Proton NMR studies of transforming and nontransforming H-ras p21 mutants.
One- and two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D NMR) and site-directed mutagenesis were used to study the influence of mutations on the conformation of the H-ras oncogene product p21. No severe structural differences between the different mutants, whether they were transforming or nontransforming, could be detected. Initially, selective incorporation of 3,5-deuterated tyrosyl residues into p21 and 2D NMR were used to identify the resonances representing the spin systems of the imidazole rings of the three histidyl residues in the protein, of six of the nine tyrosyl rings, and of four of the five phenylalanyl rings. The spin systems of the phenyl rings of Phe28, Phe78, and Phe82 could be assigned by using mutant proteins, since no severe structure-induced spectral changes in the aromatic part of the spectra of the mutant proteins were detected. Sequence-specific assignments of the histidine imidazole resonances could be obtained by comparison of the distance information obtained by nuclear Overhauser enhancement spectroscopy (NOESY) experiments with the crystal structure. The change in the chemical shift values of the Hl' proton and the alpha-phosphate of the bound GDP in the NMR spectra of the p21(F28L) mutant and the 28-fold increase in the GDP dissociation rate constants of this mutant suggest a strong interaction between Phe28 and the p21-bound nucleotide. In solution, the p21-bound GDP.Mg2+ has an anti conformation, and the phenyl ring of Phe28 is close to the ribose of the bound GDP.Mg2+.


[Benign paroxysmal positional vertigo with and without manifest positional nystagmus: an 18-month follow-up study of 70 patients].
In this follow-up study of approximately 18 months we assessed parameters of medical management in a sample of 70 patients suffering from benign paroxysmal positional vertigo. Apart from demographic data, we evaluated the time interval from the appearance of the first symptoms until a diagnostic positional manoeuvre was performed, the efficacy of liberatory manoeuvres, the prescription of medication, the use of technical diagnostic resources and the relapse rate. None of the patients had received a diagnostic positioning test until then. Moreover, in one out of three cases a further unnecessary technical diagnostic procedure was carried out. There was a tendency for the right labyrinth to be more frequently affected, a fact that was statistically independent from age and sex, as well as from overall prognosis, which was characterized by a 15.6% recurrence rate. All patients with manifest positional nystagmus were successfully treated: 87.2% immediately after the repositioning manoeuvre and the rest within 10 days by self-performing Brandt-Daroff exercises. Our retrospective analysis revealed that, given a normal neuro-otological examination, a typical medical history without manifest positioning nystagmus leads safely to the correct diagnosis. The delay between the onset of symptoms and the diagnosis of BPPV is very often unduly long. A focused medical history may be diagnostic even in the absence of nystagmus during the Dix-Hallpike manoeuvre.


Characterization of Chlamydia pneumoniae persistence in HEp-2 cells treated with gamma interferon.
Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study demonstrated the effects of gamma interferon (IFN-gamma)-mediated indoleamine 2,3-dioxygenase activity on C. pneumoniae persistence in HEp-2 cells, inclusion morphology, and ultrastructure. C. pneumoniae replication showed a dose-dependent decrease when treated with increasing concentrations of IFN-gamma and a phenotypic switch resulting in a decrease in typical inclusions with an increase in smaller, less-dense atypical inclusions. Ultrastructural analysis of IFN-gamma-treated C. pneumoniae revealed atypical inclusions containing large reticulatate-like aberrant bodies with no evidence of redifferentiation into elementary bodies.


Chemical exposure and occupational symptoms among Portuguese hairdressers.
Hairdressing is predominantly a female activity, in which several chemicals are handled, some of which are known to be allergenic and potentially carcinogenic. Several epidemiological studies showed an association between occupational exposure to chemicals in hairdressing salons and skin and respiratory-tract conditions. The aim of this study were to characterize the occupational exposure to total volatile organic compounds (VOC) and ammonia (NH₃) in 50 Portuguese hairdressers' salons and to analyze the prevalence of respiratory and skin symptoms in 134 hairdressing professionals. Data indicated that internal sources of total VOC are mainly due to indoor sources, with average concentrations (1.4 mg/m³) above the Portuguese reference levels (0.6 mg/m³). Of the hairdressers' salons studied, 4% had a mean NH₃ concentration higher than Portuguese (20 ppm) and American Conference of Industrial Hygienists (ACGIH) (25 ppm) reference levels. Hand dermatitis was the occupational symptom most reported by hairdressers (50%), followed by eye irritation (43%). The results of this study suggest that hairdressers' occupational activities are linked with higher risk of developing hand and wrist/arm dermatitis and symptoms in the upper respiratory tract. The proper use of disposable gloves, hands, wrists, and arms skin monitoring, and the frequent use of moisturizers in the workplace are effective measures to prevent the occurrence of dermatitis in these professionals. Displacement ventilation and/or local exhaust with adequate air exchange rate are recommended particularly in technical areas where hairdressing chemicals are mixed.


Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo.
The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 μg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects.


Regulation of sperm gene expression by the GATA factor ELT-1.
Cell fate specification is mediated primarily through the expression of cell-type-specific genes. The regulatory pathway that governs the sperm/egg decision in the hermaphrodite germ line of Caenorhabditis elegans has been well characterized, but the transcription factors that drive these developmental programs remain unknown. We report the identification of ELT-1, a GATA transcription factor that specifies hypodermal fate in the embryo, as a regulator of sperm-specific transcription in the germ line. Computational analysis identified a conserved bipartite sequence element that is found almost exclusively in the promoters of a number of sperm genes. ELT-1 was recovered in a yeast one-hybrid screen for factors that bind to that sperm consensus site. In vitro assays defined the sperm consensus sequence as an optimal binding site for ELT-1. We determined that expression of elt-1 is elevated in the sperm-producing germ line, and that ELT-1 is required for sperm function. Deletion of the ELT-1 binding site from a sperm promoter abrogates sperm-specific expression of a reporter transgene. This work demonstrates a role for the ELT-1 transcription factor in sperm, and provides a critical link between the germ line sex determination program and gamete-specific gene expression.


Treatment of walking impairment in multiple sclerosis with dalfampridine.
Potassium channel blockade has long been considered a potential therapeutic strategy for treatment of multiple sclerosis (MS) based on the pathophysiology of demyelinated axons. Dalfampridine, which is also known as fampridine or 4-aminopyridine (4-AP), is the potassium channel blocker that has been studied most extensively in MS and other demyelinating neurologic disorders. An extended-release formulation of dalfampridine was recently approved by the US Food and Drug Administration to improve walking in patients with MS. In randomized, double-blind, placebo-controlled trials, with dalfampridine extended release tablets 10 mg taken twice daily, about 12 h apart, walking speed was improved in approximately one-third of treated patients; in these patients, average walking speed on therapy was about 25% above baseline. This improvement was clinically meaningful as assessed by concurrent measurement of patient-reported severity of walking-related disability. Dalfampridine extended release tablets were generally well tolerated, with a range of adverse effects that appear to be related to increases in central nervous system excitation. There is a dose-dependent increase in the occurrence of seizures at doses higher than the recommended 10 mg twice daily.


A Triggering Mechanism for Cyber-Attacks in Naval Sensors and Systems.
In the maritime sector, the integration of radar systems, Automatic Identification System (AIS) and Electronic Chart Display and Information System (ECDIS) through digital technologies enables several benefits to maritime operations, but also make ships prone to cyberattacks. In this context, this work investigates the feasibility of an attacker using a radar system or AIS as open door to remotely send commands to a cyber threat hosted on a ship, even if the ship's systems are air gapped-i.e., are not connected to other networks. The received commands are intended to trigger a cyber threat located in the ship. Although the literature covers several analyzes on cyber risks and vulnerabilities in naval systems, it lacks exploiting mechanisms capable of acknowledging attack commands received through radar and AIS. To this end, this work proposes a triggering mechanism that uses a template matching technique to detect specific patterns transmitted by the attacker to the ship's radar or AIS. The results show the effectiveness of the proposed technique as a tool to acknowledge the received attack commands and activate a malicious code previously installed on the ship. In the case of attacks on a radar system, the accuracy achieved by the proposed method is 0.90. In the case of attacks on an AIS/ECDIS setup it presents an accuracy of 0.93. In both cases the proposed mechanism maintains the due safety against accidental attack activations.


[Bio-characteristic profiling related to clinic:thought and practice on quality evaluation of Chinese materia medica].
The quality evaluation of Chinese materia medica(CMM) is an important and difficult topic research in traditional Chinese medicine, due to its inherent complexity, and incompatibility of evaluation patterns and their key techniques. To solve the issue, it is necessary to break the limit of conventional evaluation, and establish the evaluation pattern and its key techniques about CMM quality related to clinic. Hence, with the strategy- "originating from clinic, validating by experiments and returning to clinic", a novel academic concept is proposed which is termed as "bio-characteristic profiling related to clinic of CMM". A series of key techniques should be established including living-cell dynamic monitoring, enzyme bioactivity dynamic monitoring, electric chemistry dynamic monitoring and isothermal titration dynamic monitoring, etc. Besides, the quality fluctuation of CMM(products) which is hard to control and assess could be evaluated when associated with clinical efficacy and safety(exemplified by Chinese herbal injection, animal medicine and joint use of drugs in clinic). It is expected to form the novel evaluation system for CMM quality based on bio-characteristic profiling related to clinic and its key techniques, which provides novel ideas and techniques for improving quality and clinical efficacy, and promotes the modernization and internationalization of CMM.


