not designed for US data. The methods described in this work will enable the development of US-based navigation system, which supports automatic feature point detection and matching from US images acquired at different times during the procedure.


Clinical efficacy and safety of crizotinib and alectinib in ALK-positive non-small cell lung cancer treatment and predictive value of CEA and CA125 for treatment efficacy.
To investigate the clinical efficacy and safety of crizotinib and alectinib in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treatment and the predictive value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) for treatment efficacy. A total of 120 patients with ALK-positive NSCLC were enrolled and randomly assigned to receive crizotinib treatment (54 patients, the control group) or alectinib treatment (66 patients, the research group). Treatment efficacy, adverse reactions, survival, and quality of life of patients were compared between the two groups. Enzyme-linked immunosorbent assay was used to determine the serum CEA and CA125 concentrations and these levels were compared between patients with certain treatment responses or no responses. Receiver operating characteristic curve was used to assess the predictive value of CEA and CA125 for treatment efficacy. The overall disease control rate, overall response rate, and number of 1-year survival patients were substantially higher in the research group compared with the control group. Moreover, the incidence of adverse reactions was significantly lower and progression-free survival and overall survival rates were higher in the research group compared with those in the control group. The area under the curve (AUC) for predicting treatment efficacy was 0.889 for CEA and 0.866 for CA125. Alectinib was clinically more efficacious and safer than crizotinib for ALK-positive NSCLC treatment. Both CEA and CA125 demonstrated excellent predictive value for treatment efficacy.


Exploring non-participation in colorectal cancer screening: A systematic review of qualitative studies.
Worldwide, colorectal cancer is a major public health issue. Despite the existence of screening programmes in many countries, global uptake remains low. This meta-ethnography aimed to analyse qualitative literature to explore attitudes towards colorectal cancer screening and reasons for non-participation in eligible people that do not participate when invited. Systematic searches were conducted in five databases in May 2021. Critical appraisal of included studies was performed using the CASP checklist for qualitative studies. Thirteen studies were included. Three main themes and eight sub-themes were developed across studies: (1) Differences in motivation, with non-participants expressing a lack of knowledge and varying levels of intention to participate but not feeling screening was personally necessary; (2) Active aversion to screening expressed by fear, discomfort, disgust or not wanting to know; and (3) Contextual barriers of the healthcare system such as practical constraints or poor relationships with healthcare professionals. Findings suggest multiple pathways to non-participation including ambivalence, aversion to the process and consequences of screening or lack of support. Persuasive messages and prompts to action to target ambivalence, reassurance regarding the screening procedures to target negative reactions, and increased support from healthcare professionals may be beneficial in increasing screening uptake.


Pluripotent stem cell model of Shwachman-Diamond syndrome reveals apoptotic predisposition of hemoangiogenic progenitors.
Shwachman-Diamond syndrome (SDS), an autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, is caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, which plays a role in ribosome biogenesis. Although the causative genes of congenital disorders frequently involve regulation of embryogenesis, the role of the SBDS gene in early hematopoiesis remains unclear, primarily due to the lack of a suitable experimental model for this syndrome. In this study, we established induced pluripotent stem cells (iPSCs) from patients with SDS (SDS-iPSCs) and analyzed their in vitro hematopoietic and endothelial differentiation potentials. SDS-iPSCs generated hematopoietic and endothelial cells less efficiently than iPSCs derived from healthy donors, principally due to the apoptotic predisposition of KDR+CD34+ common hemoangiogenic progenitors. By contrast, forced expression of SBDS gene in SDS-iPSCs or treatment with a caspase inhibitor reversed the deficiency in hematopoietic and endothelial development, and decreased apoptosis of their progenitors, mainly via p53-independent mechanisms. Patient-derived iPSCs exhibited the hematological abnormalities associated with SDS even at the earliest hematopoietic stages. These findings will enable us to dissect the pathogenesis of multiple disorders associated with ribosomal dysfunction.


