Lack of Activation of Mitophagy during Endurance Exercise in Human.
This study aimed to determine whether fission and mitophagy are activated by acute endurance exercise in human skeletal muscle and to investigate if this activation is dependent upon the nutritional state. Trained athletes (n = 7) cycled for 2 h at 70% V˙O2peak in a fed or fasted state. Vastus lateralis muscle biopsies were obtained at baseline, before, immediately after, and 1 h after exercise. Protein and mRNA markers for mitophagy, mitochondrial biogenesis, fission, and fusion were analyzed using quantitative real-time polymerase chain reaction and Western blot. Fission, assessed by phospho-DRP1 in the mitochondrial fraction, increased postexercise and 1 h postexercise only in the fed state. LC3bII and p62/SQSTM1 in the mitochondrial fraction were unchanged, whereas the LC3bII/LC3bI ratio was decreased only postexercise in the fasted state (P = 0.019), indicating a reduced mitophagy. Genes implicated in fission and mitophagy, such as Drp1, Bnip3, and Bnip3L, and proteins involved in fission (Fis1) or mitophagy (BNIP3) were all more expressed after exercise in the fed state (P < 0.05). As expected, the mRNA levels of PGC1α, Tfam, and Hsp60, all markers of mitogenesis, were increased after endurance exercise, but to a larger extent in the fed than that in the fasted state. The present study provides the very first evidence that mitophagy is not activated during and early after high-intensity endurance exercise in human, whatever the nutritional state, despite a selective activation of fission in the fed state. However, when nutrient availability is optimal, muscle cells seem capable of preparing mitochondria for lysosomal degradation. Thus, we may not exclude an activation of mitophagy at a later stage after exercise.


The mTOR/p70S6K1 signaling pathway in renal fibrosis of children with immunoglobulin A nephropathy.
The purpose of this study was to explore whether mTOR/p70S6K1 signaling is activated in renal fibrosis of immunoglobulin A nephropathy. Seventy-two children with immunoglobulin A nephropathy were divided into three groups according to their clinical features and pathological grades. Six normal renal specimens were included in the control group. The expression levels of angiotensin II, mTOR, p70S6K1, E-cadherin, and α-smooth muscle actin in renal tissues were determined by immunohistochemistry method, the potential correlations of these indexes and relationship between these indexes and the clinicopathological indexes were analyzed. Compared to the control group, the expression levels of angiotensin II, mTOR, p70S6K1, and α-smooth muscle actin were significantly higher and the expression levels of E-cadherin were lower both in glomeruli and tubulointerstitium of immunoglobulin A nephropathy children. And the most significant differences were found in the nephrotic syndrome group and pathological grade IV group. In immunoglobulin A nephropathy renal tissues, the expression levels of angiotensin II in glomeruli and tubulointerstitium were both positively correlated with the expression levels of mTOR and α- smooth muscle actin, and negatively correlated with the expression levels of E-cadherin. The mTOR/p70S6K1 signaling was activated in renal tissues of children with immunoglobulin A nephropathy, and future studies will need to address the mechanism of mTOR/p70S6K1 signaling in the progress of renal fibrosis in immunoglobulin A nephropathy.


Context-dependent modulation of interlimb cutaneous reflexes in arm muscles as a function of stability threat during walking.
Cutaneous reflexes evoked in the muscles of the arms with electrical stimulation of nerves of the foot ("interlimb reflexes") are observed during walking. These reflexes have been suggested to coordinate the actions of the legs and arms when walking is disturbed. Recently, we showed that cutaneous reflexes evoked in the leg muscles after stimulation at the foot are modulated according to the level of postural threat during walking. We hypothesized that the amplitude of interlimb cutaneous reflexes would similarly be modulated when subjects walk in unstable environments. Subjects walked on a treadmill under four walking conditions: 1) normal; 2) normal with unpredictable anterior-posterior (AP) perturbations; 3) arms crossed; and 4) arms crossed with unpredictable AP perturbations. Interlimb reflexes evoked from electrical stimulation of the right superficial peroneal or sural nerves were recorded bilaterally, at four points of the step cycle. These reflexes were compared between conditions in which the arms were moving in a similar manner: 1) normal versus AP walking and 2) arms crossed versus arms crossed with AP perturbations. Differences in reflex amplitudes between arms-crossed conditions were observed in most upper limb muscles when subjects were perturbed while walking compared with undisturbed walking. This effect was less apparent when the arms were swinging freely. The results indicate that the strength of interlimb connections is influenced by the level of postural threat (i.e., the context of the behavior), thereby suggesting that these reflexes serve a functional link between the legs and arms during locomotion.


The WHO abortion care guideline: Law and policy-Past, present, and future.
In the 2022 Abortion Care Guideline, the World Health Organization (WHO) undertook systematic evidence reviews of seven law and policy interventions to assess their health and social impacts. Distinct recommendations were formulated for each. The present article highlights how the Guideline reconceptualizes abortion regulation as a complex structural intervention that shapes clinical care and service delivery and distributes risks and resources within these systems and in the care relations that define them. It then presents the Guideline recommendations and summarizes their evidence base, drawing on recent legal and policy developments to emphasize their real-world significance. The article concludes by anticipating the future of abortion law and policy, focusing on service delivery innovations and diverse care models, drug regulation and the supply of abortion pills, and protective interventions crafted in the context of political crisis and immediate need that serve policy objectives and take regulatory forms different from the past.


Beneficial effects of the β-secretase inhibitor GRL-8234 in 5XFAD Alzheimer's transgenic mice lessen during disease progression.
The β-secretase enzyme BACE1, which initiates the cleavage of amyloid precursor protein (APP) into the amyloid-β (Aβ) peptide, is a prime therapeutic target for Alzheimer's disease (AD). However, recent investigations using genetic animal models raise concern that therapeutic BACE1 inhibition may encounter the dramatic reduction of efficacy in ameliorating AD-like pathology and memory deficits during disease progression. Here, we compared the effects of the potent and selective small-molecule BACE1 inhibitor GRL-8234 in different pathological stages of AD mouse model. Specifically, we administered GRL-8234 (33.4 mg/kg, i.p.) once daily for 2 months to 5XFAD transgenic mice, which showed modest (4 months) and massive (10 months of age) Aβ plaque deposition at starting points. Chronic treatments with GRL-8234 reversed memory impairments, as tested by the spontaneous alternation Y-maze task, in the younger 5XFAD group concomitant with significant reductions in cerebral Aβ42 levels. In contrast, only marginal reductions of Aβ42 were observed in 12-month-old 5XFAD mice treated with GRL-8234 and their memory function remained impaired. We found that not only BACE1 but also full-length APP expression was significantly elevated with progressive Aβ accumulation in 5XFAD mice, while GRL-8234 failed to affect these detrimental mechanisms that further accelerate plaque growth in brains of older 5XFAD mice. Therefore, our results provide important insights into the mechanisms by which Aβ accumulation and related memory impairments become less responsive to rescue by BACE1 inhibition during the course of AD development.


Vibrational and electronic circular dichroism of delta-TRISPHAT [tris(tetrachlorobenzenediolato)phosphate(V)] anion.
Herein is reported an experimental and theoretical study of the circular dichroism properties of TRISPHAT (1) anion. ECD analysis of the [tetramethylammonium][delta-1] salt confirms the absolute configuration assignment obtained through X-ray crystallographic analysis of the parent cinchonidium salt. The structure, infrared, and vibrational circular dichroism (VCD) spectra derived from density functional theory (DFT) calculations are compared with experimental data.


In vivo calcium imaging reveals functional rewiring of single somatosensory neurons after stroke.
Functional mapping and microstimulation studies suggest that recovery after stroke damage can be attributed to surviving brain regions taking on the functional roles of lost tissues. Although this model is well supported by data, it is not clear how activity in single neurons is altered in relation to cortical functional maps. It is conceivable that individual surviving neurons could adopt new roles at the expense of their usual function. Alternatively, neurons that contribute to recovery may take on multiple functions and exhibit a wider repertoire of neuronal processing. In vivo two-photon calcium imaging was used in adult mice within reorganized forelimb and hindlimb somatosensory functional maps to determine how the response properties of individual neurons and glia were altered during recovery from ischemic damage over a period of 2-8 weeks. Single-cell calcium imaging revealed that the limb selectivity of individual neurons was altered during recovery from ischemia, such that neurons normally selective for a single contralateral limb processed information from multiple limbs. Altered limb selectivity was most prominent in border regions between stroke-altered forelimb and hindlimb macroscopic map representations, and peaked 1 month after the targeted insult. Two months after stroke, individual neurons near the center of reorganized functional areas became more selective for a preferred limb. These previously unreported forms of plasticity indicate that in adult animals, seemingly hardwired cortical neurons first adopt wider functional roles as they develop strategies to compensate for loss of specific sensory modalities after forms of brain damage such as stroke.


Bedside diagnostics in dermatology: Parasitic and noninfectious diseases.
In addition to aiding the diagnosis of viral, bacterial, and fungal diseases, mineral oil preparation, Tzanck smear, and other techniques can be used to diagnose parasitic infections, neonatal pustular dermatoses, blistering diseases, Stevens-Johnson syndrome, and a plethora of other benign and malignant conditions, including granulomatous diseases and tumors. In many cases, these techniques are specific, reliable, and easy to perform and interpret. In others, a certain amount of training and expertise are required. In the proper clinical scenario, these tests are rapid, economical, and compare favorably with other diagnostic methods.


Vapor-phase synthesis of indium (III) oxide nanocrystals.
A new way for chemical vapor deposition of indium (111) oxide is presented. It can be used to obtain both polycrystalline films and different arrays of nanocrystals. Used as a catalyst, In or Au thin films can afford selective deposition on an arbitrary spot of surface. The obtained materials were characterized electron microscopy, X-ray diffraction and cathodoluminescence methods.


Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN).
Proliferation of squamous cell carcinoma of the head and neck (SCCHN) depends on epidermal growth factor receptor (EGFR) expression. The EGFR activates different signal pathways leading to gene transcription in the nucleus due to cell cycle progression and proliferation of tumor cells. AKT, STAT3 and MAPK play central roles in these pathways. However, they are not only regulated by the EGFR. We therefore investigated whether a specific inhibitor of the EGFR tyrosine kinase (ZD 1839 or Iressa) is able to inhibit phosphorylation of these three signals at the same time. Western blot analysis of pretreated SCCHN cells revealed that ZD 1839 greatly reduces the amount of phosphorylated AKT, STAT3 as well as MAPK Surprisingly, this effect was not dose-dependent between the concentration range of 5.15 to 41.2 microM/ml. We conclude that Iressa has a high potency to inhibit nuclear gene transcription responsible for cell cycle progression. Furthermore, dose reduction of Iressa in the case of toxicity may not severely influence the response to treatment.


Less efficient information transfer in Cys-allele carriers of DISC1: a brain network study based on diffusion MRI.
Previous neuroimaging studies of brain networks have revealed less efficient information transfer in patients with schizophrenia. However, the underlying genetic basis remains largely unexplored. In this study, we investigated the brain anatomical networks of 278 healthy volunteers with different genotypes in the common missense variant (Ser704Cys) of the Disrupted-in-Schizophrenia-1 (DISC1) gene, which is one of the main susceptibility genes of schizophrenia and other psychiatric disorders. The anatomical brain network for each individual was constructed using fiber tractography technique based on diffusion magnetic resonance imaging (dMRI). The properties of this network were then calculated using graph theory. This revealed that Cys-allele carriers showed significantly lower global efficiency of their brain networks than Ser homozygotes, thereby supporting our hypothesis that genetic variation in DISC1 may relate to the risk of schizophrenia by affecting the efficiency of brain network. Additional dMRI analyses were also performed at different levels, with a convergent trend towards decreased white matter integrity being consistently observed in Cys-allele carriers. Together these findings not only provide new clues for understanding DISC1 function, but also suggest that network analyses based on graph theory combined with neuroimaging techniques may reveal structural disruptions related to genetic risk in the brains of healthy individuals.


PCR/RFLP-based allelic variants of streptokinase and their plasminogen activation potencies.
PCR-restriction fragment length polymorphism (PCR/RFLP)-based analysis of β-domain variable region of streptokinase genes (sk) has previously identified 14 sk alleles (sk1-sk14) in group A (GAS), C (GCS) and G (GGS) streptococci isolates from a few geographically distinct regions. However, the relation of sk allelic variants to their plasminogen activation potencies remained as a matter of debate. Herein, employing the same PCR/RFLP assay, we analysed sk allelic variants of GAS and GCS/GGS isolates from Iranian patients. In total, 21 sk allelic variants including 14 new alleles (sk14-sk28) were identified. Results implied the horizontal gene transfer of sk fragments between GAS and GCS/GGS strains and did not prove the specificity of particular sk alleles to GCS/GGS or GAS groups. Measurement of streptokinase (SK) activity in streptococcal culture supernatants by colorimetric assay (S2251 substrate) ranged from 9 to 182 IU mL(-1). Although some strains with the highest SK activity were detected in definite variants, no significant correlation between sk alleles and plasminogen activation was detected (P value > 0.05). Analysis of DNA sequences and restriction site mapping of selective sk variants with similar SK activity pointed to the inadequacy of the currently available PCR/RFLP method for differentiation of critical/silent nucleotides to precisely categorize sk alleles for their functional properties.


Heuristic Iron-Cobalt-Mediated Robust pH-Universal Oxygen Bifunctional Lusters for Reversible Aqueous and Flexible Solid-State Zn-Air Cells.
Rechargeable aqueous zinc-air cells (ZACs) promise an extremely safe and high energy technology. However, they are still significantly limited by sluggish electrochemical kinetics and irreversibility originating from the parasitic reactions of the bifunctional catalysts and electrolytes. Here, we report the preferential in situ building of interfacial structures featuring the edge sites constituted by FeCo single/dual atoms with the integration of Co sites in the nitrogenized graphitic carbon frameworks (FeCo SAs@Co/N-GC) by electronic structure modulation approach. Compared to commercial Pt/C and RuO2, FeCo SAs@Co/N-GC reveals exceptional electrochemical performance, reversible redox kinetics, and durability toward oxygen reduction and evolution reactions under universal pH environments, i.e., alkaline, neutral, and acidic, due to synergistic effect at interfaces and preferred charge/mass transfer. The aqueous (alkaline, nonalkaline, and acidic electrolytes) ZACs constructed with a FeCo SAs@Co/N-GC cathode tolerate stable operations, have significant reversibility, and have the highest energy densities, outperforming those of noble metal counterparts and state-of-the-art ZACs in the ambient atmosphere. Additionally, flexible solid-state ZACs demonstrate excellent mechanical and electrochemical performances with a highest power density of 186 mW cm-2, specific capacity of 817 mAh gZn-1, energy density of 1017 Wh kgZn-1, and cycle life >680 cycles with extremely harsh operating conditions, which illustrates the great potential of triphasic catalyst for green energy storage technologies.


Group self-identification and adolescent cigarette smoking: a 1-year prospective study.
As an extension of previous work, we analyzed the longitudinal relations between group self-identification and adolescent cigarette smoking. The predictive precedence of cigarette smoking and identification with 6 different types of peer groups was examined. Results indicated that 7th-grade group self-identification predicted 8th-grade cigarette smoking, whereas 7th-grade cigarette smoking did not predict 8th-grade group self-identification. Group self-identification also was compared with 7 other psychosocial variables as predictors of smoking 1 year later. The pattern of results suggests that group self-identification is about as good a predictor of smoking as other psychosocial variables, and that group self-identification is more than a mere proxy of other psychosocial variables.


Purified compounds and extracts from Euclea species with antimycobacterial activity against Mycobacterium bovis and fast-growing mycobacteria.
Naphthoquinones and other compounds with antimycobacterial activity against Mycobacterium tuberculosis have previously been isolated from Euclea species. In this study, several constituents of Euclea natalensis and E. undulata, as well as organic extracts of the leaves, were assessed for efficacy against the zoonotic pathogen, Mycobacterium bovis. Also included in the battery of test organisms were M. bovis BCG and the fast-growing species M. smegmatis and M. fortuitum. The acetone extract of E. natalensis had potent activity against M. bovis (MIC=26 microg/ml). The naphthoquinone 7-methyljuglone was the most active compound, with an MIC as low as 1.55 microg/ml against pathogenic M. bovis. M. bovis BCG was not as susceptible to the test compounds as the pathogenic strain, but similar patterns of activity were observed between all the strains tested. M. smegmatis appeared to be a better predictor of antimycobacterial activity against pathogenic M. bovis (and M. tuberculosis), while MIC values obtained using M. fortuitum correlated well with those of M. bovis BCG.


Ras-related protein Rap2c promotes the migration and invasion of human osteosarcoma cells.
Ras-related protein (Rap)2a and Rap2b are members of the GTP-binding protein family, and serve an important function in tumor progression. However, the associations between Rap2c and cancer cell functions have not yet been reported. Osteosarcoma is a type of bone cancer; its high degree of invasion is considered to be a major treatment challenge. The present study first investigated the biological role of Rap2c in human osteosarcoma cells and investigated the underlying mechanism of Rap2c on osteosarcoma cell migration and invasion. The results of the present study demonstrated that Rap2c overexpression promoted the migratory and invasive ability of cancer cells, and increased the activity of matrix metalloproteinase-2 (MMP2). Correspondingly, the knockdown of Rap2c inhibited tumor cell migration and invasion, whereas alterations to Rap2c had no effect on osteosarcoma cell proliferation or rate of apoptosis. Furthermore, Rap2c overexpression may decrease the protein level of tissue inhibitor of metalloproteinases 2 and increase the phosphorylation level of protein kinase B (Akt). Collectively, these results indicated that Rap2c has a key function in tumor migration and invasion, and the Akt signaling pathway may be involved in Rap2c-induced MMP2 expression.


Hotspots and trends in fNIRS disease research: A bibliometric analysis.
To summarize the general information and hotspots of functional near-infrared spectroscopy (fNIRS)-based clinical disease research over the past 10 years and provide some references for future research. The related literature published between 1 January 2011 and 31 January 2022 was retrieved from the Web of Science core database (WoS). Bibliometric visualization analysis of countries/regions, institutions, authors, journals, keywords and references were conducted by using CiteSpace 6.1.R3. A total of 467 articles were included, and the annual number of articles published over nearly a decade showed an upward trend year-by-year. These articles mainly come from 39 countries/regions and 280 institutions. The representative country and institution were the USA and the University of Tubingen. We identified 266 authors, among which Andreas J Fallgatter and Ann-Christine Ehlis were the influential authors. Neuroimage was the most co-cited journal. The major topics in fNIRS disease research included activation, prefrontal cortex, working memory, cortex, and functional magnetic resonance imaging (fMRI). In recent years, the Frontier topics were executive function, functional connectivity, performance, diagnosis, Alzheimer's disease, children, and adolescents. Based on the burst of co-cited references, gait research has received much attention. This study conducted a comprehensive, objective, and visual analysis of publications, and revealed the status of relevant studies, hot topics, and trends concerning fNIRS disease research from 2011 to 2022. It is hoped that this work would help researchers to identify new perspectives on potential collaborators, important topics, and research Frontiers.


