Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis.
Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and meta-analysis was undertaken to clarify the numerous aspects of long-term treatment with ATD. Medline and the Cochrane Library for trials published between 1950 and May 2016 were systematically searched. Studies containing data for long-term (>24 months) ATD treatment were included. Summary estimates of pooled prevalence, odds ratio, and weighted mean difference were calculated with a random effects model. Of 587 related articles found, six fulfilled the inclusion criteria. Long-term ATD treatment induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that was higher in adults than in non-adults (61% vs. 53%). The rate of complications was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual remission rate for each year of treatment was 16% [CI 10-27%], which was higher in adults than non-adults (19% vs. 14%). However, it should be noted that this is not a true linear correlation, but a positive relationship can be suggested between time and remission rate. Meta-regression revealed that smoking had a significant lowering effect on remission rate. Long-term ATD treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for Graves' disease.


Hallermann-Streiff syndrome associated with complete agenesis of the corpus callosum.
Hallermann-Streiff syndrome is a rare clinical entity with unknown etiology characterized by a birdlike face, microphthalmia, a beaked nose, hypotrichosis, and proportional small stature. We present a 4-year-old boy in whom magnetic resonance imaging showed complete agenesis of the corpus callosum, which has not been presented in the literature.


Chromosome Painting in Callicebus nigrifrons Provides Insights into the Genome Evolution of Titi Monkeys and the Ancestral Callicebinae Karyotype.
We studied the chromosomes of Callicebus nigrifrons with conventional and molecular cytogenetic methods. Our chromosome painting analysis in C. nigrifrons together with previous reports allowed us to hypothesize an ancestral Callicebinae karyotype with 2n = 48. The associations of human chromosomes (HSA) 2/22, 7/15, 10/11, and the inverted HSA2/16 would link Callicebus, Cheracebus, and Plecturocebus and would thus be present in the ancestral Callicebinae karyotype. Four fusions (HSA1b/1c, 3c/8b, 13/20, and 14/15/3/21) and 1 fission (HSA2/22) are synapomorphies of Callicebus. The associations HSA3/15 and HSA3/9 are chromosome features linking Callicebus and Cheracebus, whereas the association HSA13/17 would represent a link between Callicebus and the moloch group (Plecturocebus). Only 6 of the 33 recognized titi monkey species have now been painted with human chromosome-specific probes. Further analyses are needed to clarify the phylogenomic relationships in this species-rich group.


New short aliphatic chain ionic liquids: synthesis, physical properties, and catalytic activity in aldol condensations.
This paper reports on the synthesis of new short aliphatic chain ionic liquids and the study of the temperature dependence of density, ultrasonic velocities, and ionic conductivity in the range of 278.15-338.15 K. Fourier transform infrared spectra establishes their simple ionic salt structure. Because of their polarity, the ionic liquids are able to dissolve polar solvents and inorganic salts, all of them showing high tolerance in hydroxylic media. The observed temperature trend of the studied properties points out the special packing of these ionic liquids, as well as the strong influence of the steric hindrance among linear aliphatic residues enclosed in anions and cations. One of them showed a very high melting temperature. A collection of slightly basic ionic liquids were used to test their catalytic activity in several aldol condensation reactions of some carbonyl compounds. The best conversions and selectivities were obtained using single ionic liquids, with no synergetic effects being observed when different concentrations of mixed ionic liquids were used as catalysts. In any case, the ionic liquid can also easily be recycled from reaction media, suggesting a promising method of process design for this kind of reaction.


NRXN1 deletions identified by array comparative genome hybridisation in a clinical case series - further understanding of the relevance of NRXN1 to neurodevelopmental disorders.
Microdeletions in the NRXN1 gene have been associated with a range of neurodevelopmental disorders, including autism spectrum disorders, schizophrenia, intellectual disability, speech and language delay, epilepsy and hypotonia. In the present study we performed array CGH analysis on 10,397 individuals referred for diagnostic cytogenetic analysis, using a custom oligonucleotide array, which included 215 NRXN1 probes (median spacing 4.9 kb). We found 34 NRXN1 deletions (0.33% of referrals) ranging from 9 to 942 kb in size, of which 18 were exonic (0.17%). Three deletions affected exons also in the beta isoform of NRXN1. No duplications were found. Patients had a range of phenotypes including developmental delay, learning difficulties, attention deficit hyperactivity disorder (ADHD), autism, speech delay, social communication difficulties, epilepsy, behaviour problems and microcephaly. Five patients who had deletions in NRXN1 had a second CNV implicated in neurodevelopmental disorder: a CNTNAP2 and CSMD3 deletion in patients with exonic NRXN1 deletions, and a Williams-Beuren syndrome deletion and two 22q11.2 duplications in patients with intronic NRXN1 deletions. Exonic deletions in the NRXN1 gene, predominantly affecting the alpha isoform, were found in patients with a range of neurodevelopmental disorders referred for diagnostic cytogenetic analysis. The targeting of dense oligonucleotide probes to the NRXN1 locus on array comparative hybridisation platforms provides detailed characterisation of deletions in this gene, and is likely to add to understanding of the importance of NRXN1 in neural development.


Unilateral solitary choroid metastasis from breast cancer: rewarding results of external radiotherapy.
Intraocular metastatic tumor is the commonest intraocular malignancy in adults, with uveal tract the commonest site. In nearly 85% of cases the choroid is the afflicted site due to its vascularity. Breast and lung are the common primaries. In breast primaries, this could be the first metastatic disease. This condition should always be kept in mind in patients with visual symptoms. Fundus examination, ultrasonography and CT/MRI of the orbit help in diagnosis. Early recognition and timely treatment can save the visual function thus imparting good quality of life to the patient. External beam radiotherapy is a good local form of treatment. Hormone therapy in hormone receptor positive tumors can have additional benefits. Here we report a case of unilateral solitary choroid metastasis in a case of breast cancer treated with external beam radiotherapy.


Killing of Staphylococcus aureus by C-8-methoxy fluoroquinolones.
C-8-methoxy fluoroquinolones were more lethal than C-8-bromine, C-8-ethoxy, and C-8-H derivatives for Staphylococcus aureus, especially when topoisomerase IV was resistant. The methoxy group also increased lethality against wild-type cells when protein synthesis was inhibited. These properties encourage refinement of C-8-methoxy fluoroquinolones to kill staphylococci.


Discrete evolutionary population models: a new approach.
In this paper, we apply a new approach to a special class of discrete time evolution models and establish a solid mathematical foundation to analyse them. We propose new single and multi-species evolutionary competition models using the evolutionary game theory that require a more advanced mathematical theory to handle effectively. A key feature of this new approach is to consider the discrete models as non-autonomous difference equations. Using the powerful tools and results developed in our recent work [E. D'Aniello and S. Elaydi, The structure of ω-limit sets of asymptotically non-autonomous discrete dynamical systems, Discr. Contin. Dyn. Series B. 2019 (to appear).], we embed the non-autonomous difference equations in an autonomous discrete dynamical systems in a higher dimension space, which is the product space of the phase space and the space of the functions defining the non-autonomous system. Our current approach applies to two scenarios. In the first scenario, we assume that the trait equations are decoupled from the equations of the populations. This requires specialized biological and ecological assumptions which we clearly state. In the second scenario, we do not assume decoupling, but rather we assume that the dynamics of the trait is known, such as approaching a positive stable equilibrium point which may apply to a much broader evolutionary dynamics.


Energy localization on q-tori, long-term stability, and the interpretation of Fermi-Pasta-Ulam recurrences.
We focus on two approaches that have been proposed in recent years for the explanation of the so-called Fermi-Pasta-Ulam (FPU) paradox, i.e., the persistence of energy localization in the "low-q " Fourier modes of Fermi-Pasta-Ulam nonlinear lattices, preventing equipartition among all modes at low energies. In the first approach, a low-frequency fraction of the spectrum is initially excited leading to the formation of "natural packets" exhibiting exponential stability, while in the second, emphasis is placed on the existence of "q breathers," i.e., periodic continuations of the linear modes of the lattice, which are exponentially localized in Fourier space. Following ideas of the latter, we introduce in this paper the concept of " q-tori" representing exponentially localized solutions on low-dimensional tori and use their stability properties to reconcile these two approaches and provide a more complete explanation of the FPU paradox.


A Descriptive Study of Open Fractures Contaminated by Seawater: Infection, Pathogens, and Antibiotic Resistance.
Aims. In this work, the main objectives were to investigate the clinical characteristics and bacterial spectrum present in open fractures contaminated by seawater. Methods. We conducted a retrospective cohort study and included all patients with open fractures from 1st January, 2012, to 31st December, 2015, in our hospital. Patients were grouped based on the presence of seawater contamination in wounds. We compared the infection rate, bacterial spectrum, and antibiotic resistance between the two groups. Results. We totally included 1337 cases of open fracture. Wounds from 107 cases (8.0%) were contaminated by seawater. The wound infection rate of seawater-contaminated group was significantly higher in patients with Gustilo-Anderson Type II and Type III open fractures. The bacterial spectrum from seawater-contaminated wounds was remarkably different from that of the remaining. Antibiotic sensitivity tests revealed that more than 90% of infecting pathogens in seawater-contaminated wounds were sensitive to levofloxacin and ciprofloxacin. Conclusion. Cephalosporin in combination with quinolone was recommended in the early-stage management of open fractures contaminated by seawater.


Dynamic affinity between dissociable coenzyme and immobilized enzyme in an affinity chromatographic reactor with single enzyme.
The affinity chromatographic reactor (ACR) is a bioreactor which utilizes the dynamic interaction or the dynamic affinity between a free coenzyme and immobilized enzymes for the highly efficient regeneration of dissociable coenzymes. Dynamic affinity between free NAD and immobilized alcohol dehydrogenase (ADH) in ACR was investigated by three different methods. ADH catalyzed both oxidation and reduction of NAD, consuming propionaldehyde and ethanol. The theoretical model under consideration elucidated a criterion for the expression of the dynamic affinity as a relationship among the affinity constants and the concentrations of a coenzyme and immobilized enzyme. This criterion was confirmed experimentally by the measurements of the retention time of NAD and the half-life period of the reactor activity after one-shot pulse injection of NAD to ACR. In the stability measurement of the immobilized enzyme, it became clear that ADH was more stable at the higher concentration in immobilization. Although the present case of coenzyme cycling by a single enzyme is very special, with limited chance for the direct application, the results obtained here provide a theoretical basis for ACR with multienzymes-which is of more general use.


