Online Density Estimation of Nonstationary Sources Using Exponential Family of Distributions.
We investigate online probability density estimation (or learning) of nonstationary (and memoryless) sources using exponential family of distributions. To this end, we introduce a truly sequential algorithm that achieves Hannan-consistent log-loss regret performance against true probability distribution without requiring any information about the observation sequence (e.g., the time horizon $T$ and the drift of the underlying distribution $C$ ) to optimize its parameters. Our results are guaranteed to hold in an individual sequence manner. Our log-loss performance with respect to the true probability density has regret bounds of $O(({CT})^{1/2})$ , where $C$ is the total change (drift) in the natural parameters of the underlying distribution. To achieve this, we design a variety of probability density estimators with exponentially quantized learning rates and merge them with a mixture-of-experts notion. Hence, we achieve this square-root regret with computational complexity only logarithmic in the time horizon. Thus, our algorithm can be efficiently used in big data applications. Apart from the regret bounds, through synthetic and real-life experiments, we demonstrate substantial performance gains with respect to the state-of-the-art probability density estimation algorithms in the literature.


Partitioning of resources: the evolutionary genetics of sexual conflict over resource acquisition and allocation.
Fitness depends on both the resources that individuals acquire and the allocation of those resources to traits that influence survival and reproduction. Optimal resource allocation differs between females and males as a consequence of their fundamentally different reproductive strategies. However, because most traits have a common genetic basis between the sexes, conflicting selection between the sexes over resource allocation can constrain the evolution of optimal allocation within each sex, and generate trade-offs for fitness between them (i.e. 'sexual antagonism' or 'intralocus sexual conflict'). The theory of resource acquisition and allocation provides an influential framework for linking genetic variation in acquisition and allocation to empirical evidence of trade-offs between distinct life-history traits. However, these models have not considered the emergence of trade-offs within the context of sexual dimorphism, where they are expected to be particularly common. Here, we extend acquisition-allocation theory and develop a quantitative genetic framework for predicting genetically based trade-offs between life-history traits within sexes and between female and male fitness. Our models demonstrate that empirically measurable evidence of sexually antagonistic fitness variation should depend upon three interacting factors that may vary between populations: (1) the genetic variances and between-sex covariances for resource acquisition and allocation traits, (2) condition-dependent expression of resource allocation traits and (3) sex differences in selection on the allocation of resource to different fitness components.


Carbenoid chain reactions: substitutions by organolithium compounds at unactivated 1-chloro-1-alkenes.
The deceptively simple "cross-coupling" reactions Alk(2)C=CA-Cl + RLi --> Alk(2)C=CA-R + LiCl (A = H, D, or Cl) occur via an alkylidenecarbenoid chain mechanism in three steps without a transition metal catalyst. In the initiating step 1, the sterically shielded 2-(chloromethylidene)-1,1,3,3-tetramethylindans 2a-c (Alk(2)C=CA-Cl) generate a Cl,Li-alkylidenecarbenoid (Alk(2)C=CLi-Cl, 6) through the transfer of atom A to RLi (methyllithium, n-butyllithium, or aryllithium). The chain cycle consists of the following two steps: (i) A fast vinylic substitution reaction of these RLi at carbenoid 6 (step 2) with formation of the chain carrier Alk(2)C=CLi-R (8), and (ii) a rate-limiting transfer of atom A (step 3) from reagent 2 to the chain carrier 8 with formation of the product Alk(2)C=CA-R (4) and with regeneration of carbenoid 6. This chain propagation step 3 was sufficiently slow to allow steady-state concentrations of Alk(2)C=CLi-Aryl to be observed (by NMR) with RLi = C6H5Li (in Et2O) and with 4-(Me3Si)C6H4Li (in t-BuOMe), whereas these chain processes were much faster in THF solution. PhC[triple bond]CLi cannot perform step 1, but its carbenoid chain processes with reagents 2a and 2c may be started with MeLi, whereafter LiC[triple bond]CPh reacts faster than MeLi in the product-determining step 2 to generate the chain carrier Alk(2)C=CLi-C[triple bond]CPh (8g), which completes its chain cycle through the slower step 3. The sterically congested products were formed with surprising ease even with RLi as bulky as 2,6-dimethylphenyllithium and 2,4,6-tri-tert-butylphenyllithium.


Noninflammatory renal microangiopathy of systemic lupus erythematosus ('lupus vasculitis').
5 (group 1) of 9 patients with systemic lupus erythematosus (SLE) who underwent a kidney biopsy during a 1-year period had a noninflammatory renal microangiopathy which significantly narrowed or occluded the lumens of arterioles and terminal segments of interlobular arteries. Though these lesions resemble those of malignant hypertension and the thrombotic microangiopathies, their distinctive features, revealed by light, immunofluorescence and electron microscopy, differentiate them from the others. 4 of these 5 (group 1) patients developed hypertension; in 3 the microangiopathy predated the hypertension. None of the remaining 4 (group 2) patients without these lesions has become hypertensive. One group-1 patient with extensive lesions involving 40% of intrarenal arterioles at biopsy developed renal failure shortly thereafter with increasing arteriolar involvement but unchanged glomerular histology.


PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.
Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.


T cell epitopes of SARS-CoV-2 spike protein and conserved surface protein of Plasmodium malariae share sequence homology.
Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading remarkably fast worldwide. Effective countermeasures require the rapid development of data and tools to monitor its spread and better understand immunogenic profile. However, limited information is available about the tools and target of the immune responses to SARS-CoV-2. In this study, we excogitated a new approach for analyzing phylogenetic relationships by using the whole prototype proteome sequences. Phylogenetic analysis on the whole prototype proteome sequences showed that SARS-CoV-2 was a direct descendant of Bat-CoV and was closely related to Pangolin-CoV, Bat-SL-CoV, and SARS-CoV. The pairwise comparison of SARS-CoV-2 with Bat-CoV showed an unusual replacement of the motif consisting of seven amino acids (NNLDSKV) within the spike protein of SARS-CoV-2. The replaced motif in the spike protein of SARS-CoV-2 was found in 12 other species, including a conserved surface protein of a malaria-causing pathogen, Plasmodium malariae. We further identified the T and B cell epitope sequence homology of SARS-CoV-2 spike protein with conserved surface protein of P. malariae using the Immune Epitope Database and Analysis Resource (IEDB). The shared immunodominant epitopes may provide immunity against SARS-CoV-2 infection to those previously infected with P. malariae.


Multiple Stimuli-Responsive Conformational Exchanges of Biphen[3]arene Macrocycle.
Conformational exchanges of synthetic macrocyclic acceptors are rather fast, which is rarely studied in the absence of guests. Here, we report multiple stimuli-responsive conformational exchanges between two preexisting conformations of 2,2',4,4'-tetramethoxyl biphen[3]arene (MeBP3) macrocycle. Structures of these two conformations are both observed in solid state, and characterized by 1H NMR, 13C NMR and 2D NMR in solution. In particular, conformational exchanges can respond to solvents, temperatures, guest binding and acid/base addition. The current system may have a role to play in the construction of molecular switches and other stimuli-responsive systems.


NH3 as simple clathrate-hydrate catalyst: Experiment and theory.
The catalytic action of NH3 within the all-vapor approach for instant clathrate hydrate (CH) formation is studied using both FTIR spectroscopy and ab initio molecular dynamics simulations. A unique property of NH3, namely, the rapid abundant penetration and occupation of the water network, creates defects, particularly Bjerrum D-defects, in the hydrate frame that are generally stabilized by guest NH3 molecules in the cages. Furthermore, insertion of NH3 seriously disturbs the hydrate network where the guest NH3 molecules also make fluxional H-bonds with the host water molecules. These defects strongly facilitate a sub-second formation of the simple NH3 s-II gas hydrate at 160 K. FTIR spectra of aerosols of the NH3 s-II CH have been measured, and the displacement of both small and large cage NH3 guests by CO2 and tetrahydrofuran is examined.


Spinal subarachnoid hematoma complicating lumbar puncture: diagnosis and management.
Two patients with altered hemostatic mechanisms developed spinal subarachnoid hemorrhage after difficult lumbar punctures. One patient had received anticoagulation therapy soon after lumbar puncture and the other had a low platelet count (63,000/mm3) at the time of lumbar puncture. In both patients a hematoma evolved, producing blockage of cerebrospinal fluid flow. Clinical manifestations consisted of severe back and radicular pain with sphincteric disturbances followed by rapidly developing severe paraparesis. Of the methods of radiographic evaluation that were used, including computed tomography (CT) without contrast enhancement, myelography, CT with intrathecally administered contrast medium, and magnetic resonance imaging, we found the best study to be myelography via lateral cervical puncture followed by CT. Unfortunately, diagnosis was delayed, and surgical evacuation of the hematomas did not substantially improve the patients' conditions. The salient clinical and radiographic features of this disorder and its pathophysiology are reviewed. Prompt recognition of these lesions is necessary so that surgical intervention may maximize chances of recovery.