Transoesophageal spinal cord stimulation for motor-evoked potentials monitoring: feasibility, safety and stability.
Specificity of transcranial motor-evoked potentials (MEPs) is low because amplitude fluctuation is common, which seems due to several technical and fundamental reasons including difficulty in electrodes positioning and fixation for transcranial stimulation and susceptibility to anaesthesia. This study aimed to investigate the feasibility, safety and stability of our novel technique of transoesophageal spinal cord stimulation to improve the stability of MEPs. Ten anaesthetized adult beagle dogs were used. Transoesophageal stimulation was performed between the oesophageal luminal surface electrode (cathode) and a subcutaneous needle electrode (anode) at the fourth to fifth thoracic vertebra level. Stimulation was achieved with a train of five pulses delivered at 2.0-ms intervals. Compound muscle action potentials were recorded from four limbs and external anal sphincter muscles. Stability to anaesthetic agents was tested at varying speeds of propofol and remifentanil, and effects of varying concentration of sevoflurane inhalation were also evaluated. Transoesophageal MEPs could be recorded without difficulty in all dogs. Fluoroscopic evaluation showed that electrodes misalignment up to 5 cm cranially or caudally could be tolerated. Stimulus intensity to achieve maximum amplitude of hindlimb muscle potentials on both sides was significantly lower by transoesophageal stimulation than by transcranial stimulation (383 ± 41 vs 533 ± 121 V, P = 0.02) and had less interindividual variability. Latency of transoesophageal MEPs was shorter than that of transcranial MEPs at every recording point. No arrhythmia was provoked during stimulation. Animals that were allowed to recover showed no neurological abnormality. In the two sacrificed animals, the explanted oesophagus showed no mucosal injury. Stability to varying dose of anaesthetic agents was similar between transoesophageal and transcranial stimulation, except for the potentials of forelimbs by transoesophageal stimulation that were resistant to anaesthetic depression. Transoesophageal stimulation for MEPs monitoring was feasible without difficulty and safe. Although its stability to anaesthetic agents was similar to that of transcranial stimulation, its technical ease and small interindividual variability warrants further studies on the response to spinal cord ischaemia.


Dicer promotes transcription termination at sites of replication stress to maintain genome stability.
Nuclear RNAi is an important regulator of transcription and epigenetic modification, but the underlying mechanisms remain elusive. Using a genome-wide approach in the fission yeast S. pombe, we have found that Dcr1, but not other components of the canonical RNAi pathway, promotes the release of Pol II from the 3? end of highly transcribed genes, and, surprisingly, from antisense transcription of rRNA and tRNA genes, which are normally transcribed by Pol I and Pol III. These Dcr1-terminated loci correspond to sites of replication stress and DNA damage, likely resulting from transcription-replication collisions. At the rDNA loci, release of Pol II facilitates DNA replication and prevents homologous recombination, which would otherwise lead to loss of rDNA repeats especially during meiosis. Our results reveal a novel role for Dcr1-mediated transcription termination in genome maintenance and may account for widespread regulation of genome stability by nuclear RNAi in higher eukaryotes.


Developmental differences according to age at onset in juvenile bipolar disorder.
This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.


Tbx2 confers poor prognosis in glioblastoma and promotes temozolomide resistance with change of mitochondrial dynamics.
Tbx2 is a cancer-related protein that was found to be overexpressed in several human malignancies. The present study aims to investigate the clinical significance and biological role of Tbx2 in human astrocytoma. We examined its protein expression in 102 cases of astrocytoma tissues using immunohistochemical staining. Negative Tbx2 staining was observed in normal astrocytes, and positive nuclear staining was found in 41 out of 102 astrocytoma specimens. The rate of Tbx2 overexpression in pylocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma multiform (GBM) were 0%, 26.1%, 40%, and 52%, respectively. Tbx2 overexpression correlated with poor prognosis in patients with astrocytoma or GBM. Tbx2 plasmid transfection was performed in A172 cells, and Tbx2 siRNA knockdown was carried out in U251 cells. Cell Counting Kit-8, cell cycle analysis, and matrigel invasion assay showed that Tbx2 overexpression upregulated cell proliferation, G1-S transition, and invasion, with corresponding change of cyclin D1, p21, and MMP 2 and 9. Importantly, we demonstrated that Tbx2 reduced apoptosis and conferred resistance to temozolomide in GBM cell lines. Further experiments showed that Tbx2 could regulate mitochondrial fission/fusion balance. Western blot showed that Tbx2 overexpression reduced caspase 3 cleavage, while it induced Bcl-2 and p-Drp1 upregulation. In conclusion, our results indicated that Tbx2 might serve as an indicator for poor prognosis and also be useful as an important therapeutic in human GBM, which inhibits apoptosis through regulation of mitochondrial function.


Invited Commentary: Improving Instruments to Counter the Bias in Their Construction.
In this issue of the Journal, Villalonga-Olives et al. (Am J Epidemiol. 2023;192(8):1264-1273) examined the psychometric properties of social capital indicators, comparing responses from Black and White people to identify whether there was differential item functioning (DIF) in social capital by race, and also when stratified by educational attainment, as a measure of socioeconomic status. The authors tested whether there is DIF in social capital items between Black and White people and found that DIF across these items was significant although not large, but they were still indicative of measurement error, which they suspected was related to the way these items were developed-that is, based on cultural assumptions tested in mainstream White America. However, some gaps remain to be fleshed out.


Dendroaxonic synapses in the substantia gelatinosa glomeruli of the spinal trigeminal nucleus of the cat.
The glomeruli in the substantia gelatinosa layer of the spinal trigeminal nucleus of the cat contain three kinds of dendritic processes. One of these, the type 2 dendrite, contains large synaptic vesicles in its spine heads and in its shafts. The type 2 dendrite receivers axodendritic synapses from primary trigeminal afferent (C) axons and an occasional axodendritic synapse from small axonal (P) endings with small synaptic vesicles. The type 2 dendrites in turn form dendroaxonic synapses on the C endings. The dendroaxonic synapse and the axodendritic synapse of the C ending typically occur in reciprocal pairs. The axodendritic synapse usually lies in the depths of scalloped depressions in the surface of the C ending while the dendroaxonic synapse is found on the rim of the depression. Type 1 spines, i.e., dendritic spines receiving axodendritic synapses from the primary ending and lacking synaptic vesicles, also receive dendrodentritic synapses from type 2 dendrites. The type 2 dendrite with its large, rounded synaptic vesicles is considered to be excitatory at its dendroaxonic and dendrodendritic synapses. The type 2 dendrites course from glomerulus to glomerulus receiving their excitatory input through the axodendritic synapses of C axons. A type 2 dendrite, in response to C axon excitation would activate type 1 spines directly through their dendrodendritic synapses (C leads to 2 leads to 1) and indirectly by increasing transmitter release at the axodendritic synapses of the C axonal endings through their dendroaxonic synapses (2 leads to C leads to 1). The type 2 dendrites could serve two functions. First, they may prolong transmitter release from the axodendritic synapses of C axonal endings beyond the time of arrival of incoming potentials because of the reciprocal pairing of dendroaxonic and axodendritic synapses (C in equilibrium 2). Second, they may extend the spatial range of the excitatory output of active primary afferent axons to type 1 spines of glomeruli whose primary afferent axons may be inactive (C leads to 2 leads to 1).


Electrochemical Properties of Graphene Oxide/Resol Composites as Electrode Materials for Supercapacitor Applications.
RGO/Resol carbon composites were prepared from a mixture of reduced GO and a low-molecular-weight phenolic resin (Resol) solution. The effects of the calcination temperature, amount of Resol added and KOH treatment on the electrochemical performance of the RGO/Resol composites were investigated. The physical and electrochemical properties of the composite materials were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Brunauer, Emmett and Teller (BET) surface areas measurements, and cyclic voltammetry (CV). The relationships between their physical properties and their electrochemical performance were examined for use as super-capacitors (SCs). The RGO/Resol composite calcined at 400 degrees C after the KOH loading showed dramatically improved electrochemical properties, showing a high BET surface and capacitance of 2190 m2/g and 220 F/g, respectively. The RGO/Resol composites calcined after the KOH treatment showed much better capacitor performance than those treated only thermally at the same temperature without KOH impregnation. The fabrication of high surface electrodes was essential for improving the SCs properties.


Pedestrian road crossing behavior (PEROB): Development and psychometric evaluation.
The aim of this study was to develop a theory-based questionnaire to measure road crossing attitudes and potentially risky pedestrian behavior. A cross-sectional validation study was carried out on a total sample of 380 young adults aged 18 to 25 years who live in Tehran, Iran. Data were collected from January 27 to May 20, 2015, using a self-administered structured pool of 76 items that was developed from research on the theory of planned behavior. A panel of subject-matter experts evaluated the items for content validity index and content validity ratio, and the questionnaire was pretested. Exploratory factor analysis (EFA) was performed to test construct validity. The Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) analyses were done to assess internal consistency and stability of the scale. From the initial 76 items, 38 items were found to be appropriate for assessing the pedestrian road crossing behavior (PEROB) of young adults in Tehran. A 9-factor solution revealed an exploratory factor analysis that jointly accounted for 63.8% of the variance observed. Additional analyses also indicated acceptable results for the internal consistency with Cronbach's alpha value ranging from 0.67 to 0.88 and ICC values ranging from 0.64 to 0.96. This psychometric evaluation of a self-administered instrument resulted in a reliable and valid instrument to assess young adult pedestrians' self-reported road crossing attitudes and behaviors in Tehran. Further development of the instrument is needed to assess its applicability to other road users, particularly older pedestrians.