A Bioinspired Switchable and Tunable Carbonate-Activated Nanofluidic Diode Based on a Single Nanochannel.
A smart nanofluidic diode that exhibits both ion gating and ion current rectification has been developed using a 1-(4-amino-phenyl)-2,2,2-trifluoro-ethanone-functionalized, conical nanochannel in a polyimide (PI) membrane. The switch-like property can be tuned by controlling the wettability and charge distribution with carbonate ions. Such a nanodevice is advantageous for precisely controlling conductive states with an ultrahigh gating ratio of up to 5000, and a high rectification ratio of 27. By virtue of the high selectivity and sensitivity for carbonate ions, this nanofluidic diode may find applications in carbonate or carbon dioxide detection.


Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.
Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.


Interlimb Asymmetries in Youth Tennis Players: Relationships With Performance.
Madruga-Parera, M, Bishop, C, Fort-Vanmeerhaeghe, A, Beltran-Valls, MR, Gonzalo-Skok, O, and Romero-Rodríguez, D. Interlimb asymmetries in youth tennis players: relationships with performance. J Strength Cond Res 34(10): 2815-2823, 2020-Change of direction speed (CODS) has been highlighted as a critical component of tennis. Interlimb asymmetries have been commonly studied in jump tests, but less attention given to the topic during CODS. The aim of this study was to quantify interlimb asymmetries in jumping and CODS (during traditional and isoinertial tests) and establish their relationship with measures of physical performance. Twenty-two elite youth tennis players (16.3 ± 1.4 years) performed single-leg countermovement jump (SLCMJ), single-leg broad jump, and single-leg lateral jump, a double 180° turn CODS test, and shuffle lateral step and crossover step with an isoinertial resistance device. Paired-samples t-tests revealed significant differences between limbs for all tests (p < 0.05). Interlimb asymmetry scores ranged from 1.83 to 15.03%, and a 1-way repeated-measures analysis of variance showed significant differences between interlimb asymmetry scores across multiple tests (p < 0.05). Spearman's rank order r correlations showed significant negative relationships between CODS asymmetry and SLCMJ performance on both limbs (r = -0.50; p = 0.02 and r = -0.53; p = 0.01) and CODS performance on both limbs (r = 0.50; p = 0.02 and r = 0.63; p = 0.002). These results show the test-specific nature of asymmetries in youth tennis athletes, with the SLCMJ presenting the greatest magnitude of asymmetry. Furthermore, interlimb differences during CODS were associated with reduced performance during jumping and CODS tests, suggesting the monitoring of asymmetries within this population may therefore be warranted.


A highly reliable copper nanowire/nanoparticle ink pattern with high conductivity on flexible substrate prepared via a flash light-sintering technique.
In this work, copper nanowires (NWs) and Cu nanoparticles (NPs) were employed to increase the reliability of a printed electrode pattern under mechanical bending fatigue. The fabricated Cu NW/NP inks with different weight fractions of Cu NWs were printed on a polyimide substrate and flash light-sintered within a few milliseconds at room temperature under ambient conditions. Then, 1000 cycles of outer and inner bending fatigue tests were performed using a lab-made fatigue tester. The flash light-sintered Cu NW/NP ink film with 5 wt % Cu NWs prepared under the flash light-sintering conditions (12.5 J·cm–2 irradiation energy, 10 ms pulse duration, and one pulse) showed a lower resistivity (22.77 μΩ·cm) than those of the only Cu NPs and Cu NWs ink (94.01 μΩ·cm and 104.15 μΩ·cm, respectively). In addition, the resistance change (ΔR·R0(–1)) of the 5 wt % Cu NWs Cu NW/NP film was greatly enhanced to 4.19 compared to the 92.75 of the Cu NPs film obtained under mechanical fatigue conditions over 1000 cycles and an outer bending radius of 7 mm. These results were obtained by the densification and enhanced mechanical flexibility of flash light-sintered Cu NW/NP network, which resulted in prevention of crack initiation and propagation. To characterize the Cu NW/NP ink film, X-ray diffraction and scanning electron microscopy were used.


Recent advances in vector control in filariasis.
Three factors are involved when vector control is incorporated into an integrated control program for filariasis: (1) the vector species or species complex of each filarial worm; (2) type of control measures employed; (3) pesticide application. Recent advances in vector control in filariasis include the use of bed nets, environmental manipulation, insecticides and biological control. Three promising advances in vectrol control are the use of pathogenic bacteria such as Bacillus thuringiensis H-14 and B. sphaericus, juvenile hormone mimics or insect growth regulator (IGR) and predatory crustaceans.


Revascularization of immature, nonvital permanent tooth using platelet-rich fibrin in children.
The purpose of this paper was to present a new approach wherein revascularization of the immature, nonvital permanent tooth was performed using platelet-rich fibrin (PRF) as a novel scaffold material. This was performed after disinfection of the root canal space using triple antibiotic paste followed by placing a PRF membrane in the root canal. The patient was followed up regularly at three-, six-, nine-, and 12-month intervals for review. After 12 months, clinical examination showed negative response to percussion and palpation tests but positive response to cold and electric pulp tests. Radiographic examination revealed continued thickening of the root dentinal walls, narrowing of root canal space, root lengthening, and closure of the root apex with normal periradicular architecture. However, more clinical research using large samples is necessary to prove it advantageous for regenerative endodontic therapy in children.


Metabolic models predict bacterial passengers in colorectal cancer.
Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial taxa are enriched in the metagenomes of CRC patients. Here, we investigate to what extent the abundance of bacterial taxa in CRC metagenomes can be explained by the growth advantage resulting from the presence of specific CRC metabolites in the tumor microenvironment. We composed lists of metabolites and bacteria that are enriched on CRC samples by reviewing metabolomics experimental literature and integrating data from metagenomic case-control studies. We computationally evaluated the growth effect of CRC enriched metabolites on over 1500 genome-based metabolic models of human microbiome bacteria. We integrated the metabolomics data and the mechanistic models by using scores that quantify the response of bacterial biomass production to CRC-enriched metabolites and used these scores to rank bacteria as potential CRC passengers. We found that metabolic networks of bacteria that are significantly enriched in CRC metagenomic samples either depend on metabolites that are more abundant in CRC samples or specifically benefit from these metabolites for biomass production. This suggests that metabolic alterations in the cancer environment are a major component shaping the CRC microbiome. Here, we show with in sillico models that supplementing the intestinal environment with CRC metabolites specifically predicts the outgrowth of CRC-associated bacteria. We thus mechanistically explain why a range of CRC passenger bacteria are associated with CRC, enhancing our understanding of this disease. Our methods are applicable to other microbial communities, since it allows the systematic investigation of how shifts in the microbiome can be explained from changes in the metabolome.


Chelation of lysosomal iron protects dopaminergic SH-SY5Y neuroblastoma cells from hydrogen peroxide toxicity by precluding autophagy and Akt dephosphorylation.
In human neuroblastoma SH-SY5Y cells, hydrogen peroxide (H(2)O(2), 200μM) rapidly (< 5 min) induced autophagy, as shown by processing and vacuolar relocation of light chain 3(LC3). Accumulation of autophagosome peaked at 30 min of H(2)O(2) exposure. The continuous presence of H(2)O(2) eventually (at > 60 min) caused autophagy-dependent annexin V-positive cell death. However, the cells exposed to H(2)O(2) for 30 min and then cultivated in fresh medium could recover and grow, despite ongoing autophagy. H(2)O(2) rapidly (5 min) triggered the formation of dichlorofluorescein-sensitive HO(·)-free radicals within mitochondria, whereas the mitochondria-associated oxidoradicals revealed by MitoSox (O(2)(·-)) became apparent after 30 min of exposure to H(2)O(2). 3-Methyladenine inhibited autophagy and cell death, but not the generation of HO(·). Genetic silencing of beclin-1 prevented bax- and annexin V-positive cell death induced by H(2)O(2), confirming the involvement of canonical autophagy in peroxide toxicity. The lysosomotropic iron chelator deferoxamine (DFO) prevented the mitochondrial generation of both HO(.) and O(2)(·-) and suppressed the induction of autophagy and of cell death by H(2)O(2). Upon exposure to H(2)O(2), Akt was intensely phosphorylated in the first 30 min, concurrently with mammalian target of rapamycin inactivation and autophagy, and it was dephosphorylated at 2 h, when > 50% of the cells were dead. DFO did not impede Akt phosphorylation, which therefore was independent of reactive oxygen species (ROS) generation but inhibited Akt dephosphorylation. In conclusion, exogenous H(2)O(2) triggers two parallel independent pathways, one leading to autophagy and autophagy-dependent apoptosis, the other to transient Akt phosphorylation, and both are inhibited by DFO. The present work establishes HO(·) as the autophagy-inducing ROS and highlights the need for free lysosomal iron for its production within mitochondria in response to hydrogen peroxide.


