Genome-Wide Identification and Expression Analysis of LBD Transcription Factor Genes in Passion Fruit (Passiflora edulis).
The lateral organ boundary domain (LBD) gene is a plant-specific transcription factor that plays a crucial role in plant growth and development, including the development of lateral vegetative organs such as leaf and root development, as well as floral organs such as sepal, petal, and pollen development. Passion fruit is a tropical fruit with important agricultural, economic and ornamental value. However, there is no systematic research report available on the LBD gene family of passion fruit. In this study, a genome-wide analysis of passion fruit LBD genes identified 33 PeLBDs that were unevenly distributed across nine chromosomes. According to phylogenetic and gene structure analysis, PeLBDs were divided into two categories: Class I (27) and Class II (6). Homologous protein modeling results showed that the gene members of the two subfamilies were structurally and functionally similar. Cis-acting element and target gene prediction analysis suggested that PeLBDs might participate in various biological processes by regulating diverse target genes involved in growth and development, metabolism, hormones and stress response. Collinearity analysis indicated that the expansion of the PeLBD gene family likely took place mainly by segmental duplication, and some duplicated gene pairs such as PeLBD13/15 might show functional redundancy, while most duplicated gene pairs such as PeLBD8/12 showed different expression profiles indicating their functional diversification. After filtering low expressed genes, all Class Id PeLBDs were more highly expressed during pollen development. At the same, all Class Ic and many other PeLBDs were relatively highly expressed during ovule development, similar with their homologous LBD genes in Arabidopsis, indicating their potential regulatory roles in reproductive tissue development in passion fruit. PeLBDs that were highly expressed in floral tissues were also expressed at a higher level in tendrils with some differences, indicating the close relationships of tendrils to floral tissues. Some genes such as PeLBD23/25 might be simultaneously related to floral development and leaf early formation in passion fruit, while other PeLBDs showed a strong tissue-specific expression. For example, PeLBD17/27/29 were specifically expressed in floral tissues, while PeLBD11 were only highly expressed in fruit, suggesting their specific function in the development of certain tissues. A qRT-PCR was conducted to verify the expression levels of six PeLBDs in different tissues. Our analysis provides a basis for the functional analysis of LBD genes and new insights into their regulatory roles in floral and vegetative tissue development.


Intra-His bundle block in acute myocardial infarction. Report of two cases.
Two patients with acute intra-His bundle block, both secondary to myocardial infarction, are described. The diagnosis of the block was proved by means of His bundle recordings during the phase of complete atrio-ventricular (A-V) block. Two His bundle potentials, one (H) following each A wave and the other (H') preceding each QRS complex, were detected. In both cases, as well as in the few cases reported in the literature, the site of the infarction was in the inferior wall, an occurrence which shows the functional importance of the posterior blood supply to the His bundle. In both cases the block developed into a chronic form, requiring the implantation of a transvenous pacemaker in one case. This evolution suggests that the post-infarction intra-His bundle block may be due to irreversible anatomic damage.


Self-assembly of [Cu(II)Tb(III)]3+ and [W(CN)8]3- tectons: a case study of a mixture containing two complexes showing slow-relaxation of the magnetization.
The reaction of [Cu(valen)] with Tb(NO(3))(3) and (Bu(3)NH)(3)[W(CN)(8)] affords two types of crystals: [{W(CN)(8)}Cu(valen)Tb(OH(2))(5)]·2H(2)O (1, a discrete trinuclear complex) and [{W(CN)(8)}Cu(valen)Tb(OH(2))(4)]·CH(3)CN·H(2)O (2, an infinite zig-zag chain), both compounds showing slow relaxation of the magnetization (H(2)valen is the Schiff base resulting from the reaction of o-vanillin with 1,2-ethanediamine).


The effect of nifedipine on serum parathyroid hormone and calcitonin in postmenopausal women.
The effect of calcium channel blockers on calcium homeostasis in postmenopausal osteoporotic women with arterial hypertension has not to date been defined. In the submitted study, the influence of nifedipine on serum parathyroid hormone (PTH), calcitonin and osteocalcin is followed in 11 patients. After one month of treatment, serum PTH markedly declined in all women and osteocalcin decreased in 10 patients. In contrast, serum calcitonin increased in five patients, whilst in another five the effect was just the opposite. In one woman this indicator was not affected. There are no mutual correlations between the mentioned indices. In conclusion, the calcitonin secretory process is not sensitive to calcium channel blockade within the present study. In spite of the fact that nifedipine inhibits PTH secretion in postmenopausal osteoporotic women, the direct effect of the drug on osteoblasts (not mediated by PTH) cannot be excluded.


Identification of a 4-lncRNA signature predicting prognosis of patients with non-small cell lung cancer: a multicenter study in China.
Previous findings have indicated that the tumor, nodes, and metastases (TNM) staging system is not sufficient to accurately predict survival outcomes in patients with non-small lung carcinoma (NSCLC). Thus, this study aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in patients with NSCLC and to provide additional prognostic information to TNM staging system. Patients with NSCLC were recruited from a hospital and divided into a discovery cohort (n = 194) and validation cohort (n = 172), and detected using a custom lncRNA microarray. Another 73 NSCLC cases obtained from a different hospital (an independent validation cohort) were examined with qRT-PCR. Differentially expressed lncRNAs were determined with the Significance Analysis of Microarrays program, from which lncRNAs associated with survival were identified using Cox regression in the discovery cohort. These prognostic lncRNAs were employed to construct a prognostic signature with a risk-score method. Then, the utility of the prognostic signature was confirmed using the validation cohort and the independent cohort. In the discovery cohort, we identified 305 lncRNAs that were differentially expressed between the NSCLC tissues and matched, adjacent normal lung tissues, of which 15 are associated with survival; a 4-lncRNA prognostic signature was identified from the 15 survival lncRNAs, which was significantly correlated with survivals of NSCLC patients. This signature was further validated in the validation cohort and independent validation cohort. Moreover, multivariate Cox analysis demonstrates that the 4-lncRNA signature is an independent survival predictor. Then we established a new risk-score model by combining 4-lncRNA signature and TNM staging stage. The receiver operating characteristics (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of the TNM stage alone, in all the cohorts. In this study, we identified a 4-lncRNA signature that may be a powerful prognosis biomarker and can provide additional survival information to the TNM staging system.


Protecting partial-hospitalization patients from suicide.
Assessing suicide potential and intervening to prevent suicide in partial-hospitalization patients. To provide information for assessing and intervening with outpatients who express suicidal thoughts and to propose a decision tree. Literature review, clinical experience. Careful assessment and sound management are required to provide treatment in outpatient settings while maintaining patient safety. A decision tree can help the clinician make sound decisions.


Comparison of the optical transmission properties of pulsed and continuous wave light in biological tissue.
The purpose of this study is to compare the optical transmission of the pulsed gold vapor laser (628 nm) to that of the continuous wave argon-pumped dye laser (630 nm) in a homogenous tissue model. Gluteal muscle was taken from a rabbit, and sections of varying thicknesses were made. The tissue samples were positioned at the aperture of an integrating sphere. The laser light was passed through an optical attenuator, coupled to a 600-microns fiber, and then directed onto the surface of the tissue. Transmitted light was collected by the integrating sphere. Light measurements were made with a radiometer. This procedure was repeated for samples of differing thickness using the gold vapor laser as the light source. The identical procedure was performed using the argon-pumped dye laser. No significant difference was found in percent transmission of light using the gold vapor laser as compared to the argon-pumped dye laser.


A simple cytochemical method for distinguishing EAC rosettes formed by lymphocytes and monocytes.
A simple cytochemical method for EAC rosettes in suspension is described which allows an easy distinction between rosettes formed by lymphocytes and monocytes. The method is based on the fact that monocytes, in contrast to lymphocytes, possess a specific cytoplasmic esterase.


Triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular events in the general population: A systematic review and meta-analysis of cohort studies.
The ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) has been regarded as a novel surrogate indicator of insulin resistance and the atherogenic index of plasma. This meta-analysis aimed to evaluate the association between the TG/HDL-C ratio and the incidence of cardiovascular events in the general population. Cohort studies reporting the association between the TG/HDL-C ratio and cardiovascular events in the general population were obtained by a systematic literature search of PubMed, Embase and Web of Science databases until April 11, 2021. 13 cohort studies with a total of 207,515 participants were included in this meta-analysis. In a random-effects model, compared with those with the lowest category of the TG/HDL-C ratio, participants with the highest category were independently associated with a higher risk of cardiovascular events (pooled HR: 1.43, 95%CI: 1.26-1.62, I2 = 72.9%). For the presence of publication bias detected by the Egger's test (p = 0.011), correction for publication bias using the trim-and-fill method reduced the HR to 1.26 (95%CI: 1.11-1.44). This result was consistent with the finding of the TG/HDL-C ratio analyzed as a continuous variable (pooled HR per unit increment of the TG/HDL-C ratio: 1.08, 95%CI: 1.04-1.12, I2 = 67.0%). Subgroup analyses indicated that population gender, geographical region, duration of follow-up, adjustment for other lipid parameters, adjustment for diabetes and categorical number did not significantly vary the relationship. Elevated TG/HDL-C ratio may be independently associated with an increased risk of cardiovascular events in the general population. More well-designed studies are needed to confirm the current findings. CRD42021244583.