Dose Effects of Ammonium Perfluorooctanoate on Lipoprotein Metabolism in APOE*3-Leiden.CETP Mice.
Epidemiological studies have reported positive associations between serum perfluorooctanoic acid (PFOA) and total and non-high-density lipoprotein cholesterol (non-HDL-C) although the magnitude of effect of PFOA on cholesterol lacks consistency. The objectives of this study were to evaluate the effect of PFOA on plasma cholesterol and triglyceride metabolism at various plasma PFOA concentrations relevant to humans, and to elucidate the mechanisms using APOE*3-Leiden.CETP mice, a model with a human-like lipoprotein metabolism. APOE*3-Leiden.CETP mice were fed a Western-type diet with PFOA (10, 300, 30 000 ng/g/d) for 4-6 weeks. PFOA exposure did not alter plasma lipids in the 10 and 300 ng/g/d dietary PFOA dose groups. At 30 000 ng/g/d, PFOA decreased plasma triglycerides (TG), total cholesterol (TC), and non-HDL-C, whereas HDL-C was increased. The plasma lipid alterations could be explained by decreased very low-density lipoprotein (VLDL) production and increased VLDL clearance by the liver through increased lipoprotein lipase activity. The concomitant increase in HDL-C was mediated by decreased cholesteryl ester transfer activity and changes in gene expression of proteins involved in HDL metabolism. Hepatic gene expression and pathway analysis confirmed the changes in lipoprotein metabolism that were mediated for a major part through activation of the peroxisome proliferator-activated receptor (PPAR)α. Our data confirmed the findings from a phase 1 clinical trial in humans that demonstrated high serum or plasma PFOA levels resulted in lower cholesterol levels. The study findings do not show an increase in cholesterol at environmental or occupational levels of PFOA exposure, thereby indicating these findings are associative rather than causal.


Female ultrasonic vocalizations have no incentive value for male rats.
Ultrasonic vocalizations (USVs) are emitted in response to a sexual partner before, during, and after copulation. These vocalizations are the so-called 50-kHz USVs and can be subdivided into flat and frequency-modulated (FM) 50-kHz trill calls. In the present series of experiments, the potential unconditioned and conditioned incentive properties of female 50-kHz USVs for male rats were examined. USVs were recorded from sexually receptive females during the precopulatory phase. A complete 10-min song, or single flat or FM trill calls were selected as auditory stimuli for Experiments 1 and 2. As FM trill calls, a multistep call was used in Experiments 1 and 2a, and an upward ramp call was used in Experiment 2b. The auditory stimuli were played back with a loudspeaker to naïve and sexually experienced male rats in a sexual incentive motivation test. The odor of a sexually receptive female rat was also used as an incentive stimulus for comparison. In a third experiment, a devocalized female, a sham female and a male rat were used as incentive stimuli. It was found that the auditory stimuli did not induce approach behavior in naïve and sexually experienced male rats, but the olfactory stimulus did. In addition, the males spent equal amounts of time in the vicinity of devocalized and vocalizing females. These data show that 50-kHz USVs neither are unconditioned nor conditioned incentives for male rats.


Overexpression of Ets-like protein 1 in human esophageal squamous cell carcinoma.
To study the expression pattern of Ets-like protein 1 (Elk-1) in human esophageal squamous cell carcinoma (ESCC) and to analyze its relationship with clinicopathologic parameters. The expression of Elk-1 in fresh esophageal cancer tissues and their corresponding normal mucosae was detected immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 13.0. Expression level of transcription factor Elk-1 increased in 78.5% (84/107) ESCC tissues compared with their matched normal esophageal epithelium. However, the expression of Elk-1 did not show any obvious correlation with degree of differentiation of esophageal carcinoma (in well-differentiated, moderately-differentiated and poorly-differentiated tumors, the increased expression was 7/8, 60/74, and 19/25, respectively, P > 0.05). Moreover, no obvious correlation was found with lymph node metastasis and depth of invasion. Increased expression of transcription factor Elk-1 may play an important role in esophageal carcinogenesis.


Multi-detector row CT attenuation measurements: assessment of intra- and interscanner variability with an anthropomorphic body CT phantom.
To determine the dependence of absolute computed tomographic (CT) attenuation values on multi-detector row CT scanner type, convolution kernel, and tube current by using an anthropomorphic phantom. A customized phantom was designed with tissue-equivalent materials to simulate contrast material-enhanced liver, spleen, pancreas, aorta, kidney, 0- and 50-HU cylindric renal cysts, muscle, and fat. The phantom was scanned with five multi-detector row CT scanners (LightSpeed QXi, GE Healthcare, Milwaukee, Wis; MX8000, Philips Medical Systems, Best, the Netherlands; and Volume Zoom, Sensation 16 and Sensation 64, Siemens Medical Solutions, Forchheim, Germany) on five separate occasions with 120 kVp, low and high tube current settings, 3.00-3.75-mm section thickness, 50% overlap, and standard and high-spatial-resolution kernels. Standardized regions of interest (ROIs) were used to obtain 3510 attenuation measurements. Attenuation dependence on scanner, kernel, and tube current was evaluated by using F tests derived with mixed-model regression. Within the mixed-model framework, the Tukey honestly significant difference procedure and a Bonferroni multiple comparison correction were used to assess differences among imaging regimens and tube current settings, respectively, in terms of tissue attenuation and ROI standard deviation. Tube current had no significant effect (P>.4) on observed tissue attenuation. Significant (P<.0001) differences were observed between imaging regimens with respect to mean attenuation for each tissue type. Convolution kernel modification had an inconsistent effect on tissue attenuation, depending on the scanner. All multi-detector row CT scanners displayed intrascanner variability in tissue attenuation (minimum range: 8.4 HU for fat tissue with the Sensation 16; maximum range: 63.4 HU for liver tissue with the Sensation 64). The scanners behaved differently at the lower range of the CT number scale, where 0-HU cyst attenuation ranged from -15.7 to 23.9 HU and one vendor's equipment showed significantly lower mean attenuation values. CT attenuation values vary significantly between different manufacturers' multi-detector row CT scanners, among different generations of multi-detector row CT scanning equipment, and with individual combinations of scanner and convolution kernel. http://radiology.rsnajnls.org/cgi/content/full/242/1/109/DC1


Anomalous settlement behavior of Ulva linza zoospores on cationic oligopeptide surfaces.
Identification of settlement cues for marine fouling organisms opens up new strategies and methods for biofouling prevention, and enables the development of more effective antifouling materials. To this end, the settlement behaviour of zoospores of the green alga Ulva linza onto cationic oligopeptide self-assembled monolayers (SAMs) has been investigated. The spores interact strongly with lysine- and arginine-rich SAMs, and their settlement appears to be stimulated by these surfaces. Of particular interest is an arginine-rich oligopeptide, which is effective in attracting spores to the surface, but in a way which leaves a large fraction of the settled spores attached to the surface in an anomalous fashion. These 'pseudo-settled' spores are relatively easily detached from the surface and do not undergo the full range of cellular responses associated with normal commitment to settlement. This is a hitherto undocumented mode of settlement, and surface dilution of the arginine-rich peptide with a neutral triglycine peptide demonstrates that both normal and anomalous settlement is proportional to the surface density of the arginine-rich peptide. The settlement experiments are complemented with physical studies of the oligopeptide SAMs, before and after extended immersion in artificial seawater, using infrared spectroscopy, null ellipsometry and contact angle measurements.


Poisonings resulting from the ingestion of magic mushrooms in Kraków.
Hallucinogenic mushrooms, also called "magic mushrooms", are becoming a more frequent cause of abuse, especially among young people, who use them experimentally for recreational purposes. In the autumn of 2004, several people were admitted to and observed in the Department of Clinical Toxicology in Krakòw after they had used magic mushrooms to experience hallucinatory sensations. Three of them had visual hallucinations, and the fourth experienced both visual and auditory hallucinations followed by the exogenous psychosis after use of Psilocybe semilanceata. One person was hospitalised for several days while the others were observed in the emergency department. The main source of information for patients about hallucinogenic mushrooms was the internet. In the cases discussed the mushroom poisoning caused no organ damage and the symptoms disappeared in about 6 hours.


Trends in community violence in England and Wales 2005-2009.
Injury records from Emergency Departments (EDs) have been studied over the last decade as part of the work of the National Violence Surveillance Network (NVSN) and provide information about local, regional and national violence levels and trends in England and Wales. The purpose of the current study is to evaluate overall, gender, age-specific and regional trends in community violence in England and Wales from an ED perspective from January 2005 to December 2009. Violence-related injury data were collected prospectively in a stratified sample of 77 EDs (Types 1, 3 and 4) in the nine Government Office Regions in England and in Wales. All 77 EDs were recruited on the basis that they had implemented and continued to comply with the provisions of the 1998 Data Protection Act and Caldicott guidance. Attendance date, age and gender of patients who reported injury in violence were identified using assault-related attendance codes, specified at the local level. Time series statistical methods were used to detect both regional and national trends. In total 221,673 (163,384 males: 74%) violence-related attendances were identified. Overall estimated annual injury rate was 6.5 per 1000 resident population (males 9.8 and females 3.4 per 1000). Violence affecting males and females decreased significantly in England and Wales over the 5-year period, with an overall estimated annual decrease of 3% (95% CI: 1.8-4.1%, p<0.05). Attendances decreased significantly for both genders across four out of the five age groups studied. Attendances were found to be highest during the months of May and July and lowest in February. Substantial differences in violence-related ED attendances were identified at the regional level. From this ED perspective overall violence in England and Wales decreased over the period 2005-2009 but increased in East Midlands, London and South West regions. Since 2006, overall trends according to Crime Survey for England and Wales (CSEW), police and ED measures were similar, though CSEW and ED measures reflect far greater numbers of violent incidents than police data. Causes of decreases in violence in regions need to be identified and shared with regions where violence increased.