[A Case of Breast Nodular Fasciitis Needed to Differentiate from Borderline Phyllodes Tumor].
A 28-year-old woman realized a left breast tumor. Mammography and ultrasonography revealed focal asymmetric density on the MI area(category 3)and a low-echoic 10 mm tumor with unclear boundaries. We performed an US-guided breast biopsy to confirm the diagnosis. The histopathological examination result suspected nodular fasciitis; however, borderline phyllodes tumor cannot be denied. Tumorectomy was performed under general anesthesia. The final histopathological examination revealed nodular fasciitis due to amplifying fibroblasts with irregular directions. Nodular fasciitis is a benign lesion and sometimes disappears spontaneously. Tumorectomy is often needed to confirm the diagnosis that cannot be identified by needle biopsy. We report a case of breast nodular fasciitis needed to differentiate from borderline phyllodes tumor.


4-[Bis(4-fluorophenyl)methyl]piperazin-1-ium picrate.
The title compound {systematic name: 4-[bis(4-fluorophenyl)methyl]piperazin-1-ium 2,4,6-tri-nitro-phenolate}, C(17)H(19)F(2)N(2) (+)·C(6)H(2)N(3)O(7) (-), is the picrate salt of a piperazine-supported amine bearing a benzhydryl substituent on one of its N atoms. During co-crystallisation, protonation took place on the N atom of the secondary amine functionality. The non-aromatic six-membered heterocycle adopts a chair conformation. In the crystal, N-H⋯O hydrogen bonds as well as C-H⋯O contacts connect the components into a three-dimensional network.


Machine Vision Automated Chiral Molecule Detection and Classification in Molecular Imaging.
Scanning probe microscopy (SPM) is recognized as an essential characterization tool in a broad range of applications, allowing for real-space atomic imaging of solid surfaces, nanomaterials, and molecular systems. Recently, the imaging of chiral molecular nanostructures via SPM has become a matter of increased scientific and technological interest due to their imminent use as functional platforms in a wide scope of applications, including nonlinear chiroptics, enantioselective catalysis, and enantiospecific sensing. Due to the time-consuming and error-prone image analysis process, a highly efficient analytic framework capable of identifying complex chiral patterns in SPM images is needed. Here, we adopted a state-of-the-art machine vision algorithm to develop a one-image-one-system deep learning framework for the analysis of SPM images. To demonstrate its accuracy and versatility, we employed it to determine the chirality of the molecules comprising two supramolecular self-assemblies with two distinct chiral organization patterns. Our framework accurately detected the position and labeled the chirality of each molecule. This framework underpins the tremendous potential of machine learning algorithms for the automated recognition of complex SPM image patterns in a wide range of research disciplines.


Beta-carotene and cancer prevention: what is the evidence?
A growing body of literature supports a possible role for beta-carotene in the prevention of human cancer. The most scientifically rigorous method for testing the hypothesis that beta-carotene has chemopreventive properties is with intervention trials, several of which are ongoing or soon to be initiated. Connecticut will be actively involved in three of these trials. This article reviews and critically evaluates the evidence supporting a role for beta-carotene in the prevention of human cancer, including animal studies, cell culture studies, epidemiologic studies, and intervention trials, and concludes with a brief description of chemoprevention research involving beta-carotene in Connecticut.


Local inhibition of GABA affects precedence effect in the inferior colliculus.
The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid (GABA). We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions: no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-aminobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.


Oxidation of dimethyl sulfide to dimethyl sulfoxide by phototrophic purple bacteria.
Enrichment cultures of phototrophic purple bacteria rapidly oxidized up to 10 mM dimethyl sulfide (DMS) to dimethyl sulfoxide (DMSO). DMSO was qualitatively identified by proton nuclear magnetic resonance. By using a biological assay, DMSO was always quantitatively recovered from the culture media. DMS oxidation was not detected in cultures incubated in the dark, and it was slow in cultures exposed to full daylight. Under optimal conditions, the second-order rate constant for DMS oxidation was 6 day mg of protein ml. The rate constant was reduced in the presence of high concentration of sulfide (>1 mM), but was not affected by the addition of acetate. DMS was also oxidized to DMSO by a pure strain (tentatively identified as a Thiocystis sp.) isolated from the enrichment cultures. DMS supported growth of the enrichment cultures and of the pure strain by serving as an electron source for photosynthesis. A determination of the amount of protein produced in the cultures and an estimation of the electron balance suggested that the two electrons liberated during the oxidation of DMS to DMSO were quantitatively used to reduce carbon dioxide to biomass. The oxidation of DMS by phototrophic purple bacteria may be an important source of DMSO detected in anaerobic ponds and marshes.


Diffuse reflectance spectrophotometry with visible light: comparison of four different methods in a tissue phantom.
The purpose of the study was to compare algorithms of four methods (plus two modifications) for spectrophotometric haemoglobin saturation measurements. Comparison was made in tissue phantoms basically consisting of a phosphate buffer, Intralipid and blood, allowing samples to be taken for reference measurements. Three experimental series were made. In experiment A (eight phantoms) we used the Knoefel method and measured specific extinction coefficients with a reflection spectrophotometer. In experiment B (six phantoms) the fully oxygenated phantoms were gradually deoxygenated with baker's yeast, and simultaneous measurements were made with our spectrophotometer and with a reference oxymeter (ABL-605) in 3 min intervals. For each spectrophotometric measurement haemoglobin saturation was calculated with all algorithms and modifications, and compared with reference. In experiment C (11 phantoms) we evaluated the ability of a modification of the Knoefel method to measure haemoglobin concentration in absolute quantities using extinction coefficients from experiment A.Results. Experiment A: with the Knoefel method extinction coefficients (+/-SD) for oxyhaemoglobin at 553.04 and 573.75 nm were 1.117 (+/-0.0396) ODmM(-1) and 1.680 (+/- 0.0815) ODmM(-1), respectively, and for deoxyhaemoglobin 1.205 (+/- 0.0514) ODmM(-1) and 0.953 (+/-0.0487) ODmM(-1), respectively. Experiment B: high correlation with the reference was found in all methods (r = 0.94-0.97). However, agreement varied from evidently wrong in method 3 and the original method 4 (e.g. saturation above 160%) to high agreement in method 2 as well as the modifications of methods 1 and 4, where oxygen dissociation curves were close to the reference method. Experiment C: with the modified Knoefel method the mean haemoglobin concentration difference from reference was 8.3% and the correlation was high (r = 0.91). We conclude that method 2 and the modifications of 1 and 4 were superior to the others, but depended on known values in the same or similar phantoms. The original method 1 was independent of results from the tissue phantoms, but agreement was slightly poorer. Method 3 and the original method 4 could not be recommended. The ability of the modified method 1 to measure haemoglobin concentration is promising, but needs further development.


ATR-FTIR Biosensors for Antibody Detection and Analysis.
Quality control of drug products is of paramount importance in the pharmaceutical world. It ensures product safety, efficiency, and consistency. In the case of complex biomolecules such as therapeutic proteins, small variations in bioprocess parameters can induce substantial variations in terms of structure, impacting the drug product quality. Conditions for obtaining highly reproducible grafting of 11-mercaptoundecanoic acid were determined. On that basis, we developed an easy-to-use, cost effective, and timesaving biosensor based on ATR-FTIR spectroscopy able to detect immunoglobulins during their production. A germanium crystal, used as an internal reflection element (IRE) for FTIR spectroscopy, was covalently coated with immunoglobulin-binding proteins. This thereby functionalized surface could bind only immunoglobulins present in complex media such as culture media or biopharmaceutical products. The potential subsequent analysis of their structure by ATR-FTIR spectroscopy makes this biosensor a powerful tool to monitor the production of biotherapeutics and assess important critical quality attributes (CQAs) such as high-order structure and aggregation level.


[Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia].
To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI). A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO15) and Shen (CO10) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain. After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01). taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.


88 W 0.5 mJ femtosecond laser pulses from two coherently combined fiber amplifiers.
The generation of 0.5 mJ femtosecond laser pulses by coherent combining of two high power high energy fiber chirped-pulse amplifiers is reported. The system is running at a repetition frequency of 175 kHz producing 88 W of average power after the compressor unit. Polarizing beam splitters have been used to realize an amplifying Mach-Zehnder interferometer, which has been stabilized with a Hänsch-Couillaud measurement system. The stabilized system possesses a measured residual rms phase difference fluctuation between the two branches as low as λ/70 rad at the maximum power level. The experiment proves that coherent addition of femtosecond fiber lasers can be efficiently and reliably performed at high B-integral and considerable thermal load in the individual amplifiers.


Local transmission of Plasmodium vivax malaria--Virginia, 2002.
Malaria transmission in the United States was largely eliminated during the mid-20th century; however, sporadic cases of locally acquired mosquito-transmitted malaria continue to occur. Since 1997, four separate probable mosquito-transmitted malaria outbreaks have been reported to CDC, including one from Virginia. This report describes the investigation of two cases of Plasmodium vivax malaria that occurred in northern Virginia in August 2002, and underscores the need for clinicians to consider the possibility of malaria in patients with fever of unknown origin.


Evidence of leptin expression in normal and polycystic human ovaries.
Leptin, the 'obese' protein, is found in cultured granulosa cells derived from human pre-ovulatory follicles. However, the occurrence of leptin has not been studied in intact ovaries, either normal or polycystic, until now. Paraffin sections from 25 human ovaries of different cycle stages and 25 wedge resections of polycystic ovaries were investigated by means of immunochemistry. Additionally, three ovaries were available for reverse transcription-polymerase chain reaction analysis. Leptin-positive cells were located in the granulosa cells of pre-antral follicles, and distinctly in the thecal layer of intact and regressing antral follicles. In the corpus luteum (CL) in the developmental stage, the former epithelioid leptin-positive thecal cells became fibroblast-like in the septum. In the CL of the secretory stage, single leptin-positive cells were detected between luteal cells. In polycystic ovaries, leptin-positive cells were noted both in the hypertrophied thecal layer and in the luteinized granulosa layer. Our findings on leptin expression at the protein level were confirmed by a positive mRNA signal for leptin in granulosa cells and in the CL. Additionally, mRNA of the full-length leptin receptor OB-R and of the short isoforms B219.1-B219.3 was identified in granulosa cells and the CL, as well as in the cortex and medulla. We conclude that leptin is produced in the ovary and may act in autocrine and paracrine ways.


