Force field parameters for S-nitrosocysteine and molecular dynamics simulations of S-nitrosated thioredoxin.
Estimation of structural perturbation induced by S-nitrosation is important to understand the mode of cellular signal transduction mediated by nitric oxide. Crystal structures of S-nitrosated proteins have been solved only for a few cases, however, so that molecular dynamics simulation may provide an alternative tool for probing structural perturbation. In this study AMBER-99 force field parameters for S-nitrosocysteine were developed and applied to molecular dynamics simulations of S-nitrosated thioredoxin. Geometry optimization at the level of HF/6-31G * was followed by a restrained electrostatic potential charge-fitting to obtain the atomic charges of S-nitrosocysteine. Force constants for bonds and angles were obtained from generalized AMBER force field. Torsional force constants for CC-SN and CS-NO were determined by fitting the torsional profiles obtained from geometry optimization with those from molecular mechanical energy minimization. Finally molecular dynamics simulations were performed with theses parameters on oxidized and reduced thioredoxin with and without S-nitrosocysteine. In all cases the root-mean-square deviations of alpha-carbons yielded well-behaved trajectories. The CC-SH dihedral angle which fluctuated severely during the simulation became quiet upon S-nitrosation. In conclusion the force field parameters developed in this study for S-nitrosocysteine appear to be suitable for molecular dynamics simulations of S-nitrosated proteins.


Heparin or a PAF antagonist (BN-52021) prevents the acute pulmonary edema induced by Tityus serrulatus scorpion venom in the rat.
Experiments were performed in pentobarbital-anesthetized rats, to study the mechanism of the acute pulmonary edema induced by Tityus serrulatus scorpion venom. In control rats injection of venom (50 micrograms/100 g, i.v.) induced arterial hypertension and lung edema (lung/body index or LBI equal to 1.01 +/- 0.09). In rats pretreated with heparin (100 IU/100 g 30 min previously) the venom induced similar hypertensive effects, but no edema was detected (LBI = 0.63 +/- 0.06, P > 0.05). Similarly, in rats pretreated with the PAF antagonist BN-52021 (0.5 mg/100 g, i.v., 30 min previously), the venom-induced hypertension was not modified but the acute pulmonary edema was prevented (LBI = 0.67 +/- 0.08, P > 0.05). It is concluded that PAF plays an important role on the genesis of pulmonary edema induced by scorpion venom in the rat. It is suggested that the inhibitory action of heparin could be related to a decrease in the vascular permeability in the lungs.


Anaesthesia with ketamine and thiopentone for short surgical procedures: with reference to anaesthesia in developing countries.
A technique of general anaesthesia using small doses of intravenous ketamine and thiopentone is described. The method provides satisfactory operating conditions combined with cardiovascular stability and an apparently safe airway at little more than half the cost of a comparable technique using ketamine alone.


[A severe obstruction of the upper airways in a child: procedure to follow].
We report the case of a tracheal stenosis in a young child as a result of prolonged intubation. The anesthetic management of the airway laser surgery is discussed. A multidisciplinary cooperation allowed good results.


Loss of FBXW7 is related to the susceptibility and poor prognosis of cervical squamous carcinoma.
To investigate the relationship between F box/WD-40 domain protein 7 (FBXW7) and cervical squamous cancer. We investigated the FBXW7 expression in 136 cervical squamous carcinoma cases through immunohistochemistry and Western-blot analysis to evaluate the clinical significance of FBXW7 and to elucidate the relationship of FBXW7 expression with progression-free survival (PFS) and overall survival (OS). Low FBXW7 expression was associated with high histologic grade, lymphovascular space invasion and lymph node metastasis, among other parameters. Patients with low FBXW7 expression exhibited poor OS and PFS. FBXW7 is related to the susceptibility and prognosis of cervical squamous carcinoma, indicating FBXW7 may be a potentially important target for the prediction of prognosis.


Epidemiology and associated factors for hospitalization related respiratory syncytial virus infection among children less than 5 years of age in Northern Thailand.
Respiratory syncytial virus (RSV) is often the main problem in young children that require hospitalization. The objective of this study was to identify factors associated with RSV-related hospitalizations in young children less than five years old. A retrospective study was conducted for acute respiratory tract infection (ARTI) at a tertiary care hospital from January 2017 to December 2021 by using binary logistic regression analysis to detect the associated factors with RSV-related hospitalizations in children. RSV-related hospitalization was detected in 293 of 410 (71.46 %) cases of RSV infection, most of which appeared in the rainy months of August to November. The most common symptoms and signs were 81.5 % rhinorrhea, 70.7 % cough, 68.5 % sore throat, 68.3 % sputum production, and 66.8 % fever. Factors associated with RSV-related hospitalization were age less than or equal to 2 years (aOR = 4.62, 95 % CI = 1.86-11.44), preterm birth (aOR = 2.61, 95 % CI = 1.05-6.10), patients with underlying disease (aOR = 3.06, 95 % CI = 1.21-10.34), and the presenting symptoms with sputum production (aOR = 16.49, 95 % CI = 3.80-71.55). Laboratory blood tests, low levels of hematocrit (aOR = 9.61, 95 % CI = 1.09-84.49) was the associated factor for hospitalization with RSV infection (p < 0.05). Factors associated with RSV-related hospitalizations in children were age less than or equal to two years, preterm birth, underlying disease, symptoms of sputum production. The low level of hematocrit was also associated with RSV-related hospitalizations in these children.


New Class of Tunable Choline Bromide-Based Hydrophobic Deep Eutectic Solvents for the Extraction of Bioactive Compounds of Varying Polarity from a Plant Matrix.
Deep eutectic solvents (DESs) are a class of sustainable solvents that have found numerous applications in different fields. One of their main attributes is the possibility of easily modifying their physicochemical properties by varying the type of hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) that comprise them. Choline chloride ([Ch+][Cl-])-based hydrophilic DESs were among the first studied and the most used because of their capacity to easily create a hydrogen bonding network that lies in its unique chemical structure, characterized by a hydroxyl substituent within the ammonium headgroup. In this study, a new class of hydrophobic [Ch+][Br-]-modified salts were synthesized to produce HBAs with similar properties to choline for the preparation of hydrophobic DESs. Six different [Ch+][Br-]-based HDESs were prepared and characterized in terms of hydrophobicity, viscosity, and solvation properties (hydrogen bonding, dispersion, dipolarity/polarizability, n-π, and π-π interactions). They were employed as solvents in a microextraction method for the determination of phytochemicals in Cannabis sativa L. plant. The extraction performance of the [Ch+][Br-]-based HDESs was compared to eutectic mixtures based on conventional hydrophobic HBAs, and the results revealed that the unique properties of [Ch+][Br-]-modified salts allowed for the extraction of both hydrophilic (i.e., flavonoids) and hydrophobic compounds (i.e., cannabinoids).


Inhibition of synaptosomal high-affinity uptake of dopamine and serotonin by estrogen agonists and antagonists.
High-affinity uptake of dopamine and serotonin into a synaptosomal preparation from rat cerebral cortex was inhibited by a number of estrogen agonists and antagonists in vitro in a stereoselective and competitive manner. The most potent estrogenic inhibitors in the dopaminergic and serotonergic system were ethinylestradiol (KI = 558 nM) and 2-hydroxyethinylestradiol (KI = 226 nM), respectively. Structure-activity relationships are discussed and compared with the effects of estrogens on noradrenaline uptake. However, as all physiologically occurring estrogens inhibited amine uptake only in the micromolar concentration range it seems unlikely that this direct interaction of estrogen with the amine carrier is responsible for the changes in dopamine and serotonin uptake observed during the estrous cycle or after in vivo administration of estrogens and/or progesterone.


Phenotypic and biomarker evaluation of zebrafish larvae as an alternative model to predict mammalian hepatotoxicity.
Zebrafish phenotypic assays have shown promise to assess human hepatotoxicity, though scoring of liver morphology remains subjective and difficult to standardize. Liver toxicity in zebrafish larvae at 5 days was assessed using gene expression as the biomarker approach, complementary to phenotypic analysis and analytical data on compound uptake. This approach aimed to contribute to improved hepatotoxicity prediction, with the goal of identifying biomarker(s) as a step towards the development of transgenic models for prioritization. Morphological effects of hepatotoxic compounds (acetaminophen, amiodarone, coumarin, methapyrilene and myclobutanil) and saccharin as the negative control were assessed after exposure in zebrafish larvae. The hepatotoxic compounds induced the expected zebrafish liver degeneration or changes in size, whereas saccharin did not have any phenotypic adverse effect. Analytical methods based on liquid chromatography-mass spectrometry were optimized to measure stability of selected compounds in exposure medium and internal concentration in larvae. All compounds were stable, except amiodarone for which precipitation was observed. There was a wide variation between the levels of compound in the zebrafish larvae with a higher uptake of amiodarone, methapyrilene and myclobutanil. Detection of hepatocyte markers (CP, CYP3A65, GC and TF) was accomplished by in situ hybridization of larvae to coumarin and myclobutanil and confirmed by real-time reverse transcription-quantitative polymerase chain reaction. Experiments showed decreased expression of all markers. Next, other liver-specific biomarkers (i.e. FABP10a and NR1H4) and apoptosis (i.e. CASP-3 A and TP53) or cytochrome P450-related (CYP2K19) and oxidoreductase activity-related (ZGC163022) genes, were screened. Links between basic mechanisms of liver injury and results of biomarker responses are described. Copyright © 2016 John Wiley & Sons, Ltd.