[SPECIFIC ASPECTS OF THE LEGISLATIVE CONSOLIDATION OF THE INSTITUTION OF EARLY CARE FOR CHILDREN WITH DISABILITIES].
For the purposes of this work, children with disabilities include disabled children or children aged 0 to 8 years who are not recognized as disabled in the prescribed manner, but who have temporary or permanent deviations in physical and (or) mental development (hereinafter - children with disabilities). The legislative basis for the implementation of the rights and opportunities of children with disabilities and their families is constituted by constitutional provisions that enshrine state guarantees for the protection of childhood, motherhood, paternity, family (part 1 of article 38, paragraph "g.1" of part 1 of article 72 of the Constitution of the Russian Federation). An early start of comprehensive care for children with disabilities contributes to the maximum possible achievements in the development of the child, maintaining his health, as well as successful socialization and inclusion of the child in the educational environment with subsequent integration into society. The research material was the international treaties and regulatory legal acts of the Russian Federation on providing early assistance to children with disabilities. The work used a set of methods of scientific knowledge, including general scientific methods: analysis, synthesis, induction, deduction, special: comparative, formal legal, etc. Legislative consolidation of the institution of providing early assistance to children with disabilities can be carried out by amending the existing legislative acts or by adopting a separate regulatory legal act of the legislative level that establishes the legal basis for providing early assistance. This article outlines the directions for improving legal regulation in terms of legislative consolidation of the institution of providing early assistance to children with disabilities by amending the current legislative acts of the federal level.


The role of oxidative stress in chemotherapy-induced gonadotoxicity in a rat model, and the protective effects of Nigella Sativa oil on oxidative stress, the anti-Müllerian hormone level, and apoptosis.
This study aimed to determine the role of oxidative stress (OS) in carboplatin-induced gonadotoxicity and whether Nigella Sativa oil (NSO), an herbal antioxidant, has a protective effect on ovarian apoptosis, OS, and the anti-Müllerian hormone (AMH) level in a rat model. The study included 24 adult female rats that were divided into 4 treatment groups. Group A saline + saline (sham group); group B: NSO + saline; group C: saline + carboplatin; group D: NSO + carboplatin. Saline, NSO, and carboplatin were administered intraperitoneally 24 and/or 48 h before sacrification as 4 mL/kg, 4 mL/kg, and 80 mg/kg, respectively. Apoptosis, OS parameters, and AMH were measured. Oxidant levels and apoptosis were higher, whereas AMH and the antioxidants were lower in group C than in group A. Apoptosis, OS parameters, and AMH levels were negatively affected by chemotherapy (CTx) in group C whilst improvement in those parameters was observed in group D following NSO pretreatment. The levels of apoptosis and malondialdehyde (MDA), an OS parameter, in group D were lower than in group C as they declined from 34.3% to 8.65% (p = 0.002) and from 199.4 nmol/g tissue to 136.4 nmol/g tissue (p = 0.002), respectively. However, the slight increase in AMH level from 2.7 ng/mL to 3.5 ng/mL due to the NSO effect was not significant between groups C and D. The present findings show that carboplatin has adverse effects on AMH, ovarian tissue apoptosis, and OS parameters. NSO pretreatment might protect ovarian tissue and decrease CTx-induced ovarian injury by decreasing OS and apoptosis, but the protective effect of NSO on AMH is limited.


[Reversible suppression and activation of immunoglobulin genes in differentiated IgG+ sublines of human RPMI-6410t B-cells].
Differentiated human B-cells of the IgG+ sublines obtained as a result of switching from IgM to IgG synthesis in the 6410t line and its IgM+ lines gradually reduce the level of IgM secretion after the inductor removal. IgG synthesis can be partially or fully recovered by treating the IgG+ sublines with a polyclonal activator of B-lymphocytes, lipopolysaccharide W from Gram negative bacteria. In the conditions of certain regulatory effects, differentiated IgG+ cells are capable to pass reversibly in the state of functional rest and synthesis initiation.


Surface plasmon excitations in cylindrical nanorods by electron-hole pair creation.
In this work we study the effect of the excitation of surface plasmons in a metallic cylindrical nanorod by a suddenly created electron-hole pair, using a classical model for the emerging electron and a quantum-mechanical model for the plasmon field in the cylinder. The electron and the hole interact independently with the plasmon field, generating electron density oscillations. Two different trajectories for the emerging electron (parallel to the axis and radial) are studied in an aluminum nanorod. The average number of excited plasmons indicates how important is the role of the hole in the excitation process. We found that the results can be very different according to the trajectory of the emerging electron. We also found that the distinction between intrinsic and extrinsic process is sometimes not applicable.


Visual functional magnetic resonance imaging in patients with Sturge-Weber syndrome.
The purpose of this study is to report different patterns of visual cortex activation in patients with Sturge-Weber syndrome as compared with healthy control subjects. Utilizing a visual paradigm of flashing lights, three children with Sturge-Weber syndrome were studied with functional magnetic resonance imaging. The results are compared with those documented in eight normal sedated children, and six young adult awake volunteers, using the same paradigms. All adult volunteers manifested bilateral activation in primary visual cortex (Brodmann's 17 and 18 areas). Two of them also had activation in secondary visual cortex (Brodmann's 19 area). In the eight sedated normal children, seven manifested activation in primary visual areas. The last exhibited no activation. The patients with Sturge-Weber syndrome demonstrated in the affected occipital lobe increased activation in one patient (11 months old), no activation in the second (12 years of age), and abnormal distribution of the activation in the third (11 months old). This report demonstrates that the vascular malformation of Sturge-Weber syndrome does not necessarily prevent cortical activation in the expected occipital cortex and may be associated with different patterns of abnormal activation. Assessing cortical function with functional magnetic resonance imaging in patients with Sturge-Weber syndrome may be helpful in decisions of surgical management and counseling.


Loop Gain Predicts the Response to Upper Airway Surgery in Patients With Obstructive Sleep Apnea.
Upper airway surgery is often recommended to treat patients with obstructive sleep apnea (OSA) who cannot tolerate continuous positive airways pressure. However, the response to surgery is variable, potentially because it does not improve the nonanatomical factors (ie, loop gain [LG] and arousal threshold) causing OSA. Measuring these traits clinically might predict responses to surgery. Our primary objective was to test the value of LG and arousal threshold to predict surgical success defined as 50% reduction in apnea-hypopnea index (AHI) and AHI <10 events/hour post surgery. We retrospectively analyzed data from patients who underwent upper airway surgery for OSA (n = 46). Clinical estimates of LG and arousal threshold were calculated from routine polysomnographic recordings presurgery and postsurgery (median of 124 [91-170] days follow-up). Surgery reduced both the AHI (39.1 ± 4.2 vs. 26.5 ± 3.6 events/hour; p < .005) and estimated arousal threshold (-14.8 [-22.9 to -10.2] vs. -9.4 [-14.5 to -6.0] cmH2O) but did not alter LG (0.45 ± 0.08 vs. 0.45 ± 0.12; p = .278). Responders to surgery had a lower baseline LG (0.38 ± 0.02 vs. 0.48 ± 0.01, p < .05) and were younger (31.0 [27.3-42.5] vs. 43.0 [33.0-55.3] years, p < .05) than nonresponders. Lower LG remained a significant predictor of surgical success after controlling for covariates (logistic regression p = .018; receiver operating characteristic area under curve = 0.80). Our study provides proof-of-principle that upper airway surgery most effectively resolves OSA in patients with lower LG. Predicting the failure of surgical treatment, consequent to less stable ventilatory control (elevated LG), can be achieved in the clinic and may facilitate avoidance of surgical failures.


A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy.
The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.


Isolation of protective antigens from Trypanosoma lewisi by using trypanostatic (ablastic) immunoglobulin G from the surface coat.
Antigens were purified from extracts of Trypanosoma lewisi on immunoadsorbent columns of trypanostatic immunoglobulin G eluted from parasite surface coats at 8 days postinfection. Eight absorbed proteins, with molecular weights between 15,000 and 70,000, were identified. These surface coat antigens (SCAgs) were then used to immunize rats. After immunization, sera were assayed in vitro for levels of circulating trypanostatic and trypanocidal antibodies. Approximately half of the immune sera had higher levels of trypanostatic antibody, compared with control sera; no trypanocidal antibodies (agglutinins) were detected in any of the sera. The rats were then challenged intraperitonally, and the parasitemias and division rates of the parasites were monitored. Parasitemias of all immunized rats were significantly (P less than 0.01) lower and of shorter duration than those of the controls. Division rates of trypanosomes were also significantly (P less than 0.01) lower in all immunized rats at all times before total cessation of division compared with control rats. A clear dose-response effect was observed, with greater amounts of SCAg eliciting higher levels of protection. Purified SCAgs were also more effective immunogens than were the crude trypanosome extracts from which they had been purified, and in which other proteins in addition to the SCAgs were present. These data provide conclusive evidence that the immunoglobulin G in the surface coats of T. lewisi, adsorbed during the course of infection, is specific antibody, in that it can be used to isolate parasite antigens that elicit a trypanostatic response in rats immunized with them.


Exchanging implements: the micro-materialities of multidisciplinary work in the operating theatre.
Surgical procedures rely upon an array of commonplace tools, implements and materials that mediate practice and disciplinary collaboration within the operating theatre. Substantial time is dedicated to the issue and provision of these artefacts and their timely exchange is critical to the successful accomplishment of surgical procedures. In this article, we consider the practice, knowledge and agency that informs how particular implements and materials are passed by the scrub nurse to the surgeon that in turn enables their deployment with regard to the particular procedure and the contingencies 'at hand'. We address the technicalities of these 'non-technical skills' and examine how they rely upon a disciplinary vision and interactional organisation that informs both the scrutiny of action and the ways in which implements and materials are handled and exchanged. We explore the implications of our analysis for our understanding of agency in action and the growing interest in developing robots or autonomous agents to support work and collaboration in health care.