A novel germ line-specific gene of the phosducin-like protein (PhLP) family. A meiotic function conserved from yeast to mice.
We identified a new member of the phosducin-like (PhLP) protein family that is predominantly, if not exclusively, expressed in male and female germ cells. In situ analysis on testis sections and analysis of purified spermatogenic cell fractions evidenced a stage-specific expression with high levels of RNA and protein in pachytene spermatocytes and round spermatids. Three mRNA species were detected, which correspond to different polyadenylation sites and vary in abundance during germ cell maturation. Only low levels of RNA were detected in whole ovary extracts, but expression of the protein became detectable within hours after hormonal induction of superovulation. The gene (Mgcphlp) is located on mouse chromosome 5 in the immediate vicinity of the Clock locus. The predicted amino acid sequence shows extensive similarities not only with the known mammalian PhLP proteins but also with the yeast phosducin-like protein Plp2, required for the production and growth of haploid cells. Expression of the murine protein was found to complement the defect of a yeast plp2 Delta mutant. We propose that MgcPhLP/Plp2 proteins exert a function in germ cell maturation that is conserved from yeast to mammals.


Canine epilepsy genetics.
There has been much interest in utilizing the dog as a genetic model for common human diseases. Both dogs and humans suffer from naturally occurring epilepsies that share many clinical characteristics. Investigations of inherited human epilepsies have led to the discovery of several mutated genes involved in this disease; however, the vast majority of human epilepsies remain unexplained. Mouse models of epilepsy exist, including single-gene spontaneous and knockout models, but, similar to humans, other, polygenic models have been more difficult to discern. This appears to also be the case in canine epilepsy genetics. There are two forms of canine epilepsies for which gene mutations have been described to date: the progressive myoclonic epilepsies (PMEs) and idiopathic epilepsy (IE). Gene discovery in the PMEs has been more successful, with eight known genes; six of these are orthologous to corresponding human disorders, while two are novel genes that can now be used as candidates for human studies. Only one IE gene has been described in dogs, an LGI2 mutation in Lagotto Romagnolos with a focal, juvenile remitting epilepsy. This gene is also a novel candidate for human remitting childhood epilepsy studies. The majority of studies of dog breeds with IE, however, have either failed to identify any genes or loci of interest, or, as in complex mouse and human IEs, have identified multiple QTLs. There is still tremendous promise in the ongoing canine epilepsy studies, but if canine IEs prove to be as genetically complex as human and murine IEs, then deciphering the bases of these canine epilepsies will continue to be challenging.


A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements.
Many members of the SWI2/SNF2 family of adenosine triphosphatases participate in the assembly/disassembly of multiprotein complexes involved in the DNA metabolic processes of transcription, recombination, repair, and chromatin remodeling. The DNA molecule serves as an essential effector or catalyst for most of the members of this particular class of proteins, and the structure of the DNA may be more important than the nucleotide sequence. Inspection of the DNA structure at sites where multiprotein complexes are assembled/disassembled for these various DNA metabolic processes reveals the presence of a common element: a double-stranded to single-stranded transition region. We now show that this DNA element is crucial for the ATP hydrolytic function of an SWI2/SNF2 family member: DNA-dependent ATPase A. We further demonstrate that a domain containing the seven helicase-related motifs that are common to the SWI2/SNF2 family of proteins mediates the interaction with the DNA, yielding specific DNA structural recognition. This study forms a primary step toward understanding the physico-biochemical nature of the interaction between a particular class of DNA-dependent ATPase and their DNA effectors. Furthermore, this study provides a foundation for development of mechanisms to specifically target this class of DNA-dependent ATPases.


["Dear Max, how much we are one, I was only clearly aware the day after leaving my last letter to you." Max Horkheimer and Karl Landauer as the first psychoanalyst at the Frankfurt Institute for Social Research].
The Frankfurt School is known to be the first institution in Germany that in 1929 has officially related psychoanalysis to a university. The most important person in this process was Karl Landauer. With him Fromm, Horkheimer and others completed their training analyzes, he decisively worked in the Institute and the first volumes of the Journal of Social Research. Landauer and Horkheimer regularly exchange information in the time of emigration and discuss their texts together. Landauer is also responsible for the reception of psychoanalysis in Horkheimer's further programs he writes for the Institute, as in his programmatic essay "Egoism and freedom-movement" from 1936. When he was murdered in concentration camp in 1945, it was a great personal and theoretical loss for Horkheimer which he hardly could overcome. Also the known dispute between Adorno and Fromm at the Institute for Social Research has as a backbone an old rivalry between the psychoanalytic institutes from Berlin and Frankfurt, which is exacerbated during the emigration and the Gleichschaltung in fascist Germany.


Isolated distal cutaneous thrombosis: an unusual presentation and an interesting etiology.
A middle-aged hypertensive male, with a fatty liver and chronic alcohol intake, relocated to a high altitude of 2100 m above sea level; in the first winter season, he developed bluish skin lesions over the tip of the nose, margins of both ear lobes, both knees, and subungual location. Systemic examination was unremarkable. Skin biopsy showed thrombi in dermal vessels without any evidence of vasculitis; immunofluorescence was negative. Investigations revealed mild elevation in plasma homocysteine levels, weakly positive antinuclear antibodies and elevated antiphospholipid antibodies, methylene tetrahydrofolate reductase C677T heterozygosity, and protein S deficiency. The patient received prednisolone for 2 weeks, aspirin and pentoxyphylline for 3 months, and continues to be on folic acid and vitamin B6. After 3 months, antiphospholipid antibodies and antinuclear antibody levels were normal. Isolated distal cutaneous thrombosis is an uncommon entity and precipitation by extreme cold in a hypertensive male with three thrombophilic states - one transient, one hereditary, and one acquired - is fascinating.


Three-dimensional soft-tissue and hard-tissue changes in the treatment of bimaxillary protrusion.
Facial convexity related to bimaxillary protrusion is prevalent in many populations. Underlying skeletal protrusion combined with increased dentoalveolar protrusion contributes to facial muscle imbalance and lip incompetence, which is undesirable for many patients. In this study, we evaluated the relationship between soft-tissue and hard-tissue changes in an orthodontically treated Asian population. Twenty-four consecutive adult Asian patients (mean age, 24 years), diagnosed with severe bimaxillary dentoalveolar protrusion, were evaluated using pretreatment and posttreatment cone-beam computed tomography. The patients were treated with 4 first premolar extractions followed by anterior retraction with either skeletal or intraoral anchorage. Serial cone-beam computed tomography radiographs were registered on the entire cranial base and fossa. Soft-tissue and hard-tissue changes were determined through landmark displacement and color mapping. Upper lip retraction was concentrated between the nasolabial folds and commissures. Lower lip retraction was accompanied by significant redistribution of soft tissues at pogonion. Soft-tissue changes correlated well with regional facial muscle activity. Significant retractions (2-4 mm) of the soft tissues occurred beyond the midsagittal region. Use of skeletal anchorage resulted in 1.5 mm greater lower lip retraction than intraoral anchorage, with greater retraction of the maxillary and mandibular incisor root apices. Profound soft-tissue changes accompanied retraction of the anterior dentition with both treatment modalities.


Orthodontic appliances did not increase risk of dental caries and periodontal disease under preventive protocol.
To assess periodontal parameters and microbial species levels after orthodontic appliance placement in patients who received oral hygiene instructions and who were monitored and motivated throughout the study. The Periodontal Index was recorded and saliva collection was performed before (T0) and 30 (T1), 60 (T2), and 90 (T3) days after orthodontic appliance placement in 15 patients (mean age 17.53 ± 8.0 years). Analysis was carried out using checkerboard DNA-DNA hybridization. Nonparametric statistical analysis was performed. The Periodontal Index did not change. The total amount of the purple and red complexes and Candida species showed a significant decrease from T2. The green, yellow, and orange complex showed a significant decrease at T3. The specific species analysis showed that Prevotella nigrescens, Pseudomonas putida, Fusobacterium periodonticum, Pseudomonas aeruginosa, Peptostreptococcus anaerobius, and Tanerella forsythia showed high incidence before bonding, and their levels decreased at T2 and T3. Only Porphyromonas gingivalis showed increased levels at T2 and displayed the highest level at T3. The Streptococcus group decreased their levels from T2 onward. A dynamic change in microbial levels was identified. The decrease in the levels of complexes present was only possible due to the mechanical method of oral hygiene implemented in this sample.


