Tracheal tube leak test--is there inter-observer agreement?
Although the leak test is recommended as a method of assessing the appropriate size of uncuffed endotracheal tubes for use in children, the reproducibility of this test has not been validated. Patients from newborn to ten years of age requiring tracheal intubation for elective surgery were studied. The endotracheal tube size was calculated using the formula: (age + 16) divided by 4 for patients > or = two years of age and at the discretion of the attending anaesthetist for patients < two years of age. After the induction of anaesthesia and administration of a nondepolarizing muscle relaxant, the patient's trachea was intubated and mid-tracheal placement was confirmed. Two of the three staff anaesthetists participating in the study assessed the leak pressure consecutively. Each participant performed a single leak determination. The leak pressure was determined as follows: the patient was supine with the head in a neutral position, fresh gas flowed into the breathing circuit at 5 L.min-1, a stethoscope was placed on the skin over the larynx and the pressure relief valve was completely closed. Pressure slowly increased in the breathing circuit until an audible leak occurred around the tracheal tube. The inter-observer difference was calculated in 212 patients. The absolute value of the difference between that of two observers increased as the mean leak pressure increased. However, the variation between observers expressed as a percent of the absolute measurement remained constant. An average variance in measurement of 38% was found at both low and high leak pressures. In conclusion, we found considerable variation between two experienced observers in assessing leak pressures.(ABSTRACT TRUNCATED AT 250 WORDS)


The risk of incident depression when assessed with the Lifestyle and Well-Being Index.
Novel findings indicate links between unhealthy lifestyles and depression based on active inflammatory processes. Thus, identifying participants with poor habits could reveal differences in trends of incident depression. This study aimed to examine the association between an objective lifestyle assessment, as measured by the Lifestyle and Well-Being Index (LWB-I), and incident depression in healthy participants of a Spanish cohort. This was a longitudinal analysis of a subsample of 10,063 participants from the Seguimiento Universidad de Navarra cohort study. Group comparisons and Cox proportional hazard models were conducted using the LWB-I, which categorizes the sample into groups with healthy and unhealthy lifestyles and well-being. The main outcome was incident depression as well as secondary outcomes. Those classified to the transition category of LWB-I were associated with a hazard ratio of 0.67 (95% confidence interval: 0.52-0.87), and those in the excellent category showed a hazard ratio of 0.44 (95% confidence interval: 0.33-0.58), which in both groups reflects a significantly lower risk of incident depression compared with the group including those classified in the poor LWB-I level. Moreover, the available sensitivity analyses concerning time of depression diagnosis or antidepressant treatment further supported the role of nutrition and physical activity on incident depression. Interestingly, throughout the follow-up, incident depression was inversely related to healthier daily habits as measured by the LWB-I. A global assessment of lifestyles such as the LWB-I provides valuable insight into the complex relationship between lifestyle factors and their link to depression risk.


Cost-effectiveness of Trastuzumab Deruxtecan for HER2-low Advanced Breast Cancer in the United States.
Trastuzumab deruxtecan has been shown to be effective for advanced breast cancer with low levels of human epidermal growth factor receptor 2. To optimize the allocation of limited health care resources, this study evaluated the cost-effectiveness of trastuzumab deruxtecan from the US payer perspective. A partitioned survival model was developed to project the disease course of advanced breast cancer. Clinical efficacy, treatment utilization, safety, and cost data were gathered from the DESTINY-Breast04 (Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer) trial and the Centers for Medicare & Medicaid Services. Transition probabilities were obtained from the reported survival probabilities per DESTINY-Breast04 group. The incremental cost-effectiveness ratio (ICER), the incremental monetary benefit, and the incremental net health benefit were measured. One-way sensitivity analysis, probabilistic sensitivity analysis, and subgroup analysis were performed to explore the uncertainty of the model. Trastuzumab deruxtecan had an ICER of $307,751 per quality-adjusted life-year (QALY) gained, with an incremental net health benefit of -0.317 QALY and an incremental monetary benefit of -$63,313 compared with the physician's choice of alternative chemotherapy agents. Subgroup analysis indicated that trastuzumab deruxtecan had an ICER of $383,776 per QALY gained for the hormone receptor-positive subgroup and an ICER of $194,424 per QALY for the hormone receptor-negative subgroup. One-way sensitivity analysis showed that the cost of trastuzumab deruxtecan had the most impact on model outcomes. The cost-effectiveness acceptability curve projected that the probability of trastuzumab deruxtecan being cost-effective was 5% in the overall population, 2% in the hormone receptor-positive subgroup, and 56% in the hormone receptor-negative subgroup at the willingness-to-pay threshold of $200,000 per QALY. Trastuzumab deruxtecan may be a cost-effective option for hormone receptor-negative patients with advanced breast cancer with low levels of human epidermal growth factor receptor 2.