Exercise improves reaction time without compromising accuracy in a novel easy-to-administer tablet-based cognitive task.
Moderate intensity aerobic exercise is known to facilitate cognitive performance but new technologies enable increasing opportunities to investigate this phenomenon under different circumstances. This study aimed to describe the effect of exercise on executive function assessed though a novel tablet-based test. Twenty healthy, active participants volunteered to take part in the randomised fully controlled trial. Participants undertook an initial test of maximal aerobic capacity as well as ventilatory threshold during an incremental cycle test. A touch screen tablet computer was placed in the middle of the handlebars at an angle of approximately 45°, and participants were asked to complete the response-inhibition cognitive task (Speed Match, Lumos Labs Inc.) at set time points. A full familiarisation trial was performed prior to subsequent visits, in which participants completed either the control (no exercise) and exercise (90% ventilatory threshold (VT)) trials in a randomised order. During the 1h trials, the cognitive task was performed prior to, during and post the intervention. Reaction time and accuracy of participant responses were recorded. Performing the cognitive task resulted in elevated heart rates and ventilation rates during control and exercise. Exercise facilitated performance in the executive function task such that reaction time was enhanced with no change in accuracy. A range of reliability measures are also reported. This method of assessing executive function during exercise displays face validity and provides promise for further investigation of cognitive function using a simple, short duration, easily administered and widely available test.


Counting is a spatial process: evidence from eye movements.
Spatial-numerical associations (small numbers-left/lower space and large numbers-right/upper space) are regularly found in simple number categorization tasks. These associations were taken as evidence for a spatially oriented mental number line. However, the role of spatial-numerical associations during more complex number processing, such as counting or mental arithmetic is less clear. Here, we investigated whether counting is associated with a movement along the mental number line. Participants counted aloud upward or downward in steps of 3 for 45 s while looking at a blank screen. Gaze position during upward counting shifted rightward and upward, while the pattern for downward counting was less clear. Our results, therefore, confirm the hypothesis of a movement along the mental number line for addition. We conclude that space is not only used to represent number magnitudes but also to actively operate on numbers in more complex tasks such as counting, and that the eyes reflect this spatial mental operation.


Photodynamic Pattern Memory Surfaces with Responsive Wrinkled and Fluorescent Patterns.
Reversible pattern systems, namely pattern memory surfaces, possessing tunable morphology play an important role in the development of smart materials; however, the construction of these surfaces is still extensively challenging because of complicated methodologies or chemical reactions. Herein, a functionalized basement is strategically integrated with a multi-responsive supramolecular network based on hydrogen bonding between aggregation-induced emission luminogens (AIEgens) and copolymers containing amidogen (poly(St-co-Dm) to establish a bilayer system for near-infrared (NIR)-driven memory dual-pattern, where both the fluorescence emission and wrinkled structures can be concurrently regulated by a noninvasive NIR input. The motion of the AIEgens and photo-to-thermal expansion of the modified base allow temporal erasing of the fluorescent wrinkling patterns. Meanwhile, when exposed to 365 nm UV radiation, the fluorescent patterns can be independently regulated through photocyclization. The fluorescent wrinkling pattern presented herein is successfully demonstrated to promote the level of information security and capacity. This strategy provides a brand-new approach for the development of smart memory interfaces.


Effects of cornstalk and sawdust coverings on greenhouse gas emissions during sheep manure storage.
Manure covered by organic materials during the storage has shown that it can effectively reduce emissions of greenhouse gases, but few studies have focused on the bacterial communities in manure or the coverage and mechanism responsible for reducing gas emissions. Therefore, this study investigated the impacts and mechanisms of cornstalk and sawdust coverings on greenhouse gas emissions during sheep manure storage. Sheep manure covered by organic material reduced nitrous oxide (N2O) emissions (42.27%-42.55%) relative to uncovered control through physical adsorption and biological transformation of Acinetobacter, Corynebacterium, Brachybacterium, Dietzia and Brevibacterium. Sheep manure covered by organic materials also increased methane (CH4) emissions (16.31%-43.07%) by increasing anaerobic zones of coverage. Overall, coverings reduced carbon dioxide equivalent (CO2eq) by 29.87%-33.60%. Coverings had less effect on the bacterial diversity and community of sheep manure, and the number of bacteria shared by sheep manure and the covering material increased with storage progress, indicating that these bacteria were transferred to the covering materials with gas emissions and moisture volatilization. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) images showed that functional group intensities of the covering materials increased and the fibrous structures became more disordered during the storage period. In general, it was safe to use organic materials as coverages during sheep manure storage, which was conducive to reducing greenhouse gas emissions.