Digital Health to Strengthen District-Based Public-Private Mix Tuberculosis Control in Purwakarta District, Indonesia: A Qualitative Research.
This study aimed to explore the problem that occurs in district-based public-private mix tuberculosis (DPPM TB) in the Purwakarta district, and how digital health can help overcome this problem. This study used a qualitative research design. By purposive sampling, 46 informants were selected to be interviewed and 9 informants participated in focus group discussion. Data were collected during January to November 2020 and analyzed using the content analysis technique. Trustworthiness is obtained through the triangulation method and peer debriefing. The problems identified in public and private partnership were the lack of communication and awareness, the under-reporting of TB cases in the private health sector, and the limitation of the existing information system. Communication is important in delivering information about a tuberculosis program, patient referrals, and contact investigation; therefore, digital health is considered as a potential strategy to facilitate that. Digital health must consider ethical issues, avoid redundancy, be user-friendly, and include intervention packages. We conclude that the lack of communication between the public and the private health sectors in TB control was a major problem in DPPM TB. Digital health is needed to ensure the flow of information and communication between the public and the private health sectors.


Kappa-opioid receptor activation during reperfusion limits myocardial infarction via ERK1/2 activation in isolated rat hearts.
We investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection by κ-opioid receptor (KOP) activation. Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Antagonists of ERK1/2 and PI3K were perfused in hearts treated with the KOP agonist U50488H (U50). Infarct size was measured after 2 h of reperfusion. The phosphorylation states of ERK1/2 and Akt by Western immunoblots were determined. Drugs were perfused for a period of 5 min before and 30 min after reperfusion. Inhibition of ERK1/2 (26.8 ± 2.9%, P < 0.05 vs. U50) but not PI3K (15.5 ± 1.1%, P > 0.05 vs. U50) completely abrogated the anti-infarct effect of U50488H. Western blot analysis revealed a significant increase in ERK1/2 but not Akt phsophorylation in U50488H-treated hearts as compared to control hearts when measured immediately after reperfusion. KOP activation effectively reduces myocardial infarction. The anti-infarct effect of U50488H is mediated by the ERK1/2, but not the PI3K-Akt pathway.


[A pilot study of photon therapy for benign prostate hyperplasia (a report of 30 cases)].
To investigate the clinical efficacy and safety of photon therapy for benign prostate hyperplasia (BPH). Thirty patients with severe BPH received brachytherapy of prostate photon treatment system irradiation for one month, with the active area of the applicator located in the rectum, and at a dosage of 726-810 cGy. International prostate symptom score (IPSS), quality of life (QOL), volume of prostate gland, maximum flow rate (Qmax), and residual urine were evaluated before and after the treatment. After one-month treatment, 18 cases remarkably improved, 9 slightly improved and 3 had no response. There was significant improvement in IPSS, QOL, volume of prostate gland, Qmax and residual urine (P<0.01, except Qmax P = 0.038). Prostate photon treatment system can be used as a safe, effective, micro-invasive, convenient and economical therapy for severe BPH, especially applicable to older and weaker patients.


Ligand Isomerism in Coordination Cages.
Complexation reactions of palladium(II) nitrate with a set of 3-pyridyl appended nonchelating bidentate ligands possessing regioisomeric phenylene-diurea functionalities as spacers were carried out. The ligands utilized in this study are 1,1'-(1,2-phenylene)bis(3-(pyridin-3-yl)urea), L1; 1,1'-(1,3-phenylene)bis(3-(pyridin-3-yl)urea), L2; and 1,1'-(1,4-phenylene)bis(3-(pyridin-3-yl)urea), L3. The complexation reactions of the ligands (L1, L2, and L3) with palladium(II) produced single discrete isomeric cages (1, 2, and 3) of Pd2L4 formulation in each case and thereby illustrated ligand-isomerism in coordination cages. All 16 hydrogen atoms of eight urea moieties present in four ligand strands are delineated completely endohedrally in cage 1 and completely exohedrally in cage 3, whereas cage 2 exhibited half of the urea hydrogens in exohedral locations and the remaining half in endohedral locations. In addition to the variable number of solvent molecules, the cavities of cages 1 and 2 lodged four and two nitrate ions, respectively, using the endohedral (H)urea atoms (i.e., NH groups) as binding sites, whereas the cavity of 3 remained anion free. The abilities of the complexes 1-3 for adsorption of CO2 gas are demonstrated, and their behaviors are compared.


0.2-4.0 THz broadband terahertz detector based on antenna-coupled AlGaN/GaN HEMTs arrayed in a bow-tie pattern.
To satisfy the demand for broadband and high-sensitivity terahertz detectors, we designed and verified a broadband terahertz detector built with antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs). Eighteen pairs of dipole antennas with different center frequency from 0.24 to 7.4 THz are arrayed into a bow-tie pattern. The corresponding eighteen transistors have common a source and a drain but different gated channels coupled by the corresponding antennas. The photocurrents generated by each gated channel are combined in the drain as the output port. With incoherent terahertz radiation from a hot blackbody in a Fourier-transform spectrometer (FTS), the detector exhibits a continuous response spectrum from 0.2 to 2.0 THz at 298 K and from 0.2 to 4.0 THz at 77 K, respectively. The results agree well with simulations taking into account the silicon lens, antenna and blackbody radiation law. The sensitivity is characterized under coherent terahertz irradiation, the average noise-equivalent power (NEP) is about 188 p W/H z at 298 K and 19 p W/H z at 77 K from 0.2 to 1.1 THz, respectively. A maximum optical responsivity of 0.56 A/W and a minimum NEP of 7.0 p W/H z at 0.74 THz are achieved at 77 K. The blackbody response spectrum is divided by the blackbody radiation intensity to obtain a performance spectrum, which is calibrated by measuring coherence performance from 0.2 to 1.1 THz to evaluate detector performance at frequencies above 1.1 THz. At 298 K, the NEP is about 1.7 n W/H z at 2.0 THz. At 77 K, the NEP is about 3 n W/H z at 4.0 THz. For further improvements in sensitivity and bandwidth, high-bandwidth coupling components, smaller series resistance, smaller gate lengths and high-mobility materials need to be considered.


Carcinoma of the floor of the mouth: a case treated with precisely controlled external beam radiotherapy.
A new external radiotherapy system has been developed for head and neck cancer and a case with T2 oral floor carcinoma treated with this system is presented in this report. The system consists of real-time tumor-tracking equipment and a gold-marker implanted mouthpiece. Accuracy of the order of 2 mm was achieved during the entire course of fractionated radiotherapy (a total of 52.5 Gy in 15 fractions). Planning target volume became smaller compared to the conventional parallel-opposed technique. Dose-volume histogram analysis demonstrated a significant reduction in the dose to the mandible bone compared to the conventional technique. A confluent fibrinous mucositis developed in the oral floor mucosa that corresponded to 90% dose area. Mucositis in the lower gum was minimal and analgesics were not required. The patient is currently free from both tumor and complication during a follow-up period of 48 months. External radiotherapy can be an option as a curative treatment for early stage carcinoma of the floor of the mouth provided that patient set-up is rigid and reproducible.


[Postoperative pyoderma gangrenosum of Cullen].
The clinical picture in pyoderma gangrenosum varies but a typical medical history with resistance to antimicrobial treatment and worsening or first manifestation of disease because of surgical procedures are indications of this diagnosis. We describe the course of a woman patient who had a pyoderma gangrenosum for more than 1.5 years. After confirming the diagnosis an immunomodulating therapy was initiated until complete remission of the ulcers. Differential diagnosis and different clinicopathologic forms of pyoderma gangrenosum are discussed and an overview of the association with internal diseases is provided.


Trypanosomes of small mammals in Iran.
Trypanosomes in the subgenera Herpetosoma, Schizotrypanom and Megatrypanum were found in 31 small mammals representing nine species of the orders Rodentia, Insectivora and Chiroptera in Iran.


Differential Effect of Dopamine D4 Receptor Activation on Low-Frequency Oscillations in the Prefrontal Cortex and Hippocampus May Bias the Bidirectional Prefrontal-Hippocampal Coupling.
Dopamine D4 receptor (D4R) mechanisms are implicated in psychiatric diseases characterized by cognitive deficits, including schizophrenia, ADHD, and autism. The cellular mechanisms are poorly understood, but impaired neuronal synchronization in cortical networks was proposed to contribute to these deficits. In animal experiments, D4R activation was shown to generate aberrant increased gamma oscillations and to reduce performance on cognitive tasks requiring functional prefrontal cortex (PFC) and hippocampus (HPC) networks. While fast oscillations in the gamma range are important for local synchronization within neuronal ensembles, long-range synchronization between distant structures is achieved by slow rhythms in the delta, theta, alpha ranges. The characteristics of slow oscillations vary between structures during cognitive tasks. HPC activity is dominated by theta rhythm, whereas PFC generates unique oscillations in the 2-4 Hz range. In order to investigate the role of D4R on slow rhythms, cortical activity was recorded in rats under urethane anesthesia in which slow oscillations can be elicited in a controlled manner without behavioral confounds, by electrical stimulation of the brainstem reticular formation. The local field potential segments during stimulations were extracted and subjected to fast Fourier transform to obtain power density spectra. The selective D4R agonist A-412997 (5 and 10 mg/kg) and antagonists L-745870 (5 and 10 mg/kg) were injected systemically and the peak power in the two frequency ranges were compared before and after the injection. We found that D4R compounds significantly changed the activity of both HPC and PFC, but the direction of the effect was opposite in the two structures. D4R agonist enhanced PFC slow rhythm (delta, 2-4 Hz) and suppressed HPC theta, whereas the antagonist had an opposite effect. Analogous changes of the two slow rhythms were also found in the thalamic nucleus reuniens, which has connections to both forebrain structures. Slow oscillations play a key role in interregional cortical coupling; delta and theta oscillations were shown in particular, to entrain neuronal firing and to modulate gamma activity in interconnected forebrain structures with a relative HPC theta dominance over PFC. Thus, the results of this study indicate that D4R activation may introduce an abnormal bias in the bidirectional PFC-HPC coupling which can be reversed by D4R antagonists.