Increased precision for analysis of protein-ligand dissociation constants determined from chemical shift titrations.
NMR is ideally suited for the analysis of protein-protein and protein ligand interactions with dissociation constants ranging from ~2 μM to ~1 mM, and with kinetics in the fast exchange regime on the NMR timescale. For the determination of dissociation constants (K ( D )) of 1:1 protein-protein or protein-ligand interactions using NMR, the protein and ligand concentrations must necessarily be similar in magnitude to the K ( D ), and nonlinear least squares analysis of chemical shift changes as a function of ligand concentration is employed to determine estimates for the parameters K ( D ) and the maximum chemical shift change (Δδ(max)). During a typical NMR titration, the initial protein concentration, [P (0)], is held nearly constant. For this condition, to determine the most accurate parameters for K ( D ) and Δδ(max) from nonlinear least squares analyses requires initial protein concentrations that are ~0.5 × K ( D ), and a maximum concentration for the ligand, or titrant, of ~10 × [P (0)]. From a practical standpoint, these requirements are often difficult to achieve. Using Monte Carlo simulations, we demonstrate that co-variation of the ligand and protein concentrations during a titration leads to an increase in the precision of the fitted K ( D ) and Δδ(max) values when [P (0)] > K ( D ). Importantly, judicious choice of protein and ligand concentrations for a given NMR titration, combined with nonlinear least squares analyses using two independent variables (ligand and protein concentrations) and two parameters (K ( D ) and Δδ(max)) is a straightforward approach to increasing the accuracy of measured dissociation constants for 1:1 protein-ligand interactions.


The anterior layer of the levator aponeurosis in blepharoptosis correction.
Conventional aponeurotic surgery for blepharoptosis has many advantages, but there is a potential for recurrence and lagophthalmos. The anatomy of the levator palpebrae muscle is relatively well studied, but the relationship of levator aponeurosis with surrounding layers is still controversial. This study aims to prove the presence of an anterior layer of the levator aponeurosis in clinical cases and to describe a technique involving its use for obtaining predictable outcomes in blepharoptosis correction. Between January 2014 and October 2018, 173 patients with blepharoptosis underwent correction surgery that involved relocating the anterior layer of the levator aponeurosis. During this procedure, after retracting the preaponeurotic fat pad, we could identify the misinserted anterior layer of the levator aponeurosis on the floor of the fat pad. The anterior layer was divided and advanced with posterior layers to 2 mm below the upper margin of the tarsus. After surgery, patients were followed up for 1 year, and surgical outcomes were evaluated. After 1 year of follow-up, 95.4% of the examined patients showed good long-term outcomes. Moreover, although 4% showed moderate outcomes and lost the double eyelid skin crease, there was no ptosis recurrence in these patients and no lagophthalmos occurred in any of the 173 patients. The authors found the misinserted anterior layer of the levator aponeurosis at the floor of preaponeurotic fat pad in blepharoptosis patients. Relocation of the anterior layer can provide predictable outcomes without lagophthalmos in blepharoptosis correction.