Tyrosinase maturation and pigment expression in B16 melanoma: relation to theophylline treatment and intracellular cyclic AMP.
We have studied the effects of theophylline treatment on pigmentation characteristics and growth of two B16 melanoma cell lines, HFH-18 and P/140. Cell counts of control and theophylline-treated cultures confirmed that the drug inhibits cell growth. Light and electron microscope cytochemistry with the L-dopa reaction indicated that the two cell lines differ in their ability to transfer Golgi-associated tyrosinase to developing premelanosomes. The results of these experiments, considered with results of electrophoretic analyses and activity measurements by the Pomerantz method, also provide evidence that increased tyrosinase synthesis occurs in response to theophylline treatment. In addition, results indicate that theophylline induces changes in the rate of synthetic or degradative posttranslational modification of tyrosinase. Measurements of intracellular cyclic AMP levels by radioimmunoassay in control cultures and in theophylline- and alpha-MSH-treated cultures were made. Although the hormone induced spectacular increases in cyclic AMP levels, theophylline produced no detectable change. These results indicate that theophylline differs from alpha-MSH because theophylline-induced changes in pigmentation may not require the participation of intracellular cyclic AMP.


[To what extent must the surgeon inform an injured patient about the choice of treatment possibilities? Comments on a ruling of the German Federal Court important for accident therapeutics].
With its judgement of May 11, 1982, the Bundesgerichtshof (Federal Court of Law) has decided that it is primarily up to the doctor to choose the therapy method by which a person injured during an accident has to be treated. The patient must be informed only if there are different risks for him involved in different methods, e.g. if the doctor wants to apply a method criticized again and again in the literature. An information that a smaller hospital doesn't eventually correspond to the standard of a specialized hospital is only necessary if adequate treatment and care is not possible in the hospital where the patient is admitted.


An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury.
Axons in the adult mammalian central nervous system fail to regenerate after spinal cord injury. Neurons lose their capacity to regenerate during development, but the intracellular processes underlying this loss are unclear. We found that critical components of the presynaptic active zone prevent axon regeneration in adult mice. Transcriptomic analysis combined with live-cell imaging revealed that adult primary sensory neurons downregulate molecular constituents of the synapse as they acquire the ability to rapidly grow their axons. Pharmacogenetic reduction of neuronal excitability stimulated axon regeneration after adult spinal cord injury. Genetic gain- and loss-of-function experiments uncovered that essential synaptic vesicle priming proteins of the presynaptic active zone, but not clostridial-toxin-sensitive VAMP-family SNARE proteins, inhibit axon regeneration. Systemic administration of Baclofen reduced voltage-dependent Ca2+ influx in primary sensory neurons and promoted their regeneration after spinal cord injury. These findings indicate that functional presynaptic active zones constitute a major barrier to axon regeneration.


The kinetics of the histochemical method for dihydrofolate dehydrogenase (dihydrofolate reductase).
The purpose of the present investigation is to report some histochemical and cytospectrophotometric observations providng more objective evidence for the specific activity of the histochemical method for dihydrofolate reductase activity (126.96.36.199-tetrahydrofolate: E.C. 126.96.36.199). Kinetic factors of the enzymic reaction, such as fixation, pH, coenzymes, substrate concentration, Michaelis constant, temperature, time of incubation, aerobiosis, and anaerobiosis, activators and inhibitors, were investigated.