Hidden demographic impacts of fishing and environmental drivers of fecundity in a sea turtle population.
Fisheries bycatch is a critical threat to sea turtle populations worldwide, particularly because turtles are vulnerable to multiple gear types. The Canary Current is an intensely fished region, yet there has been no demographic assessment integrating bycatch and population management information of the globally significant Cabo Verde loggerhead turtle (Caretta caretta) population. Using Boa Vista island (Eastern Cabo Verde) subpopulation data from capture-recapture and nest monitoring (2013-2019), we evaluated population viability and estimated regional bycatch rates (2016-2020) in longline, trawl, purse-seine, and artisanal fisheries. We further evaluated current nesting trends in the context of bycatch estimates, existing hatchery conservation measures, and environmental (net primary productivity) variability in turtle foraging grounds. We projected that current bycatch mortality rates would lead to the near extinction of the Boa Vista subpopulation. Bycatch reduction in longline fisheries and all fisheries combined would increase finite population growth rate by 1.76% and 1.95%, respectively. Hatchery conservation increased hatchling production and reduced extinction risk, but alone it could not achieve population growth. Short-term increases in nest counts (2013-2021), putatively driven by temporary increases in net primary productivity, may be masking ongoing long-term population declines. When fecundity was linked to net primary productivity, our hindcast models simultaneously predicted these opposing long-term and short-term trends. Consequently, our results showed conservation management must diversify from land-based management. The masking effect we found has broad-reaching implications for monitoring sea turtle populations worldwide, demonstrating the importance of directly estimating adult survival and that nest counts might inadequately reflect underlying population trends.


Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.
Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These results extend our understanding of the electrophysiological signature of BOLD RSNs and demonstrate the intrinsic connection between the fast neuronal activity and slow hemodynamic fluctuations.


MRA of the lower extremities in patients with pulmonary embolism using a blood pool contrast agent: initial experience.
To evaluate the feasibility of blood pool contrast-enhanced magnetic resonance angiography (MRA) to visualize the arterial and venous vessel tree and to detect deep venous thrombosis (DVT) of the lower extremities. Nine consecutive patients with pulmonary embolism (mean age = 46 +/- 9) were randomized to various doses of NC100150 (between 0.75 and 6 mg of Fe/kg of body weight). A T1-weighted (T1W) 3D gradient recalled echo (GRE) sequence (TE = 2.0 msec, TR = 5.0 msec) was used. Two observers blinded to the dose of contrast agent assessed image quality, contrast attenuation, and appearance of thrombi. Qualitative assessment of overall MRA image quality and semiquantitative vessel scoring revealed good to excellent delineation of venous and arterial vessel segments independent of the dose of NC100150. However, quantitative region of interest analysis revealed a significantly higher signal-to-noise ratio (SNR) in the high-dose group than in the mid- and low-dose groups of NC100150 (P < 0.01). Between dose groups, the SNR was independent of vessel type (artery or vein) and vessel segment localization (proximal or distal). All seven venous thrombi (mean length = 7.2 +/- 0.95 cm) were characterized by a very low signal intensity (SI), which was only 16.6 +/- 7% of the SI in adjacent venous segments (P < 0.0001). High-quality MR angiograms of the lower extremities can be obtained using low concentrations of NC100150 in combination with a strong T1W 3D GRE sequence. The obvious delineation of venous thrombi suggests that this technique may be potentially used as a noninvasive "one-stop shopping" tool in the evaluation of thromboembolic disease.


Continuous versus cyclic parenteral nutrition during bone marrow transplantation: assessment and follow-up.
The aim of this prospective, randomized clinical trial was to compare the efficacy of parenteral nutrition (PN) in adult bone marrow transplant (BMT) patients on a continuous (CON) versus a cyclic (CYC) regimen. Twelve patients received CON PN and 12 CYC PN. The groups were homogeneous. CON PN received 27.2 +/- 3.7 kcal/kg/day and for CYC PN 25.9 +/- 4.2 kcal/kg/day (P= 0.45). The duration of PN was 20.4 +/- 7.9 days and 27.3 +/- 13.4 days respectively (P = 0.14). There were no differences between initial and final body weights, either within or between groups. The initial pre-albumin levels were 16.1 +/- 7.5 mg/dl and 20.1 +/- 4.9 mg/dl in CON PN and CYC PN, respectively (P= 0.22), and these were maintained throughout the study. Blood glucose levels did not differ between groups. Measures of liver function were moderately increased, but with no significant differences between groups. There were no significant differences regarding the efficacy of PN or the appearance of complications between CON PN and CYC PN in patients with BMT.


Assessing the role of landscape connectivity on Opisthorchis viverrini transmission dynamics.
Opisthorchis viverrini (Ov) is one of the most important human parasitic diseases in Southeast Asia. Although the concept of connectivity is widely used to comprehend disease dispersal, knowledge of the influences of landscape connectivity on Ov transmission is still rudimentary. This study aimed to investigate the role of landscape connectivity in Ov transmission between the human and the first intermediate snail hosts. Fieldwork was conducted in three villages respectively in Kamalasai District, Kalasin Province, Phu Wiang District, Khon Kaen Province, and Nong Saeng District, Udon Thani Province. Bithynia snails were collected to examine parasitic infections, water samples were analyzed for fecal contamination, and locations of septic tanks and connections between habitat patches with observable water movement were surveyed. Euclidean distance, topological link and distance, and graph measures were employed to quantify the connectivity between human and snail habitats. The findings showed that snail patches with higher fecal contents were generally located nearer to septic tanks. The statistically significant results for the topological link and distance measures highlighted the importance of water in functionally facilitating Ov transmission. Graph measures revealed differences in landscape connectivity across the sites. The site with the largest landscape component size and the most mutually connected snail patches coincided with the presence of Ov parasite, reinforcing its higher risk for human to snail transmission. The site with the dissected landscape structure potentially limited the transmission. This study underscored the potential effect of landscape connectivity on Ov transmission, contributing to the understanding of the spatial variation of Ov infection risk.


Intermittent disturbance benefits colony size, biomass and dominance of Microcystis in Lake Taihu under field simulation condition.
Wind-driven wave disturbance is one of the environmental factors that shapes the formation of Microcystis blooms. Here we present data on the effect of different disturbance modes (continuous vs intermittent disturbances) on colony size, biomass and dominance of Microcystis in Lake Taihu under field conditions. Small submersible pumps were used to simulate different disturbance modes at turbulent dissipation rate (ε) of 2.98 × 10-6 m2 s-3. Our results show that the mean colony sizes of Microcystis in intermittent and continuous disturbance group were 1.94 and 1.23 times that of the control group, respectively. The mean densities of Microcystis in intermittent and continuous disturbance group were 4.23 and 2.91 times that of the control group, respectively. The mean proportion of Microcystis to total algae abundance in control group and continuous disturbance group changed from 78.3% at beginning of the experiment to 4.5% and 9.1% at the end of the experiment. However, the proportion of Microcystis to total algae cells in intermittent disturbance group was 65.7-94.3% during the whole experiment. The results demonstrated intermittent disturbances favored colony morphology, biomass and dominance of Microcystis. Our results suggested that intermittent disturbance benefited the formation of Microcystis bloom and was important in the development of predictive models for toxic cyanobacterial blooms under changing climates in shallow lakes.


Ventilator-associated events: From surveillance to optimizing management.
Mechanical ventilation (MV) is a life-support therapy that may predispose to morbid and lethal complications, with ventilator-associated pneumonia (VAP) being the most prevalent. In 2013, the Center for Disease Control (CDC) defined criteria for ventilator-associated events (VAE). Ten years later, a growing number of studies assessing or validating its clinical applicability and the potential benefits of its inclusion have been published. Surveillance with VAE criteria is retrospective and the focus is often on a subset of patients with higher than lower severity. To date, it is estimated that around 30% of ventilated patients in the intensive care unit (ICU) develop VAE. While surveillance enhances the detection of infectious and non-infectious MV-related complications that are severe enough to impact the patient's outcomes, there are still many gaps in its classification and management. In this review, we provide an update by discussing VAE etiologies, epidemiology, and classification. Preventive strategies on optimizing ventilation, sedative and neuromuscular blockade therapy, and restrictive fluid management are warranted. An ideal VAE bundle is likely to minimize the period of intubation. We believe that it is time to progress from just surveillance to clinical care. Therefore, with this review, we have aimed to provide a roadmap for future research on the subject.


Prevention of recurrent sudden cardiac arrest: role of provocative electropharmacologic testing.
This study evaluates the usefulness of serial provocative electropharmacologic testing for predicting the efficacy of prophylactic antiarrhythmic treatment regimens in patients resuscitated from sudden cardiac arrest in the absence of acute myocardial infarction. Testing was carried out in 34 consecutive patients (28 men and 6 women) who required cardiopulmonary resuscitation and direct current countershock for treatment of primary ventricular fibrillation (28 patients), ventricular tachycardia (5 patients) or excessively rapid heart rate during atrial fibrillation with preexcitation (1 patient). In 8 (24%) of the 34 patients, drug testing either was not feasible because of absence of inducible arrhythmia or was incomplete because of patient withdrawal from study; and 3 of these 8 patients had recurrent sudden cardiac arrest within 10 to 19 months. In an additional five patients, treatment regimens failed to prevent initiation of sustained ventricular tachyarrhythmias in the catheterization laboratory, and two of these five patients had cardiac arrest recurrences within 2 weeks to 25 months of follow-up. In the remaining 21 (62%) of the 34 patients, including 3 patients with preexcitation syndrome, a drug regimen or surgical treatment, or both, was found that prevented inducible life-threatening tachyarrhythmias in the laboratory. Subsequently, only 1 (5%) of these 21 patients died suddenly within a 7 to 38 month (mean +/- standard deviation, 18 +/- 8.3) follow-up period. Thus, provocative electropharmacologic testing appears to be useful in predicting response to therapy in survivors of sudden cardiac arrest.


Effectiveness of the physiotherapy interventions on complex regional pain syndrome in patients with stroke: A systematic review and meta-analysis.
Complex Regional Pain Syndrome (CRPS) is an umbrella term for a variety of clinical presentations characterized by persistent pain usually in the hands or feet that is disproportionate to any preceding injury and characterized by many autonomic, sensory, and motor symptoms. CRPS is among the most common causes of post stroke shoulder pain in approximately 80% of stroke survivors. This study reviewed the available literature of physiotherapy treatment for CRPS following a stroke. Two electronic databases; PubMed and Google Scholar were searched to screen the articles from 2008 to March 2021 to be included in the study. Meta-analysis was done using the RevMan version 5.4 software. Higgins I2 and Chi-square (Tau2) statistical tests were used to assess heterogeneity. Out of all 389 studies, only 4 RCT's were included for systematic review and meta-analysis. Mirror therapy, Laser therapy and Fluidotherapy was found to be effective than control in improving pain intensity (SMD 4.13, 95% CI 3.51 to 4.74, I2 = 99%) and functional independence (SMD 2.07, 95% CI 1.45 to 2.70, I2 = 100%) in patients with CRPS following stroke. This review concluded that physiotherapy interventions in the form of exercise therapy and electrotherapy has proven to be effective in treating the symptoms of CRPS following stroke. This commonest and devastating condition has not been studied to an extent in clinical settings, there is an utmost need for further studies using the available literature.


Effectiveness of Dupilumab in the Treatment of Adult and Older Adult Patients with Severe, Uncontrolled CRSwNP.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease that significantly impacts patients' quality of life. New therapeutic strategies and in particular biologic treatments are now available for these patients. It has been demonstrated that Dupilumab (an anti IL-4/IL-13 biologic drug) is effective in reducing the size of nasal polyps and in improving patients' symptoms and thus, quality of life. No real-world studies examining Dupilamab's efficacy in the elderly with respect to other adult age groups have as yet been carried out. The aim of this multicentric study was to evaluate Dupilumab's efficacy in young-middle adults as opposed to an older adult population affected by severe, uncontrolled CRSwNP. Of the 96 patients included in the study, 22 were 65 years old or older. Significant improvements were observed in all the parameters considered in both age groups after treatment was begun (T0 mean values for SNOT-22 = 58.5 ± 20.3, VAS NO = 7.6 ± 2.2, VAS smell = 8.6 ± 2.1, NPS = 5.6 ± 1.4, PNIF = 101.6 ± 59.4, S'S = 5.1 ± 3.1), T4 mean values for SNOT-22 = 15.1 ± 12.7, VAS NO = 1.7 ± 1.8, VAS smell = 2.4 ± 3, NPS = 1.7 ± 1.7, PNIF = 162.4 ± 43.2, S'S = 10.4 ± 3.7) (p < 0.0001). No differences in the variables considered were observed between the two age groups during the study, with the exception of the Peak Nasal Inspiratory Flow (PNIF), which was marginally higher; this was also the case according to multivariate analyses (p = 0.008) in the young-middle adult group with respect to the elderly one (p = 0.07). At multivariate analyses, asthma and the female sex negatively influenced the PNIF values (p = 0.001 and p = 0.012, respectively). Age negatively influenced the Visual Analog Scale (VAS) for nasal obstruction (p = 0.0032) and Endoscopic Sinus Surgery (ESS) negatively influenced the patents' olfactory performance (p = 0.028) to the same degree in both groups. Dupilumab was found to be effective to the same degree in both age groups. It can be considered a safe and reliable option for the treatment of elderly patients with severe, uncontrolled CRSwNP.


Congenital herpes simplex type II infection with extensive hepatic calcification, bone lesions and cataracts: complete postmortem examination.
True congenital herpes simplex viral (HSV) infections have been reported infrequently and have been associated with various 'congenital' malformations. Microcephaly, microphthalmia, intracranial calcifications, chorioretinitis, congenital heart disease and abnormal digits have been associated with presumed congenital HSV infection. This report describes the clinical and pathological features of an infant with a congenital type-II HSV infection. In addition to the findings previously reported with this form of HSV infection, extensive hepatic calcifications, osseous lesions and cataracts were observed for the first time. The effect of congenital HSV infection on the developing central nervous system is discussed.


Enhancement of carotid chemoreceptor reflex and cardiac chemosensitive reflex in the acute phase of myocardial infarction of the anesthetized rabbit.
In the acute phase of cardiac ischemia there is an imbalance of the autonomic outflow with a depression of the baroreceptor reflex. Carotid chemoreceptor stimulation evokes an increase on arterial blood pressure and bradycardia in the anesthetized and paralyzed animal. The activation of cardiac chemosensitive fibers elicit the Bezold-Jarisch reflex comprising a decrease of arterial blood pressure and bradycardia. In the present study, we studied the modifications of the carotid chemoreceptor reflex and the Bezold-Jarisch reflex elicited during the acute phase of myocardial infarction (MI) in the anesthetized and paralyzed rabbit. Rabbits were anesthetized with pentobarbitone, paralyzed and artificially ventilated. The carotid sinus region was exposed and a cannula was inserted retrogradely through the external carotid artery into the carotid bifurcation; the carotid body was stimulated by a lobeline injection. A catheter was advanced, via the right carotid artery, to the origin of the aorta and the Bezold-Jarisch reflex was evoked by an injection of ATP. The baroreflex was provoked by an increase in after-load or by clamping the common carotid artery. Heart ischemia was provoked by ligation of the descending coronary artery. Arterial blood pressure, carotid artery pressure, heart rate and electrocardiogram were monitored. Stimulation of cardiovascular and cardiac receptors was performed before and after coronary ligation. Results show an overall increase in the cardiovascular reflex responses elicited by stimulation of chemically activated receptors and an overall decrease of the baroreceptor responses after MI. In conclusion, these data show the existence of an enhancement of the reflex cardiovascular responses to carotid chemoreceptor and cardiac chemosensitive receptors stimulation and confirmed the depression of baroreceptor reflexes following heart ischemia that could account for the imbalance of the autonomic output observed in the acute phase of myocardial infarction.


Pulmonary artery origin of the left coronary artery: diagnosis by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow mapping.
Five children, aged 0.2 to 6.7 years, with pulmonary artery origin of the left coronary artery proved by angiography underwent echocardiographic examination from 1985 through 1986. Prospective identification of this condition was achieved by two-dimensional echocardiography alone in two patients. Using a parasagittal plane from the second or third intercostal space, identification of the anomalous origin from the pulmonary artery was also possible in the other children on subsequent examination. In all of these studies the right coronary artery was considerably enlarged. The ratio of the diameters of the right coronary artery and the aortic root was 0.25 to 0.33 (normal 0.12 +/- 0.02). Flow mapping by color Doppler ultrasound in three children studied most recently and peripheral arterial or aortic root contrast echocardiography identified the site of entry of the coronary flow into the pulmonary artery. The flow disturbance was detected on the aortic surface of the pulmonary artery opposite the portion from where the flow from a patent ductus is usually identified. Pulsed Doppler ultrasound identified the flow disturbance in the pulmonary artery in only three of the children. The two youngest patients did not demonstrate turbulence on pulsed Doppler ultrasound, but they were not examined by color Doppler ultrasound. The accuracy of noninvasive detection of pulmonary artery origin of the left coronary artery by ultrasound is improved by the use of a combined echocardiographic approach.


Five-year survivors after aggressive surgery for stage IV gallbladder cancer.
To describe 5-year survivors after radical surgery for stage IV gallbladder cancer and to determine the characteristics leading to potential long-term survival. Of 59 patients undergoing radical resection for stage IV disease between 1979 and 1994, 6 patients who have survived for more than 5 years were followed up. Three patients had developed obstructive jaundice due to involvement of the hepatic hilum, but the other three had not. The jaundiced patients had remarkable tumor spread over the bile duct and right hepatic artery within the hepatoduodenal ligament. However, the proper and left hepatic arteries and the portal trunk and its left branch were free from tumor involvement. The nonjaundiced patients had N1 or N2 lymph node metastasis. However, none underwent bile duct resection or pancreatoduodenectomy to establish radical lymphadenectomy. Selected patients with stage IV gallbladder cancer may be candidates for 5-year survival when the primary tumor is fairly localized even if it forms a large mass and involves neighboring organs including the hepatic duct, lymph node metastasis is limited to N1 and N2 except for the celiac and superior mesenteric nodes and is less infiltrative, and distant metastasis including that in the paraaortic area is absent.


Anterior versus posterior approach for treatment of cervical spondylotic myelopathy: a systematic review.
Systematic review. We performed a systematic review to determine the comparative effectiveness and safety profiles of anterior versus posterior decompression procedures for multilevel cervical spondylotic myelopathy (CSM). CSM is a common cause of neurological dysfunction. It is well established that surgical decompression of the cervical spinal cord is an effective treatment option for CSM. Because of the lack of well-designed prospective studies, there remains a lack of consensus whether multilevel spondylotic compression is best treated via an anterior or posterior surgical route and whether one of these surgical approaches is superior in terms of patient outcomes and/or complication profiles. We conducted a systematic search for literature published through September 2012. We sought to identify comparative studies (e.g., randomized controlled trials, cohort studies) comparing anterior with posterior procedures in patients with 2-level or greater cord compression resulting in CSM. Standardized mean differences were calculated to allow comparisons of the change (i.e., improvement or decline) in scores between anterior and posterior surgical procedures by study. Clinical recommendations were made through a modified Delphi approach by applying the GRADE (Grading of Recommendation Assessment, Development and Evaluation)/AHRQ (Agency for Healthcare Research and Quality) criteria. We identified 8 level III retrospective cohort studies that met the inclusion criteria from a total of 135 possible studies for review. With regard to effectiveness between the 2 approaches, improvements in JOA (Japanese Orthopaedic Association) scores were similar, whereas canal diameter change was larger after posterior surgery. With regard to safety, postoperative C5 palsy rates were similar, infection rates were lower with anterior surgery, and dysphagia rates were lower with posterior surgery. This systematic review demonstrates that, for both effectiveness and safety, there is no clear advantage to either an anterior surgical approach or a posterior surgical approach when treating patients with multilevel CSM. With that, a surgical strategy developed on a patient-to-patient basis should be used to achieve optimal patient outcomes. In addition, development of a consensus for standardized reporting of outcome measures and complication profiles would facilitate improved comparisons across differing treatment centers and surgical techniques. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: We recommend an individualized approach when treating patients with CSM accounting for pathoanatomical variations (ventral vs. dorsal, focal vs. diffuse, sagittal, dynamic instability) because there are similar outcomes between the anterior and posterior approaches with regard to effectiveness and safety. Low. Strong.


The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation.
Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus. We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis). Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls. Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls. Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena.


Risk factors for postoperative bleeding after thyroid surgery.
Postoperative bleeding after thyroid surgery is a feared and life-threatening complication. The aim of the study was to identify risk factors for postoperative bleeding, with special emphasis on the impact of the individual surgeon and the time to diagnosis of the complication. Data on consecutive thyroid operations were collected prospectively in a database over 30 years and analysed retrospectively for potential risk factors for postoperative bleeding. There were 30,142 operations and postoperative bleeding occurred in 519 patients (1·7 per cent). Risk factors identified were older age (odds ratio (OR) 1·03 per year), male sex (OR 1·64), extent of resection (OR up to 1·41), bilateral procedure (OR 1·99) and operation for recurrent disease (OR 1·54). The risk of complications among individual surgeons differed by up to sevenfold. Postoperative bleeding occurred in 336 (80·6 per cent) of 417 patients within the first 6 h after surgery. Postoperative bleeding was diagnosed after 24 h in ten patients (2·4 per cent), all of whom had bilateral procedures. Nine patients required urgent tracheostomy. Three patients died, giving a mortality rate of 0·01 per cent overall and 0·6 per cent among patients who had surgery for postoperative bleeding. Observation for up to 24 h is recommended for the majority of patients undergoing bilateral thyroid surgery in an endemic goitre area. Same-day discharge is feasible in selected patients, especially after a unilateral procedure. Quality improvement by continuous outcome monitoring and retraining of individual surgeons is suggested.


Experimental and DFT studies on the vibrational and electronic spectra of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
Vibrational and electronic spectral measurements were made for 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Optimized geometrical structure and harmonic vibrational frequencies were computed by DFT(B3LYP, CAMB3LYP, B3P86, M062X, mPW3PBE and PBE1PBE) using 6-311++G(d,p) basis set. Complete assignments of the observed spectra were proposed. The absorption spectra of the compound were computed both in gas-phase and in CH(2)Cl(2) solution using TDCAMB3LYP/6-311++G(d,p) and PCM-TDCAMB3LYP/6-311++G(d,p) approaches, respectively, the calculated results provide a good description of positions of the bands maxima in the observed electronic spectrum.


Correlation between matrix structural order and compressive stress exerted on silicon nanocrystals embedded in silicon-rich silicon oxide.
Silicon nanocrystals embedded in a silicon oxide matrix were deposited by radio frequency reactive magnetron sputtering. By means of Raman spectroscopy, we have found that a compressive stress is exerted on the silicon nanocrystal cores. The stress varies as a function of silicon concentration in the silicon-rich silicon oxide layers varies, which can be attributed to changes of nanocrystal environment. By conducting the Fourier transform infrared absorption experiments, we have correlated the stresses exerted on the nanocrystal core to the degree of matrix structural order. PACS: 78.67.Bf, 78.67.Pt, 73.63.Bd, 78.47.D, 74.25.Nd.


Risk models for progression to advanced age-related macular degeneration using demographic, environmental, genetic, and ocular factors.
To expand our predictive models for progression to advanced stages of age-related macular degeneration (AMD) based on demographic, environmental, genetic, and ocular factors, using longer follow-up, time varying analyses, calculation of absolute risks, adjustment for competing risks, and detailed baseline AMD and drusen status. Prospective, longitudinal study. We included 2937 individuals in the Age-Related Eye Disease Study, of which 819 subjects progressed to advanced AMD during 12 years of follow-up. Cox proportional hazards regression analyses were performed to calculate hazard ratios for progression. Covariates included demographic and environmental factors, 6 variants in 5 genes, baseline macular drusen size, and presence and type of advanced AMD in 1 eye at baseline. To assess the ability of risk scores based on all covariates to discriminate between progressors and nonprogressors, an algorithm was developed and the area under the receiver operating characteristic curve (AUC) was calculated. To validate the overall model, the total sample was randomly subdivided into derivation and test samples. Another model was built based on the derivation sample and assessed for calibration and discrimination in the test sample. Sample sizes needed for testing new treatments in clinical trials were estimated based on models with and without genetic variables. Progression to advanced AMD, including geographic atrophy and neovascular disease. In multivariate models, age, smoking, body mass index, single nucleotide polymorphisms in the CFH, ARMS2/HTRA1, C3, C2, and CFB genes, as well as presence of advanced AMD in 1 eye and drusen size in both eyes were all independently associated with progression. The AUC for progression at 10 years in the model with genetic factors, drusen size, and environmental covariates was 0.915 in the total sample. In the test sample, based on a model estimated from the derivation sample, the AUC was 0.908. The sample sizes needed for clinical trials were estimated to be lower when genetic susceptibility was considered. Factors reflective of nature and nurture were incorporated into an expanded algorithm for risk prediction, which performed very well in both derivation and test samples. Risk scores and predicted progression rates will be useful for AMD surveillance and for designing clinical trials. Proprietary or commercial disclosure may be found after the references.


Mechanisms and structures of crotonase superfamily enzymes--how nature controls enolate and oxyanion reactivity.
Structural and mechanistic studies on the crotonase superfamily (CS) are reviewed with the aim of illustrating how a conserved structural platform can enable catalysis of a very wide range of reactions. Many CS reactions have precedent in the 'carbonyl' chemistry of organic synthesis; they include alkene hydration/isomerization, aryl-halide dehalogenation, (de)carboxylation, CoA ester and peptide hydrolysis, fragmentation of beta-diketones and C-C bond formation, cleavage and oxidation. CS enzymes possess a canonical fold formed from repeated betabetaalpha units that assemble into two approximately perpendicular beta-sheets surrounded by alpha-helices. CS enzymes often, although not exclusively, oligomerize as trimers or dimers of trimers. Two conserved backbone NH groups in CS active sites form an oxyanion 'hole' that can stabilize enolate/oxyanion intermediates. The range and efficiency of known CS-catalyzed reactions coupled to their common structural platforms suggest that CS variants may have widespread utility in biocatalysis.


Management of pituitary gonadal function via gonadotrophin releasing hormone (GnRH) antagonists, including ovulation induction by co-administration of either gonadotrophins or pulsatile GnRH.
GnRH agonists are now familiar clinical agents and are often the drugs of choice for suppression of the pituitary gonadal axis as part of various clinical indications. GnRH antagonists, which are likely to become clinically available soon, offer several advantages over the currently available GnRH agonists for many applications including ovulation induction. Here, we review the results from a series of pre-clinical studies designed to evaluate the potential clinical utility of this new class of compounds for ovulation induction protocols.


Myoclonic spasms during treatment with high doses of intravenous morphine in renal failure.
Myoclonic spasms occurred in a patient suffering from renal failure after high doses of continuous intravenous morphine (100 mg/h). The concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide (mumol/l) in plasma were: 1.93, 52.06 and 381.8, and in cerebrospinal fluid were: 1.02, 5.86 and 61.82, respectively. The role of morphine and morphine glucuronides in myoclonic spasms is discussed.


Resilience Is Associated With Larger Dentate Gyrus, While Suicide Decedents With Major Depressive Disorder Have Fewer Granule Neurons.
Early life adversity (ELA) increases major depressive disorder (MDD) and suicide risk and potentially affects dentate gyrus (DG) plasticity. We reported smaller DG and fewer granular neurons (GNs) in MDD. ELA effects on DG plasticity in suicide decedents with MDD (MDDSui) and resilient subjects (ELA history without MDD or suicide) are unknown. We quantified neural progenitor cells (NPCs), GNs, glia, and DG volume in whole hippocampus postmortem in four groups of drug-free, neuropathology-free subjects (N = 52 total): psychological autopsy-defined MDDSui and control subjects with and without ELA (before 15 years of age). ELA was associated with larger DG (p < .0001) and trending fewer NPCs (p = .0190) only in control subjects in whole DG, showing no effect on NPCs and DG volume in MDDSui. ELA exposure was associated with more GNs (p = .0003) and a trend for more glia (p = .0160) in whole DG in MDDSui and control subjects. MDDSui without ELA had fewer anterior and mid DG GNs (p < .0001), fewer anterior DG NPCs (p < .0001), and smaller whole DG volume (p = .0005) compared with control subjects without ELA. In MDDSui, lower Global Assessment Scale score correlated with fewer GNs and smaller DG. Resilience to ELA involves a larger DG, perhaps related to more neurogenesis depleting NPCs, and because mature GNs and glia numbers do not differ in the resilient group, perhaps there are effects on process extension and synaptic load that can be examined in future studies. In MDDSui without ELA, smaller DG volume, with fewer GNs and NPCs, suggests less neurogenesis and/or more apoptosis and dendrite changes.


Segmental linkage disequilibrium within the dopamine transporter gene.
The dopamine transporter gene (DAT) has been implicated in a variety of disorders, including bipolar disorder, attention-deficit hyperactivity disorder, cocaine-induced paranoia, Tourette's syndrome, and Parkinson's disease. As no clear functional polymorphism has been identified to date, studies rely on linkage disequilibrium (LD) to assess the possible genetic contribution of DAT to the various disorders. A better understanding of the complex structure of LD across the gene is thus critical for an accurate interpretation of the results of such studies, and may facilitate the mapping of the actual functional variants. In the process of characterizing the extent of variation within the DAT gene, we have identified a number of single nucleotide polymorphisms (SNPs) suitable for LD studies, 14 of which have been analyzed, along with a 3' repeat polymorphism, in a sample of 120 parent-proband triads. Calculations of pairwise LD between the SNPs in the parental haplotypes revealed a high degree of LD (P < 0.00001) in the 5' (distal promoter through intron 6) and 3' (exon 9 through exon 15) regions of DAT. This segmental LD pattern is maintained over approximately 27 kb and 20 kb in these two regions, respectively, with very little significant LD between them, possibly due to the presence of a recombination hotspot located near the middle of the gene. These analyses of the DAT gene thus reveal a complex structure resulting from both recombination and mutation, knowledge of which may be invaluable to the design of future studies.


The prevalence of professional burnout among dentists: a systematic review and meta-analysis.
Professional burnout refers to mental weariness caused by occupational stress. However, there is a lack of systematic studies on the prevalence of professional burnout among dentists. The purpose of this study was to investigate the prevalence of professional burnout among dentists. Databases including PubMed, PsycINFO, Embase, Cochrane, and Web of Science were systematically searched from inception to 28 October 2021. The random-effects model and forest plots were used to assess the pooled prevalence of professional burnout among dentists. A total of 15 studies with a total of 6038 study subjects were included in the meta-analysis, and the overall professional burnout among dentists was 13% (95%CI: 6-23). Subgroup analysis suggested a high prevalence of burnout in Europe, and the least in the Americas. The pooled burnout prevalence in cross-sectional surveys was significantly lower than that in longitudinal studies. In addition, the overall burnout prevalence in the last decade was significantly lower than that of a decade ago. This meta-analysis demonstrated that the prevalence of burnout was relatively low among dentists, and there was a downward trend. Therefore, it is important to continue to pay close attention to the mental health of dentists and effectively prevent and treat professional burnout to better maintain the provision of health care services.


Targeted gene expression analysis in hemimegalencephaly: activation of beta-catenin signaling.
Hemimegalencephaly (HMEG) is a developmental brain malformation characterized by unilateral hemispheric enlargement, cytoarchitectural abnormalities, and an association with epilepsy. To define the developmental pathogenesis of HMEG, the expression of 200 cell signaling, growth, angiogenic, and transcription factor genes was assayed in HMEG samples (n=8) with targeted cDNA arrays. Differential expression of 31 mRNAs across the 4 gene families was identified in HMEG compared with control cortex. Increases in growth and transcription factor genes included JNK-1, cyclic AMP response element binding protein (CREB), and tuberin mRNAs and decreases included insulin-like growth factor-1 (IGF-1), transforming growth factor beta-3 (TGF-beta3), and NFkB mRNAs. Increased expression of cyclin D1, c-myc, and WISP-1 mRNAs in HMEG suggested activation of the Wnt-1/beta-catenin cascade. Western analysis demonstrated increased levels of non-phosphorylated beta-catenin, which transcriptionally activates cyclin D7 and c-myc genes, but reduced levels of Ser33/Ser37/Thr41 phospho-beta-catenin, which is essential for beta-catenin-inactivation, in HMEG. Altered expression of 31 mRNAs from 4 gene families in human HMEG may lead to aberrant cell growth and hemispheric enlargement during brain development. Enhanced cyclin D1 and c-myc transcription likely reflects increased transcriptionally active beta-catenin due to decreased Ser33/Ser37/Thr41 phospho-beta-catenin and suggests activation of the Wnt-1/beta-catenin cascade in HMEG.


Thoracico-abdominal respiratory correlations in infants: constancy and variability in different sleep states.
28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. Data were analysed by 20-sec epochs. Relationships between thoracic (3rd-4th rib level) and abdominal respiratory movements were studied according to their maximum out-of-phase occurring (180 degrees maximum) in every 20-sec period. The thoracico-abdominal phase relationships according to sleep states do not change during the first trimester of life. In quiet sleep, while in-pase thoracico-abdominal respiration was the most frequent pattern, the out-of-phase one was also a possible pattern. In active sleep, out-of-phase respiration is characteristic, in-phase relation being a rare exception. In transitional sleep, respiratory relationships could be those appropriate for the preceding or the following sleep state. Nasal air flow always occurred in the phase with abdominal movements. Total flatteninf of thoracicorespiratory movements only were found in all sleep states; these thoracic flattenings must be differentiated from apnea. Transient fluctuations in the degree of phase relations are possible. There exists both interand intraindividual variability in normal infants. Variability of fusimotor system tonus is probably the neurological mechanism underling these phenomena.


Bifrontal and bioccipital transcranial direct current stimulation (tDCS) does not induce mood changes in healthy volunteers: a placebo controlled study.
Transcranial direct current stimulation (tDCS) is the application of a weak electrical direct current (1.5 mA), which has the ability to modulate spontaneous firing rates of the cortical neurons by depolarizing or hyperpolarizing the neural resting membrane potential. tDCS in patients with depressive disorders has been proven to be an interesting therapeutic method potentially influencing pathologic mood states. Except one study, no alterations in mood could be confirmed applying tDCS in healthy participants. In this study, bifrontal or bioccipital stimulation was applied in 17 healthy subjects during 20 minutes with 1.5 mA in a placebo-controlled manner. Bifrontal stimulation consisted of both anodal and cathodal placement on right and left dorsolateral prefrontal cortex (DLPFC) in two separate sessions. Using a set of self-reported moodscales (SUDS, POMS-32, PANAS, BISBAS) no significant mood changes could be observed, neither with bifrontal nor bioccipital tDCS. As already demonstrated by previous studies, we confirmed the minimal side effects and the safety of this neuromodulation technique.


Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging.
Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40-3.07; LASA: HR = 1.33, 95%CI = 1.01-1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74-6.28; LASA: HR = 1.70, 95%CI = 1.30-2.21). Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore.


The N-degradome of Escherichia coli: limited proteolysis in vivo generates a large pool of proteins bearing N-degrons.
The N-end rule is a conserved mechanism found in Gram-negative bacteria and eukaryotes for marking proteins to be degraded by ATP-dependent proteases. Specific N-terminal amino acids (N-degrons) are sufficient to target a protein to the degradation machinery. In Escherichia coli, the adaptor ClpS binds an N-degron and delivers the protein to ClpAP for degradation. As ClpS recognizes N-terminal Phe, Trp, Tyr, and Leu, which are not found at the N terminus of proteins translated and processed by the canonical pathway, proteins must be post-translationally modified to expose an N-degron. One modification is catalyzed by Aat, an enzyme that adds leucine or phenylalanine to proteins with N-terminal lysine or arginine; however, such proteins are also not generated by the canonical protein synthesis pathway. Thus, the mechanisms producing N-degrons in proteins and the frequency of their occurrence largely remain a mystery. To address these issues, we used a ClpS affinity column to isolate interacting proteins from E. coli cell lysates under non-denaturing conditions. We identified more than 100 proteins that differentially bound to a column charged with wild-type ClpS and eluted with a peptide bearing an N-degron. Thirty-two of 37 determined N-terminal peptides had N-degrons. Most of the proteins were N-terminally truncated by endoproteases or exopeptidases, and many were further modified by Aat. The identities of the proteins point to possible physiological roles for the N-end rule in cell division, translation, transcription, and DNA replication and reveal widespread proteolytic processing of cellular proteins to generate N-end rule substrates.


Copper induced alterations of biochemical parameters in the gill and plasma of Oreochromis niloticus.
The main objective of this study was to determine the effects of copper exposure on copper accumulated in branchial tissue, gill Na+/K+-ATPase activity and plasma Na+, Cl-, osmolality, protein, glucose and cortisol, in Oreochromis niloticus. Fish were experimentally exposed to 40 and 400 microg L(-1) of waterborne copper and sacrified after 0, 3, 7, 14 and 21 days. Copper accumulation and Na+/K+-ATPase activity were determined in branchial tissue, whereas osmolality, Na+, Cl-, protein, glucose and cortisol concentrations were measured in plasma samples. Gill copper accumulation increased linearly with exposure time and concentration, whereas gill Na+/K+-ATPase activity was maximally inhibited after 3 days of exposure and showed a significant negative correlation with copper tissue levels. Plasma Cl- values decreased with time of exposure but only at 400 microg L(-1) of copper. Plasma Na+, protein and osmolality decreased with exposure time at the highest copper concentration tested, whereas at 40 microg L(-1) of copper this effect was only observed after 21 days of exposure. Plasma glucose and cortisol levels increased in a dose and time dependent manner, while showing complex fluctuations during the intermediate exposure times. In conclusion, copper induces an early maximum inhibition of gill Na+/K+-ATPase activity in O. niloticus. The subsequent slow decrease in ion plasma levels was related to compensatory mechanisms involving a non-specific stress response that appeared overcome at long-term exposures.


A Quality Improvement Initiative to Reduce Pediatrician Burnout Led by the American Academy of Pediatrics Section on Internal Medicine and Pediatrics (Med-Peds).
Physician burnout impacts care (of self and patient), productivity, longevity of career, and overall cost to the system. While burnout rates for pediatricians are lower than average, they have not improved significantly over time. While strategies at the system level have been more successful than those at the individual level, both aspects are vital. This quality improvement study explores physician wellness and burnout trends of a sample population of pediatricians at the 2018 and 2019 AAP National Conference and Exhibition (NCE), using the Physician Health and Wellness Booth (PHWB). A rapid cycle approach with the Plan-Do-Check-Act (PDCA) framework was utilized. The aim was to observe if reported burnout decreased by 20% over six months. Of the pediatricians who interacted with the PHWB, 56 were randomly selected to participate. This included men and women and those in various practice settings, ranging from resident physicians to providers in practice for over 20 years. Baseline surveys included elements from a modified Maslach Burnout Inventory and the Stanford Physician Wellness Survey, focusing on burnout components (emotional exhaustion, depersonalization, and fulfillment) and wellness activities. Individual-based interventions were provided at the PHWB, including adult preventative health guidelines, resources on sleep, stress mitigation, and complementary medicine. Participants received a movie ticket and Starbucks gift card. Follow-up included six monthly newsletters with strategies from seven wellness domains. Post-intervention surveys at six months assessed all baseline questions plus the effectiveness of monthly newsletters. A second PDCA cycle was conducted from the 2019 NCE. All individual-based interventions continued with an added aromatherapy oil station. Additional system-based resources included sample institutional wellness initiatives and burnout cost analyses, all focusing on advocating for cultural change at their respective home organizations. Interactive monthly wellness calendars addressing seven wellness domains were emailed for six months follow-up. Results from 10 post-intervention surveys (10/56=18% of respondents) from the initial cohort reported an average of 25% decrease in burnout (p=0.09). This was measured on a scale of 1-10 (from "never" burned out to "very often") and improved from 6.68 ("sometimes" to "often" burned out) to 5.0 ("rarely" to "sometimes" burned out). Results from Cohort 2 reflected a decrease in burnout from 4.94 ("rarely" to "sometimes" burned out) to 2.85 ("never" to "rarely" burned out) in return from 20 post-intervention surveys (20/48=42% of respondents, p=0.003). Participants noted a lack of control over work schedules and a disconnect with organizational values as drivers of burnout. Both the PHWB and monthly newsletters were rated as valuable as reminders about wellness practices. Limitations included low response rate, which was notable, and inability to prove causation of improvement from our intervention. Future steps include utilizing subject identification numbers to allow for anonymity in a prospective cohort study with a third PDCA cycle. This would allow anonymous but matched same-subject comparison of pre- and post-survey results despite the small sample size. Follow-up incentives could be beneficial. Lastly, data from both cohorts revealed the highest level of burnout in early career physicians within 10 years of training, paving an opportunity for future study.


Toxicokinetics of monochloroacetic acid: a whole-body autoradiography study.
Monochloroacetic acid (MCA) is a toxic chemical used as a herbicide and in the synthesis of various organic compounds. MCA has also been shown to be present in chlorinated drinking waters. In order to understand the mechanism of MCA toxicity, we studied the tissue distribution of [1-14C]MCA in rats, by whole-body autoradiographic technique. Male Sprague-Dawley rats were given a tracer dose of [1-14C]MCA [6.8 micrograms/100 g (40 mu Ci) body weight] by tail vein and euthanized at different time intervals (5 min, 1, 4, 12, 24 and 48 h). The animals were embedded in carboxymethyl cellulose and frozen immediately. Frozen animals were sectioned and processed using whole-body autoradiographic techniques. Analysis of developed sections showed that at 5 min, there was a rapid accumulation of 14C-activity in the kidney cortex and stomach walls. The radioactivity was rapidly removed from the circulation. There was high accumulation of 14C-activity in the myocardial tissues. The liver was also loaded with MCA and/or its metabolites. After 1 h following administration of [14C]MCA, radioactivity was extensively excreted into the small intestinal lumen. the accumulation of 14C-activity in the brain, thymus, salivary glands and tongue was prominent at 1 h. After 4 h the liver and other tissues started to eliminate most of the radioactivity. Contrary to other tissues, however, the central nervous system, thymus and pancreas started to accumulate the radioactivity at later time periods. These observations suggest the accumulation of MCA and/or its metabolites into hydrophilic tissues at earlier time periods and into lipophilic tissues at later times.


In vitro evaluation of efficacy of 5 methods of disinfection on mouthpieces and facemasks contaminated by strains of cystic fibrosis patients.
Home-nebulizers are a potential source of bacterial infection of the respiratory tract in patients suffering from cystic fibrosis. Recommendations for disinfecting this equipment are often arbitrary and sometimes contradictory. To assess in vitro the effectiveness of 5 methods of disinfecting this equipment. 160 mouthpieces and 160 masks of nebulizers were artificially and massively contaminated with 16 strains of germs found in patients with cystic fibrosis (Staphylococcus aureus, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cenocepacia, Alcaligenes xylosoxydans). A controlled comparison was carried out of the five methods of disinfection (hypochlorite solution (0.02% active chlorine), acetic acid 3.5%, Hexanios 0.5%, washing-up detergent 0.5% and a dishwasher), tested with and without drying. Standardised bacteriological sampling took place 4 h after disinfecting. Following treatment, the disappearance of the germ was recorded in 84.1% of cases, and effective disinfecting (reduction>5 log CFU/mL) in another 10.6%. Disinfection failure (5.3%) was found almost only in the case of acetic acid against Staphylococcus aureus. With the exception of acetic acid, the methods of disinfecting tested in this study appeared to be effective against common bacterial pathogens in cystic fibrosis.


Differential Myocardial Fibre Involvement by Strain Analysis in Patients With Aortic Stenosis.
Aortic stenosis (AS) is the most common valvular heart disease and can result in left ventricular (LV) systolic impairment. LV myocardial fibres are organised in layers: the subendocardial layer is orientated longitudinally and the subepicardial layer circumferentially. We hypothesised that there is differential involvement of myocardial fibres in patients with aortic stenosis. We performed multi-directional, multi-layered systolic strain analysis in 70 patients (aged 72±10.7years) with varying grades of AS severity (mean gradient 32.3±20mmHg, aortic valve area 1.1±0.6cm2) and in 30 controls. Clinical, demographic and resting echocardiographic data were recorded. Left ventricular subendocardial and subepicardial systolic strains were measured in the longitudinal, radial and circumferential axes. Systolic subendocardial strain was significantly higher than subepicardial strain in all three axes in patients and in controls. There were significant differences in longitudinal, but not in circumferential and radial strain, or left ventricular ejection fraction (LVEF), between patient groups. Aortic valve mean gradient (MG) and valve area (AVA) correlated better with subendocardial longitudinal strain (r=0.548, p<0.001; r=-0.54, p<0.001 respectively) than with subepicardial longitudinal strain (r=0.496, p<0.001, r=-0.544, p<0.001 respectively). Correlations between circumferential and radial strain and MG or AVA were poor. There was differential impairment in LV systolic strain in all three cardiac axes in patients with AS. Left ventricular longitudinal strain impairment was proportional to AS severity. Subendocardial longitudinal strain correlated better with AS severity than subepicardial longitudinal strain while correlations between circumferential and radial strain and AS severity were weak.


Happy emotion cognition of bimodal audiovisual stimuli optimizes the performance of the P300 speller.
Prior studies of emotional cognition have found that emotion-based bimodal face and voice stimuli can elicit larger event-related potential (ERP) amplitudes and enhance neural responses compared with visual-only emotional face stimuli. Recent studies on brain-computer interface have shown that emotional face stimuli have significantly improved the performance of the traditional P300 speller system, but its performance needs to be further improved for practical applications. Therefore, we herein propose a novel audiovisual P300 speller based on bimodal emotional cognition to further improve the performance of the P300 system. The audiovisual P300 speller we proposed is based on happy emotions, with visual and auditory stimuli that consist of several pairs of smiling faces and audible chuckles (E-AV spelling paradigm) of different ages and sexes. The control paradigm was the visual-only emotional face P300 speller (E-V spelling paradigm). We compared the ERP amplitudes, accuracy, and raw bit rate between the E-AV and E-V spelling paradigms. The target stimuli elicited significantly increased P300 amplitudes (p < .05) and P600 amplitudes (p < .05) in the E-AV spelling paradigm compared with those in the E-V paradigm. The E-AV spelling paradigm also significantly improved the spelling accuracy and the raw bit rate compared with those in the E-V paradigm at one superposition (p < .05) and at two superpositions (p < .05). The proposed emotion-based audiovisual spelling paradigm not only significantly improves the performance of the P300 speller, but also provides a basis for the development of various bimodal P300 speller systems, which is a step forward in the clinical application of brain-computer interfaces.


Osteoarthritis year in review 2020: rehabilitation and outcomes.
Systematically review and synthesize guidelines, systematic reviews, or randomized controlled trials (RCTs) published between April 1, 2019 and April 30, 2020 which evaluated or made recommendations for rehabilitation of persons with osteoarthritis. Five electronic databases (Medline, EMBASE, Cochrane CENTRAL, CINHAL, Web of Science) were searched with a comprehensive search strategy. Guidelines for rehabilitation of persons with osteoarthritis, and systematic reviews and RCTs evaluating osteoarthritis rehabilitation that included at least one patient-reported outcome measure and/or clinical test of function were included. Two authors independently screened records and assessed methodological quality using the AGREE-II (guidelines), AMSTAR-2 (systematic reviews) or PEDro scale (RCTs). Data were extracted to summarize included records and a narrative synthesis of findings related to core recommended osteoarthritis rehabilitation treatments performed. Of 2,479 potential records, 253 records were reviewed. Two guidelines, 18 systematic reviews and 38 RCTs were included. 84% (n = 49) of included records related to knee osteoarthritis, 13% (n = 8) to hip, 10% (n = 6) to hand, 3% (n = 2) to mixed, and 1% (n = 1) to foot osteoarthritis. Exercise-therapy, methods to deliver exercise-therapy remotely, and approaches to facilitate exercise-therapy behaviour change were the most commonly evaluated interventions (n = 27). 94% of systematic reviews and 63% of RCTs rated high-quality. Osteoarthritis rehabilitation research continues to focus on knee osteoarthritis and exercise-based interventions. Emerging topics include rehabilitation of comorbid populations, exercise behaviour change and technology supports. A better understanding of rehabilitation of osteoarthritis in joints other than the knee, and methods to determine and promote ideal exercise-therapy prescription are needed.


A novel functional assay for fungal histidine kinases group III reveals the role of HAMP domains for fungicide sensitivity.
Signal transduction systems comprising histidine kinases are suggested as new molecular targets of antibiotics. The important human fungal pathogen Candida albicans possesses three histidine kinases, one of which is the type III histidine kinase CaNik1, which activates the MAP kinase Hog1. We established a screening system for inhibitors of this class of histidine kinases by functional expression of the CaNIK1 gene in S. cerevisiae. This transformant was susceptible to fungicides to which the wild type strain was resistant, such as fludioxonil and ambruticin. Growth inhibition correlated with phosphorylation of Hog1 and was dependent on an intact Hog1 pathway. At the N-terminus the histidine kinase CaNik1 has four amino acid repeats of 92 amino acids each and one truncated repeat of 72 amino acids. Within these repeats we identified 9 HAMP domains with a paired structure. We constructed mutants in which one or two pairs of these domains were deleted. S. cerevisiae transformants expressing the full-length CaNIK1 showed the highest sensitivity to the fungicides, any truncation reduced the susceptibility of the transformants to the fungicides. This indicates that the HAMP domains are decisive for the mode of action of the antifungal compounds.


Metabolism of asialoglycoproteins in cultured rat hepatocytes: evidence for receptor mediated uptake and degradation which is not feed-back regulated.
1. Cultured rat hepatocytes took up and degraded asialofetuin by a saturable mechanism. 2. The uptake was specific for desialylated fetuin; native fetuin and was taken up to a much lesser extent. 3. Degradation was inhibited by lysosomotropic agents; both uptake and degradation were, however, unaffected by cycloheximide. 4. The uptake was also unaffected by incubating the cells for 24 hr in the presence of large extracellular concentrations of unlabelled asialofetuin. 5. The data suggest that the asialoglycoprotein receptor is recycled and not subject to down-regulation.


Differences in the constitutive forms of hepatic cytochrome P-450 in male and female adult beagle dogs.
Cytochrome P-450 isoenzymes were prepared from the solubilized liver microsomes of untreated adult male and female dogs, then separated into groups by high-performance liquid chromatography (HPLC). Partial purification was also completed through DEAE-52 cellulose and phosphocellulose ion-exchange chromatography. For comparison, solubilized hepatic cytochromes P-450 were obtained from rats dosed with phenobarbital (PB), beta-naphthoflavone (BNF) or pregnenolone-16 alpha-carbonitrile. Minimal molecular masses of cytochrome P-450 subpopulations were determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. HPLC and ion-exchange chromatography results suggested the presence of two or three major and several minor cytochrome P-450 subpopulations. Three distinct groups were predominant in the female and two major and two or three minor subpopulations were found in the male. One of two isoenzymes prominent in BNF-dosed rats was present in the male but was missing in the female dog; another minor canine cytochrome similar to one found in PB-dosed rats was missing from the male. These data indicate qualitative and quantitative sex-dependent differences in the constitutive cytochrome P-450 populations of the dog and suggest that HPLC analysis may be useful for the interpretation of toxicological studies where microsomal enzyme induction is suspected.


CACNA1C risk variant affects facial emotion recognition in healthy individuals.
Recognition and correct interpretation of facial emotion is essential for social interaction and communication. Previous studies have shown that impairments in this cognitive domain are common features of several psychiatric disorders. Recent association studies identified CACNA1C as one of the most promising genetic risk factors for psychiatric disorders and previous evidence suggests that the most replicated risk variant in CACNA1C (rs1006737) is affecting emotion recognition and processing. However, studies investigating the influence of rs1006737 on this intermediate phenotype in healthy subjects at the behavioral level are largely missing to date. Here, we applied the "Reading the Mind in the Eyes" test, a facial emotion recognition paradigm in a cohort of 92 healthy individuals to address this question. Whereas accuracy was not affected by genotype, CACNA1C rs1006737 risk-allele carries (AA/AG) showed significantly slower mean response times compared to individuals homozygous for the G-allele, indicating that healthy risk-allele carriers require more information to correctly identify a facial emotion. Our study is the first to provide evidence for an impairing behavioral effect of the CACNA1C risk variant rs1006737 on facial emotion recognition in healthy individuals and adds to the growing number of studies pointing towards CACNA1C as affecting intermediate phenotypes of psychiatric disorders.


Unilateral lesion of the intrinsic cells in the medial forebrain bundle depresses self-stimulation but not stimulus-bound locomotor activity.
The intrinsic neurons of the medial forebrain bundle were unilaterally destroyed, in rats, through local injection of ibotenic acid (4 micrograms in 0.5 microliter). Ten days later, electrodes were bilaterally implanted, one in the lesioned lateral hypothalamus, the other into the contralateral hypothalamus. Firstly, self-stimulation was studied with stimulation of each electrode separately. Later on, the effect of non-contingent electrical stimulation on evoked locomotor activity in the open-field was analysed for each electrode. While self-stimulation of the lesion area was greatly depressed in comparison with the unlesioned lateral hypothalamus, the increase in locomotor activity produced by stimulation, at the intensity applied, was the same whether the stimulated hypothalamus was lesioned or not.


TinyLev acoustically levitated water: Direct observation of collective, inter-droplet effects through morphological and thermal analysis of multiple droplets.
Understanding the crystallization of atmospheric water can require levitation techniques to avoid the influence of container walls. Recently, an acoustic levitation device called the TinyLev was designed, which can levitate multiple droplets at room temperature. Proximal crystallization may affect droplet phase change and morphological characteristics. In this study, acoustically levitated pure water droplets were frozen individually and in pairs or triplets using a TinyLev device. Nucleation, bulk crystal growth, and melting were observed using digital and infrared cameras concurrently. Initially, the acoustic field forced the droplets into an oblate spheroid shape, though the counteracting force of the cooling stream caused them to circularize. Droplet geometry was thus the net result of streaming forces and surface tension at the acoustic boundary layer/air-liquid interface. Nucleation was determined to be neither homogeneous nor heterogeneous but secondary, and thus dependent on the cooling rate and not on the degree of supercooling. It was likely initiated by aerosolized ice particles from the air or from droplets that had already nucleated and broken up. The latter secondary ice production process resulted in multi-drop systems with statistically identical nucleation times. Notably, this meant that the presence of interfacial rupture at an adjacent droplet could influence the crystallization behaviour of another. After the formation of an initial ice shell around the individual droplets, dendritic protrusions grew from the droplet surface, likely seeded by the same ice particles that caused nucleation, but at a quasi-liquid layer. When freezing was complete, it was determined that the frozen core had undergone a volumetric expansion of 30.75%, compared to 9% for pure, sessile water expansion. This significantly greater expansion may have resulted from entrained air bubbles at the inner solid-liquid interface and oscillations at the moving phase boundary caused by changes in local acoustic forces. Soon after melting began, acoustic streaming, the buoyancy of the remaining ice, and convective currents caused by both an inner thermal gradient and thermocapillary effects along the air-liquid interface, all contributed to the droplet spinning about the horizontal axis.


Osteoporosis and quality of life psychosocial outcomes and interventions for individual patients.
Despite the substantial psychosocial impact of osteoporosis, little research has evolved in this area. Early reports conceptualized these nonskeletal problems as psychosocial in nature, but more recent investigations focus on health-related quality of life (HRQOL). Multiple HRQOL instruments have been designed to measure this construct in people with osteoporosis, and each has its strengths and weaknesses. Unfortunately, so much investigative energy has been spent on psychometric testing that these instruments have not been put to work efficiently to identify problem areas in HRQOL. It is from such results that interventions to improve HRQOL will occur.


[Tubal actinomycosis as a complication of intrauterine contraception].
A case of actinomycosis of the uterine tube occuring in a 29-year-old clerk is reported. The disease became manifest clinically a month after the introduction of IUD. In spite of intensive antiinflammatory therapy the disease was in progress and cachexia developed. The case was cured only after radical surgical intervention and antibiotic treatment.


Amino-acid substitutions at the domain interface affect substrate and allosteric inhibitor binding in α-isopropylmalate synthase from Mycobacterium tuberculosis.
α-Isopropylmalate synthase (α-IPMS) is a multi-domain protein catalysing the condensation of α-ketoisovalerate (α-KIV) and acetyl coenzyme A (AcCoA) to form α-isopropylmalate. This reaction is the first committed step in the leucine biosynthetic pathway in bacteria and plants, and α-IPMS is allosterically regulated by this amino acid. Existing crystal structures of α-IPMS from Mycobacterium tuberculosis (MtuIPMS) indicate that this enzyme has a strikingly different domain arrangement in each monomer of the homodimeric protein. This asymmetry results in two distinct interfaces between the N-terminal catalytic domains and the C-terminal regulatory domains in the dimer. In this study, residues Arg97 and Asp444 across one of these unequal domain interfaces were substituted to evaluate the importance of protein asymmetry and salt bridge formation between this pair of residues. Analysis of solution-phase structures of wild-type and variant MtuIPMS indicates that substitutions of these residues have little effect on overall protein conformation, a result also observed for addition of the feedback inhibitor leucine to the wild-type enzyme. All variants had increased catalytic efficiency relative to wild-type MtuIPMS, and those with an Asp444 substitution displayed increased affinity for the substrate AcCoA. All variants also showed reduced sensitivity to leucine and altered biphasic reaction kinetics when compared with those of the wild-type enzyme. It is proposed that substituting residues at the asymmetric domain interface increases flexibility in the protein, particularly affecting the AcCoA binding site and the response to leucine, without penalty on catalysis.


What is the value added by human intervention in protein structure prediction?
This article presents results of blind predictions submitted to the CASP4 protein structure prediction experiment. We made two sets of predictions: one using the fully automated SAM-T99 server and one using the improved SAM-T2K method with human intervention. Both methods use iterative hidden Markov model-based methods for constructing protein family profiles, using only sequence information. Although the SAM-T99 method is purely sequence based, the SAM-T2K method uses the predicted secondary structure of the target sequence and the known secondary structure of the templates to improve fold recognition and alignment. In this article, we try to determine what aspects of the SAM-T2K method were responsible for its significantly better performance in the CASP4 experiment in the hopes of producing a better automatic prediction server. The use of secondary structure prediction seems to be the most valuable single improvement, though the combined total of various human interventions is probably at least as important.


The ultrastructural variability of non-specific lipopigments.
Abnormally structured lipofuscin granules found in various cell types of different conditions not related to the neuronal lipofuscinoses (NCL), emphasize the ultrastructural diversity of non-specific lipofuscin morphologically marked by paracristalline inclusions, pseudo-fingerprint enclosures, and stacks of parallel filaments, all of them embedded in the granular matrix of the lipopigments. Though lipofuscin consisting of the regular granulo-vacuolar ultrastructure was also present in many cells of the same tissues, our findings suggest differences, though of unknown biochemical nature, in lysosomal catabolism resulting in varying lipopigment structures within similar cellular compartments.


Bone marrow alterations in COVID-19 infection: The root of hematological problems.
The 2019 coronavirus disease (COVID-19) is a respiratory infection caused by the SARS-CoV-2 virus with a significant impact on the hematopoietic system and homeostasis. The effect of the virus on blood cells indicates the involvement of the bone marrow (BM) as the place of production and maturation of these cells by the virus and it reminds the necessity of investigating the effect of the virus on the bone marrow. To investigate the effects of COVID-19 infection in BM, we reviewed literature from the Google Scholar search engine and PubMed database up to 2022 using the terms "COVID-19; SARS-CoV-2; Bone marrow; Thrombocytopenia; Hemophagocytosis; Pancytopenia and Thrombocytopenia. Infection with the SARS-CoV-2 virus is accompanied by alterations such as single-line cytopenia, pancytopenia, hemophagocytosis, and BM necrosis. The presence of factors such as cytokine release syndrome, the direct effect of the virus on cells through different receptors, and the side effects of current treatments such as corticosteroids are some of the important mechanisms in the occurrence of these alterations. To our knowledge, this review is the first study to comprehensively investigate BM alterations caused by SAR-CoV-2 virus infection. The available findings show that the significant impact of this viral infection on blood cells and the clinical consequences resulting from them are deeper than previously thought and it may be rooted in the changes that the virus causes in the BM of patients.


Ketamine-induced 1-Hz oscillation of spontaneous neural activity is not directly visible in the hemodynamics.
The extent to which resting-state hemodynamics reflects the underlying neural activity is still under debate. Especially in the delta frequency band (0.5-4 Hz), it is unclear whether the hemodynamics can directly track the dynamics of underlying neural activity. Based on a recent report showing that ketamine administration induced a 1-Hz neural activity oscillation in the retrosplenial cortex, we conducted simultaneous recordings of the calcium signal and hemodynamics in mice and examined whether the hemodynamics tracked the oscillatory neural activity. Although we observed that the oscillation induced by ketamine appeared in the calcium signal, no sign of oscillation was detected in the simultaneously recorded hemodynamics. Consistently, there was a notable decrease in the correlation between simultaneously recorded calcium signal and hemodynamics. However, on a much longer time scale (10-60 min), we unexpectedly observed an ultraslow increase of hemodynamic signals specifically in the same cortical region exhibiting the neural activity oscillation. These results indicated that hemodynamics cannot track the 1-Hz oscillation in neural activity, although the presence of neural activity oscillation was detectable on a longer timescale. Such ultraslow hemodynamics may be useful for detecting abnormal neural activity induced by psychotic drugs or mental disorders.


Can Nucleobase Pairs Offer a Possibility of a Direct 3D Self-assembly?
The nucleobase pairs are characterized by their conformational diversity in the wild. Yet a modern nanobiotechnology utilizes their planar conformations only, developing what can be called a "planar approach". It is well established that the most energetically favorable conformations of the complementary nucleobase pairs are planar and correspond to the classical Watson-Crick nucleobase pairs. The point of interest lies in a study of a conformational capacity of the nucleobase pairs to expand the diversity of a spatial configuration and to produce the complex 3D objects from the non-planar conformations. If such a goal could be achieved, then that could definitely open the perspectives for a novel "stereo approach". For the first time, basing on the first principles, we reveal an ability of the heteroassociates of the m(1)Cyt · m(1)Thy to form up to ten observable molecular complexes under standard conditions. The first three of them have population of ~90 % at standard conditions and are highly non-planar. The most energetically favorable structure has a T-shape, while the next two have an L-shape. At the same time, we show the lack of any experimental data covering a self-assembly of the m(1)Cyt · m(1)Thy base pairs. We present a theoretical evidence of the fact that the conformational capacity of the nucleobase pairs is much richer from the perspective of their self-assembly than it is considered in the modern nanobiotechnology. The capability of a modified cytosine and a modified thymine to create significantly non-planar structures opens a way for the innovative "stereo approach" to construction of the nanobiotechnological devices. We believe that a modern nanobiotechnological basis can and should be extended with the new nucleic base pairs with innate ability for non-planar structures. We would like to especially emphasize a prognostic role of our algorithm in obtaining the new results.


Vascular permeability in acute triethyltin-induced brain edema studied with FITC-dextrans, sodium fluorescein and horseradish peroxidase as tracers.
In golden hamsters, a study was made on the vascular permeability changes which might take place during the formation of triethyltin (TET)-induced brain edema. For this purpose, the animals received a single intravenous (i.v.) injection of TET sulphate (5-10 mg/kg b.wt) and groups of animals were studied 4 to 24 h thereafter. By the use of a new density gradient technique based on polyvinylcoated silica particles (1), it was shown that white matter edema was present already at 4 h after the TET injection. The edema then progressed during the following 20 h. Electron microscopy revealed that fluid accumulated in myelin vacuoles of the hamsters in the same way as has been described in other animal species. The macromolecular tracer, horseradish peroxidase mol.wt 40,000 injected i.v., did not leak out of the cerebral vessels during the period when edema developed. In order to find out if the formation of edema is associated with a vascular permeability increase to other and smaller markers, we used several fractions of FITC-dextrans varying from mol.wt 3,000 to 70,000 and determined their intracerebral localization with a histotechnical procedure. FITC-dextrans, mol.wt 70,000, did not leak out of the cerebral vessels in any of the TET intoxicated hamsters during the observation period of 24 h. The same was true for most animals given the other dextran fractions. However, FITC-dextrans, mol.wt 3,000-20,000 were present outside the vessels in the edematous optic nerves and corpus callosum in a few TET treated animals taken 16-24 h after the TET injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the latencies between bone and air conduction in the auditory brain stem evoked potential.
Brain stem auditory evoked potentials obtained by air and bone conduction were investigated in 22 subjects. The necessity for a carefully selected stimulus being presented to the headphone and the bone vibrator is discussed. Latency values of both responses are presented for wave V. Bone conduction showed latencies which were longer than those obtained by air conduction (about 0.9 msec). Possible mechanisms for this delay are discussed.


Driver behavior indices from large-scale fleet telematics data as surrogate safety measures.
Large-scale telematics data enable a high-resolution inference of road network's safety conditions and driver behavior. Although many researchers have investigated how to define meaningful safety surrogates and crash predictors from telematics, no comprehensive study analyzes the driver behavior derived from large-scale telematics data and relates them to crash data and the road networks in metropolitan cities. This study extracts driver behavior indices (e.g., speed, speed variation, hard braking rate, and hard acceleration rate) from large-scale telematics data, collected from 4000 vehicles in New York City five boroughs. These indices are compared to collision frequencies and collision rates at the street level. Moderate correlations were found between the safety surrogate measures and collision rates, summarized as follows: (i) When normalizing crash frequencies with traffic volume, using a traffic AADT model, safety-critical regions almost remain the same. (ii) The correlation magnitude of hard braking and hard acceleration varies by road types: hard braking clusters are more indicative of higher collision rates on highways, whereas hard acceleration is a stronger hazard indicator on non-highway urban roads. (iii) Locations with higher travel times coincide with locations of high crash incidence on non-highway roads. (iv) However, speeding on highways is indicative of collision risks. After establishing the spatial correlation between the driver behavior indices and crash data, two prototype safety metrics are proposed: speed corridor maps and hard braking and hard acceleration hot-spots. Overall, this paper shows that data-driven network screening enabled by telematics has great potential to advance our understanding of road safety assessment.


Inhibition of TGF-β repairs spinal cord injury by attenuating EphrinB2 expressing through inducing miR-484 from fibroblast.
Spinal cord injury (SCI) can lead to severe loss of motor and sensory function with high disability and mortality. The effective treatment of SCI remains unknown. Here we find systemic injection of TGF-β neutralizing antibody induces the protection of axon growth, survival of neurons, and functional recovery, whereas erythropoietin-producing hepatoma interactor B2 (EphrinB2) expression and fibroblasts distribution are attenuated. Knockout of TGF-β type II receptor in fibroblasts can also decrease EphrinB2 expression and improve spinal cord injury recovery. Moreover, miR-488 was confirmed to be the most upregulated gene related to EphrinB2 releasing in fibroblasts after SCI and miR-488 initiates EphrinB2 expression and physical barrier building through MAPK signaling after SCI. Our study points toward elevated levels of active TGF-β as inducer and promoters of fibroblasts distribution, fibrotic scar formation, and EphrinB2 expression, and deletion of global TGF-β or the receptor of TGF-β in Col1α2 lineage fibroblasts significantly improve functional recovery after SCI, which suggest that TGF-β might be a therapeutic target in SCI.