Versatile intraoperative MRI in neurosurgery and radiology.
Several models for the application of intra-operative magnetic resonance imaging (IMRI) have recently been reported, most of them unique. Two fundamental issues need to be addressed: optimal use of the scanner to ensure a wide base for research, development and clinical application, and an organisational model that facilitates such use. While in our setting the IMRI project was initiated by the neurosurgeons, the need for wider use of the facilities was recognised since the beginning of the planning phase in 1996. An organisational model was developed that allowed for development of neurosurgical applications, radiological imaging, and radiological interventions and for the research and development work of the vendor. A resistive 0.23 T MR scanner was installed in a dedicated operating room environment. Unique to this scanner is the ability to turn off the magnet, allowing for normal OR activities and devices, and to turn on the magnet as needed with a relatively short six-minute ramp up time. A staged surgical technique was perfected, allowing for transfer of data to the neuronavigator outside the scanner during surgery. In neurosurgery, IMRI was used as one part of a neuronavigational system that included ultrasound imaging, intra-operative cortical stimulation during awake procedures, electrocorticography and two neuronavigators. 34 neurosurgical cases included 27 brain tumour resections, 5 brain tumour biopsies, 1 extirpation of an arterio-venous malformation, and 1 haematoma evacuation. The scanner could also be used for normal clinical imaging where obese patients, children, claustophobic patients and postoperative control examinations were the major groups. The radiologists performed 110 interventions, including bone and abdominal biopsies, nerve root infiltrations and local pain therapies, with the optical needle tracking system under continuous MRI guidance. The organisational model allowed frequent use of the facilities for both neurosurgery and radiology and continuous development of the facilities. Intra-operative ultrasound was used in 20 tumour resections and in two open brain biopsies. This resulted in reduction of the number of MR imaging sessions during surgery. Five of the 27 resections were performed as awake craniotomies with cortical stimulation. For two of the resections, electrocorticography and depth electrode registrations were used. Furthermore, various non-MRI-compatible instruments and devices were used. Intra-operative MRI is an imaging tool that can be useful especially in the context of neuronavigation. A scanner that can be turned off during surgery is particularly appropriate for neurosurgery. The concept of joint use of such facilities with other clinicians is mutually worthwhile.


Characterization and outlook of climatic hazards in an agricultural area of Pakistan.
Many dimensions of human life and the environment are vulnerable to anthropogenic climate change and the hazards associated with it. There are several indices and metrics to quantify climate hazards that can inform preparedness and planning at different levels e.g., global, regional, national, and local. This study uses biased corrected climate projections of temperature and precipitation to compute characteristics of potential climate hazards that are pronounced in the Gomal Zam Dam Command Area (GZDCA)- an irrigated agricultural area in Khyber Pakhtunkhwa province of Pakistan. The results answer the question of what the future holds in the GZDCA regarding climate hazards of heatwaves, heavy precipitation, and agricultural drought. The results of heatwaves and agricultural drought present an alarming future and call for immediate actions for preparedness and adaptation. The magnitude of drought indices for the future is correlated with the crop yield response based on AquaCrop model simulations with observed climate data being used as input. This correlation provides insight into the suitability of various drought indices for agricultural drought characterization. The results elaborate on how the yield of wheat crop grown in a typical setting common in the South Asian region respond to the magnitude of drought indices. The findings of this study inform the planning process for changing climate and expected climate hazards in the GZDCA. Analyzing climate hazards for the future at the local level (administrative districts or contiguous agricultural areas) might be a more efficient approach for climate resilience due to its specificity and enhanced focus on the context.


Fewer medical graduates are choosing general practice: a comparison of four cohorts, 1980-1995.
To compare general practice career choices of four cohorts of medical graduates. Retrospective longitudinal study of medical graduates. Data on employment since graduation, nature of current employment, and postgraduate qualifications were collected by postal survey in 2003. Four cohorts of Monash University Medical School graduates who completed their degrees in 1980, 1985, 1990 and 1995 (n = 386). Proportion of each cohort pursuing a general practice career. At 8 years after graduation, half of the graduates in the 1980 and 1985 cohorts were working in general practice, compared with 38% of 1990 graduates and 33% of 1995 graduates. Differences were mainly attributable to fewer female graduates working as GPs: female GPs comprised 62% of the 1980 cohort compared with 31% of the 1995 cohort. Graduates in more recent cohorts also entered the general practice workforce at a later stage than those in earlier cohorts. A rapidly declining proportion of new graduates from Monash University Medical School, particularly female graduates, are choosing general practice as a career. This will exacerbate future shortages in the general practice workforce.


How genetic modifiers influence the phenotype of spinal muscular atrophy and suggest future therapeutic approaches.
Both complex disorders and monogenetic diseases are often modulated in their phenotype by further genetic, epigenetic or extrinsic factors. This gives rise to extensive phenotypic variability and potentially protection from disease manifestations, known as incomplete penetrance. Approaches including whole transcriptome, exome, genome, methylome or proteome analyses of highly discordant phenotypes in a few individuals harboring mutations at the same locus can help to identify these modifiers. This review describes the complexity of modifying factors of one of the most frequent autosomal recessively inherited disorders in humans, spinal muscular atrophy (SMA). We will outline how this knowledge contributes to understanding of the regulatory networks and molecular pathology of SMA and how this knowledge will influence future approaches to therapies.


The intracellular pathway and kinetics of digestive enzyme secretion in an insect midgut cell.
The opaque zone cells of the midgut of the stablefly, Stomoxys calcitrans display a cyclical series of ultrastructural events in response to feeding, which it has been suggested are related to the synthesis and secretion of digestive enzymes. These cells have been studied in vivo using a combination of biochemical, morphometric and electron microscopical autoradiographic techniques. The cyclical nature, timing and relationship of the ultrastructural events to enzyme secretion has been confirmed. The autoradiographic data presented is in good agreement with the classical synthetic pathway for exported proteins. The kinetics of the cellular process have been described: transfer of newly synthesized product from the rough endoplasmic reticulum to Golgi apparatus begins ca. 13-14 min after labelling of the fly and from the Golgi apparatus to secretory granules after ca. 24-26 min. Secretion of this newly synthesized material begins before 60 min and possibly as early as 30 min after labelling of the fly. The data are discussed in relation to the comparable studies in other tissues.


Hydroxylated polychlorinated biphenyl metabolites (OH-PCBs), maternal smoking and size at birth.
In a sample of 442 births from the Child Health and Development Studies cohort, we examined associations between maternal prenatal exposure to hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) and pregnancy outcomes, and whether associations were mediated by maternal thyroid hormone levels and/or modified by maternal smoking. Compared to nonsmokers, smokers had twice the mean concentration of 4-OH-CB107 (p<0.001) and lower levels of its parent compound, PCB118 (p=0.001). Among mothers who smoked, the birth weight of newborns with maternal concentrations of 4-OH-CB107 in the upper quartile was 316g lighter (95% confidence interval (CI) 566, 65) compared to those with maternal concentrations in the lowest quartile, after control for PCB118 and other potential confounders. This association was not observed for non-smoking mothers and was not mediated by maternal thyroid hormone levels. Maternal prenatal 4-OH-CB107 levels appear to be influenced by maternal smoking and contribute to lower birth weight among smokers.


Effect of the high voltage waveform on the ionic wind produced by a needle-to-plate dielectric barrier discharge.
Although corona discharges are used in many industrial applications because of their ability to produce chemical species, the ionic wind they induce is less known and often ignored. Therefore, the present study aims at investigating the ionic wind produced by a corona discharge ignited between a high voltage needle and a grounded plate electrode covered by a dielectric material. More specifically, the work focuses on the influence of the high voltage waveform on the temporal behavior of the ionic wind. The results highlight that the high voltage waveform plays a key role on the dynamics of the flow produced inside the discharge. On the one hand, for the sine, triangle and sawtooth waveforms, there is a flow acceleration during both the positive and the negative half-cycles, the positive discharge being more effective in velocity production. On the other hand, for the square waveform, the increase in velocity occurs during the rises and falls of the voltage, because of the strengthening of the electric field due to the ions remaining from the previous half-cycle at the wall of the dielectric material.


A flexible and salt-rejecting electrospun film-based solar evaporator for economic, stable and efficient solar desalination and wastewater treatment.
Recently, interfacial solar evaporation has been developed for water treatment. However, the high cost and low stability of solar evaporators significantly hinder their practical applications. In this study, layered graphene and polymethylmethacrylate were used to fabricate a composited film (GF) by electrospinning, which acted as a solar absorber. Together with a water transporter (polyurethane sponge) and a thermal insulator (polystyrene foam), the GF-based evaporator was constructed for solar distillation. Taking advantage of the porous three-dimensional structure of GF, the light path could be extended, rendering an efficient broadband solar absorption (92%). More importantly, although the content of layered graphene in the GF-based evaporator (1.75 g m-2) was only 5.8-17.5% of that in the current reported graphene-based evaporators (10-30 g m-2), a comparable water evaporation efficiency was acquired, which was induced by the much higher utilization efficiency of photothermal nanomaterials in the GF-based evaporator than that in the reported devices, ensuring its economic feasibility. Meanwhile, more than 99.9% heavy metal ions and 99.8% organic dye could be removed by the GF-based evaporator. Combining the merits of long-term and stable evaporation, salt rejection, and resistance to harsh environment, the GF-based evaporator was promising for freshwater recycling from both seawater and wastewater.


Prophylaxis for postoperative deep-vein thrombosis. Synergistic effect of heparin and dihydroergotamine.
Randomized clinical trials in 300 patients undergoing major abdominal surgery or hip replacement arthroplasty were performed to investigate the efficacy of dihydroergotamine mesylate, heparin calcium, or a combination of dihydroergotamine with heparin in preventing postoperative deep-vein thrombosis (DVT). The diagnosis of DVT was established by an uptake test using fibrinogen labeled with iodine 125; in patients undergoing hip replacement, phlebography was also employed to confirm or refute the presence of isotopic thrombi. The data indicate that the combination of dihydroergotamine and heparin is more effective than heparin or dihydroergotamine alone in preventing DVT.