Tolerance Interval Approach for the Determination of Overfill of Liquid Parenteral Drug Products.
Liquid parenteral products contain an overfill to ensure withdrawal of the declared volume. The overfill must be sufficiently high to compensate for the expected loss during product preparation and administration, but it should also be minimized to prevent accidental overdosing and unforeseen dose splitting of single-dose products. Finding the right balance between too much and too little overfill with an acceptable risk of product failure is challenging and requires consideration of the relevant sources of variability of the extractable volume. This article provides a novel approach for the calculation of the required overfill based on tolerance interval methodology. In a first step, a tolerance interval multiplier from the literature is proposed, and a simulation study is conducted to assess the appropriateness of its use for overfill determination. In a second step, this multiplier is adapted to cover operator-to-operator variability in the loss data and compared with other multipliers via a second simulation study. Use of a tolerance interval multiplier enables adaptation of the overfill such that the risk of not reaching the minimum extractable volume fulfills predefined acceptance criteria. By this, the scientific justification of the selected overfill is strengthened and control over a critical quality attribute is improved.


MRI study of transient cerebral ischemia in the gerbil: interest of T2 mapping.
The aim of this study was to evaluate the diagnostic use of MRI and, more precisely, the use of quantitative T2 imaging at 7 T for the early detection of neuronal cerebral alterations after transient ischemia in the gerbil. One hundred forty-seven Mongolian gerbils were separated into four groups for which a bicarotid artery occlusion lasted for 4, 6, 8, or 10 minutes, respectively. The animals were scanned before carotid artery occlusion and at 3, 6, 10, 24, and 48 hours and 5 days after the ischemic incident. MR images were acquired on a Bruker Avance DRX300 mini-imaging system. Our results show that T2 mapping is able to localize brain damage induced by transient ischemia and to detect early perturbations in water content (as early as 6 hours after ischemia). T2 measurements in the striata are correlated with the severity of the ischemic incident, since the changes observed on the T2 images are directly proportional to the duration of occlusion.


Molecular hydrogen tweezers: structure and mechanisms by neutron diffraction, NMR, and deuterium labeling studies in solid and solution.
The mechanism of reversible hydrogen activation by ansa-aminoboranes, 1-N-TMPH-CH(2)-2-[HB(C(6)F(5))(2)]C(6)H(4) (NHHB), was studied by neutron diffraction and thermogravimetric mass-spectroscopic experiments in the solid state as well as with NMR and FT-IR spectroscopy in solution. The structure of the ansa-ammonium borate NHHB was determined by neutron scattering, revealing a short N-H···H-B dihydrogen bond of 1.67 Å. Moreover, this intramolecular H-H distance was determined in solution to be also 1.6-1.8 Å by (1)H NMR spectroscopic T(1) relaxation and 1D NOE measurements. The X-ray B-H and N-H distances deviated from the neutron and the calculated values. The dynamic nature of the molecular tweezers in solution was additionally studied by multinuclear and variable-temperature NMR spectroscopy. We synthesized stable, individual isotopic isomers NDDB, NHDB, and NDHB. NMR measurements revealed a primary isotope effect in the chemical shift difference (p)Δ(1)H(D) = δ(NH) - δ(ND) (0.56 ppm), and hence supported dihydrogen bonding. The NMR studies gave strong evidence that the structure of NHHB in solution is similar to that in the solid state. This is corroborated by IR studies providing clear evidence for the dynamic nature of the intramolecular dihydrogen bonding at room temperature. Interestingly, no kinetic isotope effect was detected for the activation of deuterium hydride by the ansa-aminoborane NB. Theoretical calculations attribute this to an "early transition state". Moreover, 2D NOESY NMR measurements support fast intermolecular proton exchange in aprotic CD(2)Cl(2) and C(6)D(6).


The Reproductive Functions of the Human Brain Regions: A Systematic Review.
Reproduction remains a vital characteristic of living things necessary for survival and continuity. Specific brain regions and structures are responsible for regulating the different aspects of human reproduction. This study systematically reviewed the brain regions that play structural, hormonal and physiological roles in controlling the various aspects of human reproduction from puberty, sexual function, gametogenesis, childbirth and fertility to infertility to inform advancement in research and therapeutic interventions in human reproductive disorders. A systematic literature search of online databases (MEDLINE, Europe PMC and Google Scholar) was made using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for observational and cross-sectional studies providing evidence for the role(s) of the brain region in human reproduction from the year 2011-2021. Out of 141 articles found, 15 studies met the inclusion criteria, including six cross-sectional and nine randomised controlled trials. The study acknowledged the roles of the pituitary gland, hypothalamus and pineal gland, widely known for regulating the human reproductive system in a gender-based approach while highlighting essential gaps and opportunities for future research. This review provides a 10-year update and overview of the role of different brain regions in human reproduction and will stimulate future research in human reproduction.


Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen.
To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.


Influence of Lime and Phosphate on Nodulation of Soil-Grown Trifolium subterraneum L. by Indigenous Rhizobium trifolii.
Previous research had identified four serogroups of Rhizobium trifolii indigenous to the acidic Abiqua soil (fine, mixed, mesic Cumulic Ultic Haploxeroll). Nodulation of subterranean clover (Trifolium subterraneum L.) by two of the serogroups, 6 and 36, was differentially influenced by an application of CaCO(3) which raised the pH of the soil from 5.0 to 6.5. These studies were designed to characterize this phenomenon more comprehensively. Liming the soil with either CaCO(3), Ca(OH)(2), MgO, or K(2)CO(3) significantly (P = 0.05) increased the percent nodule occupancy by serogroup 36, whereas the percent nodule occupancy by serogroup 6 was decreased, but the decrease was significant (P = 0.05) only after application of either CaCO(3) or Ca(OH)(2). Application of KH(2)PO(4) (25 mg of P kg of soil), which did not change soil pH, also significantly (P = 0.05) increased the percent nodule occupancy by serogroup 36. Application of KH(2)PO(4) in combination with Ca(OH)(2) produced the same increase in nodule occupancy by serogroup 36 as did individual application of the two materials. Soil populations of serogroup 36 consistently, and in the majority of cases significantly (P = 0.05), outnumbered those of serogroup 6 before planting and after harvest regardless of soil treatment or the outcome of nodulation. Soil chemical and plant analyses provided no evidence that liming was simulating phosphate addition by increasing the availability and subsequent uptake of soil P(i) by the subclover plants. Liming did, however, result in a significant transformation (30 to 50 mg of P kg of soil) of P(i) from the residual soil P(i) fraction into an NaOH-extractable organic P fraction during the preplant equilibration period.


Effect of dietary canthaxanthin and iodine on the production performance and egg quality of laying hens.
In this study, we aimed to evaluate the effect of canthaxanthin (CX) and iodine (I) on the production of laying hens, on counteracting debilitation of the vitelline membrane, and on inhibiting Salmonella growth in eggs stored at 30°C. Three hundred hens were reared in cages. Birds were divided into six feeding groups (10 hens × 5 repetitions) that were administered 0, 3 or 6 ppm of CX and 1 or 10 ppm of I with their diets. Laying rate, egg weights, and feed conversion ratios were controlled. The quality of fresh eggs was assessed in wks 25-26, 48-50 and 62-63 of hens lives. An additional batch of eggs was incubated at the temperature of 30°C, and egg quality changes were monitored on days 3, 6 and 9 of storage. Additionally, eggs collected from four experimental groups of hens whose diets had been iodated with 1 or 10 ppm of I and supplemented with 0 or 6 ppm of CX were infected under laboratory conditions with Salmonella, and incubated for 5 and 10 d. The laying rate, egg weights, and feed conversion ratio were significantly improved. Dietary inclusion of CX contributed to a higher resistance of the vitelline membrane of egg yolks, but only for fresh eggs. Vitelline membrane degradation during egg storage at 30°C was significantly counteracted by dietary inclusion of I at a dose of 10 ppm. The same I dose resulted in the complete inhibition of Salmonella growth until day 10 of incubation, but exclusively for eggs collected from 40-week-old hens. Dietary supplementation with 10 ppm of I was found to impart high level of resistance to the vitelline membrane against the growth of Salmonella in case of eggs stored at 30°C; therefore, I was found to be more beneficial by ensuring longer preservation than that of CX. However, dietary supplementation with CX was found to increase the resistance of vitelline membrane in fresh eggs.


[Paget's disease of bone: study of 314 patients].
To describe the clinical and laboratory features of Paget's disease of bone at the time of diagnosis. This multicenter and retrospective study included 314 patients. Diagnosis was performed by means of characteristic radiological findings and typical bone scintigraphy. The variables analyzed included: epidemiological variables, cause of diagnosis, bone involvement, disease extension (Coutris index), complications, alkaline phosphate (AP) levels and disease activity (Renier index). There were 159 (50.5%) males and the mean age was 64.9 years (SD 12.6). Diagnosis was casual in 228 (72.6%) patients. Polyostotic involvement was detected in 201 (63.9%) patients. More common locations were pelvis, skull and lumbar spine. Sacrum was more frequently involved in men than in women (p < 0.05), whereas skull involvement was more common in women (p < 0.05). The number of bones involved was 3.1 SD 3 and the percentage of skeletal involvement was 8.7 % (SD 6.5). One hundred ninety eigth (63%) patients had complications. The disease was active in 242 (77%) patients with a mean AP value of 377 IU/L (SD 493); the activity of the disease measured by the Renier index was 34 (SD 46); the activity was greater in the skull and the humerus. Paget's disease of bone is usually asymptomatic. Polyostotic involvement and activity are common at the time of diagnosis. Knowledge of the extension and activity by means of a mathematical model may aid to make therapeutical decisions.