Nursing factors associated with length of stay and readmission rate of the elderly residents from nursing home based on LTCfocus database.
Nursing factors have been found to be associated with a reduction in readmission rates. Nevertheless, few attentions have been given to the effect of nursing factors on nursing home (NH) residents. This study was to assess the impact of nursing factors on the hospital readmissions and length of stay (LOS) of the elderly residents from the NH. This was a cross-sectional study. Data were extracted from the NH of the LTCFocus.org data set between 2011 and 2018. The study included residents aged ≥55 years who were admitted to NH in the United States, following a hospitalization event. The nursing factors included facility-level data elements and medical care personnel. An unsupervised machine learning algorithm (K-means) was used to cluster NH according to readmission rate and LOS. Multivariate logistic regression analysis was performed. This study consisted of 107,000 NH-year observations. The median readmission rate was 17%, with a median LOS was 28.00 days. Three clusters were identified: cluster 1 was a high readmission rate with high LOS, cluster 2 was a low readmission rate with low LOS, and cluster 3 was a high readmission rate with low LOS. Multifacility and admission/bed were associated with a reduction in readmission rate and LOS in both cluster 1 vs cluster 2 and cluster 3 vs cluster 2. The special care unit and registered nurses' ratio were associated with decreased readmission rate and LOS in cluster 1 vs cluster 2. Total beds and Alzheimer unit decreased the readmission rate and LOS, whereas certified nursing assistant increased the readmission rate and LOS in cluster 3 vs cluster 2. NH for profit was associated with elevated readmission rate and LOS in cluster 1 vs cluster 2 and decreased readmission rate and LOS in cluster 3 vs cluster 2. Based on the subgroup analysis, the certified nursing assistant decreased readmission rate and LOS in cluster 1 vs cluster 2 and increased readmission rate and LOS in cluster 3 vs cluster 2 (all P < 0.005). This study indicates the importance of the improvement of nurse number and level and the inputs of facility characteristics in NH.


[Single-port laparoscopic ligation with suture silk for varicocele: a report of 20 cases].
To evaluate the clinical effect of single-port laparoscopic ligation (SPLL) with suture silk for the management of varicocele. We analyzed the clinical effects of SPLL with suture silk in the treatment of 20 cases of varicocele, and compared them with those of conventional three-port laparoscopic ligation (TPLL) for another 24 varicocele patients. All the operations were successful. The operation time was 20-35 (mean 28) minutes and the hospital stay was 2 days for SPLL, as compared with 15-28 (mean 20) minutes and 3 days for TPLL. The cure rate was 75% for the former, and 67% for the latter, with no signification difference between the two groups (P > 0.05). SPLL with suture silk for the treatment of varicocele has more advantages over TPLL for minimal invasiveness, faster recovery, and less scarring and extraneous residual.


The role of glutathione and glutathione S-transferases in fatty acid ozonide detoxification.
The ozonide derived from methyl linoleate was shown to cause a dose dependent inhibition of the phagocytosis of rat alveolar macrophages exposed in vitro to concentrations varying from 10(-5) to 10(-4) M. Vitamin C was demonstrated to detoxify the ozonide. In analogy to their behaviour on exposure to ozone, vitamin E supplemented cells demonstrated a decreased and glutathione depleted cells an increased sensitivity towards the compound. The characteristics of antioxidant protection of cells against the ozonide were thus comparable to those for protection against ozone. Preincubation with glutathione also detoxified the ozonide model compound. Survival of rat alveolar macrophages exposed to a toxic concentration of the ozonide (86 microM final concentration), measured by phagocytosis of the cells, increased significantly (P less than 0.01) from 23 to 54% after a 2.5-h preincubation of the ozonide with glutathione (5 mM final concentration). The detoxification of methyl linoleate ozonide by glutathione could be catalyzed by the rat liver glutathione S-transferases. After a 2.5-h preincubation of the ozonide (86 microM final concentration) with glutathione and glutathione S-transferases (final concentrations, respectively, 5 mM and 0.01 mg/ml), its toxicity was completely abolished, as demonstrated by the 98% survival (P less than 0.001) of subsequently exposed cells. A Km(app) (at 1 mM glutathione) for the ozonide of 0.80 mM and a Vmax(app) (at pH 6.5) of 94 nmol glutathione converted X min-1 X mg protein-1 or (at pH 7.4) of 34 nmol glutathione converted X min-1 X mg protein-1, were found. This glutathione S-transferase catalyzed detoxification of the potential intermediates in ozone induced cell damage, offers a new viewpoint on the role of glutathione in the protection of cells against ozone.