Exploring incidence and risk factors for persistent postoperative opioid use in adult surgical patients: a systematic review protocol.
The objective of this review is to determine the incidence of persistent postsurgical use of opioids in adult patients and the associated risk factors. Surgery has been identified as an independent risk factor for unwarranted chronic opioid use, contributing to opioid-related harm in the community. Persistent opioid use after surgery is associated with morbidity and mortality from opioid-related adverse events, indicating a significant yet mitigable public health concern. There is substantial variation in the reported incidence and risk factors for postoperative opioid use, which require evaluation for future evidence-based risk-reduction strategies. This review will include studies investigating the persistent use of opioids after 90 postoperative days in adult (≥18 y) patients undergoing surgery of any type, including patients with cancer pain. Selected evidence must report on opioid use prior to surgery. Analytical and descriptive observational studies, and experimental and quasi-experimental studies, published in the previous decade will be eligible for inclusion. The proposed study methods follow the JBI methodology for systematic reviews of prevalence and incidence. A systematic search will be conducted in PubMed, Embase, CINAHL, Cochrane Central, and Web of Science, and a search of gray literature will include Google Scholar and ClinicalTrials.gov. Study selection, critical appraisal, and data extraction will be performed by 2 independent reviewers aided by the relevant JBI systematic review tools. We aim to produce a narrative synthesis of results and conduct a meta-analysis where feasible, in addition to subgroup analyses of suitable populations. The results are intended to promote safe, evidence-based postoperative opioid prescribing when considering risk factors for persistent postoperative opioid use. PROSPERO CRD42022320691.


Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma.
The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.


Crohn's disease. Results of excisional surgery in 133 patients.
Of a series of 133 patients treated surgically for Crohn's disease during the years 1962-78, 21 had recurrence after previous operations in other hospitals. In addition, 40 of the patients underwent altogether 52 reoperations for recurrent disease; hence the total number of operations was 185. Five patients died in the postoperative period (2.7%). There were five late deaths related to Crohn's disease. The annual recurrence rate after all operations performed was rather constant, averaging 13.1%, and the cumulative recurrence rate after 10 years was 76.1%. The annual rate of reoperation tended to decline, with a cumulative reoperation rate of 35.8% after 10 years. The recurrence rate was not significantly different after primary operations and operations for recurrent disease. There was a higher risk of relapse during the first 2 years after non-radical excision of diseased gut than after radical excision. At follow-up examination in 108 patients most were in good general condition. Only eight patients had severe, disabling symptoms with reduced working capacity.


The current state of ultrasound training in canadian emergency medicine programs: perspectives from program directors.
There is a paucity of data about emergency ultrasound (EUS) training in emergency medicine (EM) residency programs accredited by the Royal College of Physicians and Surgeons of Canada (Royal College) and the College of Family Physicians of Canada (CFPC). Historically the progress of EUS in Canada has been different from that in the United States. We describe the current state of EUS training in both Royal College and CFPC-EM programs. All Royal College EM program directors and all CFPC-EM program directors were invited to participate in a website-based survey. Main outcome measures were characteristics of currently offered EUS training. The response rate of the survey was 100% (30/30). EUS is part of the formal residency curriculum in 100% (13/13) of Royal College EM programs and in 88% (15/17) of CFPC-EM programs. EM resident rotations in ultrasound (US) are provided by 77% (10/13) of Royal College programs but only 47% (8/17) of CFPC-EM programs. There are specific requirements for numbers of EUS exams to be completed by graduation in 77% (10/13) of Royal College programs and 47% (8/17) of CFPC-EM programs. EM faculty and residents make clinical decisions and patient dispositions based on their EUS interpretation without a consultative study by radiology in 100% (13/13) of Royal College programs and 88% (15/17) of CFPC-EM programs. However, 69% (9/13) of Royal College programs and 53% (9/17) of CFPC-EM programs have no formal quality assurance program in place. EUS training in Canadian EM programs is prevalent, but there are considerable discrepancies among residency programs in scope of training, curricula, determination of proficiency, and quality assurance. These findings suggest variability in both the level and the quality of EUS training in Canada.


Concomitant aseptic meningitis and bacterial urinary tract infection in young febrile infants.
We evaluated the incidence and implications of coexistent bacterial urinary tract infection and aseptic meningitis in 1629 young febrile infants (age 1 to 60 days) who underwent sepsis work-up. Urinary tract infection was diagnosed in 13.2% and aseptic meningitis in 8.8%. Eleven patients (0.7%) had both infections. In view of possible coinfection initial laboratory results may be insufficient for decision-making regarding treatment in young febrile infants.


The influence of the nucleotide sequences of random Shine-Dalgarno and spacer region on bovine growth hormone gene expression.
To investigate the effects of the nucleotide sequences in Shine-Dalgarno (SD) and the spacer region (SD-ATG) on bovine growth hormone (bGH) gene expression, the expression vectors under the control of the T7 promoter (pT7-7 vector) were constructed using bGH derivatives (bGH1 & bGH14) which have different 5'-coding regions and were induced in E. coli BL21(DE3). Oligonucleotides containing random SD sequences and a spacer region were chemically synthesized and the distance between the SD region and the initiation codon were fixed to nine bases in length. The oligonucleotides were annealed and fused to the bGH1 and bGH14 cDNA, respectively. When the bGH gene was induced with IPTG in E. coli BL21(DE3), some clones containing only bGH14 cDNA produced considerable levels of bGH in the range of 6.9% to 8.5% of total cell proteins by SDS-PAGE and Western blot. Otherwise, the bGH was not detected in any clones with bGH1 cDNA. Accordingly, the nucleotide sequences of SD and the spacer region affect on bGH expression indicates that the sequences sufficiently destabilize the mRNA secondary structure of the bGH14 gene. When the free energy was calculated from the transcription initiation site to the +51 nucleotide of bGH cDNA using a program of nucleic acid folding and hybridization prediction, the constructs with values below -26.3 kcal/mole (toward minus direction) were not expressed. The constructs with the original sequence of bGH cDNA also did not show any expression, regardless of the free energy values. Thus, the disruption of the mRNA secondary structure may be a major factor regulating bGH expression in the translation initiation process. Accordingly, the first stem-loop among two secondary structures present in the 5'-end region of the bGH gene should be disrupted for the effective expression of bGH.


Parents and their child--and the analyst in the middle.
The first part of this paper explains how the transgenerational mandate influences the mental activity of the child. When a child acts the denied suffering of the parental couple, the analyst risks being imprisoned by the transgenerational mandate. Frequently the analyst is unconsciously asked by the parents to cure without curing because the child's psychological birth, still in the making, threatens the defensive equilibrium of the parents. The analyst is thus caught between the parents and the child and must find his/her own way forward in order to free the child from the burden of the mandate. In the second part of the paper, an analysis of a 5-year-old child is presented. The author shows how a transgenerational mandate may hold a traumatic potential because it can impair heavily the child's capacity to think. The author also describes the way in which she works with the parents and how she manages the setting and the style of the interpretation. She insists in particular on the need to sustain the child's perceptions in order to gradually allow the child to take roots in his/her experiences and therefore develop his/her own identity.


Purification of messenger ribonucleic acids for fast and slow myosin heavy chains by indirect immunoprecipitation of polysomes from embryonic chick skeletal muscle.
Fast and slow myosin heavy chain mRNAs were isolated by indirect immunoprecipitation of polysomes from 14-day-old embryonic chick leg muscle. The antibodies were prepared against myosin heavy chains purified by NaDod-SO4-polyacrylamide gel electrophoresis and were shown to be specific for fast and slow myosin heavy chains. The RNA fractions directed the synthesis of myosin heavy chains in a cell-free translation system from wheat germ. Several smaller peptides were also synthesized in lower concentrations. These probably are partial products of myosin heavy chains, since they are immunoprecipitated with antibodies to myosin heavy chains. Immunoprecipitation of the translation products with the antibodies to fast and slow myosin heavy chains showed the RNA preparations to be approximately 94% enriched for fast myosin heavy chain mRNA and approximately 84% enriched for slow myosin heavy chain mRNA with respect to myosin HC type. Peptides having slightly different mobilities on NaDodSO4-polyacrylamide gels were immunoprecipitated by antibodies to fast and slow myosin heavy chains.


EEGNet: a compact convolutional neural network for EEG-based brain-computer interfaces.
Brain-computer interfaces (BCI) enable direct communication with a computer, using neural activity as the control signal. This neural signal is generally chosen from a variety of well-studied electroencephalogram (EEG) signals. For a given BCI paradigm, feature extractors and classifiers are tailored to the distinct characteristics of its expected EEG control signal, limiting its application to that specific signal. Convolutional neural networks (CNNs), which have been used in computer vision and speech recognition to perform automatic feature extraction and classification, have successfully been applied to EEG-based BCIs; however, they have mainly been applied to single BCI paradigms and thus it remains unclear how these architectures generalize to other paradigms. Here, we ask if we can design a single CNN architecture to accurately classify EEG signals from different BCI paradigms, while simultaneously being as compact as possible. In this work we introduce EEGNet, a compact convolutional neural network for EEG-based BCIs. We introduce the use of depthwise and separable convolutions to construct an EEG-specific model which encapsulates well-known EEG feature extraction concepts for BCI. We compare EEGNet, both for within-subject and cross-subject classification, to current state-of-the-art approaches across four BCI paradigms: P300 visual-evoked potentials, error-related negativity responses (ERN), movement-related cortical potentials (MRCP), and sensory motor rhythms (SMR). We show that EEGNet generalizes across paradigms better than, and achieves comparably high performance to, the reference algorithms when only limited training data is available across all tested paradigms. In addition, we demonstrate three different approaches to visualize the contents of a trained EEGNet model to enable interpretation of the learned features. Our results suggest that EEGNet is robust enough to learn a wide variety of interpretable features over a range of BCI tasks. Our models can be found at: https://github.com/vlawhern/arl-eegmodels.


Paxillin's LD4 motif interacts with bcl-2.
Bcl-2 is the founding member of a family of proteins which influences cell survival in response to a variety of stimuli including those from growth factor receptors and integrins. However, how these activities are coordinated through bcl-2 requires further investigation. bcl-2 interacts with paxillin, potentially linking cell survival and cell adhesive pathways. Paxillin is an adapter protein implicated in growth factor and integrin-mediated signal transduction pathways. Previous work in this laboratory demonstrated that loss of bcl-2 affects cell adhesion and migration characteristics of renal epithelial cells, perhaps through disruption of its interaction with paxillin. Here studies were performed to determine the bcl-2 binding motif in paxillin. The amino-terminal portion of paxillin, specifically its LD4 motif, was found to associate with bcl-2. However, the amino-terminal portion of paxillin with the LD4 domain deleted did not associate with bcl-2. The corresponding LD motif in other paxillin family members, Hic-5 and leupaxin, did not associate with bcl-2. Mutations in paxillin's LD4 motif made to mimic Hic-5 and leupaxin LD4-like motifs (E(268) --> R or S(272) --> H) abolished its association with bcl-2. Incubation of embryonic kidneys with paxillin's LD4 motif disrupted ureteric bud branching and morphogenesis, while incubation with the comparable Hic-5 LD motif did not significantly affect morphogenesis. These data suggest that paxillin's association with bcl-2 plays a unique role during kidney development that other paxillin family members may not be able to fulfill.


Sparse logistic regression for diagnosis of liver fibrosis in rat by using SCAD-penalized likelihood.
The objective of the present study is to find out the quantitative relationship between progression of liver fibrosis and the levels of certain serum markers using mathematic model. We provide the sparse logistic regression by using smoothly clipped absolute deviation (SCAD) penalized function to diagnose the liver fibrosis in rats. Not only does it give a sparse solution with high accuracy, it also provides the users with the precise probabilities of classification with the class information. In the simulative case and the experiment case, the proposed method is comparable to the stepwise linear discriminant analysis (SLDA) and the sparse logistic regression with least absolute shrinkage and selection operator (LASSO) penalty, by using receiver operating characteristic (ROC) with bayesian bootstrap estimating area under the curve (AUC) diagnostic sensitivity for selected variable. Results show that the new approach provides a good correlation between the serum marker levels and the liver fibrosis induced by thioacetamide (TAA) in rats. Meanwhile, this approach might also be used in predicting the development of liver cirrhosis.


Deep Fungal Infections Among General Hospital Inpatients in Southwestern China: A 5-Year Retrospective Study.
Deep fungal infection is a type of life-threatening opportunistic infection. Its incidence has been increasing in recent years. This infection can affect the prognosis of patients, prolong hospital stays and raise costs for patients and their families. We aimed to understand the current situation of deep fungal infections in the First Affiliated Hospital of Kunming Medical University and to provide a basis for the clinical diagnosis and treatment of deep fungal infections. This was a retrospective analysis of 528,743 cases in the hospital from 2015 to 2019, including the epidemiological characteristics, treatment and prognosis of deep fungal infections. A total of 274 cases (0.05%) with deep fungal infections were identified, accounting for 0.05% of the total number of hospitalizations. The incidence of deep fungal infections in the hospital showed an increasing trend from 2015 to 2019. The most commonly infected site was the respiratory tract (93.07%). Among patients with deep fungal infections, 266 specimens were positive for fungal culture, by which 161 cultured Candida albicans (C. albicans), accounting for 60.53%, the main pathogen causing deep fungal infection. From 2015 to 2019, the percentage of C. albicans cases showed a downward trend, while that of non-C. albicans showed an opposite trend. Antibiotics were the most common predisposing factor for deep fungal infections (97.45%). Among the underlying diseases of patients with deep fungal infections, infectious diseases (59.49%) were the most common. Those with underlying diseases such as renal insufficiency and neurological diseases had a worse prognosis. Indwelling catheters, nervous system disease and tumors were risk factors for a poor prognosis. We report for the first time the epidemiological data of deep fungal infections in a general hospital in southwestern China from 2015 to 2019. In the past 5 years, the number of patients with deep fungal infections in the First Affiliated Hospital of Kunming Medical University has been increasing. Although the clinical data are limited, these results can provide references for the diagnosis and treatment of deep fungal infections.


Development of a stroke family support and education program.
An interdisciplinary stroke family support and education program can provide families with basic information about stroke and rehabilitation in addition to providing support to families as they adapt to the crisis of stroke. The theoretical basis for such a program is discussed in this article as well as program development, implementation and evaluation. Included are program goals, content outlines and a referral process.


17β-estradiol regulates the sexually dimorphic expression of BDNF and TrkB proteins in the song system of juvenile zebra finches.
Mature brain derived neurotrophic factor (BDNF) plays critical roles in development of brain structure and function, including neurogenesis, axon growth, cell survival and processes associated with learning. Expression of this peptide is regulated by estradiol (E2). The zebra finch song system is sexually dimorphic - only males sing and the brain regions controlling song are larger and have more cells in males compared to females. Masculinization of this system is partially mediated by E2, and earlier work suggests that BDNF with its high affinity receptor TrkB may also influence this development. The present study evaluated expression of multiple forms of both BDNF and TrkB in the developing song system in juvenile males and females treated with E2 or a vehicle control. Using immunohistochemistry and Western blot analysis, BDNF was detected across the song nuclei of 25-day-old birds. Westerns allowed the pro- and mature forms of BDNF to be individually identified, and proBDNF to be quantified. Several statistically significant effects of sex existed in both the estimated total number of BDNF+ cells and relative concentration of proBDNF, varying across the regions and methodologies. E2 modulated BDNF expression, although the specific nature of the regulation depended on brain region, sex and the technique used. Similarly, TrkB (both truncated and full-length isoforms) was detected by Western blot in the song system of juveniles of both sexes, and expression was regulated by E2. In the context of earlier research on these molecules in the developing song system, this work provides a critical step in describing specific forms of BDNF and TrkB, and how they can be mediated by sex and E2. As individual isoforms of each can have opposing effects on mechanisms, such as cell survival, it will now be important to investigate in depth their specific functions in song system maturation.


Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries.
Endothelial cells regulate vascular tone through the release of nitric oxide and other relaxing factors. The role of these substances was studied in isolated intramyocardial porcine coronary resistance arteries suspended in myographs for isometric tension recording. The inhibitor of nitric oxide formation NG-monomethyl-L-arginine (L-NMMA; 10(-7)-10(-4)M), but not D-NMMA, caused endothelium-dependent contractions that could be reversed by L-arginine but not by D-arginine. In preparations with endothelium, L-NMMA potentiated the contractions induced by acetylcholine and the relaxations to 3-morpholino-sydnonimine. Under both conditions, the effect of endothelial removal was slightly more pronounced than that of L-NMMA. Bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine evoked endothelium-dependent relaxations. L-NMMA as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) prevented the relaxations induced by clonidine, reduced those to serotonin, but hardly affected those to bradykinin. Thus, in porcine coronary resistance arteries, endothelium-derived nitric oxide is continuously produced from L-arginine. Endothelium-dependent relaxations to clonidine are fully mediated and those to serotonin partially mediated by nitric oxide; its release does not involve a Gi protein. An endothelium-derived relaxing factor different from nitric oxide must mediate the relaxations to bradykinin and contribute to those evoked by serotonin.


Intracellular mechanisms underlying increases in glucose uptake in response to insulin or exercise in skeletal muscle.
This review will provide insight on potential intracellular signalling mechanisms by which insulin and exercise/contraction increases glucose metabolism and gene expression. Glucose transport, the rate limiting step in glucose metabolism, is mediated by glucose transporter 4 (GLUT4) and can be activated in skeletal muscle by two separate and distinct signalling pathways; one stimulated by insulin and the second by muscle contractions. Impaired insulin action on whole body glucose uptake is a hallmark feature of type II (non-insulin-dependent) diabetes mellitus. Defects in insulin signal transduction through the insulin-receptor substrate-1/phosphatidylinositol 3-kinase pathway are associated with reduced insulin-stimulated glucose transporter 4 translocation and glucose transport activity in skeletal muscle from type II diabetic patients. Studies performed using glucose transporter 4-null mice show that this glucose transporter isoform plays a major role in mediating exercise-stimulated glucose uptake in skeletal muscle. Level of physical exercise has been linked to improved glucose homeostasis and enhanced insulin sensitivity. Exercise training leads to alterations in expression and activity of key proteins involved in insulin signal transduction. These changes may be related to increased signal transduction through the mitogen-activated protein kinase (MAPK) signalling cascades. Because MAPK is associated with increased transcriptional activity, these signalling cascades are candidates for these exercise-induced changes in protein expression. Understanding the molecular mechanism for the activation of signal transduction pathways will provide a link for defining new strategies to enhance glucose metabolism and improve health in the general population.


Pharmacogenetics of Antiretroviral Drug Response and Pharmacokinetic Variations in Indigenous South African Populations.
Interindividual and interethnic differences in response to antiretroviral drugs (ARVs) are influenced by genetic variation. The few genomic studies conducted among African-Americans and African ethnic groups do not reflect the extensive genetic diversity within African populations. ARVs are widely used in Africa. Therefore, genomic characterization of African populations is required before genotype-guided dosing becomes possible. The aim of this study was to determine and report on the frequency of genetic variants in genes implicated in metabolism and transport of ARVs in South African populations. The study comprised 48 self-reported South African Colored (SAC) and 296 self-reported Black African (BA) individuals. Allele and genotype frequency distributions for 93 variants contributing to metabolism and transport of ARVs were compared between groups, and other global populations. Fifty-three variants had significant differences in allele and genotype frequencies when comparing SAC and BA groups. Thirteen of these have strong clinical annotations, affecting efavirenz and tenofovir pharmacokinetics. This study provides a summary of the genetic variation within genes implicated in metabolism and transport of ARVs in indigenous South African populations. The observed differences between indigenous population groups, and between these groups and global populations, demonstrate that data generated from specific African populations cannot be used to infer genetic diversity within other populations on the continent. These results highlight the need for comprehensive characterization of genetic variation within indigenous African populations, and the clinical utility of these variants in ARV dosing for global precision medicine. Population pharmacogenetics is a nascent field of global health and warrants further research and education.


[Meta-analysis: effect of chemotherapy on intelligence of children treated for leukemia].
Leukemia is the most common pediatric malignancy. Acute lymphoblastic leukemia (ALL) is the most commonly observed subtype. To assess cognitive functioning in children and adolescents with ALL post-treatment: chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS We searched in PubMed and PsycINFO (OvidSP). Relevant data were analyzed using statistical program Comprehensive Meta-Analysis (version 2). 44 studies were included in the overall meta-analysis with a total of 5059 patients. A weighted mean IQ of 100.1 (95% CI 99.1-101.0) was found overall after ALL treatment. In subanalyses, we found for CT-only a weighted mean IQ of 100.7 (95% CI: 99.5-101.9) and for CTRT-treatment a weighted mean IQ of 98.2 (95%100.7 (95% CI: 96.3-100.3). There was no significant difference from the normative control (mean: 100.0; SD: 15). No significant cognitive sequelae were shown in childhood survivors of leukemia who were exposed to either CT-only or CTRT therapy. Prospective studies are needed with inclusion of pre-and post-treatment IQ measurements, ideally compared to age and socio-economic status matched control groups.


The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men.
Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident Alzheimer disease. However, so far there is no evidence directly linking the FTO gene to functional cognitive processes. Here we examined whether the FTO rs9939609 A allele is associated with verbal fluency performance in 355 elderly men at the age of 82 years who have no clinically apparent cognitive impairment. Retrieval of verbal memory is a good surrogate measure reflecting frontal lobe functioning. Here we found that obese and overweight but not normal weight FTO A allele carriers showed a lower performance on verbal fluency than non-carriers (homozygous for rs9939609 T allele). This effect was not observed for a measure of general cognitive performance (i.e., Mini-Mental State Examination score), thereby indicating that the FTO gene primarily affects frontal lobe-dependent cognitive processes in elderly men.


Risk factors for failure after treatment of a periprosthetic fracture of the femur.
Periprosthetic fracture of the femur is an uncommon complication after total hip replacement, but appears to be increasing. We undertook a nationwide observational study to determine the risk factors for failure after treatment of these fractures, examining patient- and implant-related factors, the classification of the fractures and the outcome. Between 1979 and 2000, 1049 periprosthetic fractures of the femur were reported to the Swedish National Hip Arthroplasty Register. Of these, 245 had a further operation after failure of their initial management. Data were collected from the Register and hospital records. The material was analysed by the use of Poisson regression models. It was found that the risk of failure of treatment was reduced for Vancouver type B2 injuries (p = 0.0053) if revision of the implant was undertaken (p = 0.0033) or revision and open reduction and internal fixation (p = 0.0039) were performed. Fractures classified as Vancouver type B1 had a significantly higher risk of failure (p = 0.0001). The strongest negative factor was the use of a single plate for fixation (p = 0.001). The most common reasons for failure in this group were loosening of the femoral prosthesis, nonunion and re-fracture. It is probable that many fractures classified as Vancouver type B1 (n = 304), were in reality type B2 fractures with a loose stem which were not recognised. Plate fixation was inadequate in these cases. The difficulty in separating type B1 from type B2 fractures suggests that the prosthesis should be considered as loose until proven otherwise.


Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea.
Recently, the development of antibiotic resistance emerged as a significant clinical problem in the eradication of Helicobacter pylori. We investigated the MICs of antibiotics for 135 H. pylori isolates from adults in Seoul, South Korea, over the past 16 years. The MICs of amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin increased from 1987 to 2003. Rates of primary resistance to clarithromycin increased from 2.8% in 1994 to 13.8% in 2003. The A2144G mutation was frequently observed in the 23S rRNA gene in clarithromycin-resistant isolates. The increase in resistance to clarithromycin seems to result in a decrease in eradication efficacy for H. pylori. These results suggest that the MICs of several antibiotics for H. pylori have increased over the past 16 years in Seoul.


[Gamma-aminobutyric acid metabolism in the rat brain after administration of nootropic agents].
N,N-bis-pyrrolidonomethyl-diaza - 18-crown-6 and piracetam, which are structural analogues of gamma-aminobutyric acid (GABA) and exhibit nootropic properties, affected the GABA metabolism, the content of total protein, DNA and RNA in rat brain after long-term administration at pharmacologically active doses of 100 mg/kg and 400 mg/kg, respectively. As compared with control values, content of GABA in rat brain was increased by 40% after administration of N,N-bis-pyrrolodonomethyl-diaza-18-crown-6 and by 28%--after treatment with piracetam. At the same time, activity of GABA transaminase was decreased by 49.4% and 39.8%, respectively, while the decarboxylase activity was unaltered.


Urinary excretion characteristics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate.
Urinary excretion characteristics of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), following intravenous administration was studied in rats. Three types of MMC-D, conjugates with dextrans of molecular weights of 10000, 70000 and 500000, were tested and urine concentration of MMC, dextran and spacer were determined by three analytical methods, i.e., bioassay, anthrone method and radioactivity counting. MMC was assayed separately as a free form and conjugated form based on antimicrobiological activity. MMC administered as a free form was excreted rapidly into urine but only a small amount of MMC was excreted following the administration of MMC-D. The excreted amount of MMC in a conjugated form varied with the size of carrier dextran while similar sustained excretion was observed regardless of the carrier size. The excretion of carrier dextran determined by anthrone method was confined as the molecular weight was increased. The effect of molecular weight was also observed in the case of spacer-introduced dextran (dextran-C6 spacer) and original dextran. Compared with neutral dextran, cationic MMC-D and anionic dextran-C6 spacer exhibited diminished excretion, indicating the effect of charge on urinary excretion. The urinary recovery of radioactivity was almost in accordance with that of carrier dextran. However, the urinary recovery of MMC based on biological activity was considerably lower than that of carrier dextran. It was suggested that MMC-D underwent inactivation to a great extent before releasing active MMC in the body. The effect of physicochemical properties such as molecular weight and electric charge on the urinary excretion of the polymeric prodrug was thus elucidated.


Brain Fingerprinting and Lie Detection: A Study of Dynamic Functional Connectivity Patterns of Deception Using EEG Phase Synchrony Analysis.
This study investigated the brain functional connectivity (FC) patterns related to lie detection (LD) tasks with the purpose of analyzing the underlying cognitive processes and mechanisms in deception. Using the guilty knowledge test protocol, 30 subjects were divided randomly into guilty and innocent groups, and their electroencephalogram (EEG) signals were recorded on 32 electrodes. Phase synchrony of EEG was analyzed between different brain regions. A few-trials-based relative phase synchrony (FTRPS) measure was proposed to avoid the false synchronization that occurs due to volume conduction. FTRPS values with a significantly statistical difference between two groups were employed to construct FC patterns of deception, and the FTRPS values from the FC networks were extracted as the features for the training and testing of the support vector machine. Finally, four more intuitive brain fingerprinting graphs (BFG) on delta, theta, alpha and beta bands were respectively proposed. The experimental results reveal that deceptive responses elicited greater oscillatory synchronization than truthful responses between different brain regions, which plays an important role in executing lying tasks. The functional connectivity in the BFG is mainly implicated in the visuo-spatial imagery, bottom-top attention and memory systems, work memory and episodic encoding, and top-down attention and inhibition processing. These may, in part, underlie the mechanism of communication between different brain cortices during lying. High classification accuracy demonstrates the validation of BFG to identify deception behavior, and suggests that the proposed FTRPS could be a sensitive measure for LD in the real application.