Multifocal hepatoblastoma: What is the risk of recurrent disease in the remnant liver?
Multifocal hepatoblastoma (HB) is often treated with total hepatectomy and transplantation owing to concerns of surgical resectability, local recurrence, and/or metachronous tumor in the remnant liver. We aimed to review HB patients to determine the risk of local recurrence in multifocal disease. We undertook retrospective cohort analysis of all HB patients at a single tertiary referral center between 2001 and 2015. Demographics, diagnostic features, operative details, and outcomes were analyzed. Sixty patients underwent surgical management of HB. 39 had unifocal, and 21 had multifocal disease. Of multifocal patients, 9 underwent liver transplantation, 10 anatomic resections, and 2 nonanatomic resections. Overall, two patients had recurrence in the remnant liver - both from the unifocal group. There were equivalent distant (lung) recurrences between the groups (8% for unifocal versus 14% for multifocal), p = 0.89. At a mean of 75 months of follow-up, overall survival was 97% for unifocal patients and 86% for multifocal patients, p = 0.12. Multifocal HB was not associated with increased local recurrence in the setting of R0 resection and chemotherapy. These data do not support the contention that all patients with multifocal HB require a total hepatectomy and transplantation to reduce the incidence of local recurrence and/or metachronous tumor development. Level III - Limited cohort analysis.


Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders.
Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology with Plasmodium vivax becoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity of P. vivax Duffy-binding protein gene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from global P. vivax populations. pvdbp-II sequences were obtained from 85 and 82 clinical P. vivax isolates from the eastern and western Myanmar borders, respectively. In addition, 504 pvdbp-II sequences from nine P. vivax populations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population. The nucleotide diversity of the pvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected in pvdbp-II gene in P. vivax isolates from the eastern Myanmar area. P. vivax parasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000-0.099). Population genetic structure analysis of the pvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) in P. vivax populations from the eastern and western borders of Myanmar. The pvdbp-II gene is genetically diverse in the eastern and western Myanmar border P. vivax populations. Positive natural selection and recombination occurred in pvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of the P. vivax populations in the GMS. These results can help understand the evolution of the P. vivax populations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.


Customized designed notch filters and applied effects on glare and contrast sensitivity in patients with dry eye syndrome.
Glare visual acuity and contrast sensitivity are important indicators of visual quality. Studies have shown that the glare visual acuity and contrast sensitivity in dry eye patients tend to degenerate, further affecting their quality of life. The objective of this study was to investigate the effect of notch filters on glare VA and contrast sensitivity in patients with dry eye or with dry eye syndrome. 36 subjects in the 20‒65 age group were diagnosed as having dry eye disease or perceived dry eye syndromes themselves who were included after the initial screening with the OSDI questionnaire, and one was subsequently excluded as they had undergone retinal detachment surgery. Finally, 35 subjects (14 male and 21 female) with a mean age of 40.66 ± 15.62 years participated in this study. All subjects wore their habitual prescriptions and four different filter lenses (namely 480, 620, dual 480 & 620 notch filter, and FL-41 tinted lens), and measured the parameters of glare visual acuity and contrast sensitivity using CSV-1000 and sine wave contrast test (SWCT), respectively. Student t-test and Repeated measurement analysis (R-ANOVA) were utilized by using SPSS 26.0 software. A dual-wavelength 480 & 620 nm optical notch filter had a significant anti-glare effect decreasing glare disabilities or discomfort, and leading to better visual quality, the same effect was also shown on a 480 nm notch filter lens. All participants showed a significant difference among the baseline, three notch filters (480 nm, 620 nm, dual-wavelength 480 & 620 nm), and FL-41 tinted lens were used on SWCT_A (1.5 cpd, F = 3.054, p = 0.019) and SWCT_E (18 cpd, F = 2.840, p = 0.049); but did not show statistical different on SWCT_B (3 cpd, F = 0.333, p = 0.771), SWCT_C (6 cpd, F = 1.779, p = 0.159), and SWCT_D (12 cpd, F = 1.447, p = 0.228). The baseline showed the best visual performance on CS at a low spatial frequency (SWCT_A, 1.5 cpd), any filter might reduce the contrast sensitivity at low spatial frequencies in the clinical trial, whereas 480 nm notch filter showed the best effectiveness on CS at a high spatial frequency (SWCT_E, 18 cpd), the FL-41 lens that also filters out the 480 nm band does not achieve the same effect. Moreover, patients with dry eye or those older than 40 years old preferred optical multilayer notch filters to FL-41 tinted lenses. The 480- & 620-nm dual-wavelength and 480-nm single-wavelength notch filters have the best effect on the glare visual acuity and contrast sensitivity (CS) at high spatial frequencies in dry eye patients. The 620-nm notch filter performs better in CS at low and mid-low spatial frequencies; the FL-41 tinted lens performs poorly for glare VA and CS spatial frequencies examination. Patients with glare disabilities or CS disturbance at high spatial frequencies may choose a 480-nm notch filter lens, and patients who have CS disturbance at low spatial frequencies may consider a 620-nm notch filter for the prescription.