Adherence to All Steps of a Pain Management Protocol in Intensive Care Patients after Cardiac Surgery Is Hard to Achieve.
Purpose. To investigate adherence to our pain protocol considering analgesics administration, number and timing of pain assessments, and adjustment of analgesics upon unacceptably high (NRS ≥ 4) and low (NRS ≤ 1) pain scores. Material and Methods. The pain protocol for patients in the intensive care unit (ICU) after cardiac surgery consisted of automated prescriptions for paracetamol and morphine, automated reminders for pain assessments, a flowchart to guide interventions upon high and low pain scores, and reassessments after unacceptable pain. Results. Paracetamol and morphine were prescribed in all 124 patients. Morphine infusion was stopped earlier than protocolized in 40 patients (32%). During the median stay of 47 hours [IQR 26 to 74 hours], 702/706 (99%) scheduled pain assessments and 218 extra pain scores were recorded. Unacceptably high pain scores accounted for 96/920 (10%) and low pain scores for 546/920 (59%) of all assessments. Upon unacceptable pain additional morphine was administered in 65% (62/96) and reassessment took place in 15% (14/96). Morphine was not tapered in 273 of 303 (90%) eligible cases of low pain scores. Conclusions. Adherence to automated prescribed analgesics and pain assessments was good. Adherence to nonscheduled, flowchart-guided interventions was poor. Improving adherence may refine pain management and reduce side effects.


Enantioselective synthesis of an all-syn four vicinal fluorine motif.
Alkanes bearing multiple vicinal fluorine atoms at adjacent stereocenters may be considered intermediate between alkanes and perfluoroalkanes, and as a class, their chemistry and behavior remain to be explored. We report here a stereoselective synthesis of an all-syn four vicinal fluorine motif as a single enantiomer. The four vicinal fluorine compound was amenable to single-crystal X-ray analysis, and the resulting structure displays gauche relationships between all four fluorines, consistent with the fluorine gauche effect, and CF...HC hydrogen bonding between adjacent fluoroalkyl chains.


Health Care Professionals' Experiences and Views of eHealth in Pediatric Care: Qualitative Interview Study Applying a Theoretical Framework for Implementation.
The development and evaluation of eHealth interventions in clinical care should be accompanied by a thorough assessment of their implementation. The NASSS (Non-adoption, Abandonment, and Challenges to the Scale-Up, Spread, and Sustainability of Health and Care Technologies) framework was designed to facilitate the implementation and scale-up of health technology programs, providing an option for analyzing the progression of these initiatives as they are implemented in real-time. Considering health care provider perspectives within the framework for implementation offers valuable insights into the early identification of barriers and facilitators in the implementation of potentially effective eHealth innovations. Nevertheless, there is a dearth of studies on eHealth interventions that encompass longer time frames and delve into the complexities of scaling up and sustaining such interventions within real-world health care environments. This study aims to investigate the perspectives and insights of health care professionals (HCPs) regarding the implementation of an eHealth intervention in pediatric health care while applying the NASSS framework to theorize and evaluate the conditions influencing the implementation of eHealth solutions. Semistructured interviews were performed with health care providers, including both staff and management personnel, within a university pediatric hospital (N=10). The data collection process occurred concurrently with a clinical trial focused on developing and assessing an eHealth app for self-management in pediatric care following hospital discharge. Using an abductive approach, the interviews were initially analyzed qualitatively and subsequently mapped onto the 7 domains of the NASSS framework to identify factors influencing implementation, encompassing facilitators, barriers, and varying levels of complexity. In the realm of pediatric care, the family was identified as the primary unit of care, and patient heterogeneity was a prominent feature. The implementation of eHealth tools, while deemed usable and flexible, was also seen as a delicate balance between safety and adaptability, highlighting challenges related to health care integration. Child participation and secrecy, especially for adolescents, contributed to the complexity of using eHealth. HCPs had high eHealth literacy, and thus challenges concerning adoption were related to work adaptations and the risk of "app overload." The readiness for implementation was experienced as induced through the research study and the pandemic situation. However, to move from research to implementation in clinical practice, organizational challenges identified a need to update the concept of care and ensure activity measurements. In a wider context, HCPs raised concerns related to regulatory requirements for documentation, public procurement, and data safety. Implementation became more complex due to a lack of overview in a large organization. Important perspectives for implementation were considerations of regulatory requirements, as well as the need for a shared vision of eHealth and the establishment of eHealth-related work as part of regular health care. Key contextual factors that support reach and impact are communication channels between different levels at the hospital and a need for paths and procedures compatible with legal, technological, and security concerns. Further research should focus on how eHealth interventions are perceived by children, adolescents, their parents, and other stakeholders. ClinicalTrials.gov NCT04150120; https://clinicaltrials.gov/ct2/show/NCT04150120.


Determination of carbonate content in barite ore by headspace gas chromatography.
This paper reports a method for determining the carbonate content in barite ore using headspace gas chromatography. Based on the acidification reaction, the carbonate in the barite ore was converted to CO2 in a closed headspace vial. When the carbonate content was significant, the pressure caused changes in the CO2 and O2 signals and affected the measurement accuracy. It was found that carbonate content is proportional to the intensity ratio of the CO2 to O2 signals. Thus, the carbonate content in barite ore can be measured indirectly using a theoretical model. The results showed that the carbonate in 3 g of barite ore sample with a particle size of 74 μm could react completely with a hydrochloric acid solution (2 mol/L) at 65°C for 5 min. The method described herein had good precision (relative standard deviation < 4.14%) and accuracy (relative differences < 6.12%). Further, the limit of quantification was 0.07 mol/L. Owing to its simplicity and speed, this method can be used for the batch determination of carbonate content in barite ore.


Entrapment of the median nerve between sublimis tendons after distal forearm fracture: an unusual case report.
We present a rare case of entrapment of the median nerve between sublimis tendons after fractures of the distal radius and ulna in an 80-year-old woman. The entrapped median nerve was elongated redundantly with two regions of constriction. To our knowledge, no case of median nerve palsy caused by such a factor has been previously reported.


Pregnancy possible after organ transplant.
Despite past concerns to the contrary, women who have had an organ transplant can become pregnant, and their chances of having a healthy baby are good, researchers at the University of Pittsburgh Medical Center say. There has been concern that the drugs given to suppress the body's rejection of transplanted organs might increase the risk of premature birth, low birthweight or other complications. In the new study, the researchers studied 14 pregnancies in 12 liver-transplant recipients given the anti-rejection drug FK506. 7 of the 12 women delivered their babies vaginally, and more than half of the mothers were able to carry their babies to the full term. Of the 14 babies in the study, 12 are alive and well. 2 babies were born prematurely and died soon after birth. The rest were born without birth defects or evidence of infection--a concern because FK506 crosses the placenta and may suppress the baby's immune system. The mothers were advised against breast feeding, since FK506 is excreted in breast milk, and the effect of chronic exposure on babies is not known. In 1993, approximately 18,000 transplants were performed in the US and 3441 of them were liver transplants. About 46% of liver transplants recipients were women.


Clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinoma.
Circulating DNA can be isolated from serum of patients with various carcinomas and p53 mutation can be observed in colorectal carcinoma. The aim of this study was to investigate the correlation between p53 mutation in DNA extracted from colorectal carcinoma and that in DNA extracted from serum of patients with colorectal carcinoma. The clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinomas was also investigated. DNA was extracted from tumors and non-tumorous colorectal tissues of 46 patients with single sporadic colorectal carcinomas of stage I (n=6), stage II (n=18), stage III (n=15), and stage IV (n=7) according to the TNM classification. Circulating DNA was also extracted from the serum of the 46 patients with colorectal carcinoma and from 7 healthy volunteers for normal control. Mutations of the p53 gene were analyzed using a fluorescence-based polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. DNA sequences were determined in DNA fragments with shifted peaks by SSCP methods. Mutations in tumors were found in 22 (48%) of 46 patients, and mutations in serum were found in 3 (14%) of these 22 patients. Of 4 patients with stage IV disease, 3 (75%) had serum p53 mutation and the mutation pattern of these 3 patients was the same in both tumor and serum. No correlation was seen between p53 mutation in serum and the level of serum DNA. There was no significant difference between the presence of p53 mutation in serum and tumor size, depth of invasion, vascular invasion, or lymph node metastasis. However, liver metastasis showed significant difference (p=0.0026). The presence of p53 mutation in serum was associated with a clinically advanced stage accompanied by liver metastasis.


Pharmacokinetics of cannabinoids.
Delta-9-tetrahydrocannabinol (Delta-9-THC) is the main psychoactive ingredient of cannabis (marijuana). The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC) and nabilone. The variability of THC in plant material (0.3% to 30%) leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152±86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively). THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes) occurs via the feces and urine. Metabolites persist in the urine and feces for several weeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h). As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokinetic-pharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response.


Analysis of Proton NMR in Hydrogen Bonds in Terms of Lone-Pair and Bond Orbital Contributions.
NMR spectroscopic parameters of the proton involved in hydrogen bonding are studied theoretically. The set of molecules includes systems with internal resonance-assisted hydrogen bonds, internal hydrogen bonds but no resonance stabilization, the acetic acid dimer (AAD), a DNA base pair, and the hydrogen succinate anion (HSA). Ethanol and guanine represent reference molecules without hydrogen bonding. The calculations are based on zero-point vibrationally averaged molecular structures in order to include anharmonicity effects in the NMR parameters. An analysis of the calculated NMR shielding and J-coupling is performed in terms of "chemist's orbitals", that is, localized molecular orbitals (LMOs) representing lone-pairs, atomic cores, and bonds. The LMO analysis associates some of the strong de-shielding of the protons in resonance-assisted hydrogen bonds with delocalization involving the π-backbone. Resonance is also shown to be an important factor causing de-shielding of the OH protons for AAD and HSA, but not for the DNA base pair. Nitromalonamide (NMA) and HSA have particularly strong hydrogen bonds exhibiting signs of covalency in the associated J-couplings. The analysis results show how NMR spectroscopic parameters that are characteristic for hydrogen bonded protons are influenced by the geometry and degree of covalency of the hydrogen bond as well as intra- and intermolecular resonance.