Outcome of COVID-19 Infection in Patients With Multiple Sclerosis Who Received Disease-Modifying Therapies: A Systematic Review and Meta-Analysis.
A systematic review and meta-analysis was performed of the outcome of Coronavirus disease 2019 (COVID-19) infection in patients with multiple sclerosis (MS) who received disease-modifying therapies (DMTs). Relevant studies published before November 2022 in the PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, and Web of Science databases were retrieved using the following search expression: ("multiple sclerosis" OR "MS") AND ("DMT" OR "disease modifying therapies") AND ("COVID-19"). Two authors independently screened the articles and extracted the data. Qualitative analyses and a meta-analysis constituted 22 of the 794 retrieved articles. Differences in the hospitalization and mortality rates were used as the main measures of efficacy, and the meta-analysis was performed using RevMan software. 22 clinical trials were selected. The hospitalization rate was lower in the 3,216 patients who received DMTs than in the 774 patients who did not receive any treatment, with a moderate effect size of 0.43 (p<0.00001). The mortality rate was also lower among patients with MS treated using DMTs than in controls (odds ratio [OR]=0.19, 95% confidence interval [CI]=0.13-0.27, p<0.00001). The hospitalization rates for COVID-19 infection in patients with MS treated with anti-CD20 therapy also increased markedly (OR=3.32, 95% CI=2.63-4.20, p<0.00001). However, there was no significant difference between patients with MS who did and did not receive DMTs. In summary, the application of DMTs was found to be valuable for patients with MS infected with COVID-19. However, more clinical studies are needed to determine the use of anti-CD20 drugs in patients with MS during the COVID-19 pandemic.


A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.
• Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery. Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 μg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale.Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted. The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05). Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery.


[THE HISTORY OF DEPARTMENT OF FACULTY THERAPY, AT THE VORONEZH HIGHER EDUCATION INSTITUTION (ON THE OCCASION OF THE CENTENARY ANNIVERSARY OF N.N. BURDENKO VORONEZH STATE MEDICAL UNIVERSITY)].
The article is devoted to the history of the Department of Faculty Therapy, N.N. Burdenko Voronezh State Medical University. The history of its creation is inextricably linked to the Derpth (Yurievsky) University that was transferred to Voronezh in 1918. While the Department of Faculty Therapy remained in Voronezh, it several times changed location making use of various city hospitals as its branches. It simultaneously expanded its activities by organizing courses of physical therapy, endocrinology, and other medical disciplines. The article focuses on the events pertaining to the formation and development of the Department of Faculty Therapy, main directions and achievements of its scientific work.


Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells.
The cell wall structure of Salmonella typhimurium has been studied for the first time during transit from free-living to parasitic lifestyles. Peptidoglycan of S. typhimurium proliferating within human epithelial cells contains a high proportion of previously unidentified muropeptides (5-10-fold higher than in extracellular bacteria). Amino acid and mass-spectrometry analyses showed that these new components consist of dimeric cross-linked muropeptides lacking one of the two disaccharide (N-acetyl-glucosamine-beta-(1-->4)-N-acetyl-muramic acid) molecules. This unique structure suggests an active role for an N-acetyl-muramyl-L-alanine-amidase in remodelling the peptidoglycan of intracellular S. typhimurium. Additional alterations observed included: (i) the absence of glycine-containing muropeptides; (ii) the increase in the relative proportion of muropeptides cross-linked by L(meso)-diaminopimelyl-D(meso)-diaminopimelic acid (L-D) peptide bridges; and, (iii) the decrease in the global cross-linkage of the macromolecule. The structural alterations observed in the peptidoglycan of intracellular bacteria do not produce loss of the cell envelope. These results show that intracellular residence of S. typhimurium within epithelial cells is accompanied by significant changes in the bacterial cell wall. Remodelling of peptidoglycan structure may constitute another sophisticated strategy of this pathogen for adapting to and colonizing the intracellular niche of eukaryotic cells.


AKT inhibition as a strategy for targeting hypoxic HPV-positive HNSCC.
Hypoxia negatively affects treatment outcome in both Human papillomavirus (HPV)-positive and -negative head and neck squamous cell carcinomas (HNSCC). Despite HPV-positive patients having a relatively good prognosis, hypoxic HPV-positive tumours are associated with poor treatment outcome, and do not respond to hypoxia modification. Earlier, we showed that hypoxia induces the pro-survival AKT pathway. In this study, we aim to investigate whether AKT inhibition affects the response to radiotherapy under hypoxia, and determine whether this is a viable treatment strategy for HNSCC patients with hypoxic HPV-positive tumours. Nine HPV-negative and 4 HPV-positive HNSCC cell lines were characterized. AKT activation was assessed by western blot. Survival in response to hypoxic incubation, AKT inhibition and/or irradiation was assessed using CCK8 assays and colony forming assays. AKT was activated under hypoxia in both HPV-negative and -positive cell lines, which could be abrogated by the AKT inhibitor MK2206. HPV-positive cell lines were highly sensitive to MK2206 at normoxia. In all HNSCC cell lines, AKT inhibition was significantly more effective in inhibiting cell growth during hypoxic conditions than under normoxia. Hypoxia significantly reduced radiosensitivity irrespective of HPV-status, yet specifically in HPV-positive cells this could be efficiently reversed by AKT inhibition. These data suggest that HNSCC tumours are dependent on AKT to survive hypoxia, and that AKT inhibition is specifically effective in radioresistant hypoxic HPV-positive cells. Targeting AKT may thus be a potential way to overcome hypoxia induced radioresistance, particularly in HPV-positive HNSCC tumours.


Effects of Lipoic Acid on High-Fat Diet-Induced Alteration of Synaptic Plasticity and Brain Glucose Metabolism: A PET/CT and 13C-NMR Study.
High-fat diet (HFD)-induced obesity is accompanied by insulin resistance and compromised brain synaptic plasticity through the impairment of insulin-sensitive pathways regulating neuronal survival, learning, and memory. Lipoic acid is known to modulate the redox status of the cell and has insulin mimetic effects. This study was aimed at determining the effects of dietary administration of lipoic acid on a HFD-induced obesity model in terms of (a) insulin signaling, (b) brain glucose uptake and neuronal- and astrocytic metabolism, and (c) synaptic plasticity. 3-Month old C57BL/6J mice were divided into 4 groups exposed to their respective treatments for 9 weeks: (1) normal diet, (2) normal diet plus lipoic acid, (3) HFD, and (4) HFD plus lipoic acid. HFD resulted in higher body weight, development of insulin resistance, lower brain glucose uptake and glucose transporters, alterations in glycolytic and acetate metabolism in neurons and astrocytes, and ultimately synaptic plasticity loss evident by a decreased long-term potentiation (LTP). Lipoic acid treatment in mice on HFD prevented several HFD-induced metabolic changes and preserved synaptic plasticity. The metabolic and physiological changes in HFD-fed mice, including insulin resistance, brain glucose uptake and metabolism, and synaptic function, could be preserved by the insulin-like effect of lipoic acid.


Synchronization and stability analysis of an exponentially diverging solution in a mathematical model of asymmetrically interacting agents.
This study deals with an existing mathematical model of asymmetrically interacting agents. We analyze the following two previously unfocused features of the model: (i) synchronization of growth rates and (ii) initial value dependence of damped oscillation. By applying the techniques of variable transformation and timescale separation, we perform the stability analysis of a diverging solution. We find that (i) all growth rates synchronize to the same value that is as small as the smallest growth rate and (ii) oscillatory dynamics appear if the initial value of the slowest-growing agent is sufficiently small. Furthermore, our analytical method proposes a way to apply stability analysis to an exponentially diverging solution, which we believe is also a contribution of this study. Although the employed model is originally proposed as a model of infectious disease, we do not discuss its biological relevance but merely focus on the technical aspects.


Synthesis and in vitro antitumor activity of (1E,4E)-1-aryl-5-(2-((quinazolin-4-yl)oxy)phenyl)-1,4-pentadien-3-one derivatives.
Cancer is one of the leading causes of death and only second to heart diseases. Recently, preclinical studies have demonstrated that curcumin had a number of anticancer properties. Thus, we planned to synthesize a series of curcumin analogs to assess their antiproliferation efficacy. A series of (1E,4E)-1-aryl-5-(2-((quinazolin-4-yl)oxy)phenyl)-1,4-pentadien-3-one derivatives (curcumin analogs) were synthesized and characterized by IR, NMR, and elemental analysis techniques. All of the prepared compounds were screened for antitumor activities against MGC-803, PC3, and Bcap-37 cancer cell lines. A significant inhibition for cancer cells were observed with compound 5f and also less toxic on NIH3T3 normal cells. The mechanism of cell death induced by compound 5f was further investigated by acridine orange/ethidium bromide staining, Hoechst 33,258 staining, TUNEL assay, and flow cytometry cytometry, which revealed that the compound can induce cell apoptosis in MGC-803 cells. This study suggests that most of the derivatives could inhibit the growth of human cancer cell lines. In addition, compound 5f could induce apoptosis of cancer cells, and it should be subjected to further investigation as a potential anticancer drug candidate.


Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors.
Transcription of the human immunodeficiency virus (HIV)-1 is controlled by the cooperation of virally encoded and host regulatory proteins. The Tat protein is essential for viral replication, however, expression of Tat after virus entry requires HIV-1 promoter activation. A sequence in the 5' HIV-1 LTR, containing a binding site for transcription factors of the interferon regulatory factors (IRF) family has been suggested to be critical for HIV-1 transcription and replication. Here we show that IRF-1 activates HIV-1 LTR transcription in a dose-dependent fashion and in the absence of Tat. This has biological significance since IRF-1 is produced early upon virus entry, both in cell lines and in primary CD4+ T cells, and before expression of Tat. IRF-1 also cooperates with Tat in amplifying virus gene transcription and replication. This cooperation depends upon a physical interaction that is blocked by overexpression of IRF-8, the natural repressor of IRF-1, and, in turn is released by overexpression of IRF-1. These data suggest a key role of IRF-1 in the early phase of viral replication and/or during viral reactivation from latency, when viral transactivators are absent or present at very low levels, and suggest that the interplay between IRF-1 and IRF-8 may play a key role in virus latency.