Impact of secondary particles on the magnetic field generated by a proton pencil beam: a finite-element analysis based on Geant4-DNA simulations.
To investigate the static magnetic field generated by a proton pencil beam as a candidate for range verification by means of Monte Carlo simulations, thereby improving upon existing analytical calculations. We focus on the impact of statistical current fluctuations and secondary protons and electrons. We considered a pulsed beam (10 μ ${\umu}$ s pulse duration) during the duty cycle with a peak beam current of 0.2 μ $\umu$ A and an initial energy of 100 MeV. We ran Geant4-DNA Monte Carlo simulations of a proton pencil beam in water and extracted independent particle phase spaces. We calculated longitudinal and radial current density of protons and electrons, serving as an input for a magnetic field estimation based on a finite element analysis in a cylindrical geometry. We made sure to allow for non-solenoidal current densities as is the case of a stopping proton beam. The rising proton charge density toward the range is not perturbed by energy straggling and only lowered through nuclear reactions by up to 15%, leading to an approximately constant longitudinal current. Their relative low density however (at most 0.37 protons/mm3 for the 0.2 μ ${\umu}$ A current and a beam cross-section of 2.5 mm), gives rise to considerable current density fluctuations. The radial proton current resulting from lateral scattering and being two orders of magnitude weaker than the longitudinal current is subject to even stronger fluctuations. Secondary electrons with energies above 10 eV, that far outnumber the primary protons, reduce the primary proton current by only 10% due to their largely isotropic flow. A small fraction of electrons (<1%), undergoing head-on collisions, constitutes the relevant electron current. In the far-field, both contributions to the magnetic field strength (longitudinal and lateral) are independent of the beam spot size. We also find that the nuclear reaction-related losses cause a shift of 1.3 mm to the magnetic field profile relative to the actual range, which is further enlarged to 2.4 mm by the electron current (at a distance of ρ = 50 $\rho =50$ mm away from the central beam axis). For ρ > 45 $\rho >45$ mm, the shift increases linearly. While the current density variations cause significant magnetic field uncertainty close to the central beam axis with a relative standard deviation (RSD) close to 100%, they average out at a distance of 10 cm, where the RSD of the total magnetic field drops below 2%. With the small influence of the secondary electrons together with the low RSD, our analysis encourages an experimental detection of the magnetic field through sensitive instrumentation, such as optical magnetometry or SQUIDs.