The roles of BECN1 and autophagy in cancer are context dependent.
Malignant tissue contains a rare population of multi-potent cells known as cancer stem-like cells (CSCs). Autophagy is an important mechanism in cancer cell survival and tumor growth; it can both suppress malignant transformation and promote the growth of established cancers. However, the molecular mechanisms underlying the tumor-promoting and tumor-suppressing functions of autophagy in CSCs are not understood. Our work demonstrates that a prosurvival autophagic pathway is critical for breast CSC maintenance. Notably, we provide new evidence for the existence of two separate, context-dependent, autophagic programs that are regulated in opposite ways by BECN1.


Potential on-shore and off-shore reservoirs for CO2 sequestration in Central Atlantic magmatic province basalts.
Identifying locations for secure sequestration of CO(2) in geological formations is one of our most pressing global scientific problems. Injection into basalt formations provides unique and significant advantages over other potential geological storage options, including large potential storage volumes and permanent fixation of carbon by mineralization. The Central Atlantic Magmatic Province basalt flows along the eastern seaboard of the United States may provide large and secure storage reservoirs both onshore and offshore. Sites in the South Georgia basin, the New York Bight basin, and the Sandy Hook basin offer promising basalt-hosted reservoirs with considerable potential for CO(2) sequestration due to their proximity to major metropolitan centers, and thus to large industrial sources for CO(2). Onshore sites are suggested for cost-effective characterization studies of these reservoirs, although offshore sites may offer larger potential capacity and additional long-term advantages for safe and secure CO(2) sequestration.


A Hybrid Speller Design Using Eye Tracking and SSVEP Brain-Computer Interface.
Steady-state visual evoked potentials (SSVEPs) have been extensively utilized to develop brain-computer interfaces (BCIs) due to the advantages of robustness, large number of commands, high classification accuracies, and information transfer rates (ITRs). However, the use of several simultaneous flickering stimuli often causes high levels of user discomfort, tiredness, annoyingness, and fatigue. Here we propose to design a stimuli-responsive hybrid speller by using electroencephalography (EEG) and video-based eye-tracking to increase user comfortability levels when presented with large numbers of simultaneously flickering stimuli. Interestingly, a canonical correlation analysis (CCA)-based framework was useful to identify target frequency with a 1 s duration of flickering signal. Our proposed BCI-speller uses only six frequencies to classify forty-eight targets, thus achieve greatly increased ITR, whereas basic SSVEP BCI-spellers use an equal number of frequencies to the number of targets. Using this speller, we obtained an average classification accuracy of 90.35 ± 3.597% with an average ITR of 184.06 ± 12.761 bits per minute in a cued-spelling task and an ITR of 190.73 ± 17.849 bits per minute in a free-spelling task. Consequently, our proposed speller is superior to the other spellers in terms of targets classified, classification accuracy, and ITR, while producing less fatigue, annoyingness, tiredness and discomfort. Together, our proposed hybrid eye tracking and SSVEP BCI-based system will ultimately enable a truly high-speed communication channel.


A novel mass spectrometry-cleavable, phosphate-based enrichable and multi-targeting protein cross-linker.
Chemical cross-linking mass spectrometry (XL-MS) is a powerful technology for obtaining protein structural information and studying protein-protein interactions. We report phospho-bisvinylsulfone (pBVS) as a novel water-soluble, MS-cleavable, phosphate-based enrichable and multi-targeting cross-linker. In this approach, the fragmentation of pBVS cross-linked peptides occurs in situ through retro-Michael addition. The phosphate group is successfully used as a small affinity tag to isolate cross-linked peptides from the highly abundant non-cross-linked peptides. In addition, the linker targets multiple types of amino acid residues, including cysteine, lysine and histidine. This method was applied to cross-link bovine serum albumin (BSA), myoglobin and Lbcpf1 demonstrating the ability to yield accurate and abundant information to facilitate protein structure elucidation.


[Image-guided endoscopic sinus surgery: a comparison of two navigation systems].
We evaluated the effectiveness of two navigation systems with optical tracking in endoscopic sinus surgery (ESS). The Signa SP/i Intraoperative navigation system (General Electric Co., Intraoperative NS) is advantageous in acquiring both real time and high-resolution images during surgery, compared to conventional image-guided navigation (Stealth Station TREON, Medtronic Inc., IGNS) that rely entirely on preoperative three-dimensional images. We studied the following in 14 patients treated with intraoperative NS and 19 treated with IGNS: 1) additional time for navigation system implementation, 2) available instrumentations in ESS, and 3) navigation system accuracy. Navigation systems required additional time to prepare ESS. The time lapse from admittance to the operating room to ESS onset was measured in patients under both systems and controls undergoing ESS without any image guidance. Preparation of the intraoperative NS required an additional 52 min and IGNS required 17 min compared to the control group. Based on operative instruments, the intraoperative NS has some limitations arising from the application of a high magnetic field. Surgical instruments must not be attracted by the magnetic field in the operating room. So those used in our study were thoroughly examined and some remanufactured using MR safe materials. All instruments in ESS could be used in surgical guidance during surgery in the IGNS. Anatomic landmarks were accurately visualized using intraoperative NS and IGNS. Intraoperative NS renews the image during surgery, so surgeons could confirm the surgical outcome during ESS. Since the average distant error in both systems was between 1 mm and 2.5 mm, we confirmed that accuracy obtained with both navigation system was suitable for ESS completion. The intraoperative NS renewed the image during navigation. In conclusion, both navigation systems are sufficient for accurate image navigation in ESS, but navigation systems must be selected based on the individual case.


Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease.
A clinically-related animal model of Parkinson's disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research.


Experimental Investigation on the Static Performance of Stud Connectors in Steel-HSFRC Composite Beams.
In this research, high strength fiber reinforced concrete (HSFRC) was used to replace the normal strength concrete (NSC) in steel-concrete composite beams to improve their working performance, which might change the static performance of stud connectors. Firstly, push-out tests were conducted to investigation on the static performance of stud connectors in steel-HSFRC composite beams and compared with steel-NSC composite beams. Studs of 8 sizes, 13 mm, 16 mm, 19 mm and 22 mm in diameter and 80 mm and 120 mm in height were adopted to study the influence of stud dimension. The test phenomenon shown that the crack resistance of HSFRC was better than that of NSC, and there were some splitting cracks on NSC slabs whereas no visible cracks on HSFRC slabs when specimens failed. Next, the load-slip curves of studs were analyzed and a typical load-slip curve was proposed which was divided into four stages. In addition, the effects of test parameters were analyzed according to the characteristic points of load-slip curve. Compared with NSC slab, HSFRC slab could provide greater restraining force to the studs, which improved the shear capacity and stiffness of studs while suppressed the ductility of studs. The shear capacity, stiffness and ductility of studs would significantly increase with the increasement of stud diameter and the studs with large diameter were more suitable for steel-HSFRC composite beams. The stud height had no obvious influence on the static performance of studs. Finally, based on the test results, the empirical formulas for load-slip curve and shear capacity of stud connectors embedded in HSFRC were developed which considered the influence factors more comprehensively and had better accuracy and applicability than previous formulas.


A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania.
Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01). Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184.


Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity.
Psoriatic plaque erosion is a rare toxic side effect of low-dose methotrexate (LDMTX) that has been reported during the treatment of psoriasis and described as a herald for impending pancytopenia. Fatalities from this have rarely been reported. Even rarer is methotrexate (MTX)-induced erosions of clinically normal skin in patients without a history of psoriasis. We report 3 rare presentations of MTX-induced cutaneous erosions, 2 fatalities occurring with MTX-induced psoriatic plaque erosions, and the sixth reported case of MTX-induced erosions with no prior history of psoriasis. Each were elderly patients on proton pump inhibitors with a history of chronic non-steroidal anti-inflammatory drug (NSAID) use. They all presented with acute onset of erosions after a recent change in their MTX dose. Pancytopenia followed in each case. Physicians' awareness of the sequelae in MTX-induced cutaneous erosions is imperative so MTX can be discontinued and treatment instituted to prevent fatal bone marrow suppression.


Neuronal Modulators from the Coral-Associated Fungi Aspergillus candidus.
Three new p-terphenyl derivatives, named 4″-O-methyl-prenylterphenyllin B (1) and phenylcandilide A and B (17 and 18), and three new indole-diterpene alkaloids, asperindoles E-G (22-24), were isolated together with eighteen known analogues from the fungi Aspergillus candidus associated with the South China Sea gorgonian Junceela fragillis. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic analysis, and DFT/NMR and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, the compounds 6, 9, 14, 17, 18 and 24 modulated spontaneous Ca2+ oscillations and 4-aminopyridine hyperexcited neuronal activity. A preliminary structure-activity relationship was discussed.


Olfactory neuroepithelioma: an immunohistochemical and ultrastructural study.
Three cases of olfactory neuroepithelioma are presented in this report. Histologically, these tumors were composed of small cells with round to oval, relatively hyperchromatic nuclei and scanty cytoplasm. The tumor cells were occasionally observed in tubular formations or rosette-like arrangements. Immunohistochemically, the tumor cells showed a positive reaction for cytokeratin AE1, cytokeratin CAM5.2, Ber-EP4, antisynaptophysin and anti-S100 protein in all cases. In two cases, LH-RH was detected in the tumor cells. Ultrastructurally, the tumor cells had the differentiation features of olfactory epithelium. Olfactory neuroepithelioma is a rare occurrence and it can be very difficult to distinguish olfactory neuroepithelioma from small cell carcinoma, neuroendocrine carcinoma and so-called "olfactory neuroblastoma" on the basis of hematoxylin and eosin stained sections alone. In controversial cases, a diagnosis of olfactory neuroepithelioma must be substantiated by ultrastructural and immunohistochemical findings, particularly regarding the detection of Ber-EP4 and LH-RH immunoreactivity.


MraZ Transcriptionally Controls the Critical Level of FtsL Required for Focusing Z-Rings and Kickstarting Septation in Bacillus subtilis.
The bacterial division and cell wall (dcw) cluster is a highly conserved region of the genome which encodes several essential cell division factors, including the central divisome protein FtsZ. Understanding the regulation of this region is key to our overall understanding of the division process. mraZ is found at the 5' end of the dcw cluster, and previous studies have described MraZ as a sequence-specific DNA binding protein. In this article, we investigate MraZ to elucidate its role in Bacillus subtilis. Through our investigation, we demonstrate that increased levels of MraZ result in lethal filamentation due to repression of its own operon (mraZ-mraW-ftsL-pbpB). We observed rescue of filamentation upon decoupling ftsL expression, but not other genes in the operon, from MraZ control. Our data suggest that regulation of the mra operon may be an alternative way for cells to quickly arrest cytokinesis, potentially during entry into the stationary phase and in the event of DNA replication arrest. Furthermore, through time-lapse microscopy, we were able to identify that overexpression of mraZ or depletion of FtsL results in decondensation of the FtsZ ring (Z-ring). Using fluorescent d-amino acid labeling, we also observed that coordinated peptidoglycan insertion at the division site is dysregulated in the absence of FtsL. Thus, we reveal that the precise role of FtsL is in Z-ring maturation and focusing septal peptidoglycan synthesis. IMPORTANCE MraZ is a highly conserved protein found in a diverse range of bacteria, including genome-reduced Mycoplasma. We investigated the role of MraZ in Bacillus subtilis and found that overproduction of MraZ is toxic due to cell division inhibition. Upon further analysis, we observed that MraZ is a repressor of its own operon, which includes genes that encode the essential cell division factors FtsL and PBP2B. We noted that decoupling of ftsL alone was sufficient to abolish MraZ-mediated cell division inhibition. Using time-lapse microscopy, we showed that under conditions where the FtsL level is depleted, the cell division machinery is unable to initiate cytokinesis. Thus, our results pinpoint that the precise role of FtsL is in concentrating septal cell wall synthesis to facilitate cell division.


Lipid-based vehicle for oral drug delivery.
With an increasing number of lipophilic drugs under development, homolipids and heterolipids have gained renewed interests as excipients for oral drug delivery systems. Oral administration has many advantages for chronic drug therapy. It is relatively safe, convenient for the patient and allows self administration. This article is not intended to review the broad area of lipid-based vehicle for oral drug delivery comprehensively. The rationale behind choosing lipids materials for pharmaceutical dosage forms and their applications is discussed. It also comments on the methods for monitoring the physicochemical properties of vehicles and formulations and describes a range of pharmacopoeial excipients suitable for these purposes. The excipients selected here are pharmacopoeial in European Pharmacopoeia 4th Ed., United States Pharmacopoeia 24th Ed./National Formulary 19th Ed. and Japanese Pharmacopoeia 13th Ed. or are drafted in Pharmaeuropa and Pharmacopoeial Forum. Widening availability of lipidic excipients with specific characteristics offer flexibility of application with respect to improving the bioavailability of poorly water-soluble drugs and manipulating release profiles.


Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project).
Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19. This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant. Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms. GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.


Rapid inactivation of the Escherichia coli Kdp K+ uptake system by high potassium concentrations.
The Kdp K+ uptake system of Escherichia coli is induced by limitation for K+ and/or high osmolarity. In the present study, the regulation of the activity of the Kdp system has been investigated in E. coli mutants possessing only the Kdp system as the mechanism of K+ accumulation. Cells grown in the presence of low K+ (0.1-1 mM) exhibit normal growth. However, growth inhibition results from exposure of cells to moderate levels of external K+ (> 5 mM). Measurement of the cytoplasmic pH, of K+ pools and of transport via the Kdp system demonstrates that the Kdp system is rapidly and irreversibly inhibited by moderate external K+. Concentrations of K+ greater than 2 mM are sufficient to cause inhibition of Kdp. At pH 6, this results in rapid lowering of the capacity for pH homeostasis, but at pH 7 the intracellular pH is unaffected. Parallel analysis of the expression of the Kdp system in a Kdp+/kdpFABC-lacZ strain shows that levels of K+ that are sufficient to inhibit Kdp activity also repress expression. As a result, growth inhibition of strains solely possessing Kdp arises jointly from inhibition of Kdp activity and repression of Kdp gene expression. These data identify an important aspect of the regulation of potassium transport via the Kdp system and also provide support for a model of regulation of Kdp expression via at least two mechanisms: sensing of both turgor and external K+ concentration.


Dissociating frontotemporal contributions to semantic ambiguity resolution in spoken sentences.
Comprehension of sentences containing semantically ambiguous words requires listeners to select appropriate interpretations, maintain linguistic material in working memory, and to reinterpret sentences that have been misinterpreted. All these functions appear to involve frontal cortical regions. Here, we attempt to differentiate these functions by varying the relative timing of an ambiguous word and disambiguating information in spoken sentences. We compare the location, magnitude, and timing of evoked activity using a fast-acquisition semisparse functional magnetic resonance imaging sequence. The left inferior frontal gyrus (LIFG) shows a strong response to sentences that are initially ambiguous (disambiguated by information that occurs either soon after the ambiguity or that is delayed until the end of the sentence). Response profiles indicate that activity, in both anterior and posterior LIFG regions, is triggered both by the ambiguous word and by the subsequent disambiguating information. The LIFG also responds to ambiguities that are preceded by disambiguating context. These results suggest that the LIFG subserves multiple cognitive processes including selecting an appropriate meaning and reinterpreting sentences that have been misparsed. In contrast, the left inferior temporal gyrus responds to the disambiguating information but not to the ambiguous word itself and may be involved in reprocessing sentences that were initially misinterpreted.


A comparative study of esophageal stromal tumors and smooth muscle tumors.
To explore the clinicopathological, immunohistochemical, and molecular biologic characteristics of esophageal stromal tumors and smooth muscle tumors. Twenty four cases of esophageal mesenchymal tumors were reclassified by a panel of antibodies such as CD117, CD34 etc. The sequence of 11 exon of c-kit gene were detected in some cases. There were 3 cases of esophageal stromal tumors, 20 leiomyomas, and 1 leiomyosarcoma. The 3 esophageal stromal tumors occurred in 3 men aged 71, 56 and 60 years respectively. The tumors originated from muscularis propria with the size of 4 cm, 8 cm and 14 cm in diameter. Microscopically, the tumor cells were spindle and epithelioid shaped with slightly basophilic appearance, arranged in intersecting fascicles, diffusing and palisading patterns. Immunohistochemically, the tumors were positive for CD117 and CD34. The mutation of 11 exon of c-kit gene was detected in one case. In comparison, esophageal leiomyomas occurred in a younger population. The age ranged from 30 to 60 years (mean age 41.6 years), 12 male cases, 8 female cases. 15 cases of esophageal leiomyomas were intramural tumors with a diameter of 0.8 - 10.5 cm (mean 4.5 cm) originating from muscularis propria and 5 cases which were intraluminal polyps with a diameter of 0.2 - 1.0 cm originating from muscularis mucosae. Leiomyomas were strongly eosinophilic in appearance, diffuse positivity for alpha-SMA, MSA, and desmin, and no c-kit gene mutation. One male case of leiomyosarcoma had a diameter of 5 cm and originated from muscularis mucosae and displayed a sausage-shaped polyp. Leiomyoma is still the most common mesenchymal tumor of the esophagus, the stromal tumor can be similar to gastrointestinal stromal tumors. Typical esophageal leiomyosarcoma is very rare and has different clinicopathologic and molecular biologic features.


Increased Small-World Network Topology Following Deployment-Acquired Traumatic Brain Injury Associated with the Development of Post-Traumatic Stress Disorder.
Cross-sectional and longitudinal studies in active duty and veteran cohorts have both demonstrated that deployment-acquired traumatic brain injury (TBI) is an independent risk factor for developing post-traumatic stress disorder (PTSD), beyond confounds such as combat exposure, physical injury, predeployment TBI, and pre-deployment psychiatric symptoms. This study investigated how resting-state brain networks differ between individuals who developed PTSD and those who did not following deployment-acquired TBI. Participants included postdeployment veterans with deployment-acquired TBI history both with and without current PTSD diagnosis. Graph metrics, including small-worldness, clustering coefficient, and modularity, were calculated from individually constructed whole-brain networks based on 5-min eyes-open resting-state magnetoencephalography (MEG) recordings. Analyses were adjusted for age and premorbid IQ. Results demonstrated that participants with current PTSD displayed higher levels of small-worldness, F(1,12) = 5.364, p < 0.039, partial eta squared = 0.309, and Cohen's d = 0.972, and clustering coefficient, F(1, 12) = 12.204, p < 0.004, partial eta squared = 0.504, and Cohen's d = 0.905, than participants without current PTSD. There were no between-group differences in modularity or the number of modules present. These findings are consistent with a hyperconnectivity hypothesis of the effect of TBI history on functional networks rather than a disconnection hypothesis, demonstrating increased levels of clustering coefficient rather than a decrease as might be expected; however, these results do not account for potential changes in brain structure. These results demonstrate the potential pathological sequelae of changes in functional brain networks following deployment-acquired TBI and represent potential neurobiological changes associated with deployment-acquired TBI that may increase the risk of subsequently developing PTSD.


The regulation of meiotic crossover distribution: a coarse solution to a century-old mystery?
Meiotic crossovers, which are exchanges of genetic material between homologous chromosomes, are more evenly and distantly spaced along chromosomes than expected by chance. This is because the occurrence of one crossover reduces the likelihood of nearby crossover events - a conserved and intriguing phenomenon called crossover interference. Although crossover interference was first described over a century ago, the mechanism allowing coordination of the fate of potential crossover sites half a chromosome away remains elusive. In this review, we discuss the recently published evidence supporting a new model for crossover patterning, coined the coarsening model, and point out the missing pieces that are still needed to complete this fascinating puzzle.


The impact of low input DNA on the reliability of DNA methylation as measured by the Illumina Infinium MethylationEPIC BeadChip.
DNA methylation (DNAm) is commonly assayed using the Illumina Infinium MethylationEPIC BeadChip, but there is currently little published evidence to define the lower limits of the amount of DNA that can be used whilst preserving data quality. Such evidence is valuable for analyses utilizing precious or limited DNA sources. We used a single pooled sample of DNA in quadruplicate at three dilutions to define replicability and noise, and an independent population dataset of 328 individuals (from a community-based study including US-born non-Hispanic Black and white persons) to assess the impact of total DNA input on the quality of data generated using the Illumina Infinium MethylationEPIC BeadChip. We found that data are less reliable and more noisy as DNA input decreases to 40ng, with clear reductions in data quality; and that low DNA input is associated with a reduction in power to detect EWAS associations, requiring larger sample sizes. We conclude that DNA input as low as 40ng can be used with the Illumina Infinium MethylationEPIC BeadChip, provided quality checks and sensitivity analyses are undertaken.


Stabilizing Nanosized Si Anodes with the Synergetic Usage of Atomic Layer Deposition and Electrolyte Additives for Li-Ion Batteries.
A substantial increase in charging capacity over long cycle periods was made possible by the formation of a flexible weblike network via the combination of Al2O3 atomic layer deposition (ALD) and the electrolyte additive vinylene carbonate (VC). Transmission electron microscopy shows that a weblike network forms after cycling when ALD and VC were used in combination that dramatically increases the cycle stability for the Si composite anode. The ALD-VC combination also showed reduced reactions with the lithium salt, forming a more stable solid electrolyte interface (SEI) absent of fluorinated silicon species, as evidenced by X-ray photoelectron spectroscopy. Although the bare Si composite anode showed only an improvement from a 56% to a 45% loss after 50 cycles, when VC was introduced, the ALD-coated Si anode showed an improvement from a 73% to a 11% capacity loss. Furthermore, the anode with the ALD coating and VC had a capacity of 630 mAh g(-1) after 200 cycles running at 200 mA g(-1), and the bare anode without VC showed a capacity of 400 mAh g(-1) after only 50 cycles. This approach can be extended to other Si systems, and the formation of this SEI is dependent on the thickness of the ALD that affects both capacity and stability.


Density dependence in establishment, growth and worm fecundity in intestinal helminthiasis: the population biology of Trichuris muris (Nematoda) infection in CBA/Ca mice.
The results are presented of an experimental study of the population biology of chronic Trichuris muris (Nematoda) infection in cortisone-treated CBA/Ca mice. Attention is focused upon both the validity of the common use of faecal egg counts to demonstrate density dependence in helminth fecundity, and the identification of other possible density-dependent mechanisms that may regulate worm numbers in chronic trichuriasis. The results show that faecal egg counts, although demonstrating high daily variation, are not an artefact of host faecal output but a significant density-dependent function of worm burden. This finding contrasts with the observations on Heligmosomoides polygyrus infection in outbred MFI mice, but accords with similar studies in a wide variety of host - helminth systems. Worm establishment in the murine host is found to be a density related function of infection dose. This is attributed to the probable existence of a physical gut-carrying capacity in the murine host for T. muris. Worm distribution in the gut is also shown to the density dependent, with worms being displaced from the caecum to the colon at increasing intensities of infection. The sex ratio of the adult parasites, however, is found to be both unitary and independent of worm burden. Evidence for a significant density-dependent decline in female T. muris growth or size is presented. The results also show a significant positive association between female T. muris weight and per capita fecundity. These findings indicate that the stunted growth of individual worms at high parasite densities may be a potential mechanism underlying density dependence in helminth fecundity.


[Risk of infection in instrumental and surgical urologic interventions with special reference to catheter drainage].
The risk of infection in instrumental and operative urological surgery is particularly high in the use of catheter drainage. Dependent on the duration of use of a fistula catheter or a transurethral catheter, infection of the urinary tract occurs in almost 100% of cases. The pathogens of hospital infection show a clearly increasing drug resistance. The occurrence of multiple resistances is remarkable. Furthermore, fluctuations in the range of pathogens can be detected. An increase of infection by Proteus and Klebsiella and a decrease of infections of the urinary tract with Escherichia coli and staphylococci have been observed. Prophylactic administration of chemotherapeutic agents cannot prevent the recurrence of iatrogenic infections of the urinary tract.


Arousal-related P3a to novel auditory stimuli is abolished by a moderately low alcohol dose.
Concurrent measures of event-related potentials (ERPs) and skin conductance responses were obtained in an auditory oddball task consisting of rare target, rare non-signal unique novel and frequent standard tones. Twelve right-handed male social drinkers participated in all four cells of the balanced placebo design in which effects of beverage and instructions as to the beverage content (expectancy) were independently manipulated. The beverage contained either juice only, or vodka mixed with juice in the ratio that successfully disguised the taste of alcohol and raised average peak blood-alcohol level to 0.045% (45 mg/dl). ERPs were sensitive to adverse effects of mild inebriation, whereas behavioural measures were not affected. Alcohol ingestion reliably increased N2 amplitude and reduced the late positive complex (LPC). A large, fronto-central P3a (280 ms latency) was recorded to novel sounds in the placebo condition, but only on the trials that also evoked electrodermal-orienting responses. Both novel and target stimuli evoked a posterior P3b (340 ms), which was independent of orienting. Alcohol selectively attenuated the P3a to novel sounds on trials with autonomic arousal. This evidence confirms the previously suggested distinction between the subcomponents of the LPC: P3a may be a central index of orienting to novel, task-irrelevant but potentially significant stimuli and is an important component of the arousal system. P3b does not have a clear relationship with arousal and may embody voluntary cognitive processing of rare task-related stimuli. Overall, these results indicate that alcohol affects multiple brain systems concerned with arousal, attentional processes and cognitive-autonomic integration.


Effect of Repeated Gathering and Age on the Quality of Zatorska Goose Feathers.
We investigated a reproductive flock of Zatorska geese. The birds were divided into four groups: three-year-old ganders (n=10), and one-, two-, and three-year-old layers (n=30). Mature feathers were collected from the birds between July and September (i.e., after breeding). Before collection, the feathers and down were evaluated to determine their maturity. The quantitative composition of each sample of feathers was evaluated manually. The evaluated quality traits of the feathers were turbidity of an aqueous extract, acidity, oxygen index number, and fat content. The data were analyzed using the SAS statistical package with multivariate analysis of variance for repeated measures. The weight of feathers collected from all three gatherings was the highest for the three-year-old ganders. In subsequent gatherings, the weight of the collected feathers tended to increase. There was a statistically significant difference in down composition between the first and the subsequent two gatherings in all age-groups of geese. Neither the age nor the gender of the birds had an effect on the quantity of down obtained, which was 80-85 g. The turbidity of the feather extract was lowest for feathers collected in the first gathering. For the layers, the turbidity of the feather extract was lowest in feathers obtained from the one-year-old birds. The feathers ranged from slightly acidic to neutral, with pH values between 5.9 and 7.2. The fat content was lowest in feathers collected in the first gathering (2.4-2.7%), and tended to increase in subsequent gatherings. There was no statistically significant difference in the oxygen index number between individual gatherings, or between the three-years-old layers and the ganders.


Seasonal variation of total phenolic, antioxidant activity and minerals in fresh tea shoots (Camellia sinensis var. sinensis).
Seasonal variation of total phenolics, antioxidant activity and minerals in fresh tea shoots, consisting of one apical bud and two adjoining leaves sampled from Muradiye, Tuglali, Gundogdu, Enstitu 9, Hamzabey, Hayrat and Pazar 20 clones grown in Eastern Black Sea region in Turkey was investigated during three harvest season (May, July and September) in both 2006 and 2007 years. The total phenolics of all clones were lower in cool months of May in both years (average 33.00-90.27 mg GAE/g dry weight basis). Thereafter, the levels of total phenolics increased throughout the warmer months from July to September. Antioxidant activity determined by beta-carotene bleaching assay showed similar trends which increased from 1st harvest (May) to 3rd harvest (September). All clones showed nearly 100% antioxidant activity at 2nd and 3rd harvest season which higher than standard synthetic antioxidant BHA (butylated hydroxyanisole). However, seasonal variation of minerals (N, P, K, Ca, Mg, Na, Fe, Cu, Mn, Zn) showed different results according to clones used. These results seem to suggest that the harvest time is crucial to determining the antioxidant potential of fresh tea shoots.