Carbon-nanotube-based materials for protein crystallization.
We report on the first use of carbon-nanotube-based films to produce crystals of proteins. The crystals nucleate on the surface of the film. The difficulty of crystallizing proteins is a major bottleneck in the determination of the structure and function of biological molecules. The crystallization of two model proteins and two medically relevant proteins was studied. Quantitative data on the crystallization times of the model protein lysozyme are also presented. Two types of nanotube films, one made with the surfactant Triton X-100 (TX-100) and one with gelatin, were tested. Both induce nucleation of the crystal phase at supersaturations at which the protein solution would otherwise remain clear; however, the gelatin-based film induced nucleation down to much lower supersaturations for the two model proteins with which it was used. It appears that the interactions of gelatin with the protein molecules are particularly favorable to nucleation. Crystals of the C1 domain of the human cardiac myosin-binding protein-C that diffracted to a resolution of 1.6 A were obtained on the TX-100 film. This is far superior to the best crystals obtained using standard techniques, which only diffracted to 3.0 A. Thus, both of our nanotube-based films are very promising candidates for future work on crystallizing difficult-to-crystallize target proteins.


The Role of Nephronectin on Proliferation and Differentiation in Human Dental Pulp Stem Cells.
The purpose of the current study was to investigate the effects of nephronectin (Npnt) in human dental pulp stem cells (hDPSCs). Npnt was coated to nontissue culture-treated polystyrene (non-PS) plates. The presence of immobilized protein on the surface was detected by polyclonal rabbit primary anti-Npnt antibody. Then the cell number was counted and compared with PBS-, bovine serum albumin- (BSA-), fish scale type I collagen- (FCOL1-), and human fibronectin- (Fn-) coated wells. Cell proliferation was assessed using CCK-8 assay. Cell morphology was observed under light microscopy and fluorescence microscopy. Lastly, the mRNA expression profiles of integrins, dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), and mineralization capacity of hDPSCs were investigated by real time RT-PCR and alizarin red staining, respectively. Npnt mediates hDPSC adhesion and spreading partially via the Arg-Gly-Asp (RGD) motif. Npnt enhanced the mRNA expression of ITGA1, ITGA4, ITGA7, and ITGB1 on day five. Npnt downregulated DSPP but significantly upregulated BSP mRNA expression at day 28. Further, Npnt and FCOL1 accelerated the matrix mineralization in hDPSCs. The current findings implicate that Npnt would be favorable to recruit hDPSCs and conducive to mineralization in hDPSCs. The combination of Npnt with hDPSCs may offer a promising approach for hard tissue regeneration.


Three-dimensional Čerenkov tomography of energy deposition from ionizing radiation beams.
Since its discovery during the 1930s the Čerenkov effect (light emission from charged particles traveling faster than the local speed of light in a dielectric medium) has been paramount in the development of high-energy physics research. The ability of the emitted light to describe a charged particle's trajectory, energy, velocity, and mass has allowed scientists to study subatomic particles, detect neutrinos, and explore the properties of interstellar matter. However, to our knowledge, all applications of the process to date have focused on the identification of particles themselves, rather than their effect upon the surroundings through which they travel. Here we explore a novel application of the Čerenkov effect for the recovery of the spatial distribution of ionizing radiation energy deposition in a medium and apply it to the issue of dose determination in medical physics. By capturing multiple projection images of the Čerenkov light induced by a medical linear accelerator x-ray photon beam, we demonstrate the successful three-dimensional tomographic reconstruction of the imparted dose distribution.


COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis.
Data of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody. We collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses. Twenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76-90%) and 91% (95% CI, 83-95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76-86%) in chronic hepatitis B, 96% (95% CI, 93-97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75-91%) in cirrhosis and 85% (95% CI, 78-90%) in non-cirrhosis, 86% (95% CI, 78-92%) for inactivated vaccine and 89% (95% CI, 71-96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55-75%) after two doses of mRNA vaccines and 88% (95% CI, 58-98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30-89%). Prevalence of adverse events was 27% (95% CI, 18-38%) and 63% (95% CI, 39-82%) among CLD and LT groups, respectively. CLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.


Universal asymptotic correlation functions for point group C_{6v} and an observation for triangular lattice Q-state Potts model.
We investigate a universal curve in asymptotic correlation functions of off-critical systems that possess C_{6v} symmetry following the argument for C_{4v} symmetry in our previous paper [Phys. Rev. E 102, 032141 (2020)2470-004510.1103/PhysRevE.102.032141]. Unlike the C_{4v} case, a minimal asymptotic form exists, which contains only two free parameters: the normalization constant and the modulus of the universal curve. We perform large-scale Monte Carlo simulations of the triangular lattice Q-state Potts model above the transition temperature. For Q=1, 2, 3, and 4, we successfully obtain numerical evidence that the minimal form gives the leading asymptotic behavior. We also discuss the possibility that the corrections to the minimal form are expressed using this form as a building block. From the minimal form with optimized parameters, we derive the equilibrium crystal shape of the honeycomb lattice Potts model, which is given by an algebraic curve of genus 1 and is universal among models with C_{6v}. Although the curve differs from those obtained in the C_{4v} case, the latter curves also have genus 1. We indicate that the birational equivalence concept can play an important role in comparing asymptotic forms for different point group symmetries, for example, C_{6v} and C_{4v}.


Design of a multicenter randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome.
To describe the study design and rationale for the first placebo-controlled, randomized clinical trial to be conducted by the Chronic Prostatitis Collaborative Research Network sponsored by the National Institutes of Health. The clinical trial will use a 2 by 2 factorial design to evaluate four treatments: placebo, tamsulosin hydrochloride alone, ciprofloxacin alone, and tamsulosin hydrochloride and ciprofloxacin combined. The primary objectives are to compare the efficacy and safety endpoints in patients with chronic prostatitis/chronic pelvic pain syndrome. The study population consists of men with symptoms of discomfort or pain in the pelvic region for at least a 3-month period. One hundred eighty-four participants will be treated for 6 weeks and followed up for an additional 6 weeks. The primary endpoint is the change in the overall National Institutes of Health Chronic Prostatitis Symptom Index from baseline to 6 weeks. Secondary endpoints include a patient-reported global assessment of response and white blood cell counts and cultures in urine, expressed prostatic secretions, and semen. The evaluation of changes from 6 to 12 weeks will be used to assess the durability of the response. This trial was opened to enrollment in July 2001. The study is expected to require 14 months of accrual and follow-up. The issues considered in the design of this clinical trial may provide guidelines for future clinical trials in chronic prostatitis/chronic pelvic pain syndrome.


Combined vitrectomy and intravitreal injection versus combined laser and injection for treatment of intractable diffuse diabetic macular edema.
The purpose of this study was to compare the safety and efficacy of combined vitrectomy, intravitreal triamcinolone acetonide (IVTA), and bevacizumab injection with that of IVTA and bevacizumab injection and subsequent macular grid laser photocoagulation for the treatment of intractable diffuse diabetic macular edema. This randomized controlled clinical trial was performed at Benha University Hospital, Benha, Egypt, and included 34 eyes from 34 diabetic patients diagnosed with intractable diffuse diabetic macular edema without vitreomacular traction. The patients were divided into two groups. In group 1, pars plana vitrectomy with removal of the posterior hyaloid was performed, and at the end of the procedure, IVTA 0.1 mL (40 mg/mL) and bevacizumab 1.25 mg were injected. In group 2, macular grid laser photocoagulation was performed 2 weeks after the same intravitreal injection combination as used in group 1. The main outcome measures were best-corrected visual acuity (BCVA) and central foveal thickness, which were measured using optical coherence tomography at 3, 6, and 12 months. Changes in BCVA and central foveal thickness at 3, 6, and 12 months from baseline were highly statistically significant (P < 0.01). Mean BCVA was better in group 1 at 3 months, nearly equal at 6 months, and less at 12 months. Mean central foveal thickness was more improved in group 1 than in group 2 at 3 months, and was better in group 2 at subsequent measurement points. The major adverse events were development of cataract (more common in group 1) and elevation of intraocular pressure (more common in group 2). The combined therapy described here could represent a solution for the treatment of intractable diabetic macular edema, and could have a favorable long-term outcome. Combined treatment of IVTA and bevacizumab plus grid laser resulted in a more favorable reduction in central foveal thickness and improvement in BCVA at 12 months than vitrectomy combined with the same injections. This small study favors the safer, cheaper, and more available line of treatment.


Plasma lactate concentration as a prognostic biomarker in dogs with gastric dilation and volvulus.
Initial and serial plasma lactate concentrations can be used to guide decision making in individual dogs with GDV but care is necessary in phrasing conversations with owners. Published data suggests that survival is more likely and the chance of complications less in dogs with an initial plasma lactate of <4 mmol/L. An initial lactate >6 mmol/L makes gastric necrosis and greater expense more likely. However, because of the overlap between groups and the good overall survival rates, exploratory laparotomy should always be recommended irrespective of the plasma lactate concentration. Falls in plasma lactate of greater than ~40% after fluid resuscitation are likely to indicate better survival. If the initial plasma lactate concentration is moderately to severely increased (5->10 mmol/L) and a sustained increase in plasma lactate occurs after fluid resuscitation, the cause should be aggressively pursued. Many dogs with persistent hyperlactatemia over 24-48 hours do not survive.