Efficacy of safety signals in the epilepsy monitoring unit (EMU): should we worry?
There is little consensus regarding the critical safety measures to prevent harm in epilepsy monitoring units (EMUs). We sought to determine whether the safety signals (SS) triggered during EMU events differed by seizure type and the efficacy of SS in alerting responders. We screened 468 consecutive EMU admissions from January 2008 until April 2011 for definitive events to evaluate the first 50 events of complex partial seizures (CPS), generalized tonic-clonic seizures (GTC), and psychogenic non-epileptic seizures (PNES). Response to telemetry signal was slower than to push button (PB). When there was PB alarm, response time was slower in patients with PNES. A higher proportion of PNES were triggered by PB. A greater percentage of epileptic seizures were missed compared with PNES. Future studies investigating more effective techniques to capture every epileptic seizure are warranted as 24/7 monitoring by healthcare professionals is not feasible in many settings.


PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2.
The purpose of this study was to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results show that PLOD2 is highly expressed in CRC tumor tissues and cell lines, both at the mRNA and protein levels. Next, we found that PLOD2 was positively correlated with tumor grade (P = 0.001), T stage (P = 0.001), N stage (P < 0.001), and an advanced TNM stage (P < 0.001). Knockdown of PLOD2 attenuated CRC cell proliferation, migration, and invasiveness, in vitro. Our analysis of the mechanism behind the effects of PLOD2 suggests that PLOD2 affected glycolysis by regulating the expression of hexokinase 2 (HK2). HK2 reverses the inhibitory effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 regulates the expression of HK2 via the STAT3 signaling pathway. Survival analysis revealed that high expression levels of PLOD2 (HR = 3.800, P < 0.001) and HK2 expression (HR = 10.222, P < 0.001) correlated with the overall survival rate. After analyzing their expression and correlation, PLOD2 positively correlated with HK2 (r = 0.590, P < 0.001). Our findings have revealed that PLOD2 is a novel regulatory factor in glucose metabolism, exerted via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.


MetaDP: a comprehensive web server for disease prediction of 16S rRNA metagenomic datasets.
High-throughput sequencing-based metagenomics has garnered considerable interest in recent years. Numerous methods and tools have been developed for the analysis of metagenomic data. However, it is still a daunting task to install a large number of tools and complete a complicated analysis, especially for researchers with minimal bioinformatics backgrounds. To address this problem, we constructed an automated software named MetaDP for 16S rRNA sequencing data analysis, including data quality control, operational taxonomic unit clustering, diversity analysis, and disease risk prediction modeling. Furthermore, a support vector machine-based prediction model for intestinal bowel syndrome (IBS) was built by applying MetaDP to microbial 16S sequencing data from 108 children. The success of the IBS prediction model suggests that the platform may also be applied to other diseases related to gut microbes, such as obesity, metabolic syndrome, or intestinal cancer, among others (http://metadp.cn:7001/).


Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress.
Perturbations in an organism's environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male's CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on environmental, and particularly current social conditions.


Efficacy and tolerability of aripiprazole once monthly for schizophrenia: a systematic review and meta-analysis of randomized controlled trials.
We conducted a systematic review and meta-analysis of the efficacy of aripiprazole once monthly (AOM) for schizophrenia. Randomized controlled trials (RCTs) on AOM, published until June 25, 2015, were retrieved from PubMed, Cochrane, and PsycINFO databases. Relative risk (RR), standardized mean difference (SMD), 95% confidence intervals (95% CIs), and numbers needed to treat/harm (NNT/NNH) were calculated. We identified four relevant RCTs (total n=1,860), two placebo-controlled trials, one noninferiority trial comparing AOM to oral aripiprazole (OA), and one including therapeutic doses of AOM and OA, as well as an AOM dose below therapeutic threshold (control arm). AOM was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD =-0.65, 95% CI =-0.90 to -0.41, n=1,126). However, PANSS total scores did not differ significantly between pooled AOM and OA groups. The pooled AOM group showed significantly lower incidence of all-cause discontinuation (RR =0.54, 95% CI =0.41-0.71, n=1,139, NNH =4) and inefficacy (RR =0.28, 95% CI =0.21-0.38, n=1,139, NNH =5) than placebo, but was not superior to placebo regarding discontinuation due to adverse events (AEs) or death. The AOM group exhibited a lower incidence of all-cause discontinuation than OA (RR =0.78, 95% CI =0.64-0.95, n=986, NNH =14), but there were no intergroup differences in discontinuation due to inefficacy, AEs, or death. There were no significant differences in extrapyramidal symptoms scale scores between AOM and placebo or between AOM and OA. AOM resulted in higher weight gain than placebo (SMD =0.41, 95% CI =0.18-0.64, n=734) but lower than OA (SMD =-0.16, 95% CI =-0.29 to -0.02, n=847). AOM has antipsychotic efficacy and low risk of discontinuation due to AEs.