Small RNA pathways are present and functional in the angiosperm male gametophyte.
Small non-coding RNAs are essential for development of the sporophyte, the somatic diploid phase of flowering plants. They are integral to key cellular processes such as defense, generation of chromatin structure, and regulation of native gene expression. Surprisingly, very little is known of their presence and function in the male haploid phase of plant development (male gametophyte/pollen grain), where dramatic cell fate changes leading to gametogenesis occur over just two mitotic divisions. We show that critical components of small RNA pathways are expressed throughout pollen development, but in a pattern that differs from the sporophyte. We also demonstrate that mature pollen accumulates a range of mature microRNAs, the class of small RNA most frequently involved in post-transcriptional regulation of endogenous gene expression. Significantly, these miRNAs cleave their target transcripts in developing pollen-a process that seemingly contributes to the purging of key regulatory transcripts from the mature pollen grain. Small RNAs are thus likely to make a hitherto unappreciated contribution to male gametophyte gene expression patterns, pollen development, and gametogenesis.


Head injuries, heading, and the use of headgear in soccer.
Soccer has more than 265 million players around the world and is the only contact sport with purposeful use of the head for controlling and advancing the ball. Head contact in soccer has the potential to cause acute traumatic brain injury including concussion or, potentially, a pattern of chronic brain injury. Although early retrospective research on the effects of soccer heading seemed to suggest that purposeful heading may contribute to long-term cognitive impairment, prospective controlled studies do not support this and, in fact, suggest that purposeful heading may not be a risk factor for cognitive impairment. Headgear has not been shown to be effective in reducing ball impact but may be helpful in reducing the force of non-ball-related impacts to the head. There are concerns that universal use of headgear may cause more aggressive heading and head challenges, leading to increased risk of injury.


Coordinated regulation of maize genes during increasing exposure to ultraviolet radiation: identification of ultraviolet-responsive genes, functional processes and associated potential promoter motifs.
Genetic gain in the yield of modern maize reflects increased stress tolerance. The manipulation of genes for deliberate alterations in tolerance relies on an understanding of the regulation and components of stress responses. Transcriptome analysis of an ultraviolet (UV) radiation time course with paired treatment and control measurements yielded groups of coordinately regulated genes and gene ontology processes. A comparison of the patterns of gene expression with patterns of morphological changes allowed the identification of physiologically relevant gene expression regulons. A set of genes significantly affected by UV radiation in maize leaves was selected by linear modelling plus order-restricted inference profile matches. This gene list was used to find upstream sequence motifs that predict the UV regulation of maize gene expression.


The air mycobiome is decoupled from the soil mycobiome in the California San Joaquin Valley.
Dispersal is a key force in the assembly of fungal communities and the air is the dominant route of dispersal for most fungi. Understanding the dynamics of airborne fungi is important for determining their source and for helping to prevent fungal disease. This understanding is important in the San Joaquin Valley of California, which is home to 4.2 million people and where the airborne fungus Coccidioides is responsible for the most important fungal disease of otherwise healthy humans, coccidioidomycosis. The San Joaquin Valley is the most productive agricultural region in the United States, with the principal crops grown therein susceptible to fungal pathogens. Here, we characterize the fungal community in soil and air on undeveloped and agricultural land in the San Joaquin Valley using metabarcoding of the internal transcribed spacer 2 variable region of fungal rDNA. Using 1,002 individual samples, we report one of the most extensive studies of fungi sampled simultaneously from air and soil using modern sequencing techniques. We find that the air mycobiome in the San Joaquin Valley is distinct from the soil mycobiome, and that the assemblages of airborne fungi from sites as far apart as 160 km are far more similar to one another than to the fungal communities in nearby soils. Additionally, we present evidence that airborne fungi in the San Joaquin Valley are subject to dispersal limitation and cyclical intra-annual patterns of community composition. Our findings are broadly applicable to understanding the dispersal of airborne fungi and the taxonomic structure of airborne fungal assemblages.


Principles of sequence-recognition in aromatic polyimides.
Pyrene-based molecular tweezers show sequence-specific binding to aromatic polyimides through sterically-controlled donor-acceptor pi-stacking and hydrogen bonding; (1)H NMR spectra of tweezer-complexes with polyimides having different sequence-restrictions show conclusively that the detection of long range sequence-information results from multiple tweezer-binding at adjacent imide residues.


Lasers or light sources for treating port-wine stains.
Port-wine stains are birthmarks caused by malformations of blood vessels in the skin. Port-wine stains manifest themselves in infancy as a flat, red mark and do not regress spontaneously but may, if untreated, become darker and thicker in adult life. The profusion of various lasers and light sources makes it difficult to decide which equipment is the best for treating port-wine stains. To study participant satisfaction, clinical efficacy, and adverse effects of the treatment of port-wine stains by lasers and light sources. We searched the following databases up to April 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (Latin American and Caribbean Health Science Information database, from 1982), and reference lists of articles. We also searched online trials registries for ongoing trials and contacted trial authors where appropriate. Randomised clinical trials (RCTs) of lasers or light sources for the treatment of port-wine stains. Our outcomes of interest were participant satisfaction, reduction in redness of the port-wine stain as determined by clinical evaluation, and short- and long-term adverse effects of the treatments. Three authors independently extracted data and assessed trial quality. We included 5 RCTs involving a total of 103 participants; all of the trials used a within-participant design. The interventions and outcomes were too varied to be combined statistically. All trials used the pulsed dye laser for comparisons.None of the studies focused on participant satisfaction, which was one of our primary outcomes, but participant preference was evaluated in three of five studies. Participants preferred the pulsed dye laser to intense pulsed light based on the clinical effect. They marginally preferred the Neodymium:YAG (yttrium-aluminium-garnet) (Nd:YAG) laser to the pulsed dye laser due to shorter lasting purpura, and pulsed dye laser in conjunction with cooling was preferred to treatment with pulsed dye laser alone.All trials examined short-term efficacy of less than six months after treatments with the pulsed dye laser, intense pulsed light, and Nd:YAG laser. The pulsed dye laser was evaluated in all five trials. Depending upon the setting of the pulsed dye laser, this resulted in more than 25% reduction in redness. This was after 1 to 3 treatments for up to 4 to 6 months postoperatively in 50% to 100% of the participants. There was only one study each of intense pulsed light and Nd:YAG laser.Two trials had no occurrence of long-term adverse effects, i.e. six months after treatment. Three trials reported pigmentary alterations in 3% to 24% of the participants, with the highest percentage occurring in Chinese participants with darker skin types. In one study one participant experienced scarring of the skin caused by a too-high dose of the laser used. Short-term side-effects included pain, crusting, and blistering in the first two weeks after treatment. The pulsed dye laser leads to clinically relevant clearance of port-wine stains. A limited number of RCTs evaluated the efficacy from intense pulsed light and other laser types. High-quality RCTs are needed to assess individual efficacy from different lasers and light sources, as well as participant satisfaction.


Using mixed methods to establish tobacco treatment acceptability from the perspective of clients and clinicians of antenatal substance use services.
Up to 95% of pregnant women with alcohol and other drug (AOD) problems also smoke tobacco. Challenging psychosocial circumstances and a lack of targeted tobacco interventions contribute to low rates of prenatal abstinence and more effective treatment strategies are required. This study explores smoking in pregnant clients of AOD treatment services from a consumer and healthcare provider perspective to examine characteristics of behaviour change and the acceptability of evidence-based tobacco treatment strategies. Outcomes will support the design and implementation of a comprehensive tobacco intervention. A mixed methods triangulated design was used. Thirteen women who smoked and attended antenatal AOD services in New South Wales, Australia, were interviewed and 28 clinicians from the same services were surveyed. Domains including experiences of tobacco smoking in pregnancy, motivators and barriers to cessation and evidence-based strategies to assist cessation during pregnancy were explored. Interviews were analysed using Iterative Categorization, with interpretation guided by Qualitative Description. Online surveys were analysed descriptively. A convergent-parallel mixed methods analysis was performed. Women and clinicians agreed that improving baby's health outcomes was the primary motivation to stop smoking. Negative experiences with nicotine replacement therapy (NRT), financial constraints and maternal contraindications restricted its uptake and effectiveness during pregnancy. Both groups agreed that other AOD use, stopping multiple substances concurrently, difficulty coping with stress and the influence of partners who smoke had the biggest impacts on cessation efforts. Clinicians favoured harm-reduction rather than abstinence-based tobacco interventions and women appeared satisfied with reduction efforts. Both views may influence the attainment of prenatal abstinence-based goals. Although previous evidence suggested the contrary, clinicians were willing to encourage simultaneous cessation of tobacco and other substances. Non-judgmental treatment approaches that provide extra support, education and motivation were important for women. Women and clinicians supported use of NRT despite concerns. Financial incentives, counselling, partner support and offering tobacco treatment with antenatal AOD care were considered acceptable treatment options. NRT, incentives, counselling and partner support could be utilized in a tobacco intervention for pregnant women with substance use concerns. Non-judgmental education, motivation, and provision of NRT including instruction for correct use are important considerations.