Kinetic magnetic resonance imaging analysis of spinal degeneration: a systematic review.
To evaluate the clinical use of kinetic magnetic resonance imaging (kMRI) in spinal degenerative diseases. A systematic search of PubMed, EMBASE and ISI databases for articles that had been published between January 1978 and February 2013 concerning patients who had undergone kMRI for spinal problems was performed. All selected patients had undergone kMRI in neutral, flexion, and extension weight-bearing positions. Evaluation of cervical and lumbar degeneration by kMRI was analyzed. kMRI showed significant reduction of mobility in cervical segments of patients with severe disc degeneration; in addition, it was more severely reduced in patients with severe cord compression than in those without it. In the cervical spine, it was found that although disc height, translational motion, and angular variation were significantly affected at the level of disc herniation, no significant changes were apparent in adjacent segments. kMRI also showed that lumbar degeneration is closely associated with disc degeneration, facet joint osteoarthritis and the pathological characteristics of the interspinous ligaments, ligamentum flavum and paraspinal muscles. Eleven articles (4162 patients) fulfilled the inclusion criteria and were reviewed. It was found that kMRI is more specific and sensitive than conventional MRI regarding relating patients' symptoms to objective findings on imaging that demonstrate pathology and biomechanics. In the kinetic position, kMRI improves detection of disc herniation by 5.78%-19.46% and thus provides a new means of studying the biomechanical mechanism(s) in degenerative spines. Kinetic MRI is effective for diagnosing, evaluating, and managing degenerative disease within the spine; however, it still has some limitations.


Nutrigenomics and metabolomics will change clinical nutrition and public health practice: insights from studies on dietary requirements for choline.
Science is beginning to understand how genetic variation and epigenetic events alter requirements for, and responses to, nutrients (nutrigenomics). At the same time, methods for profiling almost all of the products of metabolism in a single sample of blood or urine are being developed (metabolomics). Relations between diet and nutrigenomic and metabolomic profiles and between those profiles and health have become important components of research that could change clinical practice in nutrition. Most nutrition studies assume that all persons have average dietary requirements, and the studies often do not plan for a large subset of subjects who differ in requirements for a nutrient. Large variances in responses that occur when such a population exists can result in statistical analyses that argue for a null effect. If nutrition studies could better identify responders and differentiate them from nonresponders on the basis of nutrigenomic or metabolomic profiles, the sensitivity to detect differences between groups could be greatly increased, and the resulting dietary recommendations could be appropriately targeted. It is not certain that nutrition will be the clinical specialty primarily responsible for nutrigenomics or metabolomics, because other disciplines currently dominate the development of portions of these fields. However, nutrition scientists' depth of understanding of human metabolism can be used to establish a role in the research and clinical programs that will arise from nutrigenomic and metabolomic profiling. Investments made today in training programs and in research methods could ensure a new foundation for clinical nutrition in the future.


Galectin-3: a novel biomarker for the prognosis of heart failure.
Heart failure (HF) is still a global burden which carries substantial risk of morbidity and mortality. Thus, appropriate approach of diagnosis and layering the prognosis of HF are of great importance. In this paper we discuss and review a novel biomarker, which is called galectin-3 and already approved by Food and Drugs Administration (FDA) as a prediction tool for HF. Galectin-3, which is secreted by macrophages under the influence of mediators like osteopontin, has been known for its significant role in mediating cardiac fibrosis and inflammation. Numerous studies have shown galectin-3 as a novel prognostic biomarker with high predictive value for cardiovascular mortality and re-hospitalization in HF patients. However, there are also other contradictive studies displayed galectin-3 inferiority against other existed HF prognostic biomarkers like NT-proBNP and ST2. Nevertheless, galectin-3 has some advantages such as more stability and resistance against hemodynamic loading and unloading state, and also it could act as an early indicator of cardiac fibrosis, ventricular remodeling, and renal impairment in HF patients.


A single clone of Acinetobacter baumannii, ST22, is responsible for high antimicrobial resistance rates of Acinetobacter spp. isolates that cause bacteremia and urinary tract infections in Korea.
We investigated the characteristics of a total of 96 Acinetobacter spp. isolates that were shown to cause bacteremia and urinary tract infections (UTIs) from 10 university hospitals located in various regions of Korea from November 2006 to August 2007. The antimicrobial susceptibilities of these isolates were determined using a broth microdilution method, and the species were identified using molecular identification. In addition, we performed multilocus sequence typing for Acinetobacter baumannii subgroup A isolates. A. baumannii subgroup A was the most prevalent in patients with both bacteremia (32 isolates, 53.3%) and UTIs (20 isolates, 55.6%), followed by Acinetobacter genomic species 13TU (15.0% and 27.8% in bacteremia and UTIs, respectively). A. baumannii subgroup B and Acinetobacter junii were found exclusively in isolates causing bacteremia (seven and five isolates, respectively). Among 96 Acinetobacter spp. isolates, 19.8% were resistant to imipenem and 25.0% were resistant to meropenem. Most carbapenem-resistant A. baumannii isolates contained PER or oxacillinase-23-like enzymes (65.2% and 78.3%, respectively). In addition, 13.5% were resistant to polymyxin B and 17.7% were resistant to colistin. A. baumannii subgroup A isolates (52 isolates, 54.2%) showed higher resistance rates to most antimicrobial agents than other species, but not to colistin. Among A. baumannii subgroup A isolates, ST22 was the most prevalent genotype (33 isolates, 63.5%) and showed higher resistance rates to all antimicrobial agents than the other genotypes. In addition, four out of five polymyxin-resistant A. baumannii group A isolates belonged to ST22. Thus, dissemination of the main clone of A. baumannii, ST22, may contribute to the high resistance rates of Acinetobacter isolates to antimicrobials, including carbapenems, in Korea.


Elucidation of the chain conformation in a glassy polyester, PET, by two-dimensional NMR
The chain conformation of glassy poly(ethylene terephthalate) (PET) was characterized by two-dimensional double-quantum nuclear magnetic resonance (NMR). In amorphous carbon-13-labeled PET, the statistics of the O-13CH2-13CH2-O torsion angle were determined, on the basis of the distinct shapes of the two-dimensional NMR patterns of trans and gauche conformations. In crystalline PET, the trans content is 100 percent, but in the amorphous PET it is only 14 percent (+/-5 percent). An average gauche torsion angle of 70 degrees (+/-9 degrees) was obtained. Implications for materials properties of polyesters are discussed.


Field experiment on the effects of sepiolite and biochar on the remediation of Cd- and Pb-polluted farmlands around a Pb-Zn mine in Yunnan Province, China.
The effects of sepiolite and biochar on the contents of available nutrients (N, P, and K); the chemical forms and available contents of Cd and Pb in soils; the biomass and growth of maize; and the contents of nutrients, Cd, and Pb in maize were studied in situ in Cd- and Pb-polluted farmlands around the Lanping Pb-Zn mine in Yunnan Province, China. Results demonstrated that sepiolite did not influence the contents of available nutrients in soils, although it significantly increased the pH value and decreased available Cd (CaCl2-extractable and exchangeable) contents and exchangeable and reducible Pb. Moreover, sepiolite increased the biomass in the aboveground part of maize, resulting in the reduction of Cd contents in maize plants and grains by 25.6-47.5%. Meanwhile, the biochar increased the contents of available nutrients in soils and decreased the contents of exchangeable Pb in soils and biomass in the aboveground part of maize plants and grains; decreased the Cd contents in maize stems and grains by 26.7% and 24.6%, respectively; and decreased the Pb content in roots by 16.2%. However, neither sepiolite nor biochar had considerable influence on the Pb content in maize grains. According to a correlation analysis, soil pH has extremely significant negative correlations with available Cd content in soils, which in turn have extremely significant positive correlation with the Cd content in maize plants and grains. These results revealed that sepiolite increases soil pH and decreases Cd bioavailability in farmland soils around the Pb-Zn mine. Furthermore, biochar increases the contents of available nutrients in farmland soils and the maize yield. Sepiolite and biochar both decrease the contents and transfer coefficients of Cd in maize plants and grains and are, thus, applicable to the immobilization remediation of Cd-polluted farmlands.


Processing of plant mitochondrial tRNAGly and tRNASer(GCU) is independent of RNA editing.
The genes encoding pea and potato mitochondrial tRNAGly and pea mitochondrial tRNASer(GCU) were analyzed with particular respect to their expression. Secondary-structure models deduced from the identical potato and pea tRNAGly gene sequences revealed A7:C66 mismatches in the seventh base pair at the base of the acceptor stems of both tRNAs. Sequence analyses of tRNAGly cDNA clones showed that these mispairings are not corrected by C66 to U66 conversions, as observed in plant mitochondrial tRNAPhe. Likewise, a U6:C67 mismatch identified in the acceptor stem of the pea tRNASer(GCU) is not altered by RNA editing to a mismatched U:U pair, which is created by RNA editing in Oenothera mitochondrial tRNACys. In vitro processing reactions with the respective tRNAGly and tRNASer(GCU) precursors show that such conversions are not necessary for 5' and 3' end maturation of these tRNAs. These results demonstrate that not all C:A (A:C) or U:C (C:U) mismatches in double-stranded regions of tRNAs are altered by RNA editing. An RNA editing event in plant mitochondrial tRNAs is thus not generally indicated by the presence of a mismatch but may depend on additional parameters.