KAMEDO report no. 77: sinking of the MS Sleipner, 26 November 1999.
The catamaran HS Sleipner struck a rock and sunk in bad weather and heavy seas on 26 November 1999. Rescue efforts were provided by helicopters and other ships. A total of 68 victims were rescued alive and 16 died, mostly by drowning. Problems were encountered with evacuation, life jackets, and life rafts. Most of those rescued alive suffered from hypothermia. Response times for rescue helicopters should be improved. Emphasis should be placed on correct manifest lists of passengers and crew. Special emphasis must be placed on media relations and cross-boundary issues. Exercises should focus on cooperation and coordination.


Stereotactic biopsy for intracranial lesions: clinical-pathological compatibility in 60 patients.
Image guided stereotactic biopsy (SB) provides cerebral tissue samples for histological analysis from minimal lesions or those that are located in deep regions, being crucial in the elaboration of therapeutic strategies, as well as the prevention of unnecessary neurosurgical interventions. Sixty patients with central nervous lesions underwent SB from November 1999 to March 2008. They were followed up to 65 months. Preoperative diagnosis was based on clinical presentation and neuro-radiological features, pathologic diagnosis, clinical outcome. The compatibility of these findings with the pathologic diagnosis was analyzed. Considering diagnosis confirmation when inflammatory hypothesis were made, our accuracy was of 76%, with 94% of those cases having clinic-pathological correspondence after an average of 65.2 months of follow up. Considering diagnosis confirmation with the preoperative hypothesis of neoplasm, our accuracy was of 69% with 90% of these cases having clinic-pathological correspondence after an average of 47.3 months of follow-up. Morbidity rate was of 5% and mortality was zero. The diagnosis rate was 95%. Stereotactic biopsy represents a safe and precise method for diagnosis. Anatomic and histopathological analyses have high compatibility with long-term clinical outcome.


Rapid detection of 17p11.2 rearrangements by FISH without cell culture (direct FISH, DFISH): a prospective study of 130 patients with inherited peripheral neuropathies.
Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with pressure palsies (HNPP) are two frequent hereditary motor and sensory neuropathies. CMT is characterized by slowly progressive weakness and atrophy, primarily in peroneal and distal leg muscles. The most frequent form, CMT1A, is due, in most cases, to the duplication of a 1.5 Mb region on chromosome 17p11.2 containing the peripheral myelin protein 22 gene (PMP22). The phenotype seems to result from dosage of the PMP22 gene. This hypothesis is reinforced by the existence of HNPP, which is clinically characterized by various recurrent truncular palsies or sensory loss precipitated by minor trauma, which is caused by deletion of the same 1.5 Mb region in 17p11.2. In clinical practice, the detection of the duplication or the deletion in 17p11.2, which permits a positive diagnosis, is still performed by time consuming methods (Southern blot or various combinations of molecular tools). We developed a method for the rapid detection of 17p11.2 rearrangements, using "direct FISH" and PRINS analyses, which does not require cell culture. In a prospective study of 92 patients with CMT and 38 with suspected HNPP, we compared this new technique to classical strategies like Southern blot. The results demonstrate the high sensitivity and specificity of the new FISH technique for the diagnosis of CMT1A and HNPP. Moreover, because of its simplicity and rapidity, this technique provides a useful alternative to the molecular approaches that have been used to diagnose segmental aneusomies, especially in the case of duplications that often go undetected.


Internalizing-externalizing comorbidity and regional brain volumes in the ABCD study.
Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability - mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing-externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.


The Combined Use of Neuropsychiatric and Neuropsychological Assessment Tools to Make a Differential Dementia Diagnosis in the Presence of "Long-Haul" COVID-19.
The longer term neurocognitive/neuropsychiatric consequences of moderate/severe COVID-19 infection have not been explored. The case herein illustrates a complex web of differential diagnosis. The onset, clinical trajectory, treatment course/response, serial neuroimaging findings, and neuropsychological test data were taken into account when assessing a patient presenting 8 months post-COVID-19 (with premorbid attention-deficit hyperactivity disorder, diabetes mellitus, mood difficulties, and a positive family history of vascular dementia). Her acute COVID-19 infection was complicated by altered mental status associated with encephalopathy and bacterial pneumonia. After recovery from COVID-19, the patient continues to experience persisting cognitive and emotive difficulties despite an ongoing psychopharmacotherapy regimen (16 + years), psychotherapy (15 + sessions), and speech-language pathology SLP; 2 × week/for 12 weeks). The purpose of her most recent and comprehensive neuropsychological evaluation was to determine the presence/absence of neurocognitive disorder. The patient is a 62-year-old Caucasian woman. Cognitive screening was completed 3 months post-acute COVID-19 as part of an SLP evaluation, and a full neuropsychological evaluation was conducted 8 months post-COVID-19 recovery on an outpatient basis (in person). The patient had serial neuroimaging. Initial neurological evaluation during acute COVID-19 included unremarkable brain computed tomography (CT)/magnetic resonance imaging. However, follow-up CT (without contrast) revealed, in part, "asymmetric perisylvian atrophy on the left." Full neuropsychological evaluation at 8 months post-COVID-19 recovery revealed a dysexecutive syndrome characterized by language dysfunction and affective theory-of-mind deficit, consistent with dementia. There is need for careful use of differential diagnosis in COVID-19 patients with multiple risk factors that make them more susceptible to long-term neurological complications post-COVID-19. Differential diagnosis should involve multidisciplinary assessment (e.g., neuropsychology, SLP, neurology, and psychiatry).


CCBE1 Is Essential for Epicardial Function during Myocardium Development.
The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a Ccbe1 knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, Ccbe1 mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. Epicardial outgrowth culture assay to assess epicardial-derived cells (EPDC) migration showed reduced invasion of the collagen gel by EPDCs in Ccbe1 KO epicardial explants. Ccbe1 KO hearts also displayed fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate. Additionally, RNA-seq data and experimental validation by qRT-PCR showed a marked deregulation of EMT-related genes in developing Ccbe1 mutant hearts. Together, these findings indicate that the myocardium defects in Ccbe1 KO mice arise from disruption of epicardial development and function.


Anion transport as a target of adaption to perchlorate in sulfate-reducing communities.
Inhibitors can be used to control the functionality of microbial communities by targeting specific metabolisms. The targeted inhibition of dissimilatory sulfate reduction limits the generation of toxic and corrosive hydrogen sulfide across several industrial systems. Sulfate-reducing microorganisms (SRM) are specifically inhibited by sulfate analogs, such as perchlorate. Previously, we showed pure culture SRM adaptation to perchlorate stress through mutation of the sulfate adenylyltransferase, a central enzyme in the sulfate reduction pathway. Here, we explored adaptation to perchlorate across unconstrained SRM on a community scale. We followed natural and bio-augmented sulfidogenic communities through serial transfers in increasing concentrations of perchlorate. Our results demonstrated that perchlorate stress altered community structure by initially selecting for innately more resistant strains. Isolation, whole-genome sequencing, and molecular biology techniques allowed us to define subsequent genetic mechanisms of adaptation that arose across the dominant adapting SRM. Changes in the regulation of divalent anion:sodium symporter family transporters led to increased intracellular sulfate to perchlorate ratios, allowing SRM to escape the effects of competitive inhibition. Thus, in contrast to pure-culture results, SRM in communities cope with perchlorate stress via changes in anion transport and its regulation. This highlights the value of probing evolutionary questions in an ecological framework, bridging the gap between ecology, evolution, genomics, and physiology.


Coronary subclavian steal syndrome due to thrombosis of the left subclavian artery aneurysm: a case report.
Coronary subclavian steal syndrome (CSSS) is an often easily overlooked cause of angina that may occur after a coronary artery bypass graft (CABG) procedure. The onset of CSSS several years after coronary revascularization has been described in case reports, and in the few retrospective reviews that compare the endovascular approach with surgical treatment. Subclavian stenosis can naturally coincide with coronary artery disease and may already be present during the initial CABG. A 59-year-old male with a history of three-vessel disease who had a left internal mammary artery (LIMA) bypass graft, exhibited a gradual worsening of angina that coincided with numbness and impaired function of the left fingers, hand, and arm. Myocardial perfusion imaging showed reversible ischaemia, and coronary angiography suggested a thrombotic lesion proximal to the LIMA ostium. Calcified and partially thrombosed proximal left subclavian artery (LSA) aneurysm was visualized using computed tomography imaging, whereas Doppler ultrasound revealed a partially reversed vertebral flow. The lowest risk treatment was a bypass between the left common carotid artery and the LSA. The procedure was immediately successful, with cessation of symptoms and a favourable medium-term outcome. As no guidelines exist for such cases, the importance of multidisciplinary co-operation in diagnostics and devising a treatment plan is underlined. Moreover, screening for subclavian artery stenosis in CABG candidates should be warranted as part of the initial preoperative assessment.


[Dilemmas in biliary tract surgery].
Operations on the biliary system rank among the most frequent abdominal surgical procedures. Discovery of the chenodeoxycholic acid brought about no changes in treatment of cholelithiasis. The paper deals with the problems of residual stones, injuries to the hepatic artery and bile ducts, surgical treatment of stenosis of the bile ducts, cholecystitis, cholangitis and papila of Vater conditions. Since the paper is conceived as a basis for the round table duscussion, it only indicates the issues to be dealt with.