Cell-Free DNA Variant Sequencing Using CTC-Depleted Blood for Comprehensive Liquid Biopsy Testing in Metastatic Breast Cancer.
Keup and colleagues provide liquid biopsy preliminary results by sequencing variants in circulating tumor cells (CTCs) and cell-free deoxyribonucleic acid (cfDNA) "all from one tube" format, in order to use the same blood sample under the same isolation conditions of both analytes to reach an unbiased comparability and consistency. We appreciated the attempt of the authors to improve technical procedures in liquid biopsy research area, but we wanted to raise several issues related to cfDNA detection, reporting our research experience. This is a feasibility study as the authors analyzed only one sample from a small case series at an advanced line of treatment. In the clinical practice to monitor the disease and predict the treatment response, the analysis should be done at multiple time points. We have previously demonstrated that the quantity and the integrity of the cfDNA are not useful to determine the evolution of early breast cancer (bc), maybe due to the fact that cfDNA is not strictly related to cancer but also to an inflammatory status. Given that a high content of cfDNA could reflect inflammatory processes, we decided to investigate the role of stimulator of interferon gene (STING), an important regulator of cancer cell growth and senescence, in bc tissue in relation to cfDNA. STING biomarker analyzed by immunohistochemistry on tumor tissue could reflect a circulating inflammatory status and needs to be further investigated, not only on CTCs but also on cfDNA. One of the major issues of cfDNA is to decide what to analyze on it, in terms of type of cells and genetic alterations. Considering that multiple tests could be done to study gene copy number alterations, mutations, and variant fusions, the proper molecular test should be chosen, on the basis of the clinical need, starting from the treatment choice to disease monitoring.


Acute gastrointestinal bleeding following aortic valve replacement in a patient with Heyde's sindrome. Case report.
A 58-year old man was admitted to the hospital because of melena. He had a 1-year history of mechanical aortic valve replacement and coronary stent placement because of myocardial infarction and he was taking warfarin and clopidogrel. Esophagogastroduodenoscopy and colonoscopy were negative for bleeding. Capsule endoscopy showed bleeding diffuse angiodysplasia of the small bowel. The patient was treated with octreotide 20 mg, at monthly interval. After 25 months there had been no recurrence of gastrointestinal bleeding. The case suggests that mechanical valve replacement may not prevent gastrointestinal bleeding in Heyde syndrome and that octreotide treatment should be considered in these cases.


Comparison of the effects of preemptive acetaminophen, ibuprofen, and meloxicam on pain after separator placement: a randomized clinical trial.
This study aims to evaluate and compare the effect of pre-procedural administration of acetaminophen, ibuprofen, and meloxicam in reducing pain after separator placement. Three hundred twenty-one patients who needed orthodontic treatment and aged above 15 were randomly assigned to one of the three study groups: group A: 650 mg acetaminophen, group B: 400 mg ibuprofen, and group C: 7.5 mg meloxicam. All subjects received a single dose of medication 1 h prior to separator placement. Using visual analog scale, patients recorded their pain perception during rest, fitting posterior teeth together, and chewing at time intervals of immediately, 2, 6, 24, and 48 h after separator placement. There was no significant difference between acetaminophen, ibuprofen, and meloxicam in post-separator placement pain control when administered 1 h before the procedure. In all the groups, at rest, pain level elevated after separator placement and reached its peak at 24 h and then subsided until 48 h. But during chewing and fitting of the posterior teeth, some of the groups reached a peak in pain at 48 h. No significant difference was found in pain experience between males and females. Meloxicam can be used as an effective analgesic in orthodontic pain control considering it has less gastric side effects compared to the conventional nonsteroidal anti-inflammatory drugs. Iranian Registry of Clinical Trials, IRCT2015041821828N1.


Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary.
Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder.


Effect of smoking on early bone healing around oxidized surfaces: a prospective, controlled study in human jaws.
This prospective and controlled histologic study evaluates the impact of smoking on bone-to-implant contact, the bone density in the threaded area, and the bone density outside the threaded area around microimplants with anodized surface retrieved from human jaws. A total of 24 subjects (mean age 51.32 + or - 7.5 years) were divided in two groups: smokers (n = 13 subjects) and non-smokers (n = 11 subjects). Each subject received one microimplant with oxidized surface during conventional mandible or maxilla implant surgery. After 8 weeks, the microimplants and the surrounding tissue were removed and prepared for histomorphometric analysis. Three microimplants placed in smokers showed no osseointegration. The newly formed bone showed early stages of maturation, mainly in the non-smokers. Marginal bone loss, gap, and fibrous tissue were present around implants retrieved from smokers. Histometric evaluation indicated that the mean bone-to-implant contact ranged between 25.97% + or - 9.02% and 40.01% + or - 12.98% for smokers and non-smokers, respectively (P <0.001). Smokers presented 28.17% + or - 10.32% of bone density in the threaded area, whereas non-smokers showed 46.34% + or - 19.12%. The mean of bone density outside the threaded area ranged between 18.76% and 25.11% for smokers and non-smokers, respectively (P >0.05). The present data obtained in human subjects confirm that smoking has a detrimental effect on early bone tissue response around oxidized implant surfaces.


Gut hormones: a weight off your mind.
The increasing prevalence of obesity and the associated morbidity and mortality has resulted in a major research effort to identify mechanisms that regulate appetite. It is well established that the hypothalamus and brain stem are major sites in the central nervous system (CNS) that regulate appetite. Until recently the missing element has been how information regarding food intake and energy stores is communicated to the CNS. Gut hormones have recently been found to be an important element in this regulation, communicating information regarding food intake to the CNS. Several gut hormones have been found to exert anorectic effects. These include members of the Pancreatic Polypeptide (PP)-fold family, namely PP itself and also peptide tyrosine-tyrosine (PYY), the first gut hormone shown to have appetite-inhibiting properties. The other main class of anorectic gut hormones are those derived by proteolytic processing from proglucagon, most importantly glucagon-like peptide-1 (GLP-1) and oxyntomodulin. All of these are currently being investigated as the basis of treatments to prevent the development of obesity. So far the only gastrointestinal hormone demonstrated to stimulate appetite is ghrelin. Potential sites and mechanisms of action and therapeutic use of these gastrointestinal hormones are discussed.


Quality of life in women with heart failure, normative groups, and patients with other chronic conditions.
In the United States, 2.5 million women have heart failure, yet little is known about their quality of life. Because most studies included small samples of women, the results are not generalizable. To compare the quality of life of women with heart failure with that of a normative group and with that of women with other chronic conditions. Descriptive techniques were applied to baseline data collected in the Studies of Left Ventricular Dysfunction trials to characterize quality of life in women with heart failure (n = 691). Global quality of life and the quality-of-life dimensions of physical function, emotional distress, social health, and general health were measured by using the Ladder of Life, items from the Profile of Mood States Inventory, the Functional Status Questionnaire, the Beta Blocker Heart Attack Trial instrument, and an item from the RAND Medical Outcomes Study instrument. Compared with the normative group of women, women with heart failure had significantly lower global quality of life; worse vigor, intermediate activities of daily living, social activity, and general health ratings; and higher ratings for anxiety and depression. Fewer than half of the women with heartfailure felt that they were healthy enough to perform normal activities. Women with heart failure have worse quality of life than do normative populations and patients with other chronic diseases such as hypertension, Parkinson disease, and cancer.


DRAWING SKILLS IN CHILDREN WITH NEURODEVELOPMENTAL DELAY AGED 2-5 YEARS.
In typically developing children, drawing development occurs in stages from uncontrolled strokes to complex drawing. In this study, we examined drawing development in children with neurodevelopmental delay (NDD). In order to do so, we observed the influence of age, intraventricular hemorrhage (IVH) and gender on the development of drawing skills. The sample consisted of 52 children with NDD, aged 2 years and 6 months to 5 years. All children were hospitalized for multidisciplinary team monitoring and developmental support. The evaluation of drawing development was administered by giving each child a blank A4 paper and the instruction to draw anything they wanted. All of the drawings were scored satisfactory or unsatisfactory. Descriptive statistics was employed on all relevant data to show results in frequencies and percentages. In order to determine differences between groups, the χ2-test was administered. The results showed greatest difference in drawing in children aged from 3 years to 3 years and 11 months. Children with lower IVH had better drawing scores than children with higher IVH levels. According to gender dissimilarities, a difference was found showing girls to have better drawing skills than boys. All study results pointed to the importance of early rehabilitation and continuous structured work with children with NDD.


Combination of vinorelbine, epirubicin, and cyclophosphamide as neoadjuvant chemotherapy for locally advanced breast cancer: phase II study.
Achievement of a pathologic complete response after primary chemotherapy in breast cancer can predict long-term outcome. We have investigated a combination of epirubicin, cyclophosphamide, and vinorelbine as neoadjuvant chemotherapy in locally advanced breast cancer (LABC). From January 1997 to May 1999, 30 chemonaive patients were treated (T2 or T3 histologically proven invasive breast carcinoma). Treatment was vinorelbine 25 mg/m2 day 1 and day 3, epirubicin 30 mg/m2/d, days 1 to 3, cyclophosphamide 350 mg/m2/d, days 1 to 3, every 14 days for 4 courses. Twenty-nine patients were evaluable. Median age: 48 years (range: 28-66 years); 26 had ductal invasive carcinoma and 4 lobular invasive carcinoma; median tumor size: 7 cm; median number of induction cycles: four. Clinical objective response was seen in 24 patients (relative risk: 86%), 14 complete responses, 10 partial responses, four stable disease (no significant changes). Twenty-nine patients had surgical treatment. Pathologic response rate was complete response in 32% (no residual tumor), in situ carcinoma: 11%, invasive or unchanged tumor remaining: 57%. Ninety-eight cycles were administered; major toxicities were hematologic: grade IV Hb in 5% and grade IV neutropenia in 60% of cycles. Ten patients required hospitalization for febrile neutropenia. Other toxicities were mild to moderate. The vinorelbine/epirubicin/cyclophosphamide regimen resulted in a high pathologic complete response rate in LABC with a good tolerance profile, and warrants further evaluation.