The genetic underpinnings of callous-unemotional traits: A systematic research review.
Callous-unemotional (CU) traits represent the affective features of psychopathy used to delineate youth at high risk for externalizing pathology. The genetic etiology CU traits is not currently well-understood. The current review surveyed the literature for studies on the genetic underpinnings of CU traits and integrated information from 39 genetic studies. The results from 24 studies with quantitative data suggest that the heritability for CU traits is likely between 36-67%. A majority of the 16 molecular genetic studies focused on candidate genes in the serotonin and oxytocin systems with results that have not been well replicated. Although two genome-wide association studies have been conducted, no genome-wide significant loci have been discovered. There is some evidence to suggest that the serotonin and oxytocin systems may play a role in CU traits; however, there is currently not enough evidence to implicate specific genetic mechanisms. The authors encourage researchers to continue to apply the most up-to-date and relevant methodology, specifically collaborations and consortiums using genome-wide and polygenic methods.


Assessment of executive functions in school-aged children: A narrative review.
In the past three decades, there has been increasing interest in assessing children's Executive Functions (EF). However, studies on the conceptualization and operationalization of this construct are incongruent and guidance for clinicians and researchers aiming to assess EF is insufficient due to measurement variability. The purpose of this article was to examine current theories and models of EF in children, identify their assessment instruments, issues, and challenges, and discuss their impact on children's cognitive, behavioral, social and/or emotional development. This narrative review reflected on English and French scholarly articles on EF assessment in children. References were identified through searches of PubMed, Medline, ScienceDirect, Google Scholar, and APA PsychNet throughout the last two decades up to June 2022. There are commonalities despite divergence in the definition and operationalization of EF. Assessment of EF requires psychometric tests as well as rating scales that must be integrated and interpreted considering the child's biological makeup, environmental background, and cultural specificities. Current EF theories, assessment tools, issues, and challenges were discussed in addition to the impact of their components' dysfunctions on children's development. Further studies should be conducted to develop new measurement methods and technologies to improve the ecological and ethological validity of youth assessment, treatment, and interventions.


Takotsubo cardiomyopathy after vaccination for coronavirus disease 2019 in a patient on maintenance hemodialysis.
Coronavirus disease-2019 (COVID-19) has affected more than 220 million individuals since the global pandemic began. There is an urgent need for safe and effective vaccines, and vaccinations, such as mRNA vaccines, have been initiated worldwide. However, the adverse effects of these vaccines remain unclear. We herein present a case of an 80-year-old female on maintenance hemodialysis who developed takotsubo cardiomyopathy 4 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. There was no obvious trigger for the onset of takotsubo cardiomyopathy other than the COVID-19 vaccination, which was the most significant event preceding her presentation. Echocardiograms obtained during her admission allowed us to monitor and show the recovery of left ventricular wall motion. We confirmed the diagnosis of takotsubo cardiomyopathy based on the findings, including transient left ventricular dysfunction, electrocardiographic abnormalities, an elevated troponin level, and the absence of occlusive coronary artery disease. In the present case, the vaccination may have triggered emotional or physical stress. Although difficulties are associated with proving the causal relationship in the present case, the temporal relationship between the vaccination and the onset of takotsubo cardiomyopathy is highly suggestive. The adverse effects associated with the vaccine are typical of COVID-19 vaccines administered to date, most of which are acceptable. Therefore, despite our experience of the present case, we still recommend the vaccination for COVID-19 because takotsubo cardiomyopathy induced by the COVID-19 vaccine is extremely rare and the prognosis of the patient was good. We herein present the first case of a patient on hemodialysis who developed takotsubo cardiomyopathy after receiving COVID-19 vaccination.


Reliability and validity of the Japanese version of the 24-item Dysfunctional Attitude Scale.
The 24-item Dysfunctional Attitude Scale (DAS-24) is a short version of the Dysfunctional Attitude Scale, which is a self-report inventory for depressogenic schemata. The object of this study was to examine the reliability and validity of the Japanese version of the DAS-24 (DAS-24-J). Subjects consisted of non-clinical sample 1 (248 university students), non-clinical sample 2 (872 Japanese company employees) and a clinical sample (59 depressed out-patients). Internal consistency was satisfactory in all three samples, Cronbach's α coefficient being higher than 0.85. Test-retest reliability was satisfactory in non-clinical sample 1. The interclass correlation coefficient was 0.79 and there was no significant difference in the average score of DAS-24-J between the two points. The DAS-24-J showed satisfactory concurrent validity with the Japanese Irrational Belief Test-20 (r= 0.76); Automatic Thoughts Questionnaire - Revised total (r= 0.46), negative (r= 0.53) and positive (r=-0.41); and the Beck Depression Inventory-II (r= 0.44 for non-clinical sample, r= 0.63 for clinical sample). The clinical sample showed a significantly higher DAS-24-J score than non-clinical sample 2. According to a factor analysis combining all three samples, three factors were extracted: factor 1 (11 items) corresponded with 'achievement' in the original version, factor 2 (6 items) with 'self-control' and factor 3 (5 items) with 'dependency'. The DAS-24-J is a reliable and valid instrument to measure depressogenic schemata in Japanese.


The Spanish and Italian Healthcare Professionals' Contribution to the Safety Attitudes Questionnaire Short Form in the Operating Room: Construct Validity and Reliability.
The aims of the study are to determine the construct validity and reliability of the Spanish and Italian versions of the Safety Attitudes Questionnaire Short Form and to study the capability of this scale of distinguishing between different countries, types of healthcare professionals, and attitudes around patient safety. This was a cross-sectional study of the scale among registered nurses, surgeons, and anesthetists providing direct patient care at surgical inpatient units within public health services in Spain (Sistema Nacional de Salud) and Italy (Servizio Sanitario Nazionale). Construct validity, in both countries, was firstly assessed by exploratory factor analysis. Then, a confirmatory factor analysis was conducted, and finally an assessment was performed by means of hypothesis testing. The reliability of the scale was calculated using Cronbach α coefficient. A total of 499 healthcare professionals completed the questionnaire (Spain, n = 183; Italy, n = 316). The questionnaire showed excellent internal consistency (α = 0.85). An exploratory factor analysis identified a new factor model of the scale. The confirmatory factor analysis performed on this new model reflected the fair dimensionality of the construct (χ2 = 1193.63, root mean square error of approximation < 0.05, standardized root mean square residual < 0.08; nonnormed fit index, comparative fit index, incremental fit index, and goodness of fit index values = 0.90, indicating a good fit). This study provides scientific evidence of the construct validity and reliability of the Safety Attitudes Questionnaire Short Form in both Spain and Italy, showing the capability of this scale of distinguishing between different countries, types of healthcare professionals, and attitudes around patient safety.


Bone-anchored hearing aid in patients with moderate mental retardation: impact and benefit assessment.
To assess the impact and the subjective benefit of Bone-anchored Hearing Aid (BAHA) implementation in patients with hearing impairment combined with moderate mental retardation. Case control study using two validated patient-oriented instruments. Tertiary referral center. Twenty-two patients with moderate mental retardation and conductive or mixed hearing loss. Rehabilitative. Subjective benefit, listening and learning capabilities. BAHA implementation in patients with moderate mental retardation, by using the Glasgow Children's Benefit Inventory and the Listening Inventory for Education, showed a subjective benefit, which was comparable with that of the control group and was consistent with the results of earlier studies. The use of BAHA proved beneficial in most patients with hearing impairment and moderate mental retardation. Extending the indications for BAHA application to this special patient group shows to be a very valuable option.


Phenolic glycosides govern the food selection pattern of willow feeding leaf beetles.
The relationship between the food selection of four leaf beetle species (Phratora vitellinae, Plagiodera versicolora, Lochmaea capreae, Galerucella lineola) and the phenolic glycosides of willow (Salix spp.) leaves was tested in laboratory food choice experiments. Four willow species native to the study area (Eastern Finland) and four introduced, cultivated willows were tested.The willow species exhibited profound differences in their phenolic glycoside composition and total concentration. The food selection patterns of the leaf beetles followed closely the phenolic glycoside spectra of the willow species. Both the total amount and the composition of phenolic glycosides affected the feeding by the beetles. Phenolic glycosides apparently have both stimulatory and inhibitory influences on leaf beetle feeding depending on the degree of adaptation of a particular insect. Very rare glycosides or exceptional combination of several glycoside types seem to provide certain willow species with high level of resistance against most herbivorous insects. Analogously the average absolute amount of leaf beetle feeding was lower on the introduced willows than on the native species to which the local herbivores have a good opportunity to become adapted.


Circulating Epstein-Barr virus DNA in serum of patients with lymphoepithelioma-like carcinoma of the lung: a potential surrogate marker for monitoring disease.
The purpose of this work was to study the sera of patients with lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA. Prospectively collected serum samples from five female patients with advanced, inoperable LELC of the lung were measured for free circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA (EBER)-1 was assayed in serial serum samples of three of the five patients, either from the start or during the initial phase of chemotherapy/radiotherapy until their terminal event or last follow-up. There was only a single-point sample for analysis in the fourth and fifth patients. Six other patients with LELC of the lung were also retrospectively identified, and their sera were tested for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the first visit only (n = 2), or the last follow-up visit only (n = 2). Prospectively collected serum samples from five patients and retrospectively collected serum samples from two patients who had clinical disease at initial serum measurement showed detectable levels of EBER-1. Retrospectively collected serum samples from four patients with no clinical disease had negative sera. There is consistent correlation between the clinical response to treatment and subsequent clinical course of LELC and serum EBER-1 levels in the three prospective patients with longitudinal serum monitoring. This study shows for the first time that free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases.


Observations and recommendations on the investigation of clinical decision-making and usage involving electrophysical agents.
Electrophysical agents (EPAs), including electrotherapy, are important components of patient/client management. A recent study by Springer et al. has elucidated the pattern of use and factors in clinical decision-making by Israeli physiotherapists regarding EPAs. It is evident from their data that EPAs, especially those related to electrotherapy, are still considered relevant to physiotherapy practice. Included in this commentary are observations on the findings of the current study, as well as recommendations on an alternative approach to the investigation of clinical decision-making and usage of EPAs. Discussion also includes a proposed and apparent de-emphasis of EPAs in physiotherapy education and practice in the USA, which may impact some of the factors found in the current study to be relevant in clinical decision-making and usage for EPAs.


A tele-home care system exploiting the DVB-T technology and MHP.
The aim of this research work is the development of a low-cost system for telemedicine based on the DVB-T technology. The diffusion of DVB-T standard and the low cost of DVB-T set-top boxes bring the vision of a capillary distribution of tele-home care monitoring systems with easy-to-use patient's interface. Exploiting the potentiality of the DVB-T set-top box, we transformed it into an "on-demand tele-home care interface". The Xlet we developed is able to govern the functionality of an external microcontroller-based unit for the acquisition of the bio-signals of interest. The uplink connection is used to send the exam results to a remote care center. The Xlet providing the patient interface on the set-top box is uploaded by a DVB-T broadcaster without any intervention in the patient's home. A prototypal low-cost base station for the acquisition of the patient's signals (1-lead ECG) has been developed. It is able to be connected to the set-top box via an infrared link. A smart-card-based system is in charge for the customization of the Xlet for every patient. The proposed system, based on a currently widespread infrastructure, is able to allow the patients monitoring from home without any installation procedure. Even untrained (or elderly) people can easily use such system due to their practice with the basic DVB-T home-entertainment equipments.


Application oriented bioaugmentation processes: Mechanism, performance improvement and scale-up.
Bioaugmentation is an optimization method with great potential to improve the treatment effect by introducing specific strains into the biological treatment system. In this study, a comprehensive review of the mechanism of bioaugmentation from the aspect of microbial community structure, the optimization methods facilitating application as well as feasible approaches of scale-up application has been provided. The different contribution of indigenous and exogenous strains was critically analyzed, the relationship between microbial community variation and system performance was clarified. Operation regulation and immobilization technologies are effective methods to deal with the possible failure of bioaugmentation. The gradual expansion from lab-scale, pilot scale to full-scale, the transformation and upgrading of wastewater treatment plants through the combination of direct dosing and biofilm, and the application of side-stream reactors are feasible ways to realize the full-scale application. The future challenges and prospects in this field were also proposed.


Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery.
The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood sample was collected at 18-24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second sample collected after 4-8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration. Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.


Early Pleistocene pollen record from the western Chinese Loess Plateau and its implications for the evolution of the East Asian Summer Monsoon.
The East Asian Summer Monsoon (EASM) is the most important and active atmospheric circulation system in Asia. However, its evolution during the Early Pleistocene, and that evolution's associated drivers, remain controversial. Here, for the first time, a high resolution pollen record was obtained from a loess-paleosol sequence located in the Lanzhou Basin, western Chinese Loess Plateau (CLP), and used to reconstruct the evolution of EASM intensity during the Early Pleistocene (2.2-1.7 Ma). The type of vegetation indicated by analysis of the pollen assemblage is comparable to the forest-steppe vegetation type currently distributed on the eastern CLP. This area's present-day mean annual temperature (MAT) and mean annual precipitation (MAP) are ~6-10 °C and ~400-550 mm, respectively, implying the existence of a stronger EASM intensity during the 2.2-1.7 Ma period. When the auxiliary function of the diversity index was applied, the Early Pleistocene EASM, as recorded by the vegetation successions identified within the loess-paleosol sequence, showed a generally stronger intensity during the 2.2-2.06 Ma period, a relatively weak intensity between 2.06 Ma and 1.97 Ma, and then a gradual intensification from 1.97 Ma until 1.7 Ma. Further comparisons demonstrated that the zonal thermal gradient in the Equatorial Pacific may have played an important role in driving the evolution of the EASM over a tectonic timescale during the Early Pleistocene. In contrast, over a sub-orbital or orbital timescale, the EASM intensity appears to have been closely correlated to global temperature variations, given that the MATs of the Early Pleistocene were higher than today's. This would imply that both low-latitude forcing and global temperature change were important drivers influencing variations in precipitation in Northern China, against a background of ongoing global warming.


Increase of salt dependence of halophilic nucleoside diphosphate kinase caused by a single amino acid substitution.
Nucleoside diphosphate kinase (HsNDK) from an extremely halophilic archaea, Halobacterium salinarum, is composed of a homo hexamer, assembled as a trimer of basic dimeric units. It requires >2 M NaCl for refolding, although it does not require NaCl for stability or enzymatic activity below 30 °C. A HisN111L mutant with an N-terminal extension sequence containing hexa-His tag, in which Asn111 was replaced with Leu, was designed to be less stable between basic dimeric units. This mutant can lose between 6 and 12 hydrogen bonds between basic dimeric units in the hexamer structure. The HisN111L mutant had enhanced salt requirements for enzymatic activity and refolding even though the secondary structure of the HisN111L mutant was confirmed to be similar to the control, HisNDK, in low and high salt solutions using circular dichroism. We reported previously that G114R and D148C mutants, which had enhanced interactions between basic dimeric units, showed facilitated refolding and stabilization in low salt solution. The results of this study help to elucidate the process for engineering industrial enzymes by controlling subunit-subunit interactions through mutations.


Aryl Polyenes, a Highly Abundant Class of Bacterial Natural Products, Are Functionally Related to Antioxidative Carotenoids.
Bacterial pigments of the aryl polyene type are structurally similar to the well-known carotenoids with respect to their polyene systems. Their biosynthetic gene cluster is widespread in taxonomically distant bacteria, and four classes of such pigments have been found. Here we report the structure elucidation of the aryl polyene/dialkylresorcinol hybrid pigments of Variovorax paradoxus B4 by HPLC-UV-MS, MALDI-MS and NMR. Furthermore, we show for the first time that this pigment class protects the bacterium from reactive oxygen species, similarly to what is known for carotenoids. An analysis of the distribution of biosynthetic genes for aryl polyenes and carotenoids in bacterial genomes is presented; it shows a complementary distribution of these protective pigments in bacteria.


The phenols and prodelphinidins of white clover flowers.
White clover flowers (Trifolium repens L.) contain an abundance of phenolics, namely cis- and trans-p-coumaric acid 4-O-beta-D-glucopyranoside, the 3-O-beta-D-galactopyranosides of myricetin, quercetin and kaempferol together with two new derivatives namely myricetin 3-O-(6"-acetyl)-beta-D-galactopyranoside and kaempferol 3-O-(6"-acetyl)-beta-D-galactopyranoside. Gallocatechin, epigallocatechin, gallocatechin-(4alpha-8)-epigallocatechin and their corresponding prodelphinidin polymers were also present. The 13C-NMR spectra showed that the polymers consisted of only gallocatechin and epigallocatechin monomeric units with the latter being about twice as abundant in the extenders but only slightly more than that in the terminating units. The average degree of polymerization was estimated by 13C-NMR and ES-MS, which gave a remarkably consistent result of about 5.8 flavanol units.


Mass spectrometer failure: an unusual cause.
A potentially serious problem is inherent in the current design of the mass spectrometer multiplex system. In spite of the filter on the sampling tube, foreign material can be aspirated into this tube, causing malfunction of the system. Prevention of this problem is discussed, and precautions are given.


Traumatic rupture of the diaphragm.
Diaphragmatic disruption is an uncommon consequence of blunt trauma and is easily overlooked unless a high index of suspicion is maintained. The diagnosis is important because of the high incidence of associated organ damage and the complications of a missed injury. This article outlines the clinical features and management of the condition.


Image findings of anti-neutrophil cytoplasmic antibody-associated vasculitis involving the skull base.
To investigate computed tomography (CT) and magnetic resonance imaging (MRI) features of skull bases involving anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). A retrospective review was undertaken to identify an institutional historical cohort of 17 patients with confirmed AAV who underwent CT or MRI and had skull base involvement between 2002 and 2021. Two radiologists reviewed the extent and features of the lesions, bone changes, and other MRI findings. A total of 17 patients (12 men; mean age ± standard deviation, 46.5 ± 17.1 years) were selected. AAV presented as infiltrative lesions with involvement at various sites. Most cases involved the paranasal sinuses (PNS; 88%, 15/17), nasopharynx (88%, 15/17), pterygopalatine fossa (82%, 14/17), and parapharyngeal space (82%, 14/17), frequently accompanied by mucosal irregularity of the PNS and nasopharynx (71%, 12/17). Central skull base and temporal bone involvement were seen in 53% (9/17) and 38% (6/16) of cases, respectively. On T1-weighted imaging (WI) and T2WI MRI, all lesions (15/15) showed predominant signal iso-intensity to grey matter. Although radiological findings of AAV are non-specific and skull base involvement is less common, AAV may be considered if infiltrative lesions predominantly involving the PNS, nasopharynx, pterygopalatine fossa, and parapharyngeal space with combined bone changes of skull base are seen.


Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free targeting of splenic dendritic cells for cancer vaccination.
Nanoparticle (NP)-based mRNA cancer vaccines hold great promise to realize personalized cancer treatments. To advance this technology requires delivery formulations for efficient intracellular delivery to antigen-presenting cells. We developed a class of bioreducible lipophilic poly(beta-amino ester) nanocarriers with quadpolymer architecture. The platform is agnostic to the mRNA sequence, with one-step self-assembly allowing for delivery of multiple antigen-encoding mRNAs as well as codelivery of nucleic acid-based adjuvants. We examined structure-function relationships for NP-mediated mRNA delivery to dendritic cells (DCs) and identified that a lipid subunit of the polymer structure was critical. Following intravenous administration, the engineered NP design facilitated targeted delivery to the spleen and preferential transfection of DCs without the need for surface functionalization with targeting ligands. Treatment with engineered NPs codelivering antigen-encoding mRNA and toll-like receptor agonist adjuvants led to robust antigen-specific CD8+ T cell responses, resulting in efficient antitumor therapy in in vivo models of murine melanoma and colon adenocarcinoma.


The effects of molsidomine and its metabolite SIN-1 on coronary vessel tone, platelet aggregation, and eicosanoid formation in vitro--inhibition of 12-HPETE biosynthesis.
We studied the action of the biologically active metabolite of molsidomine, N-morpholino-N-nitrosoamino-acetonitrile (SIN), on eicosanoid formation and functional behavior of bovine coronary arteries and human platelets in vitro. Glyceryltrinitrate (GTN) and prostaglandin (PG) I2 were used as reference compounds. SIN dose-dependently inhibited the thrombin-, collagen-, and primary ADP-induced platelet aggregation. The IC50 was in the range of 0.1-0.8 mumol/L. At these concentrations SIN also inhibited thromboxane formation, but did not influence the PGI2 biosynthesis of coronary vessels. Molsidomine itself was inactive. GTN stimulated vascular PGI2 formation, but did not modify the platelet aggregation at comparable concentrations. A particularly interesting finding was the dose-dependent and apparently complete inhibition of formation of the hydroperoxide of 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) in human platelets by SIN. The IC50 amounted to 1.7 +/- 0.4 mumol/L and was in the same range as with 5,8,11,14-eicosatetraynoic acid (2.0 +/- 0.3 mumol/L). Although the results may not suggest a common mechanism of the antiaggregatory action of GTN and SIN, they provide no evidence of a similar or dissimilar mechanism of action in vascular smooth muscle.


Electrophysiological assessment of the human depth-perception threshold.
The cortical response to stereoscopic stimuli was measured as a function of disparity using visual evoked potentials (VEP). The stereoscopic stimulus consisted of a dynamic random-dot pattern that portrayed a three-dimensional horizontal grating. Disparity of the grating was variable between 0 and 18 arc min, step size being 4.22 arc s. Evoked responses were recorded using a "random-sequence sweep technique." The VEP amplitude increased approximately linearly with the logarithm of disparity and allowed an estimation of the stereo threshold by linear extrapolation. The evoked potential estimates of the stereo threshold of 16 subjects were compared to psychophysically obtained thresholds. Several threshold-estimation techniques are discussed. Evoked potential and psychophysical threshold estimates had the lowest discrepancy when the VEP amplitude was linearly extrapolated to the logarithmic disparity axis. The difference between the evoked potential estimate and the psychophysical threshold was less than 20% in 56% of all cases; 16 of 18 cases (89%) agreed within a factor of 2.


Investigational use of PEGylated carboxyhemoglobin bovine in a Jehovah's Witness with hemorrhagic shock.
Jehovah's Witnesses pose a clinical challenge in the setting of critical anemia. Most do not accept transfusions, but some accept hemoglobin-based oxygen carriers on a compassionate-use basis. PEGylated carboxyhemoglobin bovine (PCHB) is an acellular dual-action carbon monoxide (CO)-releasing and oxygen transfer agent currently being investigated in Phase II clinical trials. We present the case of a 42-year-old Jehovah's Witness with an acute upper gastrointestinal bleed and hemorrhagic shock who required emergent PCHB for stabilization during lifesaving interventions. After PCHB infusion, the patient's shock and encephalopathy improved with decreased vasopressor requirement. Through gastroenterology and interventional radiology procedures, the patient's bleeding stabilized. While receiving five additional doses of PCHB and other supportive therapies (iron, folate, vitamin B12, darbepoetin alfa), the patient was extubated and weaned off vasopressors. PCHB was used to stabilize (bridge) a critically ill anemic patient for lifesaving interventions without adverse effects. Additional studies are warranted to explore the drug's safety profile and efficacy in patients declining blood products.


Measurements of Operational Wind Turbine Noise in UK Waters.
The effects of wind farm operational noise have not been addressed to the same extent as their construction methods such as piling and drilling of the foundations despite their long operational lifetimes compared with weeks of construction. The results of five postconstruction underwater sound-monitoring surveys on wind farms located throughout the waters of the British Isles are discussed. These wind farms consist of differing turbine power outputs, from 3 to 3.6 MW, and differing numbers of turbines. This work presents an overview of the results obtained and discusses both the levels and frequency components of the sound in several metrics.


Surgical ablation for idiopathic ventricular tachycardia.
A 33-year-old man with a right-bundle branch, left-axis deviation ventricular tachycardia was medically treated unsuccessfully. Surgical mapping and ablation was performed with a successful surgical result. A discussion of surgical results for this problem is provided.


Treatment of severe lesions of the lower cervical spine (C3-C7). A clinical study and technical considerations in 102 cases.
The authors report 102 cases of severe lesions of the lower cervical spine, in which operation was mandatory. The characteristics of these fractures are discussed, together with the different operative procedures. Posterior osteosynthesis using Roy-Camille's plates was preferred.


Fractional Langevin model of gait variability.
The stride interval in healthy human gait fluctuates from step to step in a random manner and scaling of the interstride interval time series motivated previous investigators to conclude that this time series is fractal. Early studies suggested that gait is a monofractal process, but more recent work indicates the time series is weakly multifractal. Herein we present additional evidence for the weakly multifractal nature of gait. We use the stride interval time series obtained from ten healthy adults walking at a normal relaxed pace for approximately fifteen minutes each as our data set. A fractional Langevin equation is constructed to model the underlying motor control system in which the order of the fractional derivative is itself a stochastic quantity. Using this model we find the fractal dimension for each of the ten data sets to be in agreement with earlier analyses. However, with the present model we are able to draw additional conclusions regarding the nature of the control system guiding walking. The analysis presented herein suggests that the observed scaling in interstride interval data may not be due to long-term memory alone, but may, in fact, be due partly to the statistics.


Validity of a point-of-care viral load test for hepatitis B in a low-income setting.
The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from <1 log10 to>7 log10 IU/mL were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p < 0.001). The Bland-Altman plot showed a small bias between the two assays, with an on average 0.23 log10 IU/mL higher viral load result of the Xpert kit; 4 samples differed by>1 log10 IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94 %, specificity of 71 %, positive predictive value of 70 %, and negative predictive value of 95 %. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.


Endosulfan: lack of cytogenetic effects in male rats.
Cytogenetic effects of endosulfan (Thiodan) a member of the chlorinated hydrocarbon insecticide was tested in male albino rats. The insecticide was administered orally to rats at 0, 11.00, 22.00, 36.60 and 55.00 mg/kg daily for 5 days. The highest doses were associated with clinical signs of insecticide poisoning and death. Cytogenetic analysis of bone marrow cells and spermatogenial cells did not reveal any significant effect of the insecticides on chromosomes. The ratio of mitotic index and frequency of chromatid break in the two cell types had no correlation with the doses tested and was not very different from those of the control group.


iSDAsoil: The first continent-scale soil property map at 30 m resolution provides a soil information revolution for Africa.
Open access, high-resolution soil property maps have been created for Africa at 30 m resolution, using machine learning trained on over 100,000 analysed soil samples. Combined with other field-level information, iSDAsoil enables the possibility of site-specific agronomy advisory for smallholder farmers.


Developing a self-rating measure of patient competence in the context of oncology: a multi-center study.
Concepts of patient competence (PC) are being increasingly used, but seldom clearly defined in the context of shared medical treatment decision making and coping with cancer. The meaning of such concepts should therefore be clarified, and measures developed that permit the assessment of different facets of this patient characteristic. Consequently, this study attempted to contribute to the definition and measurement of PC. Employing literature reviews and qualitative interviews, we developed a working definition of PC in the context of cancer from which we designed a self-rating measure of this patient characteristic that was then tested for validity and reliability in a sample of N=536 patients with cancer. Using factor analyses, we developed five problem- and three emotion-focused subscales that measure distinct facets of PC with satisfactory reliability. Additional analyses provide preliminary evidence of the instruments' validity. This study represents an essential first step in developing a reliable self-rating measure of PC in the context of cancer. Although further refinement of this measure is clearly required, it provides a preliminary methodological basis for empirically investigating the determinants and potential health effects of PC.


Detection of cochlear amplification and its activation.
The operation of the mammalian cochlea relies on a mechanical traveling wave that is actively boosted by electromechanical forces in sensory outer hair cells (OHCs). This active cochlear amplifier produces the impressive sensitivity and frequency resolution of mammalian hearing. The cochlear amplifier has inspired scientists since its discovery in the 1970s, and is still not well understood. To explore cochlear electromechanics at the sensory cell/tissue interface, sound-evoked intracochlear pressure and extracellular voltage were measured using a recently developed dual-sensor with a microelectrode attached to a micro-pressure sensor. The resulting coincident in vivo observations of OHC electrical activity, pressure at the basilar membrane and basilar membrane displacement gave direct evidence for power amplification in the cochlea. Moreover, the results showed a phase shift of voltage relative to mechanical responses at frequencies slightly below the peak, near the onset of amplification. Based on the voltage-force relationship of isolated OHCs, the shift would give rise to effective OHC pumping forces within the traveling wave peak. Thus, the shift activates the cochlear amplifier, serving to localize and thus sharpen the frequency region of amplification. These results are the most concrete evidence for cochlear power amplification to date and support OHC somatic forces as its source.


UM171 cooperates with PIM1 inhibitors to restrict HSC expansion markers and suppress leukemia progression.
The pyrimido-indole derivative UM171 promotes human Hematopoietic Stem Cells Expansion (HSCE), but its impact on leukemia is not known. Herein, we show in a mouse model of erythroleukemia that UM171 strongly suppresses leukemia progression. UM171 inhibits cell cycle progression and apoptosis of leukemic cells in culture. The effect of UM171 on leukemia differentiation was accompanied by increased expression of HSCE markers. RNAseq analysis combined with Q-RT-PCR and western blotting revealed that the PIM1 protein kinase is highly elevated in response to UM171 treatment. Moreover, docking analysis combined with immunoprecipitation assays revealed high binding affinity of UM171 to PIM1. Interestingly, pan-PIM kinase inhibitors counteracted the effect of UM171 on HSCE marker expression and PIM1 transcription, but not its suppression of leukemic cell growth. Moreover, combination treatment with UM171 and a pan-PIM inhibitor further suppressed leukemic cell proliferation compared to each drug alone. To uncover the mechanism of growth inhibition, we showed strong upregulation of the cyclin-dependent kinase inhibitor P21CIP1 and the transcription factor KLF2 by UM171. In accordance, KLF2 knockdown attenuated growth inhibition by UM171. KLF2 upregulation by UM171 is also responsible for the activation of P21CIP1 in leukemic cells leading to a G1/S arrest and suppression of leukemogenesis. Thus, suppression of leukemic growth by UM171 through KLF2 and P21CIP1 is thwarted by PIM-mediated expansion of leukemic stemness, uncovering a novel therapeutic modality involving combined UM171 plus PIM inhibitors.


Neonatal urinary ascites secondary to ureteropelvic junction obstruction.
A case of neonatal urinary ascites resulting from a ureteropelvic junction obstruction in a solitary kidney is reported. This is an uncommon cause of urinary ascites in the newborn, reported but once heretofore.


Analysis of transporter associated with antigen presentation (TAP) genes polymorphisms with HIV-1 infection.
Human leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR-RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06-1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56-7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case-control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.


A comparison of the roles of protein kinase C in long-term potentiation in rat hippocampal areas CA1 and CA3.
1. Using agonists and antagonists with specificity toward various isozymes, we have examined the role of protein kinase C (PKC) in long-term potentiation (LTP) in rat hippocampal areas CA1 and CA3. 2. Agonists (indolactum V but not phorbol ester) and antagonists (sphingosine, staurosporine, chelerytherene) acting at all PKC isozymes reduce or block LTP induction at both sites. 3. However ingenol, a relatively specific agonist at the delta and epsilon isozymes, blocks LTP in the MF-CA3 pathway, but not in the SC-CA1 pathway. 4. Go6976, a relatively specific antagonist of the alpha and beta isozymes, blocks LTP in the SC-CA1 pathway at both ages tested (30- and 60-day-old animals), but blocks LTP in the MF-CA3 in 60 but not 30-day-old animals. 5. Our studies indicate that different PKC isozymes are crucial to LTP induction in these two areas of hippocampus, and that there are development changes in the profile of isozymes.


Expression of WWOX and FHIT is downregulated by exposure to arsenite in human uroepithelial cells.
Ecological studies in Taiwan, Chile, Argentina, Bangladesh, and Mexico have confirmed significant dose-dependent associations between ingestion of arsenic-contaminated drinking water and the risk of various human malignancies. The FHIT and WWOX genes are active in common fragile sites FRA3B and FRA16D, respectively. Reduced expression of FHIT or WWOX is known to be an early indicator of carcinogen-induced cancers. However, the effect of arsenite on the expressions and molecular mechanisms of these markers is still unclear. The aims of this study were (i) to observe the expression of ATR, WWOX and FHIT proteins in urothelial carcinoma (UC) between endemic and non-endemic areas of blackfoot disease (BFD) by immunohistochemical analyses; (ii) to compare expression of these genes between arsenite-treated SV-HUC-1 human epithelial cells and rat uroepithelial cells; and (iii) to determine the role of DNMT and MEK inhibitors on expressions of WWOX and FHIT in response to arsenite in SV-HUC-1. The experiments revealed that expressions of ATR, WWOX and FHIT in UC significantly differed between BFD areas and non-BFD areas (p=0.003, 0.009 and 0.021, respectively). In fact, the results for the arsenite-treated groups showed that ATR, WWOX and FHIT are downregulated by arsenite in SV-HUC-1. However, the inhibitors suppressed the effects of arsenite on WWOX and FHIT proteins and mRNA expression. In conclusion, arsenite decreased expressions of ATR, WWOX and FHIT via ERK1/2 activation in SV-HUC-1 cells. These findings confirm that dysregulations of these markers may contribute to arsenite-induced carcinogenesis.


How does employees' behavior change how we feel about their organization? Transfer of affective impressions between employees and organizations.
Stable impressions of how good, powerful, and active an organization is may be jointly shared with their employees, yet the impression produced by employees' behavior may be transferred back to the organization. Our first studies shows that stable impressions, or sentiments, of organizations (e.g., a library) are fairly similar to those of their employees (e.g., an employee of a library), with organizations viewed as more powerful and morally extreme than their employees. Our principal studies along with affect control theory simulations show how the impressions created by an employee's behavior toward a customer (e.g., an employee of a library shouts at a customer) transfer to the employee's organization. Affect control theory simulations predict the impressions of an organization as well as they predict impressions of the individual employee. Regression and classification analyses give support to impression transfer, with the most transfer occurring for evaluation impressions, and more so for transferring bad impressions rather than good ones. Therefore, this research shows how a single behavior by a rank-and-file employee can shape outsider's impressions of organizations and the potential for applying affect control theory predictions to impressions of organizations.


Benign Fibro-Osseous Lesions of the Jaws.
Fibro-osseous lesions are grouped together because histologically they show similar cellular and mineralization patterns. Despite the histologic ubiquity, their behaviors vary significantly. Because of the histologic similarity and the broad range of morbidity among them, it is important to be able to differentiate between them in the preliminary diagnostic process. The radiographic presentations along with the location of the bony changes are often extremely critical diagnostic features to help render a differential or working diagnosis in lieu of an automatic biopsy procedure. Therefore the unique and specific radiographic presentations may be one of the main criteria for preliminary diagnosis.


Interaction of methotrexate with melanins and melanosomes from B16 melanoma.
It has been demonstrated that methotrexate forms stable complexes with melanin and melanosomes isolated from B16 melanoma. The number of binding sites and binding constants for methotrexate binding by intact melanosomes and melanin were n = 0.046 mumol/mg, K = 0.32 x 10(4) M-1 and n = 0.063 mumol/mg, K = 1.08 x 10(4) M-1, respectively. Binding of methotrexate to synthetic DOPA-melanin used for comparison also shows a single class of binding sites, n = 0.060 mumol/mg with binding constant K = 2.34 x 10(4) M-1. The possibility of side effects caused by methotrexate-melanin interactions after treatment of neoplasms is discussed.


Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells.
Overexpression of CD30 and constitutive NF-kappaB activation characterizes tumor cells of Hodgkin's disease (HD), Hodgkin and Reed-Sternberg (H-RS) cells. We report that in H-RS cells overexpression of CD30 leads to self-aggregation, recruitment of TRAF2 and TRAF5, and NF-kappaB activation, independent of CD30 ligand. CD30 and TRAF proteins co-localized in H-RS cell lines and in lymph nodes of HD. An adenovirus-vector carrying a decoy CD30 lacking the cytoplasmic region or a dominant negative IkappaBalpha mutant blocks NF-kappaB activation, down regulates IL-13 expression and induces apoptosis. Thus, in H-RS cells, ligand-independent activation of CD30 signaling drives NF-kappaB activation and this leads to constitutive cytokine expression, which provides a molecular basis for HD. Inhibition of NF-kappaB activation by adenovirus vector-mediated gene transfer may provide a novel strategy of cell- and target molecule-specific therapy for patients with HD.


Cherax snowden, a new species of crayfish (Crustacea, Decapoda, Parastacidae) from the Kepala Burung (Vogelkop) Peninsula in Irian Jaya (West Papua), Indonesia.
A new species, Cherax snowden sp. n., from the Oinsok River Drainage, Sawiat District in the central part of the Kepala Burung (Vogelkop) Peninsula, West Papua, Indonesia, is described, figured and compared with the closest related species, Cherax holthuisi Lukhaup & Pekny, 2006. This species is collected and exported for ornamental purposes and its commercial name in the pet trade is "orange tip" or "green orange tip". Both species may be easily distinguished morphologically or by using sequence divergence, which is substantial, for considering Cherax snowden sp. n. to be a new species.


A review of the ketogenic diet for endurance athletes: performance enhancer or placebo effect?
The ketogenic diet has become popular among endurance athletes as a performance enhancer. This paper systematically reviews the evidence regarding the effect of the endurance athlete's ketogenic diet (EAKD) on maximal oxygen consumption (VO2 max) and secondary performance outcomes. PubMed and Web of Science searches were conducted through November 2019. Inclusion criteria were documentation of EAKD (< 50 g daily carbohydrate consumed by endurance athletes), ketosis achieved (measured via serum biomarker), VO2 max and/or secondary outcomes, English language, and peer reviewed-publication status. Articles were excluded if they were not a primary source or hypotheses were not tested with endurance athletes (i.e., individuals that compete at submaximal intensity for extended time periods). Study design, diet composition, adherence assessment, serum biomarkers, training protocols, and VO2 max/secondary outcomes were extracted and summarized. Searches identified seven articles reporting on VO2 max and/or secondary outcomes; these comprised six intervention trials and one case study. VO2 max outcomes (n = 5 trials, n = 1 case study) were mixed. Two of five trials reported significant increases in VO2 max across all diets; while three trials and one case study reported no significant VO2 max findings. Secondary outcomes (n = 5 trials, n = 1 case study) were Time to Exhaustion (TTE; n = 3 articles), Race Time (n = 3 articles), Rating of Perceived Exertion (RPE; n = 3 articles), and Peak Power (n = 2 articles). Of these, significant findings for EAKD athletes included decreased TTE (n = 1 article), higher RPE (n = 1 article), and increased Peak Power (n = 1 article). Limited and heterogeneous findings prohibit definitive conclusions regarding efficacy of the EAKD for performance benefit. When compared to a high carbohydrate diet, there are mixed findings for the effect of EAKD consumption on VO2 max and other performance outcomes. More randomized trials are needed to better understand the potentially nuanced effects of EAKD consumption on endurance performance. Researchers may also consider exploring the impact of genetics, recovery, sport type, and sex in moderating the influence of EAKD consumption on performance outcomes.


A randomized trial of human chorionic gonadotropin support following in vitro fertilization and embryo transfer.
This article reports on the effects of human chorionic gonadotropin (hCG) on progesterone (P) and estradiol (E2), luteal phase length, and conception in 116 cycles treated by in vitro fertilization and embryo transfer (IVF-ET). In 60 cycles, the luteal phase was supported by hCG, 1500 IU three times at 2-day intervals from the day of ET. The remaining 56 cycles served as controls. hCG significantly increased the P level (93 +/- 53 versus 62 +/- 46 ng/ml), the P/E2 ratio, and the luteal phase length (17.4 +/- 1.3 versus 12.2 +/- 1.7 days). However, the total pregnancy rate did not significantly differ between the two groups, though the pregnancy rate after transfer of two or three embryos was slightly higher in the hCG group (26.9 versus 22% in the control group), as was the rate of implanted embryo per transferred embryo after transfer of two or three embryos (25 versus 15.3%). It was concluded that, while hCG increased the magnitude and duration of the luteal P secretion, it did not clearly improve the pregnancy rate.


Posterior iris-claw aphakic intraocular lens implantation in children.
To evaluate the indications, visual outcomes, and complication rate after posterior implantation of an iris-claw aphakic intraocular lens (IOL) in children. Noncomparative retrospective cohort study. setting: Institutional practice. patients/intervention procedures: Seven eyes of 4 children without adequate capsular support had posterior chamber iris-claw aphakic IOL implantation between 2007 and 2012. main outcome measures: Visual acuity, endothelial cell changes, intraoperative and postoperative complications. The mean age of the 3 boys and 1 girl was 12.0 ± 3.4 (SD) years (range 8-16 years). In all eyes, the mean postoperative best spectacle-corrected visual acuity (0.13 ± 0.17 logMAR) was statistically significantly better at the last follow-up than at 1 day preoperatively (0.60 ± 0.39 logMAR) (P < .05). The mean follow-up was 31 months (range 10-64 months). The mean endothelial cell density decreased from 3013 ± 155 cells/mm(2) preoperatively to 2831 ± 236 cells/mm(2) at last follow-up, representing a mean endothelial cell loss of 6.4%. No corneal decompensation, iritis, secondary glaucoma, or pupillary block occurred after surgery in any eye. Postoperative complications included transient postoperative hypotony in 1 eye and a traumatic dislocation of a posterior aphakic iris-claw IOL in 1 eye. The posterior implantation technique of aphakic iris-claw IOL provided good visual outcomes with a favorable complication rate and can be used as a reasonable alternative for a wide range of indications in pediatric eyes without adequate capsular support.


Treatment of older patients with chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is typically a disease of older individuals. Yet most of the literature on various chemotherapeutic regimens includes patients who are 10 to 15 years younger than the median age at diagnosis of this disease. The older patient population is grossly underrepresented in clinical trials. Currently available therapies are often too toxic for this older patient population, so their efficacy is reduced. This review discusses some of the results of treatment in older patients with CLL. A discussion of factors that often affect outcome, such as comorbidities, renal function, bone marrow reserve, and infection, are also reviewed, along with quality of life.


Recombinant Human Albumin in Cell Culture: Evaluation of Growth-Promoting Potential for NRK and SCC-9 Cells In Vitro.
Serum-derived albumin has for a long time been used in cell culture media, but the exact role of albumin and/or impurities bound to albumin has not been precisely defined. In this study, recombinant human albumin was evaluated for its growth-promoting activity on two cell lines, NRK and SCC-9. For NRK cells, the recombinant human albumin was found to exert an inhibitory effect. The fact that fatty acid free HSA was also inhibitory while HSA fraction V was stimulatory suggested a role for fatty acids or some other bound moieties in growth stimulation by HSA fraction V. Addition of oleic acid, cholesterol, phosphatidylcholine, phosphatidylserine or a combination of these lipids, however, did not significantly improve the growth stimulating activity of either fatty acid free HSA or the recombinant human albumin. For SCC-9 cells, both recombinant human albumin and fatty acid free HSA showed slight stimulation (although they were not as active as HSA fraction V), suggesting that in some cell systems, the albumin molecule per se may promote cell growth and survival.


Circulating CD34+VEGFR-2+ endothelial progenitor cells correlate with revascularization-mediated long-term improvement of cardiac function in patients with coronary chronic total occlusions.
Endothelial progenitor cells (EPCs) participate in angiogenesis and neocollateralization. This study assessed if circulating EPCs can predict long-term improvement of global left ventricular systolic function in patients with coronary chronic total occlusions (CTOs) underwent successful percutaneous coronary intervention (PCI). In this single-center, prospective, observational study, 115 consecutive patients with CTOs were evaluated by standard transthoracic echocardiography (ECHO) before and 9-12 months after PCI. Numbers of circulating putative EPCs were determined by flow cytometry analysis of mononuclear cells isolated from peripheral blood samples drawn before and 72 h after PCI. At mean 11.3 ± 2.5 months post vs. before PCI (all P < .05): by SAQ-7 summary scores, angina frequency, physical limitation and quality of life scores were greater; by ECHO, LVEDd decreased and LVEF increased, which were more significant in patients with Rentrop grades 2/3 vs. 0/1. At 72 h post vs. before PCI, CD34+VEGFR-2+CD133- (0.82 ± 0.32 × 106/L vs. 1.00 ± 0.39 × 106/L, P = .003), CD34+VEGFR-2+CD133+ (0.24 ± 0.12 × 106/L vs. 0.27 ± 0.14 × 106/L, P = .028), and CD14+Tie2+VEGFR-2+ (6.60 ± 3.32 × 106/L vs. 7.82 ± 3.91 × 106/L, P = .006) cell numbers were lower. The baseline levels of CD34+VEGFR-2+cells (P = .001) and CD14+Tie2+VEGFR-2+cells (P < .001) were association with the grade of collateralization. In addition, the baseline and peri-procedural decrease of circulating CD34+VEGFR-2+ cells correlated with the increase of LVEF (P < .001, P < .001, respectively) and the decrease of LVEDd (P = .022, P = .029, respectively) at follow-up. In this small study, the baseline levels of circulating CD34+VEGFR-2+ EPCs and its reduction after successful revascularization of CTOs correlated with long-term improvement in global LV systolic function.


Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1.
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor with grave prognosis. Despite the growing understanding of the complex signaling networks responsible for the initiation and progression of GBM, many experimental therapies have fallen short of their treatment goals. In the present study, we investigated the novel molecular mechanisms responsible for synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells. We tested the combined effects of TMZ and VEGF blockade in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resistant CRT-MG and LN215-MG cells, which correlated with MGMT promoter methylation status. Treatment of TMZ along with a sublethal dosage range of SU1498, a chemical inhibitor of the VEGF receptor signaling, induced significant cell death in both TMZ-sensitive and TMZ-resistant GBM cells without changing the status of the MGMT promoter methylation. Treatment with TMZ specifically reduced the expression of NRP-1, a coreceptor of VEGF but not those of VEGF-R1 and VEGF-R2. We further confirmed the key role of NRP-1 by showing that the reduction of NRP-1 by siRNA also increased the SU1498-induced cytotoxicity of LN215-MG. These results collectively indicate that combined treatment of TMZ can sensitize GBM cells to blockade of autocrine VEGF signaling through specific down-regulation of NRP-1, which provide a rationale for further evaluation and a potential clinical trial of combinatorial therapy of TMZ and SU1498 or other VEGF inhibitors for intractable brain tumors.


Virtual simulation studies in nursing education: A bibliometric analysis of the top 100 cited studies, 2021.
Bibliometrics is an emerging science in nursing. Quantitative methods were used to conduct a bibliometric analysis of highly cited virtual simulation nursing education articles to describe rank order, breadth of topics and authorship patterns. A desktop analysis of publication performance was conducted using the Scopus database as the source of article citation data. The top 100 cited articles clustered over 14-years, 2008 to 2021. Citations per paper ranged from 88 to a low of 3 (median 18, mean 22.1) and in the top 10 studies, from 88 to 41. The citation trajectory was moderately correlated with article maturity (r = -.384, p ≤0.001). Article citations in subsequent publications commenced the first year after publication and three-year-old papers reached the mean citation rate of 22. Nurse Education Today was the most cited journal. There was no significant impact of article type (72% primary research, 17% literature reviews, 11% descriptive papers) (p = 0.755). International representation was strong, as first authors in 21 countries were cited - many (43%) from USA. One highly cited author (M. Verkuyl) from Canada led six papers, with six other authors each leading two studies. Virtual simulation modalities included virtual simulation, virtual reality simulation, 3D virtual reality simulation, virtual games and virtual worlds. The top 10 articles offer a diverse resource for faculty and educators who wish to consider using virtual simulation. Virtual simulation studies in nursing education cover an emerging field of research that has relatively low citation rates. Nursing researchers and faculty need to understand the usefulness and limitations of bibliometric analysis as this methodology can make a unique contribution to research, policy, and funding decisions, and enable productivity assessments of faculty staff and departments.


[Vertical vergence adaptation in cases of superior oblique palsy].
To investigate the characteristics of vertical adaptation (VA) in superior oblique muscle palsy (SOP). VA was examined in 15 patients with unilateral congenital SOP, 7 patients with unilateral acquired SOP, and 35 normal volunteers. An adaptive change in the fusion-free ocular alignment, VA, was measured with a computer-aided mirror haploscope. The fusion-free ocular alignment was measured before inserting a 3 prismdiopter vertical prism, immediately after inserting the prism, and at 10 minutes and 30 minutes after insertion. We investigated VA gain, age, vertical fusional range, response of prism adaptation test (PAT), and superior oblique muscle atrophy in magnetic resonance imaging (MRI). The VA gain (mean +/- standard deviation, %) at 30 minutes in congenital, acquired, and normal groups was 86 +/- 53, 34 +/- 23 and 58 +/- 16, respectively. The mean of the VA gains at 30 minutes in the congenital group was greatest, and that in the acquired group was least(p < 0.01). In the congenital group there was a correlation between VA gain and response of PAT (p = 0.02, r = 0.60). The VA gain did not significantly correlate with age, vertical fusional range, or muscle atrophy. The VA gain observed in congenital SOP was greater than that of acquired SOP, and affected the response of PAT.


Receptor Tyrosine Kinase Fusions as an Actionable Resistance Mechanism to EGFR TKIs in EGFR-Mutant Non-Small-Cell Lung Cancer.
Tumor resistance to EGFR tyrosine kinase inhibitors (TKIs) occurs invariably, and receptor tyrosine kinase (RTK) fusions have emerged as rare but actionable resistance mechanisms. In 2015, the detection of RTK fusions as acquired resistance (AR) in two cases was first reported. Subsequently, a survey of FGFR3-TACC3 fusion and other RTK fusions from a large commercial genomic sequencing company database was published, followed by large-scale clinical trials of EGFR TKIs demonstrating the emergence of RTK fusions in AR. However, detailed examination of the AR RTK fusion landscape in non-small-cell lung cancer is lacking. Hence, we conducted a comprehensive review to categorize these fusion events by the generation of EGFR TKIs, the specific RTK fusions and their fusion partners, the founder EGFR mutations, and their methods of detection. To support the actionability and clinical significance of AR RTK fusions we present all available data demonstrating clinical benefit of concurrent dual blockade of the AR RTK fusion and the original EGFR mutation.


AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients.
Experimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases. However, their effects on markers of insulin sensitivity appear to be minimal, potentially because of insufficient exposure. Systemic drug levels vary from sub-pharmacological to demonstrating pharmacodynamic effects but with dose-limiting adverse events. Here we report results from a phase 1 multiple ascending dose study of AKR-001, an Fc-FGF21 fusion protein engineered for sustained systemic pharmacologic exposure, in individuals with type 2 diabetes. With a half-life of 3-3.5 days, the peak-to-trough ratio under steady-state conditions is approximately 2 following QW dosing. AKR-001 appears to demonstrate pharmacodynamic effects on serum markers of insulin sensitivity and acceptable tolerability up to and including 70 mg QW. Positive trends in lipoprotein profile, including triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, HDL-C, and apolipoproteins B and C3 are consistent with other FGF21 analogs. AKR-001's clinical profile supports further evaluation as a treatment for metabolic diseases.


Automated Segmentation of the Left and Right Ventricles in 4D Cardiac SPAMM Images.
In this paper we describe a completely automated volume-based method for the segmentation of the left and right ventricles in 4D tagged MR (SPAMM) images for quantitative cardiac analysis. We correct the background intensity variation in each volume caused by surface coils using a new scale-based fuzzy connectedness procedure. We apply 3D grayscale opening to the corrected data to create volumes containing only the blood filled regions. We threshold the volumes by minimizing region variance or by an adaptive statistical thresholding method. We isolate the ventricular blood filled regions using a novel approach based on spatial and temporal shape similarity. We use these regions to define the endocardium contours and use them to initialize an active contour that locates the epicardium through the gradient vector flow of an edgemap of a grayscale-closed image. Both quantitative and qualitative results on normal and diseased patients are presented.


Fe(III)-Catalyzed Cross-Dehydrogenative Arylation (CDA) between Oxindoles and Arenes under an Air Atmosphere.
An efficient Fe(III)-catalyzed cross-dehydrogenative arylation (CDA) of 3-substituted oxindoles with activated arenes under an air atmosphere was developed to provide 3,3'-disubstituted oxindoles in good yields.


Neuromodulation in male chronic pelvic pain syndrome: rationale and practice.
This review explores the treatment of male chronic pelvic pain syndrome (CPPS) (i.e., chronic prostatitis) through the use of neuromodulation, which is the electrical stimulation of the nervous system. Neuromodulation has been used for the treatment of chronic pain for decades, and this review will examine the theory and use of neuromodulation and the various techniques available for the treatment of CPPS. Existing literature on the use of neuromodulation of the pelvic nerves for the treatment of chronic urogenital pelvic pain was reviewed. Because of limited published research, much of the data are not explicitly for male CPPS. Neuromodulation techniques used for chronic pelvic pain conditions include SNS, PTNS and pudendal nerve stimulation. Only SNS and PTNS are currently approved by the US Food and Drug Administration for the treatment of urinary symptoms, and none of these methods are acknowledged as standard therapies for treating chronic pelvic pain syndromes. The improvement of urinary symptoms is more clearly defined than improvements in pain, but at least a subset of patients in most of the published studies and case series derive some benefit in the short term and limited evidence suggests that long-term improvement of symptoms is possible. However, explantation rates are high in all long-term series of patients receiving implantable neuromodulation devices. Neuromodulation appears to provide benefits for patients with CPPS. However, because of the paucity of data and the limitations of small studies, the conclusions of the existing literature must be carefully considered. Because we are still becoming familiar with the pathophysiology of the pain syndromes and the mechanism of neuromodulation on urinary and pain symptoms, we cannot yet predict a particular individual's response to neuromodulation. To determine the long-term efficacy of this therapy, more clinical study is needed to explore the use of neuromodulation in the treatment of male CPPS.


CircRNAs and lung cancer: Insight into their roles in metastasis.
Lung cancer is the leading cause of cancer-related mortality worldwide. A major contributing factor to the poor survival rates in lung cancer is the high prevalence of metastasis at the time of diagnosis. To address this critical issue, it is imperative to investigate the mechanisms underlying lung cancer metastasis. Circular RNAs (circRNAs), a distinct type of ribonucleic acid characterized by their unique circular structure, have been implicated in the progression of various diseases. Recent studies have highlighted the close association between circRNAs and the occurrence and development of lung cancer, particularly in relation to metastasis. In this review, we provide a concise overview of the expression patterns and prognostic significance of circRNAs in lung cancer. Additionally, we summarized the current understanding of the clinical relevance of circRNAs in lung cancer metastasis. Furthermore, we systematically focused on the roles of circRNAs in each step of lung cancer metastasis, reflecting the sequential progression of this process. Notably, circRNAs exhibit dual functionality in lung cancer metastasis, acting both as facilitators and inhibitors of metastatic processes. Given their potential, circRNAs hold promise as novel biomarkers and therapeutic targets for lung cancer metastasis, warranting further investigation.


A significant correlation between kinetics of nitrobenzene reduction by sulfide and electron transfer capacity of mediating dissolved humic substances.
Dissolved humic substances (DHS) are ubiquitous in surface and subsurface aquatic environments and greatly affect the redox transformation of organic contaminants as reactants and/or electron transfer mediators. However, little is known about the quantitative relationship between the mediation efficiency of DHS and the physicochemical properties of DHS. Using sulfide-induced nitrobenzene reduction as a model system, we measured the reduction rate of nitrobenzene in the presence of 12 different DHS (20 mgC·L-1), including 4 commercial humic substances (Suwannee River humic and fulvic acids and Pahokee Peat humic and fulvic acids) and 8 soil humic substances collected as leachates from a wide variety of soils. In addition to the UV-vis absorption and fluorescence spectra, the electron donating/accepting capacities (EDC/EAC) of the tested DHS were measured using an electrochemical approach. A significant linear correlation (r = 0.99, P < .0001) was observed between the observed pseudo-first-order rate constant (kobs) of nitrobenzene reduction and the sum of EDC and EAC which is defined as electron transfer capacity (ETC) of DHS. A relatively good positive correlation (r = 0.69, P < .2) was shown between the kobs and the specific UV-absorbance at 254 nm (SUVA254), whereas no good correlation was shown between the kobs and the fluorescence of the C1-C4 components identified by the excitation emission matrices and parallel factor (EEM-PARAFAC) analysis. This study provides a new framework for accurate prediction of the capability of DHS in mediating the redox transformation of organic contaminants. CAPSULE: A significant linear correlation exists between the kinetics of nitrobenzene reduction by sulfide and electron transfer capacity of mediating dissolved humic substances.


Leptopterna dolobrata (L.) (Holarctis) and Calocoris roseomaculatus (De Geer) (Palaearctis) are single-brooded in the whole range of their distribution and hibernate in the egg stage. Both species are active only for 21/2 months, while the egg stage lasts over 9 months.The main food plants of Leptopterna are Dactylis glomerata and Alopecurus pratensis. Whereas the instars I-III feed on the ears of the grasses only, the later stages, including the adults, may change to the stems and leaves. In the field the bugs settle on other grass species when the blossoms of Dactylis and Alopecurus are exhausted. Because of the position of the eggs in the interior of the grass stem the serosal cuticle must lengthen to permit the process of hatching.The course of development is not influenced by the photoperiod.Dormancy during embryogenesis of Leptopterna always occurs before unfolding of the embryo. In the field this stage is already reached at the end of July. The initiation of dormancy does not depend on external factors and therefore belongs to the obligatory type of diapause. Four phases of diapause can be distinghished: prae-, meso-, meta-and postdiapause. Only during the meso-and metadiapause is development arrested. It could be shown that in mesodiapause temperatures between-1° and +16° C on the deviation of this stage, which lasts about 6 months, had no influence. The metadiapause is an interphase before the normal development of the postdiapause: it is favoured by temperatures below +10°C whereas higher temperatures are injurious. At constant temperatures complete development of the egg stage is only possible in the small range from +10° to 16° C owing to the different temperature reactions of the 4 phases of diapause. The protracted egg diapause synchronizes the appearance of larvae and adults with their food plants.At different constant temperatures in the range of +10° to 28° C larval development follows the formula of the time-temperature hyperbola with the threshold of development at +5° C. Alternating temperatures accelerate larval development as compared with corresponding constant temperatures. At +10° C only a few larvae reach the adult stage, but their gonads do not ripen.The egg diapause of Calocoris, too, lasts more than 9 months. The species differ only in the length of their temperature independent mesodiapause (Leptopterna: 180 days, Calocoris: 84 days).A new system of the main types of insect dormancy is given.