Role of block copolymer morphology on particle percolation of polymer nanocomposites.
In this study, the effects of nanoparticle volume fraction, block stiffness, and diblock composition on the microstructure and electrical properties of composites are investigated using molecular dynamics simulation. It is shown that selective localization of conductive nanoparticles in a continuous block of diblock copolymer can dramatically reduce the percolation threshold. In the flexible-flexible copolymer systems with a relatively low particle loading, as the ratio of two blocks varies, one sees four kinds of phase structure: signal continuous, lamellar, co-continuous, and dispersed, corresponding to the order-disorder and continuity-dispersion transitions. In consideration of particle connectivity, the best electrical performance can be achieved with a special tri-continuous microstructure. While in the semi-flexible systems, the existence of rigid blocks can destroy the lamellar structure. If particles are located in the flexible block, a moderate stiffness of the rigid block can extensively enlarge the tri-continuous region, and high conductivity can be realized over a wide range of diblock compositions. If particles are located in the rigid block, however, high conductivity only emerges in a narrow composition range. In addition, the block should be prevented from becoming overstiff because this will cause direct particle aggregation.


Hydrolysis of casein accelerates gastrointestinal transit via reduction of opioid receptor agonists released from casein in rats.
Protein hydrolysate accelerates gastrointestinal transit (GIT) and feeding advancement in preterm infants compared to native protein. In rat pups, opioid receptor agonists released from casein during digestion such as beta-casomorphins slow down GIT. We hypothesized that hydrolysis of casein reduces the opioid activity released during digestion thereby accelerating GIT compared to native casein. The aim of the present study was to investigate whether casein hydrolysate accelerates GIT compared to native casein and whether pretreatment with naloxone, an opioid receptor blocker, abolishes this difference in rat pups. In a randomized controlled trial following a 2 x 2 factorial design, 216 female Wistar rat pups were fed with pellets based on hydrolyzed or native casein. After pretreatment with naloxone or normal saline, carmine red was administered by oro-gastric gavage as a tracer for GIT velocity measurement. Four hours later the animals were sacrificed, their intestine was removed and the length of the colon from the cecocolonic junction to the anus was measured. GIT was recorded as percentage of the total colonic length (percentage of colonic transit) passed by carmine red. Data were given as mean +/- SD. GIT was significantly higher with hydrolyzed casein compared to native casein formula (77.4 +/- 17 and 51.2 +/- 20%), but there was no difference after naloxone pretreatment (77.1 +/- 16 and 76.5 +/- 17%). The present data suggest that hydrolysis of casein accelerates GIT via reduction of opioid activity released during digestion. Further studies are required to investigate to which extent these rat pub data apply to preterm infants.


Loss of alleles in vestibular schwannomas: use of microsatellite markers on chromosome 22.
Using highly informative microsatellite markers flanking the neurofibromatosis type 2 gene, we determined the frequency of chromosome 22 allele loss in vestibular schwannomas. Peripheral lymphocyte/vestibular schwannoma DNA pairs were analyzed with five different microsatellite markers on chromosome 22. Samples were taken from 32 patients (17 females and 15 males). Twenty-seven tumors occurred sporadically, and five were from patients with neurofibromatosis type 2. Using the microsatellite markers D22S351, CRYB2, D22S268, D22S304, and interleukin type 2RP3, we found loss of heterozygosity for at least two markers in 12 tumors. Ten tumors showed loss of heterozygosity for markers flanking the neurofibromatosis type 2 gene. Although microsatellite markers require little DNA for analysis and are highly informative, allele patterns may be difficult to interpret in some cases. Loss of heterozygosity of chromosome 22 alleles was a frequent event in vestibular schwannomas. In 10 tumors, heterozygosity was lost for centromeric and telomeric markers indicating likely monosomy 22. However, 63% of tumors did not reveal a detectable chromosomal loss. Unless a second vestibular schwannoma locus exists, these tumors likely harbor point mutations in the neurofibromatosis type 2 gene or deletions below the level of resolution of the markers used in this study.


Nonleukemic granulocytic sarcoma of orbit after blunt trauma: A case report and review of literature.
Granulocytic sarcoma without invasion of bone marrow or blood is very rare. The diagnosis of it is usually overlooked and the treatment has not reached a consensus. Meanwhile, the onset of this kind of disease is not clear. Diagnose patients in early stage and help choose the right treatment strategies. The ultimate diagnosis was nonleukemic granulocytic sarcoma after blunt trauma. Surgery was the initial treatment option. Chemotherapy including idarubicin (70 mg, D1-D3) and cytosine arabinoside (100 mg, D1-D7) and radiotherapy of total 3,060 cGy were then administered but failed to control the disease. Hematopoietic stem cell transplantation was finally administered. No evidence of disease progression or spread according to the latest follow-up. The etiology of nonleukemic granulocytic still remains unclear, though trauma seems to be a potential predisposing factor and deserves more attention for early diagnosis and timely and proper treatment. Systemic chemotherapy is more effective than radiotherapy or surgery. Hematopoietic stem cell transplantation is an alternative choice after the failure of chemotherapy.


Prisoners' perception of informing to the authorities: an analysis in terms of functional moral judgment.
A series of functional measurement experiment show that prisoners modulate their moral judgments of violations of their in-group regulations. The participants were 67 women and 80 men, sentenced for at least three years for murder, robbery, drug-traffic or white collar offenses. Each was asked, individually, to imagine a series of incidents where incriminating information on in-group or out-group inmates is delivered to the prison authorities or to an ingroup source and to rate the deserved denigration of the informer, who was characterized as a leader or not and as a drug-addict or not who had a prison-leave or not. An assignment of approximately equal weight for social status, drug use and prison leave was found, beyond gender and type of offense. In line with the hypothesis of judgmental modularity, informing to an out-group source was judged much more severely than informing to in-group arbiter and than informing on an out-group inmate.


Modification of the cardiovascular effects of L-dopa by decarboxylase inhibitors.
Intravenously infused L-dopa (0.3 mg/kg per min) produced hypertension and cardiac arrhythmias in halothane anesthetized dogs. Biochemical studies showed that the heart, kidney, and brain of these animals accumulated significant amounts of catecholamines formed from the administered precursor. Pretreatment of dogs with an extracerebral inhibitor of dopa decarboxylase [D,L-alpha-hydrazino-alpha-methyl-beta-(3.4-dihydroxyphenyl) propionic acid] prevented the development of hypertension and arrhythmias with infusion of L-dopa. Instead, these animals developed significant hypotension. The heart and kidney of these animals accumulated markedly reduced amounts of catecholamines formed from L-dopa compared with dogs receiving L-dopa alone: the amount of catecholamines accumulated in brain was unchanged. L-dopa, after extracerebral decarboxylase inhibition, appeared to produce hypotension by reducing peripheral vascular resistance without altering sympathetic nerve function. During hypotension, cardiac output was not altered and arterial pressure in perfused hindlimbs fell, even though flow was maintained. The pressor response to intravenous injections of norepinephrine and dopamine was unchanged. Hindlimb arterial pressure response to direct electrical stimulation of the lumbar sympathetic trunk was also unchanged. Pretreatment with a drug which inhibits brain as well as extracerebral dopa decarboxylase [D,L-seryl-2,3,4-trihydroxybenzylhydrazine hydrochloride] abolished all effects of L-dopa on blood pressure. In these animals, there was a marked reduction of catecholamine formation from L-dopa in the brain as well as the heart and kidney. It appears that L-dopa produces opposite effects on blood pressure depending on the site of accumulation of its metabolic products, dopamine and norepinephrine. If L-dopa is rapidly decarboxylated to catecholamines in peripheral organs, hypertension and cardiac arrhythmias occur. If peripheral dopa decarboxylase is selectively inhibited, a centrally mediated hypotensive effect, probably secondary to the accumulation of catecholamines in the brain, becomes apparent. If dopa decarboxylase is inhibited in the brain in addition to extracerebral organs, L-dopa has no effect on blood pressure.


FAST in the deployed military setting.
Focused assessment with sonography in trauma (FAST) is historically an effective method of assessing the patient in the trauma bay in order to aid decision-making and optimise patient outcomes. However, in the UK civilian practice, the use of FAST may decline given a recent change in National Institute for Health and Care Excellence guidance as a result of improvement in CT availability and resuscitation techniques. In the Role 3 Medical Treatment Facility, Camp Bastion, 187 patients with trauma who received FAST in the trauma bay in 2014 were reviewed to determine the accuracy of FAST in the deployed environment. The data demonstrates the sensitivity and specificity of FAST to be 75% and 99.3%, respectively. This study demonstrates that FAST is accurate on operations. FAST is provided by the integrated radiologist as part of damage control radiology, which gives the team leader rapid diagnostic information to improve decision-making and ultimately patient outcomes. CT is heavily utilised in civilian practice; however, the military operates in a different environment often with multiple casualties and limited access to CT, as a result, portable ultrasound will continue to be a valuable tool on operations if used properly. The next challenge is to develop and maintain this high diagnostic accuracy in future deployments where the memories of our prior success may fade.