Technical note: Evaluation of a system for monitoring individual feeding behavior and activity in beef cattle.
Behavioral observations are important to detect illness in beef cattle. However, traditional observation techniques are time and labor intensive and may be subjective. The objective was to validate a system for monitoring individual feeding behavior and activity in beef cattle (Fedometer [FEDO]; ENGS, Rosh Pina, Israel). Sixteen steers (initial BW ± SD = 326 ± 46 kg) were fitted with data loggers (FEDO) on their left front leg and housed in a pen with a feedbunk equipped with an antenna emitting an electromagnetic field that reached 30 ± 2 cm in front of the feedbunk. Feedbunk attendance (duration of visit and frequency of meals) measured by FEDO was compared with live observations (27 observational periods lasting between 72 and 240 min; mean 126 min). Lying time and frequency of lying bouts were compared with previously validated accelerometers fitted to the hind leg (10 steers equipped for 10 to 12 d; HOBO Pendant G Acceleration Data Logger [HOBO]; Onset Computer Corporation, Pocasset, MA). Step counts were compared with video recordings (15 observations for 6-min intervals in 6 steers). Concordance correlation coefficients (CCC), accounting for repeated measures, and limits of agreement were computed. Comparison between FEDO and observed time at the feedbunk yielded a CCC of 0.98 (95% confidence interval [CI] 0.97-0.99). All 68 meal events observed were recorded by FEDO. However, FEDO recorded 4 meal events during the 27 observational periods that were not observed. Lying time measured by HOBO and FEDO were highly correlated (CCC = 0.98; 95% CI 0.97-0.99). However, frequency of lying bouts measured by FEDO was only moderately correlated to HOBO (CCC = 0.71; 95% CI 0.63-0.77); FEDO underestimating the number of lying bouts (on average, 0.4 fewer bouts per 6 h). Step count by FEDO was moderately correlated to video observations (CCC = 0.75; 95% CI 0.49-0.89); FEDO overestimating the number of steps (on average, 5 more steps per 6 min). In conclusion, the FEDO system accurately measured duration of feedbunk attendance, frequency of meals, and lying time. However, it overestimated the number of steps and underestimated the frequency of lying bouts.


[Amniotic infection syndrome after amniocentesis--a case report].
A severe amniotic infection syndrome with a septic shock and a consumption coagulopathy is reported after an amniocentesis in second trimester. In literature, the risk of an amnionitis after amniocentesis amounts to 0.1%-0.4% and the risk of a severe maternal infection reaches 0.03%-0.19%. The available data show, that the clinical symptoms (rise in temperature, signs of septic shock) start 24-36 hours after the punction. The earlier treatment (evacuation of the uterus or - if necessary - hysterectomy) is accomplished, the more favourable will be the course of the disease with respect to septic shock and DIC. Determination of germs in each amniotic fluid seems to be of prognostic value; thus treatment can be started before infection becomes detrimental for the mother.


Medical perception of stroke care conditions in Brazil.
Stroke is currently the second leading cause of death in Brazil. Neurologists' reports on the absence of adequate resources for stroke care are frequent; however, there are no objective data on this perception.To assess the perception of neurologists of stroke care conditions in Brazil. Neurologists from all over Brazil were surveyed by means of an anonymous questionnaire about the main shortcomings in stroke care, focusing particularly on physical structure and infrastructure (diagnostic methods, patient transport, availability of beds, multi-professional team). The main shortcomings are indicated: the worst conditions, among all items surveyed, were found in the public sector. In the private sector, conditions were better. Care conditions are worse in the public sector with regard to both infrastructure and human resources. Future public health policies for the prevention and treatment of stroke should be formulated, taking into consideration neurologists' perceptions.


Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis.
Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function. This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy. Twenty-one participants were randomized 1:2 to placebo or oral riociguat (0.5 mg three times daily [tid] for 14 days, increased to 1.0 mg tid for the subsequent 14 days). The primary and secondary efficacy endpoints were change in sweat chloride concentration and percent predicted forced expiratory volume in 1 second (ppFEV1), respectively, from baseline to Day 14 and Day 28 with riociguat compared with placebo. Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV1) at doses up to 1.0 mg tid after 28 days. The most common drug-related adverse event (AE) was headache occurring in three participants (21%); serious AEs occurred in one participant receiving riociguat (7%) and one participant receiving placebo (14%). This safety profile was consistent with the underlying disease and the known safety of riociguat for its approved indications. The Rio-CF study was terminated due to lack of efficacy and the changing landscape of CF therapeutic development. The current study, within its limits of a small sample size, did not provide evidence that riociguat could be a valid treatment option for CF. NCT02170025.


Large bowel obstruction caused by incarcerated inguinal hernia: report of three cases.
We report two patients with left colonic obstruction and one patient with cecal obstruction caused by incarceration in inguinal hernias. None of the patients had colonic malignancies within the hernial sacs. Reduction of the hernias was followed by resolution of the bowel obstruction and successful hernial repair in all patients.


Observations of fast radio bursts at frequencies down to 400 megahertz.
Fast radio bursts (FRBs) are highly dispersed millisecond-duration radio flashes probably arriving from far outside the Milky Way1,2. This phenomenon was discovered at radio frequencies near 1.4 gigahertz and so far has been observed in one case3 at as high as 8 gigahertz, but not at below 700 megahertz in spite of substantial searches at low frequencies4-7. Here we report detections of 13 FRBs at radio frequencies as low as 400 megahertz, on the Canadian Hydrogen Intensity Mapping Experiment (CHIME) using the CHIME/FRB instrument8. They were detected during a telescope pre-commissioning phase, when the sensitivity and field of view were not yet at design specifications. Emission in multiple events is seen down to 400 megahertz, the lowest radio frequency to which the telescope is sensitive. The FRBs show various temporal scattering behaviours, with the majority detectably scattered, and some apparently unscattered to within measurement uncertainty even at our lowest frequencies. Of the 13 reported here, one event has the lowest dispersion measure yet reported, implying that it is among the closest yet known, and another has shown multiple repeat bursts, as described in a companion paper9. The overall scattering properties of our sample suggest that FRBs as a class are preferentially located in environments that scatter radio waves more strongly than in the diffuse interstellar medium in the Milky Way.


DsbA-mediated disulfide bond formation and catalyzed prolyl isomerization in oxidative protein folding.
The interrelationship between the acquisition of ordered structure, prolyl isomerization, and the formation of the disulfide bonds in assisted protein folding was investigated by using a variant of ribonuclease T1 (C2S/C10N-RNase T1) with a single disulfide bond and two cis-prolyl bonds as a model protein. The thiol-disulfide oxidoreductase DsbA served as the oxidant for forming the disulfide bond and prolyl isomerase A as the catalyst of prolyl isomerization. Both enzymes are from the periplasm of Escherichia coli. Reduced C2S/C10N-RNase T1 is unfolded in 0 M NaCl, but native-like folded in > or = 2 M NaCl. Oxidation of 5 microM C2S/C10N-RNase T1 by 8 microM DsbA (at pH 7.0, 25 degrees C) is very rapid with a t1/2 of about 10 s (the second-order rate constant is 7 x 10(3) s-1 M-1), irrespective of whether the reduced molecules are unfolded or folded. When they are folded, the product of oxidation is the native protein. When they are denatured, first the disulfide bond is formed in the unfolded protein chains and then the native structure is acquired. This slow reaction is limited in rate by prolyl isomerization and catalyzed by prolyl isomerase. The efficiency of this catalysis is strongly decreased by the presence of the disulfide bond. Apparently, the rank order of chain folding, prolyl isomerization, and disulfide bond formation can vary in the oxidative folding of ribonuclease T1. Such a degeneracy could generally be an advantage for protein folding both in vitro and in vivo.


ACR TI-RADS: Pitfalls, Solutions, and Future Directions.
The high prevalence of thyroid nodules combined with the generally indolent growth of thyroid cancer present a challenge for optimal patient care. Risk classification models based on US features have been created by multiple professional societies, including the American College of Radiology (ACR), which published the Thyroid Imaging Reporting and Data System (TI-RADS) in 2017. ACR TI-RADS uses a standardized lexicon for assessment of thyroid nodules to generate a numeric scoring of features, designate categories of relative probability of benignity or malignancy, and provide management recommendations, with the aim of reducing unnecessary biopsies and excessive surveillance. Adopting ACR TI-RADS may require practice-level changes involving image acquisition and workflow, interpretation, and reporting. Significant resources should be devoted to educating sonographers and radiologists to accurately recognize features that contribute to the scoring of a nodule. Following a system that uses approved terminology generates reproducible and relevant reports while providing clarity of language and preventing misinterpretation. Comprehensive documentation facilitates quality improvement efforts. It also creates opportunities for outcome data and other performance metrics to be integrated with research. The authors review ACR TI-RADS, describe challenges and potential solutions related to its implementation based on their experiences, and highlight possible future directions in its evolution. ©RSNA, 2019 See discussion on this article by Hoang.


Suppression of myofibrillar proteolysis in chick skeletal muscles by alpha-ketoisocaproate.
We previously reported that L-leucine suppresses myofibrillar proteolysis in chick skeletal muscles. In the current study, we compared the effects of L- and D-enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (24 h) chicks were orally administered 225 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 2 h. L-Leucine administration had an obvious inhibitory effect on myofibrillar proteolysis (plasma N(tau)-methylhistidine concentration) in chicks while D-leucine and alpha-KIC were much more effective. We also examined the expression of the proteolytic-related genes (ubiquitin, proteasome, m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal muscles. Ubiquitin mRNA expression was decreased by D-leucine and alpha-KIC but not L-leucine. Proteasome and m-calpain mRNA expressions as well as cathepsin B mRNA expression were likewise decreased by L-leucine, D-leucine and alpha-KIC. These results indicate that D-leucine and alpha-KIC suppress proteolytic-related genes, resulting in an decrease in myofibrillar proteolysis while L-leucine is much less effective in skeletal muscle of chicks, may be explain by conversion of D-leucine to alpha-KIC.


BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia.
Primary cilia perceive the extracellular environment through receptors localized in the ciliary membrane, but mechanisms directing specific proteins to this domain are poorly understood. To address this question, we knocked down proteins potentially important for ciliary membrane targeting and determined how this affects the ciliary trafficking of fibrocystin, polycystin-2, and smoothened. Our analysis showed that fibrocystin and polycystin-2 are dependent on IFT20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these components. In addition, we found that polycystin-2, but not smoothened or fibrocystin, requires the biogenesis of lysosome-related organelles complex-1 (BLOC-1) for ciliary delivery. Consistent with the role of BLOC-1 in sorting from the endosome, we find that disrupting the recycling endosome reduces ciliary polycystin-2 and causes its accumulation in the recycling endosome. This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium.