Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury.
The long-term clinical effects of wartime traumatic brain injuries (TBIs), most of which are mild, remain incompletely described. Current medical disability cost estimates from world conflicts continually surpass projections. Additional information regarding long-term functional trajectory is needed to reduce this extensive public health burden. To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same patients and to identify early risk factors for long-term disability. This prospective, longitudinal study enrolled active-duty US military after concussive blast injury (n = 50) in the acute to subacute stage and combat-deployed control individuals (n = 44) in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. One- and 5-year clinical evaluations were completed in the United States. All concussive blast injuries met the Department of Defense definition of mild, uncomplicated TBI. In-person clinical evaluations included standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden that were essentially identical to the evaluations completed at 1-year follow-up. Data were analyzed from October 1 through November 30, 2016. Changes in the in-person standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden from the 1- to 5-year follow-up. Predictive modeling was used to identify early risk factors for long-term disability. Among the 94 participants (87 men [93%] and 7 women [7%]; mean [SD] age, 34 [8] years), global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the 5-year evaluation. Logistic regression on the dichotomized Extended Glasgow Outcome Scale (GOS-E) at 5 years as a measure of overall disability identified brain injury diagnosis, preinjury intelligence, motor strength, verbal fluency, and neurobehavioral symptom severity at 1 year as risk factors for a poor outcome at 5 years, with an area under the curve of 0.92 indicating excellent prediction strength. Thirty-six of 50 patients with concussive blast TBI (72%) had a decline in the GOS-E from the 1- to 5-year evaluations, in contrast with only 5 of 44 combat-deployed controls (11%). Worsening of symptoms in concussive blast TBI was also observed on measures of posttraumatic stress disorder and depression. Service members with concussive blast TBI experienced evolution, not resolution, of symptoms from the 1- to 5-year outcomes. Considerable decline was observed in military service members with concussive blast TBI when comparing 1- and 5-year clinical outcomes. These results advocate for new treatment strategies to combat the long-term and extremely costly effect of these wartime injuries.


Extreme lateral ruptures of lumbar intervertebral discs.
Several cases are presented of extreme lateral rupture of the lumbar intervertebral disc in which symptoms of localized nerve root compression were not manifest and in which myelography was negative or misleading. Ordinary exploration techniques failed to disclose these lesions. The most striking pain patterns seen in these patients were flank pain, gluteal, groin, and sometimes upper anterior thigh pain, induced or aggravated by back motion. This pain, plus radiating leg pain, when it occurred, was generally exceedingly severe and disproportionate to the neurological deficit. Lumbar discography was useful in detecting these ruptures.


The sirtuins, oxidative stress and aging: an emerging link.
Reactive oxygen species (ROS) are a family of compounds that can oxidatively damage cellular macromolecules and may influence lifespan. Sirtuins are a conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that regulate lifespan in many model organisms including yeast and mice. Recent work suggests that sirtuins can modulate ROS levels notably during a dietary regimen known as calorie restriction which enhances lifespan for several organisms. Although both sirtuins and ROS have been implicated in the aging process, their precise roles remain unknown. In this review, we summarize current thinking about the oxidative stress theory of aging, discuss some of the compelling data linking the sirtuins to ROS and aging, and propose a conceptual model placing the sirtuins into an ROS-driven mitochondria-mediated hormetic response.


Guidance for future HTA applications to vaccines: the HPV lesson.
The HTA is a multidisciplinary approach which is increasingly applied worldwide in order to support decision-makers in the introduction of health technologies. The application of HTA to vaccines is quite recent and linked to the increasing number of vaccines available or in development, especially to those intended to non pediatric immunization. In this article a description of the HTA approach used in the evaluation of the bivalent HPV vaccine in Italy is provided; moreover the reasons for keeping HTA process "alive" and identifying new or pending Public Health issues are discussed. In fact, the project raised questions and challenges about the standardization and sharing of HTA methods in Italy. Recently the need of updating the results is starting to be seen as urgent due to the evolution of scientific knowledge, the availability of the first results after technology introduction and the observed differences in vaccination strategies among Italian regions. Moreover in these last two years after the completion of the HTA project a number of new issues have risen in the Italian context as immunization rates, regional vaccination strategies, processes for vaccine selection and health economic issues.


[Soil heavy metal pollution in Ryazan: ecological and hygienic aspects].
The paper presents the results of investigations evaluating the soil pollution with heavy metals in Ryazan. The authors have determined the priority pollutants, geochemical anomalies on the territory of the town and the qualitative and qualitative composition of the pollutants in relation to the source of waste and to the specific features of an atmospheric and technogenic transfer. They propose measures to improve the urban ecological and sanitary status, which are associated with the utilization of the plants that accumulate heavy metals and with the replacement of the polluted soil with artificial soil-like masses.


Ex situ synthesis and characterization of a polymer-carbon nanotube-based hybrid nanocatalyst with one of the highest catalytic activities and stabilities for the hydrolytic dehydrogenation of hydrazine-borane at room temperature conditions.
In this study, a facile ex situ synthesis of a polyaniline-multiwalled carbon nanotube-based Pt nanocatalyst (Pt@PANI-MWCNT) with an average particle size of 3.18 ± 0.12 nm was performed successfully. The obtained Pt@PANI-MWCNT nanocatalysts were isolated from the solution medium by centrifugation and then were characterized by spectroscopy and microscopy methods. The characterization studies showed that the prepared Pt nanoparticles were formed on PANI-MWCNT surface, and H2 evolution was obtained by the dehydrogenation of hydrazine-borane in water as a model reaction under room temperature conditions, with the help of the synthesized nanocatalyst. It was observed that the Pt@PANI-MWCNT nanocatalyst had a very high catalytic activity for the hydrolytic dehydrogenation of hydrazine-borane and generated 2.95 mol of H2 for 1 mol of hydrazine-borane. The initial turn-over frequency (TOFinitial) value of the prepared nanocatalyst for the model reaction at room temperature conditions was found to be 168.5 min-1. The calculations for the kinetics of the hydrolytic dehydrogenation reaction showed that the hydrazine-borane catalytic reaction kinetics are first order, with respect to the catalyst concentration; several activation parameters, such as entropy (ΔS#, app = -72.11 ± 3 J/mol K), enthalpy (ΔH#, app = 43.5 ± 2 kJ/mol) and activation energy (Ea,app = 45.5 ± 2 kJ/mol), of the catalytic reaction with the Pt@PANI-MWCNT nanocatalyst were calculated using these kinetic data.


A small segment of polyoma virus DNA enhances the expression of a cloned beta-globin gene over a distance of 1400 base pairs.
The hemoglobin beta-1 gene of the rabbit was linked to a 244 bp DNA fragment from the beginning of the polyoma virus late region, not including the viral origin of replication. After transfection of such recombinant DNAs into mouse 3T6 and human HeLa cells, the polyoma sequences were found to strongly enhance the level of correct beta-globin gene transcripts over a distance of at least 1400 bp. These findings are similar to those obtained with a segment of DNA from the corresponding region of the SV40 genome (J. Banerji, S. Rusconi and W. Schaffner, 1981, Cell, in press) which, however, shows very limited sequence homology to the polyoma 244 bp segment. Using the same assay, a complete copy of polyoma virus DNA was found to interfere with the enhancement of globin gene expression in a cell type-specific manner which may be due to incorrect transcription. In contrast to the complete polyoma virus genome, the 244 bp DNA fragment will be particularly useful as a component of mammalian expression vectors since it almost exclusively yielded high levels of correct beta-globin gene transcripts.


Genetic Linkage and Physical Mapping for an Oyster Mushroom (Pleurotus cornucopiae) and Quantitative Trait Locus Analysis for Cap Color.
Oyster mushrooms are grown commercially worldwide, especially in many developing countries, for their easy cultivation and high biological efficiency. Pleurotus cornucopiae is one of the main oyster mushroom species because of its gastronomic value and nutraceutical properties. Cap color is an important trait, since consumers prefer dark mushrooms, which are now represented by only a small portion of the commercial varieties. Breeding efforts are required to improve quality-related traits to satisfy various demands of consumers. Here, we present a saturated genetic linkage map of P. cornucopiae constructed by using a segregating population of 122 monokaryons and 3,449 single nucleotide polymorphism (SNP) markers generated by the 2b-RAD approach. The map contains 11 linkage groups covering 961.6 centimorgans (cM), with an average marker spacing of 0.27 cM. The genome of P. cornucopiae was de novo sequenced, resulting in 425 scaffolds (>1,000 bp) with a total genome size of 35.1 Mb. The scaffolds were assembled to the pseudochromosome level with the assistance of the genetic linkage map. A total of 97% SNP markers (3,357) were physically localized on 140 scaffolds that were assigned to 11 pseudochromosomes, with a total of 32.5 Mb, representing 92.5% of the whole genome. Six quantitative trait loci (QTL) controlling cap color of P. cornucopiae were detected, accounting for a total phenotypic variation of 65.6%, with the highest value for the QTL on pseudochromosome 5 (18%). The results of our study provide a solid base for marker-assisted breeding for agronomic traits and especially for studies on biological mechanisms controlling cap color in oyster mushrooms. IMPORTANCE Oyster mushrooms are produced and consumed all over the world. Pleurotus cornucopiae is one of the main oyster mushroom species. Dark-cap oyster mushrooms are becoming more and more popular with consumers, but dark varieties are rare on the market. Prerequisites for efficient breeding programs are the availability of high-quality whole genomes and genetic linkage maps. Genetic studies to fulfill some of these prerequisites have hardly been done for P. cornucopiae. In this study, we de novo sequenced the genome and constructed a saturated genetic linkage map for P. cornucopiae. The genetic linkage map was effectively used to assist the genome assembly and identify QTL that genetically control the trait cap color. As well, the genome characteristics of P. cornucopiae were compared to the closely related species Pleurotus ostreatus. The results provided a basis for understanding the genetic background and marker-assisted breeding of this economically important mushroom species.


Open Source HMIS Enabled Evaluation of Financial Burden of Disease and Patient Coverage in Three University Hospitals in Great Lakes Africa.
Since the eighties, case mix evaluation methods based on diagnosis-related groups (DRG) were gradually introduced in developed countries. These methods of assessing the costs of diseases to measure the productivity of the hospital have been introduced in management softwares that are not accessible to low-income countries. In this study, the authors applied these methods to an open source hospital management information system (HMIS) implemented in three university hospitals in Great Lakes Africa. A comparative study of the financial burden of five major diseases, monitored as part of a universal health coverage (UHC) analysis, was carried out. The level of coverage of patients in the hospitals was evaluated and the impact of UHC policies demonstrated. Although the financial protection of patients treated in the three hospitals had improved, HIV and tuberculosis treatments that ought to be free, remained a considerable financial burden for the patient.


Cortisol responses to the insulin hypoglycaemia test in children.
To determine the timing of the peak cortisol response to the insulin hypoglycaemia (IH) test in children and to establish paediatric reference data. We retrospectively reviewed all IH tests in a tertiary paediatric endocrine referral centre over a 6-year period. Inclusion criteria were age <16 years and adequate hypoglycaemia (glucose < or =2.0 mmol/l). Patients with an impaired hypothalamic-pituitary-adrenal axis or receiving glucocorticoid medication were excluded. Fifty-four subjects (35 males) met the criteria. Blood samples were collected at -30, 0, 20, 30, 60, 90, 120, and 150 min in relation to insulin bolus injection (0.15 U/kg) at 0 min. Glucose, cortisol, and growth hormone (GH) were measured in all samples. Peak cortisol and GH responses occurred by 90 min in all subjects. Peak cortisol was inversely correlated with age (rs -0.65, p<0.0001). The median (5th centile) peak cortisol value was 689 nmol/l (547 nmol/l) in children younger than 10 years as compared with 555 nmol/l (468 nmol/l) in those older than 10 years (p<0.0001). Peak cortisol was not related to peak GH (rs -0.20, p=0.15). Blood sampling in the IH test may be curtailed 90 min after injection. The peak cortisol response to IH is age related.


The effects of oestradiol-17beta on the ribonucleic acid polymerases of immature rabbit uterus.
Measurements of the endogenous RNA polymerase activities of nuclei isolated from immature rabbit uteri have shown that prior treatment of the animals with oestradiol-17beta has a profound effect on the apparent activities of both RNA polymerases A and B. Within 1 h of hormone treatment, the activity of RNA polymerase A is increased and continues to rise until about 4h when it reaches a plateau and remains steady until at least 8h. The activity of RNA polymerase B increases sharply after oestradiol treatment reaching an early maximum at 30-45 min. Thereafter this activity declines until by 1-2h it approaches control values but a second increase in activity then occurs with a maximum at 3-4h. Treatment of the rabbits with alpha-amanitin before the administration of oestradiol inhibits the hormone-induced stimulation of RNA polymerase A activity in isolated nuclei but when the administration of alpha-amanitin is delayed until after the early rise of RNA polymerase B activity, the oestradiol-induced stimulation of RNA polymerase A is retained. Similar results have been obtained in experiments with cycloheximide suggesting that the stimulation of RNA polymerase A activity by oestradiol is dependent on the hormone-induced stimulation of RNA polymerase B and the subsequent synthesis of protein using the RNA product of the early increase in RNA polymerase B activity. Measurement of the activities of RNA polymerases A and B after isolation of the enzymes from immature rabbit uterine nuclei before and after oestradiol treatment failed to show any differences. Therefore it would appear that the changes in the observed activities of RNA polymerases A and B in isolated nuclei are consequences of changes in the structure and function of chromatin rather than the results of modifications in the RNA polymerases themselves.


Mandibles grafted with fresh-frozen bone: an evaluation of implant outcome.
In the last decade several studies have been performed to evaluate the clinical outcome of implants inserted into grafted mandibles with autologous bone, but none is available on mandibles grafted with fresh-frozen bone. Thus, we planned a retrospective study on a series of implants inserted into homologue fresh-frozen bone to evaluate their clinical outcome. Twenty-one patients were operated on, 28 onlay grafts were inserted into the mandible, and 63 implants placed. Patients had total and partial edentulism in 11 and 10 cases, respectively. The mean follow-up was 20 months. No or reduced crestal bone resorption was considered an indicator of success rate to evaluate the effect of several host-, implant-, and occlusal-related factors. The difference between the implant-abutment junction and the bone crestal level was defined as the implant abutment junction (IAJ) and calculated at the time of operation and during follow-up by means of radiographs. Delta IAJ, the difference between theIAJ at the last check-up and the IAJ recorded just after the operation, were stratified according to variables of interests. Kaplan-Meier algorithm and Cox regression were then performed to detect those variables statistically associated with the delta IAJ. Only 2 of 63 implants were lost (i.e., survival rates = 96.8%) and no differences were detected among the studied variables. On the contrary, Cox regression showed that prosthetic restoration (i.e., removable dentures) was the only factor correlated with a statistically significant lower delta IAJ (i.e., reduced crestal bone loss) and thus a better clinical outcome. Implants inserted into mandibles grafted with fresh-frozen bone allografts have high survival rates and success rate, which are comparable with those obtained with autologous iliac crest bone grafts.


The uncoupling protein 2 Ala55Val polymorphism is associated with diabetes mellitus: the CARDIA study.
Uncoupling proteins (UCPs) reduce ATP generation with concomitant increased release of heat. The activities of UCPs have been related to obesity and energy metabolism. We investigated the association of the commonly observed UCP2 Ala55Val (V) polymorphism with diabetes mellitus and impaired fasting glucose (IFG) among 3684 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The V frequency was approximately 45% in blacks and 42% in whites. Those with the Val/Val (VV) genotype had a higher incidence of diabetes than those having the Ala/Ala (AA) genotype (5.8% vs 3.3%; P = 0.02). Similarly, the incidences of diabetes in participants without abdominal obesity were 2.8% and 1.0% (P = 0.03) in the VV and AA groups, and 12.4% and 8.3% (P = 0.15) in participants with abdominal obesity. The incidence of IFG was higher in VV vs AA only in those without abdominal obesity (12.9% vs 9.2%). These trends persisted in minimally and fully adjusted models, and in strata of blacks and whites and men and women. The homeostasis model assessment for insulin resistance was highest in VV in the combined group of those with IFG or untreated diabetes, but not in those with normal fasting glucose. The VV genotype of the UCP2 polymorphism was positively related to diabetes. It may involve increased insulin resistance in those with impaired glucose homeostasis.


Plasma beta-phenylethylamine in Parkinson's disease.
Plasma beta-phenylethylamine (PEA) levels were determined in 27 patients with Parkinson's disease (PD) in order to evaluate its relation with the severity or clinical course of PD. The plasma PEA concentrations in PD patients were significantly lower (mean +/- SD, 862 +/- 554 pg/ml) than those in the control group (1765 +/- 790 pg/ml) (p < 0.0001). The concentrations of PEA in plasma did not correlate with Hoen and Yahr stage. However, in serial measurements of the PEA of 5 patients in the progressive group of the clinical course of PD, the plasma PEA levels revealed a downward trend after one or two years. On the other hand, in 3 patients of non-progressive group, the plasma PEA remained at the same level. This study suggests that plasma PEA level might reflect nigrostriatal degeneration in patients with PD.


[Structure and antitumor activity of polysaccharides from the micelles of Aspergillus oryzae].
Three polysaccharide fractions active against mammary gland adenocarcinoma Ca-755 in mice but inactive against sarcoma C-180 were isolated from Aspergillus oryzae strain 5214. The main fraction, extracted from the mycelium by cold dilute alkali in the presence of sodium borohydride, was shown to be linear (1----3)-a-D-glucopyranan (pseudonigeran) according to 13C NMR spectroscopy, partial acid hydrolysis and periodate oxidation data.


Further evidence that papillomavirus capsids exist in two distinct conformations.
Cell surface heparan sulfate proteoglycans (HSPGs) serve as primary attachment receptors for human papillomaviruses (HPVs). To demonstrate that a biologically functional HPV-receptor interaction is restricted to a specific subset of HSPGs, we first explored the role of HSPG glucosaminoglycan side chain modifications. We demonstrate that HSPG O sulfation is essential for HPV binding and infection, whereas de-N-sulfated heparin interfered with VLP binding but not with HPV pseudoinfection. This points to differences in VLP-HSPG and pseudovirion-HSPG interactions. Interestingly, internalization kinetics of VLPs and pseudovirions, as measured by fluorescence-activated cell sorting analysis, also differ significantly with approximate half times of 3.5 and 7.5 h, respectively. These data suggest that differences in HSPG binding significantly influence postbinding events. We also present evidence that pseudovirions undergo a conformational change after cell attachment. A monoclonal antibody (H33.J3), which displays negligible effectiveness in preattachment neutralization assays, efficiently neutralizes cell-bound virions. However, no difference in H33.J3 binding to pseudovirions and VLPs was observed in enzyme-linked immunosorbent assay and virus capture assays. In contrast to antibody H33.B6, which displays equal efficiencies in pre- and postattachment neutralization assays, H33.J3 does not block VLP binding to heparin, demonstrating that it interferes with steps subsequent to virus binding. Our data strongly suggest that H33.J3 recognizes a conformation-dependent epitope in capsid protein L1, which undergoes a structural change after cell attachment.


Protein molecular defect detection method based on a neural network algorithm.
Proteins, as the largest macromolecules in the body, are among the most important components of the body and play very vital and important roles. These substances are made up of a series of amino acid chains that, depending on the type of protein, the number of these amino acids can reach several thousand. Proteins function differently depending on the type and location of their presence, including enzymatic activity to catalyze the process, identify microbes and cancer cells, transport substances such as respiratory gases, and signalize. In the biochemical experiment, the problem of optimizing the detection of protein molecular defects, because of the randomness of the information, parameters, selection and setting, limits the detection accuracy of protein molecular defects. Based on the characteristics of fast learning speed and a robust network of neural network algorithm, a protein molecular defect detection method based on a neural network algorithm was proposed. Firstly, the protein secondary structure was predicted by the method of protein secondary structure prediction based on the generalized regression neural network to obtain the protein structural features; secondly, the protein defective molecular sequence classification model based on the neural network was used to classify the protein defective molecular sequence to achieve the protein molecular defect detection. The results showed that the detection accuracy of the proposed method was very high, which meets the needs of protein molecular defect detection, and has some application advantages compared with similar detection methods.


Indicators of resilience during the transition period in dairy cows: A case study.
The transition period is a demanding phase in the life of dairy cows. Metabolic and infectious disorders frequently occur in the first weeks after calving. To identify cows that are less able to cope with the transition period, physiologic or behavioral signals acquired with sensors might be useful. However, it is not yet clear which signals or combination of signals and which signal properties are most informative with respect to disease severity after calving. Sensor data on activity and behavior measurements as well as rumen and ear temperature data from 22 dairy cows were collected during a period starting 2 wk before expected parturition until 6 wk after parturition. During this period, the health status of each cow was clinically scored daily. A total deficit score (TDS) was calculated based on the clinical assessment, summarizing disease length and intensity for each cow. Different sensor data properties recorded during the period before calving as well as the period after calving were tested as a predictor for TDS using univariate analysis of covariance. To select the model with the best combination of signals and signal properties, we quantified the prediction accuracy for TDS in a multivariate model. Prediction accuracy for TDS increased when sensors were combined, using static and dynamic signal properties. Statistically, the most optimal linear combination of predictors consisted of average eating time, variance of daily ear temperature, and regularity of daily behavior patterns in the dry period. Our research indicates that a combination of static and dynamic sensor data properties could be used as indicators of cow resilience.


Structural insights into the dimer-tetramer transition of FabI from Bacillus anthracis.
Enoyl-ACP reductase (ENR, also known as FabI) has received considerable interest as an anti-bacterial target due to its essentiality in fatty acid synthesis. All the FabI structures reported to date, regardless of the organism, are composed of homo-tetramers, except for two structures: Bacillus cereus and Staphylococcus aureus FabI (bcFabI and saFabI, respectively), which have been reported as dimers. However, the reason for the existence of the dimeric form in these organisms and the biological meaning of dimeric and tetrameric forms of FabI are ambiguous. Herein, we report the high-resolution crystal structure of a dimeric form of Bacillus anthracis FabI (baFabI) and the crystal structures of tetrameric forms of baFabI in the apo state and in complex with NAD+ and with NAD+-triclosan, at 1.7 Å, 1.85 Å, 1.96 Å, and 1.95 Å, respectively. Interestingly, we found that baFabI with a His6-tag at its C-terminus exists as a dimer, whereas untagged-baFabI exists as a tetramer. The His6-tag may block the dimer-tetramer transition, since baFabI has relatively short-length amino acids (255LG256) after the 310-helix η7 compared to those of FabI of other organisms. The dimeric form of baFabI is catalytically inactive, because the α-helix α5 occupies the NADH-binding site. During the process of dimer-tetramer transition, this α5 helix rotates about 55° toward the tetramer interface and the active site is established. Therefore, tetramerization of baFabI is required for cofactor binding and catalytic activity.


Pre-end-stage renal disease care not associated with dialysis facility neighborhood poverty in the United States.
Receipt of nephrology care prior to end-stage renal disease (ESRD) is a strong predictor of decreased mortality and morbidity, and neighborhood poverty may influence access to care. Our objective was to examine whether neighborhood poverty is associated with lack of pre-ESRD care at dialysis facilities. In a multi-level ecological study using geospatially linked 2007-2010 Dialysis Facility Report and 2006-2010 American Community Survey data, we examined whether high neighborhood poverty (≥20% of households in census tract living below poverty) was associated with dialysis facility-level lack of pre-ESRD care (percentage of patients with no nephrology care prior to dialysis start) in mixed-effects models, adjusting for facility and neighborhood confounders and allowing for neighborhood and regional random effects. Among the 5,184 facilities examined, 1,778 (34.3%) were located in a high-poverty area. Lack of pre-ESRD care was similar in poverty areas (30.8%) and other neighborhoods (29.6%). With adjustment, the absolute increase in percentage of patients at a facility with no pre-ESRD care associated with facility location in a poverty area versus other neighborhood was only 0.08% (95% CI -1.32, 1.47; p = 0.9). Potential effect modification by race and income inequality was detected. Despite previously reported detrimental effects of neighborhood poverty on health, facility neighborhood poverty was not associated with receipt of pre-ESRD care, suggesting no need to target interventions to increase access to pre-ESRD care at facilities in poorer geographic areas.


Infection of Human Dental Pulp Stromal Cells by Streptococcus mutans: Shedding Light on Bacteria Pathogenicity and Pulp Inflammation.
Cariogenic Streptococcus mutans (S. mutans) is implicated in the dental pulp necrosis but also in cardiovascular tissue infections. Herein, the purpose was to elucidate how human dental pulp derived stromal cells (DPSCs) react toward a direct interaction with S. mutans. DPSCs were challenged with S. mutans. Following 3 h of interaction, DPSCs were able to internalize S. mutans (rate < 1%), and F-actin fibers played a significant role in this process. S. mutans persisted in the DPSCs for 48 h without causing a cytotoxic effect. S. mutans was, however, able to get out of the DPSCs cytoplasm and to proliferate in the extracellular environment. Yet, we noticed several adaptive responses of bacteria to the extracellular environment such as a modification of the kinetic growth, the increase in biofilm formation on type I collagen and polyester fabrics, as well as a tolerance toward amoxicillin. In response to infection, DPSCs adopted a proinflammatory profile by increasing the secretion of IL-8, lL-1β, and TNF-α, strengthening the establishment of the dental pulp inflammation. Overall, these findings showed a direct impact of S. mutans on DPSCs, providing new insights into the potential role of S. mutans in infective diseases.


Assessing COVID-19 vaccination strategies in varied demographics using an individual-based model.
New variants of SARS-CoV-2 are constantly discovered. Administration of COVID-19 vaccines and booster doses, combined with the application of non-pharmaceutical interventions (NPIs), is often used to prevent outbreaks of emerging variants. Such outbreak dynamics are further complicated by the population's behavior and demographic composition. Hence, realistic simulations are needed to estimate the efficiency of proposed vaccination strategies in conjunction with NPIs. We developed an individual-based model of COVID-19 dynamics that considers age-dependent parameters such as contact matrices, probabilities of symptomatic and severe disease, and households' age distribution. As a case study, we simulate outbreak dynamics under the demographic compositions of two Israeli cities with different household sizes and age distributions. We compare two vaccination strategies: vaccinate individuals in a currently prioritized age group, or dynamically prioritize neighborhoods with a high estimated reproductive number. Total infections and hospitalizations are used to compare the efficiency of the vaccination strategies under the two demographic structures, in conjunction with different NPIs. We demonstrate the effectiveness of vaccination strategies targeting highly infected localities and of NPIs actively detecting asymptomatic infections. We further show that different optimal vaccination strategies exist for each sub-population's demographic composition and that their application is superior to a uniformly applied strategy. Our study emphasizes the importance of tailoring vaccination strategies to subpopulations' infection rates and to the unique characteristics of their demographics (e.g., household size and age distributions). The presented simulation framework and findings can help better design future responses against the following emerging variants.


Air pollution and skin diseases: Adverse effects of airborne particulate matter on various skin diseases.
Environmental air pollution encompasses various particulate matters (PMs). The increased ambient PM from industrialization and urbanization is highly associated with morbidity and mortality worldwide, presenting one of the most severe environmental pollution problems. This article focuses on the correlation between PM and skin diseases, along with related immunological mechanisms. Recent epidemiological studies on the cutaneous impacts of PM showed that PM affects the development and exacerbation of skin diseases. PM induces oxidative stress via production of reactive oxygen species and secretion of pro-inflammatory cytokines such as TNF-α, IL-1α, and IL-8. In addition, the increased production of ROS such as superoxide and hydroxyl radical by PM exposure increases MMPs including MMP-1, MMP-2, and MMP-9, resulting in the degradation of collagen. These processes lead to the increased inflammatory skin diseases and skin aging. In addition, environmental cigarette smoke, which is well known as an oxidizing agent, is closely related with androgenetic alopecia (AGA). Also, ultrafine particles (UFPs) including black carbon and polycyclic aromatic hydrocarbons (PAHs) enhance the incidence of skin cancer. Overall, increased PM levels are highly associated with the development of various skin diseases via the regulation of oxidative stress and inflammatory cytokines. Therefore, anti-oxidant and anti-inflammatory drugs may be useful for treating PM-induced skin diseases.


A distributed architecture for activating the peripheral nervous system.
We present a new system for functional electrical stimulation (FES) applications based on networked stimulation units. They embed an advanced analog circuit, which provides multipolar and multiphasic stimulation profiles, and digital circuits, which ensure safety, locally executed programmed profiles, and communication with the master controller. This architecture is thus based on distributed stimulation units (DSU) that need only a two-wire bus to communicate, regardless of the number of poles of each DSU-driven electrode. This structure minimizes the required bandwidth between master and distributed units, increases the safety and stimulation features and decreases the complexity of the surgical approach. We have successfully tested this network-based stimulation architecture on benchtop stimulators. This original approach allows broad exploration of all possible methods to stimulate peripheral nerves, particularly in the goal of restoring the motor function. It provides a powerful research device to determine the optimal, least aggressive and the most efficient way to activate the peripheral nervous system using an implanted FES system that is less invasive than other existing devices.


Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus.
Atacicept reduced SLE disease activity in the phase 2b ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II. In the 24-week, randomized, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo. Atacicept was continued at the same dose in atacicept-treated patients in the LTE; placebo-treated patients switched to atacicept 150 mg. Long-term safety was the primary endpoint. Secondary endpoints included SLE responder index (SRI)-4 and SRI-6 response rates and flares. In total, 253 patients entered the ADDRESS II LTE; 88 received atacicept 150 mg, 82 atacicept 75 mg and 83 placebo/atacicept 150 mg. Median active treatment duration in the LTE was 83.8 weeks. Frequencies of treatment-emergent adverse events (TEAEs) were similar across groups (90.4-93.2%), and 12.5%, 14.6% and 21.7% of patients in the atacicept 150 mg, atacicept 75 mg and placebo/atacicept 150 mg groups reported serious TEAEs during the treatment period. The proportions of patients with TEAEs leading to discontinuation were 5.7%, 4.9% and 10.8%, respectively. SRI-4 and SRI-6 response rates were maintained with atacicept in the modified intent-to-treat and HDA populations and those on continuous 150 mg had a reduced risk of first severe flare and longer time to first severe flare vs those who initially received placebo. Long-term treatment with atacicept 150 mg in SLE patients had an acceptable safety profile, with durable efficacy. ClinicalTrials.gov, http://clinicaltrials.gov, NCT02070978.


Call for algorithmic fairness to mitigate amplification of racial biases in artificial intelligence models used in orthodontics and craniofacial health.
Machine Learning (ML), a subfield of Artificial Intelligence (AI), is being increasingly used in Orthodontics and craniofacial health for predicting clinical outcomes. Current ML/AI models are prone to accentuate racial disparities. The objective of this narrative review is to provide an overview of how AI/ML models perpetuate racial biases and how we can mitigate this situation. A narrative review of articles published in the medical literature on racial biases and the use of AI/ML models was undertaken. Current AI/ML models are built on homogenous clinical datasets that have a gross underrepresentation of historically disadvantages demographic groups, especially the ethno-racial minorities. The consequence of such AI/ML models is that they perform poorly when deployed on ethno-racial minorities thus further amplifying racial biases. Healthcare providers, policymakers, AI developers and all stakeholders should pay close attention to various steps in the pipeline of building AI/ML models and every effort must be made to establish algorithmic fairness to redress inequities.


Chronic hypoxia increases rat diaphragm muscle endurance and sodium-potassium ATPase pump content.
The effects of chronic hypoxia (CH) on respiratory muscle are poorly understood. The aim of the present study was to examine the effects of CH on respiratory muscle structure and function, and to determine whether nitric oxide is implicated in respiratory muscle adaptation to CH. Male Wistar rats were exposed to CH for 1-6 weeks. Sternohyoid and diaphragm muscle contractile properties, muscle fibre type and size, the density of fibres expressing sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2 and sodium-potassium ATPase (Na+,K+-ATPase) pump content were determined. Muscle succinate dehydrogenase (SDH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) dehydrogenase activities were also assessed. Acute and chronic blockade of nitric oxide synthase (NOS) was employed to determine whether or not NO is critically involved in functional remodelling in CH muscles. CH improved diaphragm, but not sternohyoid, fatigue tolerance in a time-dependent fashion. This adaptation was not attributable to increased SDH or NADPH dehydrogenase activities. The areal density of muscle fibres and relative area of fibres expressing SERCA2 were unchanged. Na+,K+-ATPase pump content was significantly increased in CH diaphragm. Chronic NOS inhibition decreased diaphragm Na+,K+-ATPase pump content and prevented CH-induced increase in muscle endurance. This study provides novel insight into the mechanisms involved in CH-induced muscle plasticity. The results may be of relevance to respiratory disorders characterised by CH, such as chronic obstructive pulmonary disease.


Effects of fatigue on motor unit firing rate versus recruitment threshold relationships.
The purpose of this study was to examine the influence of fatigue on the average firing rate versus recruitment threshold relationships for the vastus lateralis (VL) and vastus medialis. Nineteen subjects performed ten maximum voluntary contractions of the dominant leg extensors. Before and after this fatiguing protocol, the subjects performed a trapezoid isometric muscle action of the leg extensors, and bipolar surface electromyographic signals were detected from both muscles. These signals were then decomposed into individual motor unit action potential trains. For each subject and muscle, the relationship between average firing rate and recruitment threshold was examined using linear regression analyses. For the VL, the linear slope coefficients and y-intercepts for these relationships increased and decreased, respectively, after fatigue. For both muscles, many of the motor units decreased their firing rates. With fatigue, recruitment of higher threshold motor units resulted in an increase in slope for the VL.


Assessing and managing the patient with headaches.
Headaches are considered the most common type of pain; more than 40 million Americans seek treatment each year. A clear understanding of the types and possible causes of headache pain is essential to adequately assess and manage the patient with headaches. Headaches can be categorized as either primary or secondary to an underlying and usually treatable cause. Most headaches are primary; this includes migraine and variants, and cluster and tension-type headaches. Before assuming a primary diagnosis, however, the clinician must rule out headaches secondary to an underlying cause so that further investigation, treatment, or referral may be initiated.


Evolutionary crossroads in developmental biology: Cnidaria.
There is growing interest in the use of cnidarians (corals, sea anemones, jellyfish and hydroids) to investigate the evolution of key aspects of animal development, such as the formation of the third germ layer (mesoderm), the nervous system and the generation of bilaterality. The recent sequencing of the Nematostella and Hydra genomes, and the establishment of methods for manipulating gene expression, have inspired new research efforts using cnidarians. Here, we present the main features of cnidarian models and their advantages for research, and summarize key recent findings using these models that have informed our understanding of the evolution of the developmental processes underlying metazoan body plan formation.


[Comparative evaluation of gastro-intestinal tract tumors on the basis of data from determination of DNA content using flow cytometry].
Morphologic and cytophotometric characteristics of tumours and tumour-like lesions of the stomach, colon and rectum from 267 patients were compared in the biopsy material. There was a diploid DNA distribution in the adenomas and tumour-like lesions of colon and rectum. The correlation between the proliferative activity and the epithelial dysplasia degree was noted in adenomas; aneuploid cells were found in 5 adenomas. 53% of gastric carcinoma and 64% of colon and rectum carcinomas were aneuploid (the difference is not significant). Poorly differentiated adenocarcinoma much more frequently (the difference is significant) was found in the aneuploid tumours, well differentiated adenocarcinoma and signet cell carcinoma- in the diploid tumours. DNA index (1.09-1.50) of the aneuploid cells of gastric carcinoma was in 42% cases in the near diploid--triploid region while in colon and rectum carcinoma (60.5%) it was in the triploid--tetraploid region. The type of DNA distribution, particularly in the diploid tumours, should be controlled cytologically.


Systems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns.
The emergence of zebrafish Danio rerio as a versatile model organism provides the unique opportunity to monitor the functions of glycosylation throughout vertebrate embryogenesis, providing insights into human diseases caused by glycosylation defects. Using a combination of chemical modifications, enzymatic digestion and mass spectrometry analyses, we establish here the precise glycomic profiles of eight individual zebrafish organs and demonstrate that the protein glycosylation and glycosphingolipid expression patterns exhibits exquisite specificity. Concomitant expression screening of a wide array of enzymes involved in the synthesis and transfer of sialic acids shows that the presence of organ-specific sialylation motifs correlates with the localized activity of the corresponding glycan biosynthesis pathways. These findings provide a basis for the rational design of zebrafish lines expressing desired glycosylation profiles.


EXPRESS: Epidemiology and Outcomes of Previously Healthy Critically Ill Patients with COVID-19: a Population-Based Cohort.
Comorbid conditions represent a major risk for severe illness among persons with COVID-19. Previously healthy people with COVID-19 can also develop severe illness, but are expected to have better outcomes than those with comorbid conditions. Nevertheless, recent data suggest that the former may have, counterintuitively, higher risk of death among those with non-COVID sepsis. However, the epidemiology and outcomes of previously healthy people among critically ill patients with COVID-19 are unknown. We used statewide data to identify ICU admissions aged ≥18 years in Texas with COVID-19 in 2020. Multilevel logistic regression was used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice) overall and with higher illness severity among ICU admissions. Among 52,776 ICU admissions with COVID-19, 6,373 (12.1%) were previously healthy. Short-term mortality among previously healthy ICU admissions and those with comorbidities was 16.9% vs 34.6%. On adjusted analyses, the odds of short-term mortality were lower among the previously healthy compared to those with comorbidities overall (adjusted odds ratio [aOR] 0.84 [95% CI 0.73-0.98]), but did not differ among those with ≥3 organ dysfunctions (aOR 1.11 [95% CI 0.84-1.46]) and the mechanically ventilated (aOR 0.87 [95% CI 0.68-1.12]), while being higher among those with do-not-resuscitate status (aOR 1.40 [95% CI 1.04-1.89]). Over 1 in 8 ICU admissions with COVID-19 were previously healthy. Although being previously healthy was associated with lower risk of death compared to those with comorbidities overall, it had no prognostic advantage among the more severely ill.


Transplants of neurosphere cell suspensions from aged mice are functional in the mouse model of Parkinson's.
Neural stem cell therapy has the potential to treat neurodegenerative disorders. For Parkinson's disease (PD), the goal is to enhance the dopamine system sufficiently to restore the control of movement and motor activities. In consideration of autologous stem cell therapy for PD, it will be necessary to propagate the cells in most cases from aged brain tissue. We isolated cells from the subventricular zone (SVZ) in the brains of 1-year-old enhanced green fluorescent protein (GFP) mice and generated neurospheres in culture. Neurospheres yielding high numbers of neurons and astrocytes "de novo" were selected and cryopreserved before evaluating the efficacy of neurosphere cell suspensions transplanted to the 6-hydroxydopamine (6-OHDA) model of PD. In mice unilaterally lesioned with 6-OHDA, transplants of neurosphere cell suspensions to the striatum yielded astrocytes and tyrosine hydroxylase positive neurons that reduced or reversed the drug-induced behavioral circling response to amphetamine and apomorphine. Control mice without the cell suspensions showed no change in the motor behavior. Our results indicate that the SVZ in the aged mouse brain contains cells that can be expanded in the form of neurospheres, cryopreserved, re-expanded and then transplanted into the damaged dopamine system to generate functional cell progeny that offset the motor disturbances in the nigrostriatal system.


Protective effect of chondroitin sulfate nano-selenium on chondrocyte of patients with Kashin-Beck disease.
To investigate the protective effect of chondroitin sulfate nano-selenium (SeCS) on chondrocyte of Kashin-Beck disease (KBD). Chondrocyte samples were isolated from the cartilage of three male KBD patients (54-57 years old). The chondrocytes were respectively divided into four groups: (a) control group, (b) SeCS supplement group (100 ng/mL SeCS), (c) T-2 + SeCS supplement group (20 ng/mL T-2 + 100 ng/mL SeCS), and (d) T-2 group (20 ng/mL T-2). Live/dead staining and transmission electron microscopy (TEM) were used to observe cell viability and ultrastructural changes in chondrocytes respectively. Expressions of Caspase-9, cytochrome C (Cyt-C), and chondroitin sulfate (CS) structure-modifying sulfotransferases including carbohydrate sulfotransferase 3, 15 (CHST-3, CHST-15), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction. After one- or three-days intervention, the number of living chondrocytes in the SeCS supplement group was higher than that in the control group, while it is opposite in the T-2 + SeCS supplement group and T-2 group. The cellular villi number in the surface increased in the SeCS supplement group compared with the control group. Mitochondrial morphology density was improved in the T-2 + SeCS supplement group compared with the T-2 group. Expressions of CHST-3, CHST-15, UST, Caspase-9, and Cyt-C on the mRNA level significantly increased in the T-2 + SeCS supplement group and T-2 group compared with the control group. SeCS supplement increased the number of living chondrocytes, improved the ultrastructure, and altered the expressions of CS structure-modifying sulfotransferases, Caspase-9, and Cyt-C.


Improving the Flame Retardant Efficiency of Layer by Layer Coatings Containing Deoxyribonucleic Acid by Post-Diffusion of Hydrotalcite Nanoparticles.
This work deals with the use of hydrotalcite nanoparticle post-diffusion in layer by layer (LbL) coatings with the aim of improving their flame retardant action on cotton. The selected LbL components, which encompass polydiallyldimethylammonium chloride and deoxyribonucleic acid, aim at the deposition of an intumescent coating. Infrared spectra pointed out a super-linear growth of the investigated assembly, indicating the ability to deposit thick coatings while maintaining a relatively low deposition number. A post-diffusion process, performed by exposing the LbL-treated fabrics to two different concentrations of hydrotalcite water suspensions (0.1 or 1 wt %), was carried out to improve the fireproofing efficiency of these coatings. Coatings treated with the lowest concentration suspension partially swelled as a consequence of their structural rearrangements while the use of the highest concentration led to nanoparticle aggregates. Horizontal flame spread tests were used for assessing the achieved flame retardant properties. The post-diffusion performed at the lowest hydrotalcite concentration lowers the minimum number of Bi-Layers required for obtaining cotton self-extinguishment while samples treated with the highest concentration showed detrimental effects on the performances of treated fabrics. This behavior is ascribed to the effects of hydrotalcite particles on the intumescence of LbL coatings, as evidenced by the morphological analyses of post-combustion residues.


A two-level large-volume epidural blood patch protocol for spontaneous intracranial hypotension: retrospective analysis of risk and benefit.
We report a retrospective analysis of a two-level, variable-volume epidural blood patch (EBP) technique for the treatment of spontaneous intracranial hypotension (SIH). Ninety-four patients with SIH underwent EBPs. Injectate volume was variable and guided by the onset of back pain, radiculopathy or symptoms referable to the EBP. Patients were a responder if no invasive treatment was necessary for SIH symptoms after the first EBP. Baseline patient characteristics, including presenting symptoms and imaging findings, were compared between responders and non-responders. Adverse events were recorded. The mean first EBP volume was 45.3±23.2 (range 4-124 mL). The responder rate was 28.7% after the first EBP, improving to 41.5% and 46.8% after a second and third EBP, respectively. Baseline characteristics were similar between groups, except for the greater prevalence of subdural fluid collections in the responder group (48% vs 18%, p=0.003). Two severe complications occurred: transient bilateral paraplegia and cauda equina syndrome from arachnoiditis. Our protocol can be used to treat SIH but carries risks that require meticulous attention. EBP volumes were variable across patients, demonstrating the variability in the elastance of the epidural space. Rigorous monitoring for neurological symptoms is necessary throughout the procedure to limit complications and determine the endpoint of the EBP. We advocate for rigorous confirmation of epidural placement of the EBP with contrast-imaging studies to limit intrathecal placement of blood, which can lead to arachnoiditis. Randomized controlled trials are needed to determine the safety and efficacy of large-volume EBPs.


Assessment of spatial genetic structure to identify populations at risk for infection of an emerging epizootic disease.
Understanding the geographic extent and connectivity of wildlife populations can provide important insights into the management of disease outbreaks but defining patterns of population structure is difficult for widely distributed species. Landscape genetic analyses are powerful methods for identifying cryptic structure and movement patterns that may be associated with spatial epizootic patterns in such cases.We characterized patterns of population substructure and connectivity using microsatellite genotypes from 2,222 white-tailed deer (Odocoileus virginianus) in the Mid-Atlantic region of the United States, a region where chronic wasting disease was first detected in 2009. The goal of this study was to evaluate the juxtaposition between population structure, landscape features that influence gene flow, and current disease management units.Clustering analyses identified four to five subpopulations in this region, the edges of which corresponded to ecophysiographic provinces. Subpopulations were further partitioned into 11 clusters with subtle (F ST ≤ 0.041), but significant genetic differentiation. Genetic differentiation was lower and migration rates were higher among neighboring genetic clusters, indicating an underlying genetic cline. Genetic discontinuities were associated with topographic barriers, however.Resistance surface modeling indicated that gene flow was diffuse in homogenous landscapes, but the direction and extent of gene flow were influenced by forest cover, traffic volume, and elevational relief in subregions heterogeneous for these landscape features. Chronic wasting disease primarily occurred among genetic clusters within a single subpopulation and along corridors of high landscape connectivity.These results may suggest a possible correlation between population substructure, landscape connectivity, and the occurrence of diseases for widespread species. Considering these factors may be useful in delineating effective management units, although only the largest features produced appreciable differences in subpopulation structure. Disease mitigation strategies implemented at the scale of ecophysiographic provinces are likely to be more effective than those implemented at finer scales.


Contrastive Learning for 3D Point Clouds Classification and Shape Completion.
In this paper, we present the idea of Self Supervised learning on the shape completion and classification of point clouds. Most 3D shape completion pipelines utilize AutoEncoders to extract features from point clouds used in downstream tasks such as classification, segmentation, detection, and other related applications. Our idea is to add contrastive learning into AutoEncoders to encourage global feature learning of the point cloud classes. It is performed by optimizing triplet loss. Furthermore, local feature representations learning of point cloud is performed by adding the Chamfer distance function. To evaluate the performance of our approach, we utilize the PointNet classifier. We also extend the number of classes for evaluation from 4 to 10 to show the generalization ability of the learned features. Based on our results, embeddings generated from the contrastive AutoEncoder enhances shape completion and classification performance from 84.2% to 84.9% of point clouds achieving the state-of-the-art results with 10 classes.


Phenolics impart Au(3+)-stress tolerance to cowpea by generating nanoparticles.
While evaluating impact of Au nanoparticles on seed germination and early seedling growth of cowpea, HAuCl4 was used as control. Seedlings of cowpea raised in HAuCl4, even at concentration as high as 1 mM, did not show any suppression in growth. Accordingly, Au(3+), despite being a heavy metal, did not alter levels of stress markers (viz. proline and malondialdehyde) in cowpea. Interestingly, cowpea turned clear pale yellow HAuCl4 solutions colloidal purple during the course of seed germination and seedling growth. These purple colloidal suspensions showed Au-nanoparticle specific surface plasmon resonance band in absorption spectra. Transmission electron microscopic and powder X-ray diffraction investigations confirmed presence of crystalline Au-nanoparticles in these purple suspensions. Each germinating seed of cowpea released ∼35 nmoles of GAE of phenolics and since phenolics promote generation of Au-nanoparticles, which are less/non toxic compared to Au(3+), it was contemplated that potential of cowpea to withstand Au(3+) is linked to phenolics. Of the different components of germinating seed of cowpea tested, seed coat possessed immense power to generate Au-nanoparticles, as it was the key source of phenolics. To establish role of phenolics in generation of Au-nanoparticles (i) seed coat and (ii) the incubation medium in which phenolics were released by germinating seeds, were tested for their efficacy to generate Au-nanoparticles. Interestingly, incubation of either of these components with Au(3+) triggered increase in generation of Au-nanoparticles with concomitant decrease in phenolics. Accordingly, with increase in concentration of Au(3+), a proportionate increase in generation of Au-nanoparticles and decrease in phenolics was recorded. In summary, our findings clearly established that cowpea possessed potential to withstand Au(3+)-stress as the phenolics released by seed coat of germinating seeds possess potential to reduce toxic Au(3+) to form non/less toxic Au-nanoparticles. Our investigations also pave a novel, simple, green and economically viable protocol for generation of Au-nanoparticles.


Cement augmentation of refractory osteoporotic vertebral compression fractures: survivorship analysis.
Retrospective cohort. To compare survivorship after cement augmentation of refractory osteoporotic vertebral compression fractures (OVCFs) with traditional inpatient pain management and bracing. OVCFs can cause debilitating pain and functional decline necessitating prolonged bed rest and high-dose narcotics. Vertebroplasty and kyphoplasty are cement augmentation procedures used to control pain and restore function in patients with OVCF's that are refractory to conservative treatment. Early mobilization is associated with improved survival after other fractures in elderly patients. A university hospital database was used to identify all participants treated with primary diagnosis of OVCF between 1993 and 2006. Chart review and imaging studies were used to confirm demographics, comorbidities, diagnosis, and treatment. Survival time was determined using hospital data, national death indices and patient follow-up. Exact Fisher tests, Mann-Whitney tests, and proportional hazards regression models with Kaplan-Meier plots compared patients treated with cement augmentation with controls treated with inpatient pain management and bracing. Patients with high-energy trauma, tumors or age more than 60 years were excluded. Within the past 12 years, 46 patients treated with cement augmentation and 129 matched controls met inclusion criteria. They did not differ with respect to age, sex, and comorbidities. A significant survival advantage was found after cement augmentation compared with controls (P < 0.001; log rank), regardless of comorbidities, age, or the number of fractures diagnosed at the start date (P = 0.565). Controlling simultaneously for covariates, the estimated hazard ratio associated with cementation was 0.10 (95% confidence interval [CI] = 0.02-0.43; P = 0.002) for year 1, 0.15 (95% CI = 0.02-1.12; P = 0.064) for year 2, and 0.95 (95% CI = 0.32-2.79; P = 0.919) for subsequent follow-up. The number of OVCFs at the start time of treatment did not affect survival benefit of cementation (P = 0.44). Cement augmentation of refractory OVCF improves survival for up to 2 years when compared with conservative pain management with bed rest, narcotics, and extension bracing, regardless of age, sex, and number of fractures or comorbidities. Therefore, aggressive management should be considered for refractory OVCFs with intractable back pain.


Premedication of pediatric tonsillectomy patients with oral transmucosal fentanyl citrate.
We assessed the safety and efficacy of oral transmucosal fentanyl citrate (Fentanyl Oralet; Abbott Laboratories, Abbott Park, IL), administered preoperatively to provide both preoperative sedation and postoperative analgesia, in a randomized, double-blind, placebo-controlled study in 40 children, 2-10 yr of age, scheduled for tonsillectomy. In the preoperative holding area, one group (Group O) received Fentanyl Oralet (fentanyl 10-15 micrograms/kg), and the other (Group IV) received only the candy matrix. Patients in Group O received an i.v. injection of saline, and those in Group IV received an i.v. injection of fentanyl (2 micrograms/kg) after removal of the first tonsil. Except for the opioid, patients received a standard anesthetic. Preoperative sedation and cooperation were assessed. Postoperative pain was evaluated using an objective pain scale. Patients in Group O were more sedated but no more cooperative at the induction of anesthesia compared with those in Group IV. No patient vomited preoperatively or experienced preoperative or postoperative desaturation. Time to postanesthesia care unit (PACU) discharge was not different between groups. There was no significant difference in the number of patients requiring morphine in the PACU (6 of 21 in Group O versus 10 of 19 in Group IV). Plasma fentanyl concentrations were not a reliable indicator of the need for postoperative morphine. Among the patients who required morphine postoperatively, there was an 11-fold variation in plasma fentanyl concentrations at the time of morphine administration. Derived pharmacokinetic parameters were similar to those previously reported in children; bioavailability of the fentanyl in Fentanyl Oralet was 0.33. We conclude that premedication with Fentanyl Oralet did not differ with i.v. fentanyl in regard to the induction of anesthesia and postoperative analgesia. In this double-blind, randomized study, we studied the efficacy of Fentanyl Oralet (10-15 micrograms/kg) preoperatively for providing postoperative analgesia in children undergoing tonsillectomy. We found no incidence of preoperative desaturation or vomiting in any patient. This is in contrast to other studies, in which there was a longer time interval between Fentanyl Oralet completion and induction of anesthesia. The bio-availability of the fentanyl in Fentanyl Oralet was estimated to be 33%, which is less than that reported in adults (approximately 50%). There was no difference in postoperative opioid requirements between patients who received 2 micrograms/kg of fentanyl i.v. and those who received Fentanyl Oralet.


[Study on risk factors of cardiovascular disease and the status of bone mineral density in women with hypoestrogenism].
To study risk factors of cardiovascular disease (CVD) and status of bone mineral density (BMD) in women with hypoestrogenism. From Jul 2011 to April 2013, a total of 256 women with hypoestrogenism in the First Affiliated Hospital of Shanxi Medical University were enrolled in this retrospective study, which were divided into four groups:133 women in ppausal group, 25 women in premature ovarian failure (POF) group, 67 women in menopausal transition group and 31 women in premature ovarian failure transition group.General statue, CVD risk factors and BMD were compared among four groups.General statue include menopausal period, menopausal symptoms (Kupperman Index), CVD risk factors include body mass index, blood pressure, waist circumference, waist-hip ratio, blood lipids and glucose, BMD include left hip, lumbar spine bone mineral density and T or Z value. (1) The median menopausal period were 3.4 years in postmenopausal group and 3.6 years in premature ovarian failure group, which did not show no statistical difference (P > 0.05).Kupperman Index in four groups were 12 in postmenopausal group, 9 in POF group, 9 in menopausal transition group and 8 in premature ovarian failure transition group, which reached statistical difference (P < 0.05).(2) The difference of body mass index (BMI), waist circumference, waist-hip ratio, diastolic blood pressure were no statistically significant among four groups(P > 0.05); the systolic blood pressure in four groups were 120, 110, 110, 110 mm Hg (1 mm Hg = 0.133 kPa), their differences were statistically significance (P < 0.05); the high-density lipoprotein (HDL-C) was 1.6 mmol/L in postmenopausal group, and 1.3 mmol/L in premature ovarian failure transition group, their differences were all statistically significance (P < 0.05); the difference of the fasting plasma glucose (FPG) was not statistically different in 4 groups (P > 0.05).(3) The abnormal rate of lower bone mass in lumbar spine were 57% (46/81) postmenopausal group, 8/15 in POF group, 32% (9/28) in menopausal transition group, 12/19 in premature ovarian failure transition group, and osteoporosis was 9% (7/81), 3/15, 1% (3/28) and 0 respectively , their differences were statistically different (P < 0.05); the abnormal rate of BMD of left hip and lumbar spine of 11/15 and 12/16 in POF group was higher than 65% (53/81) in postmenopausal group. In the mean time, the abnormal rate of BMD of left hip and lumbar spine were, 12/19 and 10/20 in premature ovarian failure transition group, which were significantly higher than 43% (12/28) and 39% (12/31) in the menopausal transition group. The menopausal symptoms resulting from hypoestrogenism in natural postmenopausal women are mostly remarkable. The decrease of BMD in lumbar spine is more significant than that of left hip among postmenopausal women.Women with earlier menopause was prone to cause the changes of blood fat and abnormal of BMD, especially HDL-C decreased significantly compared with those natural postmenopause, it is more likely to cause CVD and osteoporosis.


Extensive degradation of myelin basic protein isoforms by calpain following traumatic brain injury.
Axonal injury is one of the key features of traumatic brain injury (TBI), yet little is known about the integrity of the myelin sheath. We report that the 21.5 and 18.5-kDa myelin basic protein (MBP) isoforms degrade into N-terminal fragments (of 10 and 8 kDa) in the ipsilateral hippocampus and cortex between 2 h and 3 days after controlled cortical impact (in a rat model of TBI), but exhibit no degradation contralaterally. Using N-terminal microsequencing and mass spectrometry, we identified a novel in vivo MBP cleavage site between Phe114 and Lys115. A MBP C-terminal fragment-specific antibody was then raised and shown to specifically detect MBP fragments in affected brain regions following TBI. In vitro naive brain lysate and purified MBP digestion showed that MBP is sensitive to calpain, producing the characteristic MBP fragments observed in TBI. We hypothesize that TBI-mediated axonal injury causes secondary structural damage to the adjacent myelin membrane, instigating MBP degradation. This could initiate myelin sheath instability and demyelination, which might further promote axonal vulnerability.


The Association between Depression Severity, Prosody, and Voice Acoustic Features in Women with Depression.
The aim was to define the association between the severity of depression, prosody, and voice acoustic features in women suffering from depression and its comparisons with nondepressed people. Prosody and acoustic features in 30 women with major depression hospitalized in a psychiatric ward and 30 healthy women were investigated in a cross-sectional study. To define the severity of depression, the Hamilton Rating Scale for Depression (HRS-D) was applied. Acoustic parameters such as jitter, shimmer, cepstral peak prominence (CPP), standard deviation of fundamental frequency (SD F0), harmonic-to-noise ratio, and F0 and also some speech prosodic features including the speed of speech, switching pause duration means, and durations of produced sentences with different modals were measured quantitatively. Also, six raters judged the patient's prosody qualitatively. SPSS V.28 was used for all statistical analyses (p < 0.05). There was a significant correlation between HRS-D with jitter, SD F0, speed of speech, and switching pause means (p ≤ 0.05). The means of CPP and duration of producing emotional sentences differed between the depression and control groups. The HRS-D scores were significantly correlated with switching pauses in patients (Pearson coefficient = 0.47, p=0.05). The results of the perceptual evaluation of prosody judged by six raters showed an 85% correlation between them (p ≤ 0.001). Some acoustic and prosodic parameters are different between healthy women and those with depression disorder (e.g., CPP and duration of emotional sentences) and may also have an association with the severity of depression (e.g., jitter, SD F0, speed of speech, and switching pause means) in women with depression disorder. It was indicated that the best sentence modal to assess prosody in patients with depression would be exclamatory ones compared to declarative and interrogative sentences.


Nucleosomes in solution exist as a mixture of twist-defect states.
The 2.0 A crystal structure of a nucleosome core particle in complex with a bivalent pyrrole-imidazole polyamide reveals that this "clamp" effectively crossbraces the two gyres of the DNA superhelix, thereby stabilizing the nucleosome against dissociation. Using X-ray crystallography and footprinting techniques, we show that the clamp preferentially binds nucleosomes over free DNA, and that nucleosomal DNA exists as a mixture of multiple twist-defect intermediates in solution. The nucleosomes exist in one of two different conformations in various crystal structures that trap twist-defect intermediates, even on a strong positioning sequence. Evidence has been obtained supporting the existence of twist-defect states in nucleosomal DNA in solution that are similar to those obtained in crystal structures. Our results also substantiate the idea that twist diffusion may represent an important means of altering the accessibility of nucleosomal DNA both in the presence and in the absence of ATP-dependent chromatin-remodelling enzymes.


Novel Antimuscarinic Antidepressant-like Compounds with Reduced Effects on Cognition.
The cholinergic nervous system has been implicated in mood disorders, evident in the fast-onset antidepressant effects of scopolamine, a potent muscarinic antagonist, in clinical studies. One prominent disadvantage of the use of scopolamine in the treatment of depression is its detrimental effects on cognition, especially as such effects might aggravate cognitive deficits that occur with depression itself. Thus, the identification of antimuscarinic drugs that are free of such detrimental effects may provide an important avenue for the development of novel therapeutics for the management of depression. The present data in rats indicate that a historical muscarinic antagonist, L-687,306, and a muscarinic antagonist of our own design, CJ2100, were as or more effective than scopolamine in antagonizing both the bradycardic effects of the muscarinic agonist arecoline in cardiovascular studies and its discriminative stimulus and rate-decreasing effects in behavioral studies. Additionally, both novel muscarinic antagonists were as effective as scopolamine in decreasing immobility in the forced swim test, a preclinical indicator of potential antidepressant activity. However, at equieffective or even larger doses, they were considerably less disruptive than scopolamine in assays of cognition-related behavior. All three drugs displayed high specificity for the mAChRs with few off-target binding sites, and CJ2100 showed modest affinity across the mAChRs when compared with L-687,306 and scopolamine. These data emphasize the dissimilar pharmacological profiles that are evident across antimuscarinic compounds and the potential utility of novel antagonists for the improved treatment of depression. SIGNIFICANCE STATEMENT: Some clinical studies with the muscarinic antagonist scopolamine document its ability to produce antidepressant effects in patients with mood disorders; however, scopolamine also has well known adverse effects on both autonomic and centrally mediated physiological functions that limit its therapeutic use. This study characterizes the cardiovascular and discriminative stimulus effects of two novel muscarinic antagonists, L-687,306 and CJ2100, that produce antidepressant-like effects in a rodent model (forced swim test) without affecting touchscreen-based cognitive performance (titrating psychomotor vigilance and delayed matching-to-position).


[Background and current use of adjuvants for regional anesthesia : From research to evidence-based patient treatment].
The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.


A multiparameter, PC-based telemetry unit for biomedical signals.
A low-cost, general-purpose telemetry system was developed for use in rural health centres, hospitals, ambulances and clinics. It was designed to transmit a range of analogue biomedical signals using various communications media. The system was tested using different telephone systems, including mobile telephony. The results showed a maximum sample rate of 1.6 kHz using the public telephone network. With three data channels the system produced sample rates of 500 Hz at 8 bit/sample. Typical overall delay times were below 100 ms. Mobile tests showed that the GSM telephone was superior to the Nordic mobile telephone (NMT 900). In field tests, sample rates of 990 Hz were obtained using GSM telephony. Bit error rates were less than 10(-7) for all applications and high-fidelity regeneration was obtained at the receiver. The tests showed that the system was well suited for telemetry of analogue biomedical signals in a broad range of telemedicine applications.


A simple grand canonical approach to compute the vapor pressure of bulk and finite size systems.
In this article we introduce a simple grand canonical screening (GCS) approach to accurately compute vapor pressures from molecular dynamics or Monte Carlo simulations. This procedure entails a screening of chemical potentials using a conventional grand canonical scheme, and therefore it is straightforward to implement for any kind of interface. The scheme is validated against data obtained from Gibbs ensemble simulations for water and argon. Then, it is applied to obtain the vapor pressure of the coarse-grained mW water model, and it is shown that the computed value is in excellent accord with the one formally deduced using statistical thermodynamics arguments. Finally, this methodology is used to calculate the vapor pressure of a water nanodroplet of 94 molecules. Interestingly, the result is in perfect agreement with the one predicted by the Kelvin equation for a homogeneous droplet of that size.


Conformational analysis of a synthetic fish kisspeptin 1 peptide in membrane mimicking environments.
Kisspeptin 1 is a neuropeptide hormone of the RFamide family, which act as an upstream regulator of brain-pituitary-gonad (BPG) axis in most vertebrates including teleosts. In the present study, a 16 amino acid long putative mature bioactive peptide (kiss 1) from preprokisspeptin 1 of golden mahseer, Tor putitora (Hamilton, 1822), was synthesized and characterized using an integrated (experimental and in silico) approach. The far-UV circular dichroism (CD) spectrum of this peptide was evaluated both in aqueous and membrane mimicking solvents (TFE, HFIP and Dioxane). The results indicate that kiss 1 peptide adopted helical, turn and β conformations in membrane like environments. The near-UV CD spectroscopy was also carried out to examine the tertiary packing around aromatic residues of kiss 1 peptide and the peptide-membrane complex. The kiss 1 peptide exhibited little signal in water, but a prominent negative band was observed at around 275 nm when membrane mimetic solution was added. The observed ordered conformations of kiss 1 peptide in the different solvents indicated its potential biological activity which could enhance the secretion of gonadotropin-releasing hormone (GnRH) at BPG axis. The conformational information generated from the present study reinforces the application prospects of bioactive synthetic peptide analogs of kisspeptin 1 in improving the reproductive performances of important cultivable fish species.


The relationship between performance and flow state in tennis competition.
The study aimed to examine 1) the validity of the nine-factor flow model in tennis competition; 2) differences in flow state between athletes who won or lost their competition match; 3) the link between flow and subjective performance; and 4) flow dimensions as predictors of performance outcome The sample consisted of 188 junior tennis players (115 male, 73 female) between 12 and 18 years of age. Participants' performance was recorded during junior ranking-list tournaments. Following the completion of a tennis competition match, participants completed the Flow State Scale-2 and a subjective performance outcome measure. Acceptable flow model fit indices of CFI, TLI, SRMR, and RMSEA were only found for winning athletes. The group of winning athletes scored significantly higher on all nine flow dimensions, except time transformation, than losing athletes, showing statistically significant differences for challenge-skills balance, clear goals, sense of control, and autotelic experience. Significant correlation coefficients were found between flow state and subjective performance assessments. The binary logistic regression revealed concentration on the task and sense of control to be significant predictors of performance outcome. The predictor variables explained 13% of the variance in games won. The study showed that athletes who win or lose perceived flow state differently. Studies using retrospective assessments need to be aware that subjective experience could be biased by performance outcomes. Pinpointing psychological variables and their impact on ecologically valid measures, such as performance results, would support the development of effective intervention studies to increase performance in sport competition.


Single bunch X-ray pulses on demand from a multi-bunch synchrotron radiation source.
Synchrotron radiation facilities routinely operate in a multi-bunch regime, but applications relying on time-of-flight schemes require single bunch operation. Here we show that pulse picking by resonant excitation in a storage ring creates in addition to the multi-bunch operation a distinct and separable single bunch soft X-ray source. It has variable polarization, a photon flux of up to 10(7)-10(9) ph s(-1)/0.1%BW at purity values of 10(4)-10(2) and a repetition rate of 1.25 MHz. The quasi-resonant excitation of incoherent betatron oscillations of electrons allows horizontal pulse separation at variable (also circular) polarization accessible for both, regular 30 ps pulses and ultrashort pulses of 2-3 ps duration. Combined with a new generation of angularly resolving electron spectrometers this creates unique opportunities for time-resolved photoemission studies as confirmed by time-of-flight spectra. Our pulse picking scheme is particularly suited for surface physics at diffraction-limited light sources promising ultimate spectral resolution.


[Replacement of the cruciate ligament with heterologous connective tissue structures].
Twenty-four implantations of heterologous connective tissue structures replacing ligaments and tendons are evaluated in order to present the early results in the heterologous replacement of cruciate ligament structures. Twenty implantations are analysed after 18 to 36 months. The biologic structure which is very strong in comparison with the autologous tissue is not modified to a great extent during a period of 21 months, i.e. the ligament prosthesis remains unchanged so that the appellation "bio-prosthesis" seems justified. At present the preliminary clinical results are satisfying. Consequently, heterologous connective tissue structures can be used in repeated surgical interventions for the stabilization of chronic ligament instabilities.


Aspergillus fumigatus variant with decreased susceptibility to multiple antifungals.
Isolates of Aspergillus fumigatus that demonstrate resistance to itraconazole (ITZ) have been described previously; however, the prevalence and clinical significance of ITZ resistance are not completely understood. In this study we assessed the ITZ susceptibilities of 128 A. fumigatus isolates that caused invasive infection in 82 stem cell transplant patients before and after the use of ITZ in our institution (study period, 1991 to 2000). The MICs for 10 isolates obtained from seven patients were high, > or 1 microg/ml. The average ITZ MIC increased after institutional use of the drug began in 1995. The majority of the isolates for which MICs were high (6 of 10) and one isolate for which the MIC was low (0.06 microg/ml) demonstrated an unusual phenotype, appearing as predominantly white colonies. For all seven atypical isolates, voriconazole MICs were high (> or = 2 microg/ml), and minimal effective concentrations of caspofungin were high (> or 4 microg/ml). For two of the seven atypical isolates, amphotericin B MICs were high (> or 2 microg/ml). The isolates appeared white due to slow sporulation; however, after prolonged incubations, the isolates sporulated with no difference in conidial color or conidiophore morphology compared with typical isolates. Randomly amplified polymorphic DNA-PCR patterns of these isolates were distinct compared with those of other A. fumigatus isolates. Sequencing of 18S rRNA genes confirmed that all were A. fumigatus; however, the mitochondrial cytochrome b gene sequences of all the atypical isolates were unique. These data suggest the potential presence of a genetically unique, poorly sporulating variant of A. fumigatus that demonstrates decreased susceptibilities to several antifungals.


Functional visual loss in amblyopia and the effect of occlusion therapy.
The aim of this study was to define the nature of functional visual loss in amblyopia and to identify those subjects whose amblyopia is chiefly due to one or more of the following deficits: abnormal contour interaction, abnormal eye movements, abnormal contrast perception, or positional uncertainty. Fifty amblyopic children with a mean age of 5.6+/-1.3 years were referred from diverse sources. In addition to routine orthoptic and optometric evaluation the principal visual deficits in the amblyopic eye of each subject were identified using the following measures of visual acuity: high contrast linear, single optotype, repeat letter and low contrast linear, plus Vernier and displacement thresholds. These measures were repeated as the children underwent a prescribed occlusion therapy regime, after parental consent. All amblyopic subjects demonstrated a functional loss in each of the tests used, and occlusion therapy appeared to improve all aspects of the amblyopia. High contrast visual acuity was not always the primary deficit in visual function, and when amblyopic subjects were divided according to their primary visual loss, this visual function was found to show the greatest improvement with treatment. These results suggest that to successfully identify the primary visual deficit and monitor the success of occlusion therapy it is necessary to assess other aspects of visual function in amblyopia.


Metabolic syndrome is associated with incidence of deep cerebral microbleeds.
Metabolic syndrome (MetS) has been associated with silent brain lesions; however, there are no data on the relationship between MetS and the incidence of cerebral microbleeds (CMBs) in Asian populations. The aim of this study was to evaluate the longitudinal association between MetS and incidence of CMBs in the Japanese population. We performed a prospective cohort study involving 684 Japanese participants (mean age, 61.7 years) with a mean 6.5 ± 3.4 years follow-up. All participants underwent 1.5 T magnetic resonance imaging, and CMBs were classified by their locations. Logistic regression analyses were performed to examine the relationship of MetS and its components with the incidence of CMBs. MetS was observed in 7.5% of the study population. Forty-nine (7.2%) subjects (36 had new deep or infratentorial CMBs, 13 had new strictly lobar CMBs) developed new CMBs during the follow-up period. In multivariable analysis, MetS was significantly associated with the incidence of deep or infratentorial CMBs (odds ratio, 4.03; 95% confidence interval, 1.72-9.41), and the elevated blood pressure component was most robustly associated with the incidence of deep or infratentorial CMBs (odds ratio, 5.16; 95% confidence interval, 2.02-13.2). Increased body mass index was also associated with incidence of deep or infratentorial CMBs (odds ratio, 2.45; 95% confidence interval, 1.06-5.67). The present study showed that MetS predicts incidence of CMBs in the deep brain regions and high blood pressure is the most important among the MetS components.


Network analysis of temporal effects of intermittent and sustained hypoxia on rat lungs.
The molecular networks underlying the lung response to hypoxia are not fully understood. We employed systems biology approaches to study temporal effects of intermittent or sustained hypoxia on gene expression in rat lungs. We obtained gene expression profiles from rats exposed to intermittent or sustained hypoxia lasting 0-30 days and identified differentially expressed genes, their patterns, biological processes, and regulatory networks critical for lung response to intermittent or sustained hypoxia. We validated selected genes with quantitative real-time PCR. Intermittent and sustained hypoxia induced two distinct sets of genes in rat lungs that displayed different temporal expression patterns. Intermittent hypoxia induced genes mostly involved in ion transport and homeostasis, neurological processes, and steroid hormone receptor activity, while sustained hypoxia induced genes principally participating in immune responses. The intermittent hypoxia-activated network suggested a role for cross talk between estrogen receptor 1 (ESR1) and other key proteins in hypoxic responses. The sustained hypoxia-activated network was indicative of vascular remodeling and pulmonary hypertension. We confirmed the temporal expression changes of 12 genes (including the Esr1 gene and 4 ESR1 target genes) in intermittent hypoxia and 8 genes in sustained hypoxia with quantitative real-time PCR. intermittent and sustained hypoxia induced distinct gene expression patterns in rat lungs. The functional characteristics of genes activated by these two distinct perturbations suggest their roles in the downstream physiological effects of intermittent and sustained hypoxia. Our results demonstrate the discovery potential of applying systems biology approaches to the understanding of mechanisms underlying hypoxic lung response.


Impact of tuberculosis disease on human gut microbiota: a systematic review.
This systematic review evaluates the gut microbiota (GM) status in tuberculosis (TB) patients compared to healthy volunteers due to the disease or its treatment. We conducted a systematic review of all articles published in PubMed, Web of Science, and Embase that assessed the impact of TB disease and anti-tubercular therapy (ATT) on GM from inception till January 2022 (Protocol registration number in PROSPERO: CRD42021261884). Regarding the microbial diversity indices and taxonomy, we found a significant difference in GM status between the TB and healthy control (HC) groups. We found an overabundance of Phylum Proteobacteria and depletion of some short-chain fatty acid-producing bacteria genera like Bifidobacteria, Roseburia, and Ruminococcus in the TB group. We found that ATT exacerbates the degree of dysbiosis caused by Mycobacteria tuberculosis disease. The modulation of GM in TB patients in clinical practice may serve as a promising target to reverse the dysbiosis caused. Moreover, this can optimistically change the TB treatment outcome. We expect that appropriate probiotic supplementation with antimycobacterial treatment during tuberculosis disease will help stabilize the GM throughout the treatment phase and protect the GM from dysbiosis.


Performing mathematical operations with metamaterials.
We introduce the concept of metamaterial analog computing, based on suitably designed metamaterial blocks that can perform mathematical operations (such as spatial differentiation, integration, or convolution) on the profile of an impinging wave as it propagates through these blocks. Two approaches are presented to achieve such functionality: (i) subwavelength structured metascreens combined with graded-index waveguides and (ii) multilayered slabs designed to achieve a desired spatial Green's function. Both techniques offer the possibility of miniaturized, potentially integrable, wave-based computing systems that are thinner than conventional lens-based optical signal and data processors by several orders of magnitude.


Irritable bowel syndrome and chronic constipation: emerging drugs, devices, and surgical treatments.
Irritable bowel syndrome (IBS) and chronic constipation (CC) are two of the most common functional disorders of the gut. CC and IBS are estimated to affect up to 20% and 27% of the North American population respectively. Although not life-threatening, CC and IBS can profoundly and negatively affect quality of life and are associated with a significant economic burden related to direct and indirect annual health-care costs. Possible etiologies for IBS and CC include alterations in visceral sensation and gastrointestinal motility. IBS may be caused by disturbances in brain-gut interactions affecting gastrointestinal motility and visceral sensitivity. Research efforts in CC have begun to identify abnormalities in myenteric neurons, alterations in neurotransmitters and their receptors, and incoordination of the muscles of the pelvic floor or anorectum. Both disorders may be influenced by genetic predisposition, environmental factors, and stress. In this article, the safety and efficacy of traditional and emerging therapies for CC and IBS are examined. In addition, their pathophysiology and symptoms are briefly reviewed.


Recent Advances in Vision-Based On-Road Behaviors Understanding: A Critical Survey.
On-road behavior analysis is a crucial and challenging problem in the autonomous driving vision-based area. Several endeavors have been proposed to deal with different related tasks and it has gained wide attention recently. Much of the excitement about on-road behavior understanding has been the labor of advancement witnessed in the fields of computer vision, machine, and deep learning. Remarkable achievements have been made in the Road Behavior Understanding area over the last years. This paper reviews 100+ papers of on-road behavior analysis related work in the light of the milestones achieved, spanning over the last 2 decades. This review paper provides the first attempt to draw smart mobility researchers' attention to the road behavior understanding field and its potential impact on road safety to the whole road agents such as: drivers, pedestrians, stuffs, etc. To push for an holistic understanding, we investigate the complementary relationships between different elementary tasks that we define as the main components of road behavior understanding to achieve a comprehensive understanding of approaches and techniques. For this, five related topics have been covered in this review, including situational awareness, driver-road interaction, road scene understanding, trajectories forecast, driving activities, and status analysis. This paper also reviews the contribution of deep learning approaches and makes an in-depth analysis of recent benchmarks as well, with a specific taxonomy that can help stakeholders in selecting their best-fit architecture. We also finally provide a comprehensive discussion leading us to identify novel research directions some of which have been implemented and validated in our current smart mobility research work. This paper presents the first survey of road behavior understanding-related work without overlap with existing reviews.


Angiogenin and tRNA fragments in Parkinson's disease and neurodegeneration.
In this review, we summarise the evidence for a role of the ribonuclease angiogenin in the pathophysiology of neurodegenerative disorders, with a specific focus on Parkinson's disease (PD). Angiogenin is a stress-induced, secreted ribonuclease with both nuclear and cytosolic activities. Loss-of-function mutations in the angiogenin gene (ANG) have been initially discovered in familial cases of amyotrophic lateral sclerosis (ALS), however, variants in ANG have subsequently been identified in PD and Alzheimer's disease. Delivery of angiogenin protein reduces neurodegeneration and delays disease progression in in vitro and in vivo models of ALS and in vitro models of PD. In the nucleus, angiogenin promotes ribosomal RNA transcription. Under stress conditions, angiogenin also translocates to the cytosol where it cleaves non-coding RNA into RNA fragments, in particular transfer RNAs (tRNAs). Stress-induced tRNA fragments have been proposed to have multiple cellular functions, including inhibition of ribosome biogenesis, inhibition of protein translation and inhibition of apoptosis. We will discuss recent evidence of tRNA fragment accumulation in PD, as well as their potential neuroprotective activities.