Seasonal variation in glucosinolate content in Brassica oleracea crops grown in northwestern Spain.
Brassica oleracea L. crops including kales, cabbages, and Tronchuda cabbages are widely grown in northwestern Spain and Portugal but little information is available on leaf glucosinolate content of these crops. The objectives were to determine the diversity for the total glucosinolate content and profile on leaves in a collection of 153 kales, 26 cabbages, and three Tronchuda cabbages varieties grown at two growing seasons and to determine the seasonal variation of glucosinolates in cabbages and Tronchuda cabbage varieties. Sinigrin, glucoiberin, and glucobrassicin were the major glucosinolates found in kales. Glucoiberin was the most common glucosinolate in Tronchuda cabbages in both planting seasons and in cabbages sown in fall season whereas glucobrassicin and glucoiberin were the most common glucosinolates in cabbages in spring season. In kales the total glucosinolate content ranged from 11.0 to 53 micromol g(-1) dw, with a mean value of 26.3 micromol g(-1) dw. Four kale varieties (MBG-BRS0468, MBG-BRS0476, MBG-BRS0060 and MBG-BRS0223) showed the highest total sinigrin or glucobrassicin contents. So, they could be good candidates for future breeding programs. In cabbages, the total glucosinolate content ranged from 10.9 to 27 g(-1) dw. Total glucosinolate concentration during spring sowing (22 micro mg(-1) dw) was higher than those in fall sowing (13 micro mg(-1) dw). Regarding both high glucosinolate content and the agronomic value, MBG-BRS0057 and MBG-BRS0074 could be good sources of beneficial glucosinolates. The presence of high concentrations of sinigrin, glucoiberin, and glucobrassicin warrant further search into their potential use to enhance the level of these important phytochemicals in these edible crops.


Herbs as a food and medicine source in Palestine.
This article describes the broad ethno-botany and folk medicine in Palestine. It presents examples of different edible plants and their use by Palestinians in a host of manners, fresh, cooked and dried, both as foodstuffs and treatment of diseases and medical disorders. Their potential application as cancer chemopreventive agents needs to be a focus of research attention.


Specific immunoreactivity of hybridoma-secreted monoclonal anti-melanoma antibodies to cultured cells and freshly derived human cells.
The specificities of monoclonal antibodies against melanoma cells were analyzed using radioimmunoassay, mixed-hemadsorption assay, and quantitative absorption on a variety of malignant and nonmalignant cells. Three of the six hybridoma-secreted antibodies bound to the majority of melanoma cell lines, melanoma tumors, and astrocytoma cell lines as well as to all normal and Epstein-Barr virus-transformed lymphocytes tested. The binding pattern coincides with the presence or absence of the DR antigen on human cells. Conversely, two other antibodies, 19-19 and Nu4B, detected two different antigens common to melanoma and astrocytoma cells only. Cloning of melanoma cells resulted in establishment of DR-positive and DR-negative clones, with the binding of Nu4B antibody retained in all.


Mexican pregnant women show higher depression and anxiety with rising age and in the case of being single.
Pregnancy is an important predisposition period to develop anxiety and depression, with a direct impact on the woman's offspring. The aim of this study was to report the correlation between depression and anxiety in pregnant women and its association with the marital status and age. A descriptive, retrospective and cross-sectional study was conducted in the outpatient care of the Psychology Service at the "Mónica Pretelini Sáenz" Maternal Perinatal Hospital (HMPMPS), Toluca, Mexico, from June 2012 to March 2019. As routine, the Beck Depression Inventory (BDI-II) and the Beck Anxiety Inventory-Trait (BAIT), were applied to all women seeking attention at the HMPMPS. Only pregnant patients were selected for this study, with the women referred for the first time to the external Psychology Clinic as inclusion criteria. Pearson's correlation coefficient and the frequency of cases for age, BDI-II, and BAIT were obtained using the IBM SPSS Statistics ® v.23 software. The study included 2947 pregnant patients with a mean age of 28.6 ± 6.9 years. Of these, 2616 (88.8%) presented with mild anxiety, 269 (9.1%) with moderate, and 62 (2.1%) with severe anxiety. On the other hand, 2149 (72.9%) patients presented with minimal depression, 341 (11.6%) mild depression, 268 (9.1%) moderate depression, and 189 (6.4%) had severe depression. The correlations between age and BDI-II was -0.026 (P = 0.152), between age and BAI was -0.038 (P = 0.037), and between BAIT and BDI-II 0.650 (P ≤ 0.001). The age group with the highest frequency of depression and anxiety was from 20 to 29 years. The absence of a stable partner represented an important risk factor for anxiety and depression during pregnancy.


[11 operated cases of spontaneous hemopneumothorax].
During the period 1984-1993, we experienced 11 operated cases of spontaneous hemopneumothorax, which correspond 7.3% of total 150 cases of operated spontaneous pneumothorax. All cases were male, 19-36 years of age. From admission to the end of operation, 6 cases with hemorrhagic shock had bleeding of 2,305-6,670 ml, the average 3,708 ml, whereas 5 cases without shock had bleeding of 1,209-2,405 ml, the average 1,979 ml. In 9 cases operated within 5 days after admission (6 cases with shock and 3 cases without shock), the source of bleeding was detected, but in 2 cases operated over 6 days after admission, the source was not detected. For the emergency operation of hemopneumothorax, we employed axillary thoracotomy by half lateral position in order to avoid the blood pressure depression due to position changing of the patient. The operation performed safely with enough exposure, and all the patients recovered without severe complication. the treatment of spontaneous hemopneumothorax is better to choose early operation by axillary thoracotomy with half lateral position.


A simple and flexible thin film evaporating device for energetic materials.
A thin film evaporation device has been developed to prepare energetic materials at atmospheric pressure. The device is intuitive, simple, and easy to manipulate. The application of the device is demonstrated for pentaerythritol tetranitrate but can be extended to other explosives and organic materials that have low saturation pressures.


Latest assessment methods for mitochondrial homeostasis in cognitive diseases.
Mitochondria play an essential role in neural function, such as supporting normal energy metabolism, regulating reactive oxygen species, buffering physiological calcium loads, and maintaining the balance of morphology, subcellular distribution, and overall health through mitochondrial dynamics. Given the recent technological advances in the assessment of mitochondrial structure and functions, mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, mild cognitive impairment, and postoperative cognitive dysfunction. This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences, from the perspectives of energy metabolism, oxidative stress, calcium homeostasis, and mitochondrial dynamics (including fission-fusion, transport, and mitophagy).


Genomic testing in neurology.
Genomic testing has been available for neurological conditions for decades. However, in recent years, there has been a significant change in its availability, range and cost, as well as improvements in the technology and knowledge that underpin how the genome is interrogated. Neurologists can encounter a wide range of genetic conditions, and so their understanding of genomic testing is fundamental to modern clinical practice.


Clinical and Epidemiological Study of Intracranial Tumors in Children and Identification of Diagnostic Biomarkers for the Most Common Tumor Subtype and Their Relationship with the Immune Microenvironment Through Bioinformatics Analysis.
Brain tumors are the second most common pediatric malignancy and have poor prognosis. Understanding the pathogenesis of tumors at the molecular level is essential for clinical treatment. We conducted a retrospective study on the epidemiology of brain tumors in children based on clinical data obtained from a neurosurgical center. After identifying the most prevalent tumor subtype, we identified new potential diagnostic biomarkers through bioinformatics analysis of the public database. All children (0-15 years) with brain tumors diagnosed histopathologically between 2010 and 2020 at the Department of Neurosurgery, Xijing Hospital, were reviewed retrospectively for age distribution, sex predilection, native location, tumor location, symptoms, and histological grade, and identified the most common tumor subtypes. Two datasets (GSE44971 and GSE44684) were downloaded from the Gene Expression Omnibus database, whereas the GSE44971 dataset was used to screen the differentially expressed genes between normal and tumor samples. Gene ontology, disease ontology, and gene set enrichment analysis enrichment analyses were performed to investigate the underlying mechanisms of differentially expressed genes in the tumor. Combined with methylation data in the GSE44684 dataset, we further analyzed the correlation between methylation and gene expression levels. Two algorithms, LASSO and SVM-RFE, were used to select the hub genes of the tumor. The diagnostic value of the hub genes was assessed using the receiver operating characteristic (ROC) curve. Finally, we further evaluated the relationship between the hub gene and the tumor microenvironment and immune gene sets. Overall, 650 children from 18 provinces in China were included in this study. The male-to-female ratio was 1.41:1, and the number of patients reached a peak in the 10-15-year-old group (41.4%).The most common symptoms we encountered in our institute were headache and dizziness 250 (28.2%), and nausea and vomiting 228 (25.7%). The predominant location is supratentorial, with a supratentorial to infratentorial ratio of 1.74:1. Low-grade tumors (WHO I/II) constituted 60.9% of all cases and were predominant in every age group. According to basic classification, the most common tumor subtype is pilocytic astrocytoma (PA). A total of 3264 differentially expressed genes were identified in the GSE44971 dataset, which are mainly involved in the process of neural signal transduction, immunity, and some diseases. Correlation analysis indicated that the expression of 45 differentially expressed genes was negatively correlated with promoter DNA methylation. Next, we acquired five hub genes (NCKAP1L, GPR37L1, CSPG4, PPFIA4, and C8orf46) from the 45 differentially expressed genes by intersecting the LASSO and SVM-RFE models. The ROC analysis revealed that the five hub genes had good diagnostic value for patients with PA (AUC > 0.99). Furthermore, the expression of NCKAP1L was negatively correlated with immune, stromal, and estimated scores, and positively correlated with immune gene sets. This study, based on the data analysis of intracranial tumors in children in a single center over the past 10 years, reflected the clinical and epidemiological characteristics of intracranial tumors in children in Northwest China to a certain extent. PA is considered the most common subtype of intracranial tumors in children. Through bioinformatics analysis, we suggested that NCKAP1L, GPR37L1, CSPG4, PPFIA4, and C8orf46 are potential biomarkers for the diagnosis of PA.


Genome sequencing of SARS-CoV-2 omicron variants in Delhi reveals alterations in immunogenic regions in spike glycoprotein.
The SARS-CoV-2 omicron variants keep accumulating a large number of mutations in the spike (S) protein, which contributes to greater transmissibility and a rapid rise to dominance within populations. The identification of mutations and their affinity to the cellular angiotensin-converting enzyme-2 (ACE-2) receptor and immune evasion in the Delhi NCR region was under-acknowledged. The study identifies some mutations (Y505 reversion, G339H, and R346T/N) in genomes from Delhi, India, and their probable implications for altering the immune response and binding affinity for ACE-2. The spike mutations have influenced the neutralizing activity of antibodies against the omicron variant, which shows partial immune escape. However, researchers are currently exploring various mitigation strategies to tackle the potential decline in efficacy or effectiveness against existing and future variants of SARS-CoV-2. These strategies include modifying vaccines to target specific variants, such as the omicron variant, developing multivalent vaccine formulations, and exploring alternative delivery methods. To address this, it is also necessary to understand the impact of these mutations from a different perspective, especially in terms of alterations in antigenic determinants. In this study, we have done whole genome sequencing (WGS) of SARS-CoV-2 in COVID-19 samples from Delhi, NCR, and analyzed the spike's mutation with an emphasis on antigenic alterations. The impact of mutation in terms of epitope formation, loss/gain of efficiency, and interaction of epitopes with antibodies has been studied. Some of the mutations or variant genomes seem to be the progenitors of the upcoming variants in India. Our analyses suggested that weakening interactions with antibodies may lead to immune resistance in the circulating genomes.


Antidepressant activity of hyperforin conjugates of the St. John's wort, Hypericum perforatum Linn.: an experimental study.
Nine extracts of H. perforatum, containing hyperforin in conjugated forms, but devoid of free hyperforin and adhyperforin, were subjected to antidepressant screening using the forced swim test (FST). The observed activity was compared with that of SJW extracts containing hyperforin and adhyperforin (in free form). Results indicate that hyperforin conjugates exhibit significant antidepressant activity as evidenced by the reduced immobility period in the FST in rats.


Judgments of infant pain: the impact of caregiver identity and infant age.
To examine whether caregiver judgments of infant pain would vary systematically with different infant caregiver groups and infant age. A total of 123 caregivers (41 parents, 41 in patient nurses, 41 pediatricians) viewed videotapes of the vigorous behavioral responses of healthy infants (aged 2, 4, 6, 12, and 18 months) to a routine immunization injection and provided ratings of both the affective distress and pain intensity observed. A principal components analysis of affective and intensity ratings yielded a weighted pain summary score for each injection event. Older infants were attributed significantly more pain than younger infants, even though the vigor of the behavioral reactions was experimentally controlled across age groups. A profile analysis contrasting observer groups indicated that pediatricians attributed significantly lower levels of pain than parents, while nurses were intermediate to the other groups, not significantly differing from either group. These systematic differences in judgments were consistent across infant age groups. The findings reveal systematic sources of significant variations in observer judgments of infant pain. Despite an absence of differences in the behavioral reactions of the children, both the type of caregiver and their knowledge of the child's age systematically influenced attributions of pain to infants. This work suggests the important role of caregiver role variation and perceived developmental maturity as determinants of infant pain judgments and highlights potential areas of difficulty in controlling the unnecessary suffering of infants.


Solar flares and energetic particles.
Solar flares are now observed at all wavelengths from γ-rays to decametre radio waves. They are commonly associated with efficient production of energetic particles at all energies. These particles play a major role in the active Sun because they contain a large amount of the energy released during flares. Energetic electrons and ions interact with the solar atmosphere and produce high-energy X-rays and γ-rays. Energetic particles can also escape to the corona and interplanetary medium, produce radio emissions (electrons) and may eventually reach the Earth's orbit. I shall review here the available information on energetic particles provided by X-ray/γ-ray observations, with particular emphasis on the results obtained recently by the mission Reuven Ramaty High-Energy Solar Spectroscopic Imager. I shall also illustrate how radio observations contribute to our understanding of the electron acceleration sites and to our knowledge on the origin and propagation of energetic particles in the interplanetary medium. I shall finally briefly review some recent progress in the theories of particle acceleration in solar flares and comment on the still challenging issue of connecting particle acceleration processes to the topology of the complex magnetic structures present in the corona.


Effects of a Mindfulness-based Intervention on diurnal cortisol pattern in disadvantaged families: A randomized controlled trial.
The present study examined the psychophysiological effects of Family-based Mindfulness Intervention (FBMI) on children and parents from disadvantaged families. This randomized controlled trial recruited parents and their children from 51 disadvantaged families in Hong Kong and randomized them into FBMI (n = 26) and waitlist control (n = 25) groups. The parent intervention included 6 sessions and the child intervention included 8 sessions with 2 half-hour joint programs. Both interventions lasted 9 hours in total each. All participants completed four salivary cortisol measures after wakeup, before lunchtime, late-afternoon, and before sleep at baseline and end of the intervention. The diurnal cortisol pattern was summarized by the morning cortisol, evening cortisol, mean cortisol, and diurnal cortisol slope. Compared to the control group, children in the FBMI group showed significant increases in morning cortisol (d = 0.50, p = 0.03) and significant decreases in diurnal cortisol slopes (d = 0.50, p = 0.04) at the end of intervention. Parents in the FBMI group displayed significant decreases in evening cortisol (d = 0.50, p = 0.04) compared to the control group at the end of intervention. No significant treatment effects were found on the mean cortisol. The present findings suggest that FBMI could improve the diurnal cortisol slope and cortisol levels of the children and parents from disadvantaged families, respectively. Future studies should elucidate its potential benefits on neuroendocrine functioning.


The effect of GM-CSF (granulocyte macrophage colony stimulating factor) on doxorubicin induced tissue necrosis and wound healing.
The effect of GM-CSF (granulocyte macrophage-colony stimulating factor) on tissue necrosis and ulceration induced with doxorubicin extravasation was studied. Adult Wistar-Albino rats (n=36) were used in the study. Doxorubicin (0.4mg/300 g) was applied subcutaneously to abdominal wall. In group I (n=18), half hours after doxorubicin injection, GM-CSF 6 microg/300 mg was applied subcutaneously to the same localization. In group II (n = 18) same amount of physiologic saline (0.5 ml) were given subcutaneously to the injection site (as vehicle control groups). Group II and I were examined for induration or ulceration on 7th and 21st day. After evaluating the lesions, the injection sites were excised. Hydroxyproline (5-HP) values of dry tissue samples were calculated and histopathologic examination was done. At day seven there were four and eight ulceration in groups I and II, while there were four and 14 ulceration in the second evaluation at day 21st (p<0.05). 5-HP values of the groups were as follows. 97.43+/-20.39 in group land 91.34+/-22.26 in group II. Although there was an increase in epithelization, eosinophil and lymphocyte infiltration and mast cell number in group I in histopathologic examinations only the increase in angiogenesis in group I was found to be statistically significant (p<0.05). It can be concluded that GM-CSF may have beneficial effect in the treatment of doxorubicin induced tissue necrosis.


Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Second communication: distribution and elimination of the new monoclonal antibody, regavirumab after repeated administration in rats, and placental transfer and milk-passage study after single administration to pregnant and lactating rats.
TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The tissue distribution or pharmacokinetics of MCA C23 was investigated after repeated administration in male rats and single administration in pregnant and lactating rats. Radioactivity and MCA C23 idiotype activity (antigenicity against idiotype antibody) in plasma increased with weekly injections during repeated administration of 125I-labeled TI-23 (2 mg/kg/week). After the fourth injection, the plasma radioactivity concentration reached a steady state and the elimination half-life was determined to be 11.2 days. No significant difference was observed between the radioactivity and the idiotype activity in plasma, indicating that MCA C23 was stable in vivo. The plasma concentration curve after repeated administration corresponded with that simulated by the pharmacokinetic parameters obtained previously and the minimum steady state concentration (Css-min) at 168 h after repeated administration was about 33 micrograms eq. of MCA C23/ml. Trans-placental tissue distribution of radioactivity was investigated after single administration of 125I-TI-23 to 19-day pregnant rats. About 12% of the dose was transferred to the fetus and the idiotype activity remained in fetal tissues at 24 h after injection. In lactating rats, some radioactivity was secreted into the milk and the ratio of milk to plasma radioactivity reached 0.28 after a single administration of 125I-TI-23. Some MCA C23 idiotype activity was observed in the milk.


Looking Backwards to the Future: The WHO Haemoglobin Colour Scale.
The Haemoglobin Colour Scale was developed for WHO as a simple, cheap, pocket-sized device for providing a reading of haemoglobin within 1 g/dL of true value. It is intended for the clinician/health worker without easy access to a laboratory, and it thus has an important role in management of anaemia in peripheral health services, especially in under-resourced areas, as well as in antenatal and child health programmes, in screening blood donors and for point-of-care anaemia checks anywhere. An international validation trial and other studies have confirmed its reliabilty when tested against reference haemoglobinometry. It is much more reliable than clinical examination in assessing the severity of anaemia and it has advantages over copper sulphate in blood donor screening.


On the risk of aortic valve replacement surgery assessed by heart rate variability parameters.
In recent years the number of arterial stenosis (AS) patients has grown rapidly and valvular disease is expected to be the next great epidemic. We studied a group of 385 arterial valve replacement (AVR) surgery patients, of whom 16 had died in the postoperational period (up to 30 d after the operation). Each patient had a heart rate variability (HRV) recording made prior to the operation in addition to a full set of medical diagnostics including echocardiography. We formed 16 age, sex, New York Heart Association (NYHA) class, and BMI adjusted control pairs for each person who died in the perioperative period. Our aim was to find indications of the risk from AVR surgery based on the medical data and HRV properties. Besides standard, linear HRV methods, we used indexes of time irreversibility introduced by Guzik (G%), Porta (P%), Ehlers (index E) and Hou (index D). In addition, we analyzed the multiscale multifractal properties of HRV calculating the Hurst surface. The nonlinear analysis methods show statistically significant indications of the risk of AVR surgery in an increase of multifractality and an increase of time irreversibility of the HRV measured prior to the operation.


[Comparison of TK gene mutation assay in TK6 and TK6-E6 cell induced by vinblastin and colcemid].
To compare TK gene mutation assay in human lymphoblastoid cell lines TK6 and TK6-E6 induced by vinblastin and colcemid. Regular TK gene mutation assays were experimented to detect cytotoxicity and mutation frequency at tk locus after TK6 and TK6-E6 human lymphoblastoid cells were treated with vinblastin and colcemid for 24h. Relative survival (RS%) and Relative suspension growth (RSG%) of TK6 and TK6-E6 cells decreased when concentrations of vinblastin and colcemid increased. RS% and RSG% of TK6-E6 cells were higher than that of TK6 cells at the same doses. TK6 and TK6-E6 cells both were induced by vinblastin and colcemid. The TK6-E6's nature mutation frequency, induced mutation frequency and percentage of slow growth mutant (SG%) were lower than TK6' s at the same dose except group CCM 5.0ng/ml in MF and group CCM 0.625ng/ml in SC%. Both TK6 and TK6-E6 cell lines can be used in TK gene mutation assay, but TK6-E6 cell line was recommended to be used in the assay for its less quantity and doubling time.


Importance of MR technique for stereotactic radiosurgery.
We investigated how frequently the imaging procedure we use immediately prior to radiosurgery--triple-dose gadolinium-enhanced MR performed with the patient immobilized in a nonrelocatable head frame and 1-mm-thick MPRAGE (magnetization-prepared rapid gradient echo) images (SRS3xGado)-identifies previously unrecognized cerebral metastases in patients initially imaged by conventional MR with single-dose gadolinium (1xGado). Between July 1998 and July 2000, the diagnoses established for 47 patients who underwent radio-surgical procedures for treatment of cerebral metastases at The Gamma Knife Center of New York University were based initially on the 1xGado protocol. In July 1998, we began using SRS3xGado as our routine imaging protocol in preparation for targeting lesions for radio-surgery, using triple-dose gadolinium and acquisition of contiguous 1-mm Tl-weighted axial images. Because our SRS3xGado scans sometimes unexpectedly revealed additional metastases, we sought to learn how frequently the initial 1xGado scans would underestimate the number of metastases. We therefore reviewed the number of brain metastases identified on the SRS3xGado studies and compared the results to the number found by the 1xGado protocol, which had initially identified the brain metastases. Additional metastases, ranging from 1 to 23 lesions per patient, were identified on the SRS3xGado scan in 23 of 47 patients (49%). In 57% of the 23 patients, only one additional lesion was identified. The mean time interval between the 1xGado and the SRS3xGado scans was 20.6 days (range, 4-83 days), and the number of additional lesions detected and the time interval between two scans were negatively correlated (-0.11). The number of lesions detected on the SRS3xGado was associated only with the number of lesions on the 1xGado and not with any other patient or tumor pretreatment characteristics such as age, gender, largest tumor volume on the 1xGado, or number of days between the 1xGado and the SRS3xGado or prior surgery. The identification of additional lesions with SRS3xGado MR may have implications for patients who are treated with stereotactic radiosurgery alone (without whole-brain irradiation) with single-dose gadolinium imaging, in that unidentified lesions may go untreated. As a result of these findings we continue to use and advocate SRS3xGado scans for radiosurgery.


Effect of colostrum ingestion on gamma-glutamyltransferase and alkaline phosphatase activities in neonatal pups.
Analysis of hepatic enzyme activities in serum samples from 1- to 3-day-old pups revealed alkaline phosphatase (ALP) activities that were 30 times higher and gamma-glutamyltransferase (GGT) activities that were 100 times higher than activities in clinically normal adult dogs. A study was conducted to investigate high enzyme activity in pups and to determine whether there is any association between serum enzyme activity and colostrum ingestion, passive transfer of maternal serum enzyme (in colostrum or in utero), or excessive renal or hepatic tissue enzymes. Serum enzyme activity was quantified in 15 neonatal pups before and after ingestion of colostrum and in 3 colostrum-deprived neonates fed a milk substitute. Serum samples were collected on postpartum days 0, 1, 10, 15, and 30. Enzyme activity was also quantified in serum from pregnant and lactating bitches (collected on days -2, 0, 1, 10, 30), hepatic and renal tissue from clinically normal adult dogs and 1-day-old pups, colostrum, milk (collected on days 10 and 30), and milk replacer. Significant (P less than 0.01) differences in serum GGT and ALP activities between colostrum-deprived and suckling pups did not exist before initial feeding. Significant (P less than 0.001) increases in serum GGT and ALP activities developed within 24 hours in suckling pups, but not in the colostrum-deprived pups. At 10 and 30 days after birth, serum GGT and ALP activities were less than values before suckling in all pups. Enzyme activities in bitches' serum remained within the normal range for adult dogs throughout whelping and lactation.(ABSTRACT TRUNCATED AT 250 WORDS)


Nail changes in connective tissue diseases: a study of 39 cases.
The objective is to identify nail unit changes associated with connective tissue diseases (CTD) and evaluate their frequency. We carried a prospective study between March 2012 and March2013 in our department. All patients with CTD were included. A clinical examination of the fingernails was done by the same dermatologist. Nail features were noted and classified and photos taken. Thirty nine patients were enrolled including: 16 systemic sclerosis, 14 lupus erythematosus (SLE), 8 dermatomyositis (DM), 1 primary Sjorgen's syndrome. The mean age was 40 years old. The mean duration of the disease was 6 years. Nail unit changes were present in 27 patients (69%). The abnormalities observed were Longitidunal ridging in 11 patients, Peri ungueal erythema in 10 patients, Peri-ungual telangiectasia in 11 patients, Ragged cuticle in 10 patients fingertips scars in 9 patients, Increase of longitudinal curvature and beaking of the nail in 4 patients, Increase in transverse curvature in 4 patients, dyschromia of the proximal nail fold in 3 patients, Subungual hyperkeratosis in 3 patients, onycholysis in 2 patients, splinter haemorrhages in 3 patients, nail plate pigmentation in 2 patients, pseudoclubbing in 1 patient, macrolunula in 1 patients, Red lunulae in one patient, bluish-black discoloration of the nail plate in one patient. The proximal nailfold was found to be most sites affected.


Serum estradiol as an aid in the diagnosis of ectopic pregnancy.
The value of serum beta-hCG measurement in the diagnosis of ectopic pregnancy is well established, and there have been recent studies on the use of serum progesterone levels. However, we have been unable to find any reports on the potential application of serum estradiol (E2) assays in the diagnosis of ectopic pregnancy. We therefore concurrently measured serum E2, progesterone, and beta-hCG in 100 women with ectopic pregnancies, as well as in 69 controls with normal intrauterine pregnancies and 36 women with threatened abortion. The mean (+/- standard deviation) E2 levels for ectopic-pregnancy patients, the normal controls, and the women with threatened abortion were 281.1 +/- 115.6, 788.2 +/- 45.5, and 788.8 +/- 40.6 pg/mL, respectively; the mean levels in the ectopic group were significantly different (P less than .0001) from those of the other two groups. All but one of the ectopic pregnancies had values below 650 pg/mL for E2 and 23 ng/mL for progesterone, and all but one of the normal intrauterine pregnancies had values above these levels. Our data suggest that the addition of the estradiol assay, with or without progesterone, to the early evaluation of patients suspected of having an ectopic pregnancy may be helpful in diagnosis.


Cylindroma: an update.
This paper reviews the recent literature on cylindroma, a rare tumor originating from the cutaneous adnexal structures of the scalp and face. Benign cylindroma is more frequent in women, and there are solitary and multiple forms, which are autosomal. Malignant cylindroma can occur in the Brooke-Spiegler syndrome, and malignant transformation is more frequent in multiple variants than in solitary tumors. Its histopathological basis is controversial, and its origin is unknown, although it is known that there is a genetic basis for onset of these tumors in Brooke-Spiegler syndrome.


Attachment impacts cortisol awakening response in chronically depressed individuals.
Early life experiences shape individual attachment, creating a template for regulating emotions in interpersonal situations, likely to persist across the lifespan. Research has shown that individual attachment creates vulnerability for depression, and also impacts the Hypothalamic-Pituitary-Adrenal (HPA) axis. Still, the relationship between attachment and the HPA axis in depressed individuals is unclear. Cortisol awakening response (CAR) has been recently investigated as a possibly useful physiological marker related to attachment insecurity and depression risk. However, research exploring the relationship between the CAR and attachment in individuals with chronic depression in either the presence or the absence of comorbid anxiety is lacking. The purpose of the current study was to fill this gap, by comparing the CAR in individuals with chronic depression with/without comorbid anxieties and controls. In addition, we also wanted to explore the relationship between attachment and the CAR in this group and to explore their predictive role for later depression severity. Individuals experiencing a current depressive episode at least six months in length (cMDD; n = 63) and healthy controls (HC; n = 57) were enrolled in the study (total n = 120). Participants completed a structured clinical diagnostic interview (SCID-I) as well as measures of depression severity (Beck Depression Inventory-II (BDI-II) and Hamilton Rating Scale for Depression) and attachment dimensions (Experiences in Close Relationships scale; ECR) at baseline. In addition, participants provided salivary samples at four time points (i.e. 0 (S1), 30, 45 and 60 min) following awakening on two consecutive days. S1 cortisol, the area under the curve with respect to ground (AUCg) and increase (AUCi) were calculated based on the average values across both days. The HC and cMDD groups were compared on all measures. The CAR for individuals with cMDD alone (n = 14) and individuals with cMDD with two or more comorbid anxiety disorders (cMDD ≥ 2Anx; n = 30) were also compared. A subset of participants (n = 59) agreed to return for follow up one year later. Participants returning for follow up repeated the BDI-II and ECR. No salivary samples were collected at follow-up. The cMDD group had significantly lower S1 cortisol and AUCg compared to the HC group (both p ≤ 0.02). cMDD and cMDD ≥ 2Anx groups did not differ in their CAR. Regression analyses revealed that depression severity and the attachment interaction term was associated with lower S1 and AUCg cortisol (p < 0.01). Greater attachment avoidance was positively associated with S1 cortisol (p = 0.02), while mean awakening time on sample days was negatively associated with S1 cortisol. We also found a significant interaction between the attachment dimensions such that at low levels of attachment anxiety, attachment avoidance had a positive relationship with S1 cortisol and AUCg. The opposite relationship existed when attachment anxiety was high. Higher baseline BDI-II score and higher baseline attachment anxiety were predictive of higher scores on the BDI-II one-year later (both p < 0.05). The current findings bring evidence that depression severity is associated with blunting of the CAR irrespective of the comorbid status with anxiety disorders. In addition, attachment avoidance may protect against the CAR blunting in individuals with low attachment anxiety. However, individuals with high attachment anxiety and avoidance might have additional CAR blunting. Attachment anxiety might be a good predictor of future depression severity.


Identity and function of a cardiac mitochondrial small conductance Ca2+-activated K+ channel splice variant.
We provide evidence for location and function of a small conductance, Ca2+-activated K+ (SKCa) channel isoform 3 (SK3) in mitochondria (m) of guinea pig, rat and human ventricular myocytes. SKCa agonists protected isolated hearts and mitochondria against ischemia/reperfusion (IR) injury; SKCa antagonists worsened IR injury. Intravenous infusion of a SKCa channel agonist/antagonist, respectively, in intact rats was effective in reducing/enhancing regional infarct size induced by coronary artery occlusion. Localization of SK3 in mitochondria was evidenced by Western blot of inner mitochondrial membrane, immunocytochemical staining of cardiomyocytes, and immunogold labeling of isolated mitochondria. We identified a SK3 splice variant in guinea pig (SK3.1, aka SK3a) and human ventricular cells (SK3.2) by amplifying mRNA, and show mitochondrial expression in mouse atrial tumor cells (HL-1) by transfection with full length and truncated SK3.1 protein. We found that the N-terminus is not required for mitochondrial trafficking but the C-terminus beyond the Ca2+ calmodulin binding domain is required for Ca2+ sensing to induce mK+ influx and/or promote mitochondrial localization. In isolated guinea pig mitochondria and in SK3 overexpressed HL-1 cells, mK+ influx was driven by adding CaCl2. Moreover, there was a greater fall in membrane potential (ΔΨm), and enhanced cell death with simulated cell injury after silencing SK3.1 with siRNA. Although SKCa channel opening protects the heart and mitochondria against IR injury, the mechanism for favorable bioenergetics effects resulting from SKCa channel opening remains unclear. SKCa channels could play an essential role in restraining cardiac mitochondria from inducing oxidative stress-induced injury resulting from mCa2+ overload.


High rate of mutation reporter gene inactivation during human T cell proliferation.
Caspase activation and degradation of deoxyribonucleic acid (DNA) damage response factors occur during in vitro T-cell proliferation, and an increased frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT)-negative variants have been reported in conditions associated with in vivo T-cell proliferation. We have applied two human somatic cell mutation reporter assays, for the HPRT and phosphatidylinositol glycan class A (PIG-A) genes, to human T cells activated in vitro with anti-CD3 and anti-CD28. We demonstrate proliferation throughout 6 weeks of cultivation, and find that the frequency of variant cells phenotypically negative for HPRT and PIG-A, respectively, increases from 10(-5) up to 10(-3) -10(-2). We also report preliminary evidence for low-density CpG methylation in the HPRT promoter suggesting that epigenetic modification may contribute to this markedly heightened rate of gene inactivation.


Training vs practice: A tale of opposition in acute cholecystitis.
Acute cholecystitis is one of the most common surgical diagnoses encountered by general surgeons. Despite its high incidence there remains a range of treatment of approaches. Current practices in biliary surgery vary as to timing, intraoperative utilization of biliary imaging, and management of bile duct stones despite growing evidence in the literature defining best practice. Management of patients with acute cholecystitis with early laparoscopic cholecystectomy (LC) results in better patient outcomes when compared with delayed surgical management techniques including antibiotic therapy or percutaneous cholecystostomy. Regardless of this data, many surgeons still prefer to utilize antibiotic therapy and complete an interval LC to manage acute cholecystitis. The use of intraoperative biliary imaging by cholangiogram or laparoscopic ultrasound has been demonstrated to facilitate the safe completion of cholecystectomy, minimizing the risk for inadvertent injury to surrounding structures, and lowering conversion rates, however it is rarely utilized. Choledocholithiasis used to be a diagnosis managed exclusively by surgeons but current practice favors referral to gastroenterologists for performance of preoperative endoscopic removal. Yet, there is evidence that intraoperative laparoscopic stone extraction is safe, feasible and may have added advantages. This review aims to highlight the differences between existing management of acute cholecystitis and evidence supported in the literature regarding best practice with the goal to change surgical practice to adopt these current recommendations.


Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires.
Molecular wires comprising a Ru(II)- or Re(I)-complex head group, an aromatic tail group, and an alkane linker reversibly inhibit the activity of the copper amine oxidase from Arthrobacter globiformis (AGAO), with K(i) values between 6 muM and 37 nM. In the crystal structure of a Ru(II)-wire:AGAO conjugate, the wire occupies the AGAO active-site substrate access channel, the trihydroxyphenylalanine quinone cofactor is ordered in the "off-Cu" position with its reactive carbonyl oriented toward the inhibitor, and the "gate" residue, Tyr-296, is in the "open" position. Head groups, tail-group substituents, and linker lengths all influence wire-binding interactions with the enzyme.


Anti-IgLON5 Encephalopathy with Concomitant Herpes Virus Encephalitis.
Anti-IgLON5 encephalopathy is a new and rare autoimmune encephalitis with unclear pathophysiology. In this study, we reported an unusual case of anti-IgLON5 encephalopathy with concomitant herpes virus encephalitis. A 51-year-old man with HLA-DQB1*05:01 and HLA-DRB1*10:01, who suffered from an episode of acute encephalitis, mental disorders, and memory impairment was admitted to our hospital. Human alpha herpes virus 1, human gamma herpes virus 4 (Epstein-Barr virus), and IgLON5-IgG were detected in the cerebrospinal fluid, indicating anti-IgLON5 encephalopathy with concomitant herpes virus encephalitis of this patient. Brain magnetic resonance imaging revealed T2 hyperintensities in the left temporal lobe and enhancement in the hippocampus. A mild sleep disorder was also found by video polysomnography. The patient was then treated with antiviral drugs, intravenous immunoglobulins, methylprednisolone, and protein A immunoadsorption. After treatment, the patient's clinical symptoms were partially improved. This is the first reported case of anti-IgLON5 encephalopathy with concomitant herpes virus encephalitis.


The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component.
Biosynthesis of glycosylphosphatidylinositol (GPI) is initiated by an unusually complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six proteins. Here, we report that human GPI-GnT requires another component, termed PIG-Y, a 71 amino acid protein with two transmembrane domains. The Burkitt lymphoma cell line Daudi, severely defective in the surface expression of GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components was formed without PIG-Y. PIG-Y appeared to be directly associated with PIG-A, implying that PIG-Y is the key molecule that regulates GPI-GnT activity by binding directly to the catalytic subunit PIG-A. PIG-Y is probably homologous to yeast Eri1p, a component of GPI-GnT. We did not obtain evidence for a functional linkage between GPI-GnT and ras GTPases in mammalian cells as has been reported for yeast cells. A single transcript encoded PIG-Y and, to its 5' side, another protein PreY that has homologues in a wide range of organisms and is characterized by a conserved domain termed DUF343. These two proteins are translated from one mRNA by leaky scanning of the PreY initiation site.


A multicenter study using causal readings, self-recordings, and ambulatory blood pressure monitoring to assess isradipine effects. AMICUS Study Group.
The antihypertensive efficacy of isradipine has been widely studied. In most studies, however, blood pressure values were assessed by causal readings (CR) only. Furthermore, whether or not such blood pressure readings are sufficient proof of efficacy is still under discussion. Thus, a multicenter study was devised wherein blood pressure were recorded by CR, self-recordings, and noninvasive ambulatory monitoring (ABM). A total of 595 patients with mild-to-moderate hypertension were treated for 6 months starting with 1.25 mg of isradipine twice daily. If, after 4 weeks of treatment, CR-determined diastolic blood pressure (DBP) was still > 90 mm Hg, this dosage was doubled (n = 327) and, at week 8, pindolol at 5 mg or spirapril at 3 mg daily was added if necessary for blood pressure control. On the basis of CR, the results confirmed that low dosages of isradipine twice daily are safe and effective in the treatment of mild-to-moderate hypertension. The mean decrease in CR-determined blood pressure was 28.5/19.0 mm Hg at week 24, and the normalization rate (DBP < or = 90 mm Hg) for all patients treated was 78.2%. However, SR-determined blood pressure reduction was 20.0/13.0 mm Hg, with a normalization rate of 42%, whereas ABM-determined blood pressure reduction was 7.0/4.2 mm Hg. On the basis of ABM recordings, 66% of the patients had a DBP < 90 mm Hg on entry into the study and their blood pressures did not decrease with treatment. Thus, it appears that CR-determined blood pressures bias study results by including normotensives and thereby overestimating efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study.
The pathologic features of a prospective study of FIGO stage I endometrial cancer is presented. The uterus, tubes, ovaries, and pelvic lymph nodes of 222 cases and aortic nodes of 157 cases have been analyzed. The surgical-pathologic specimen would suggest a negligible risk for lymph node metastasis if: cancer is confined to the endometrium irrespective of grade, invasion is superficial for grades 1 and 2 tumor, the intermediate third of the myometrium is invaded for grade 1 tumor only, and occult disease is not present in the cervix and/or adnexa. Conversely, a substantial risk for lymph node metastasis exists if the surgical-pathologic study identifies superficial myometrial invasion by grade 3 cancer, intermediate myometrial invasion by grade 2 or 3 cancer, deep myometrial invasion by cancer of any grade, vascular space involvement, and extension of tumor to the cervix and/or adnexa.