Neodymium yttrium aluminum garnet laser treatment of hemobilia via a percutaneous biliary catheter track.
The authors describe the use of neodymium yttrium aluminum garnet laser introduced via a percutaneous catheter track for photocoagulation of a bleeding bile duct tumor.


Cytotoxic and genotoxic properties of tert.-butyl-p-quinone (TBQ) in an in vitro assay system with Chinese hamster V79 cells and in strain D7 of Saccharomyces cerevisiae.
tert.-Butyl-p-quinone (TBQ), a major metabolite of the phenolic antioxidant tert.-butyl-4-hydroxyanisole (BHA), was examined for cytotoxic and genotoxic properties in an in vitro assay system with Chinese hamster V79 cells and in diploid strain D7 of Saccharomyces cerevisiae. TBQ was prepared from BHA by oxidative demethylation with sodium nitrite at low pH. Spectroscopic analyses identified the crystalline reaction product as TBQ with a purity close to 100%. Cytotoxicity of TBQ was determined by cloning efficiency in the absence of hepatocyte activation. TBQ reduced colony size of V79 cells at 0.4 micrograms/ml, prevented growth of 50% of the cells at 0.6 micrograms/ml, and was lethal to 100% of the cells at concentrations above 1.0 micrograms/ml. TBQ was 6-7 times more cytotoxic to V79 cells than TBHQ, a related BHA metabolite, and 100 times more cytotoxic than BHA. At dose levels of 0.2, 0.4 and 0.6 micrograms/ml of medium, TBQ did not increase significantly the frequency of sister-chromatid exchanges (SCE) in V79 cells and did not consistently increase the frequency of mutation to thioguanine resistance (TGR) at the hgprt gene locus either alone or with activation by rat hepatocytes. Incubation with TBQ for 4 h at pH 3.6 without activation resulted in only small increases in the frequency of gene conversion and reverse mutation in strain D7 of Saccharomyces cerevisiae. However, exposure to TBQ alone in growth medium for 24 h, produced inconsistent results. From these studies it was concluded that TBQ was cytotoxic but not genotoxic to V79 cells; and may be weakly genotoxic to strain D7 of S. cerevisiae.


Multidose cardioplegia in a complex arterial switch procedure.
Integrated cardioplegia techniques have gained wide acceptance by surgeons performing adult cardiac surgery, because patients being referred are likely to have poor ventricular function and energy-depleted hearts. In addition, the increasing complexity of available procedures has led to an increased threat of reperfusion injury and calcium contracture ("stone heart") after prolonged ischemia. In this report, we describe the case of a newborn with transposition of the great arteries that survived almost 6 hours of ischemic time and has normal ventricular function postoperatively. We attribute this outcome to the myocardial protection employed throughout the procedure which allowed successful correction of a technical problem.


Secular trends in fitness, moderate-to-vigorous physical activity, and TV-viewing among first grade school children of Crete, Greece between 1992/93 and 2006/07.
To assess secular changes in physical fitness (PF), moderate-to-vigorous-physical activity (MVPA) and TV-viewing in 1st-grade children from Crete, Greece. Cross-sectional cohorts examined in academic years 1992/93 and 2006/07. Two representative samples of children, aged 5.9-7.8 years, were studied during 1992/93 (N=606) and 2006/07 (N=361). PF (sit-and-reach, standing-broad-jump, sit-ups and 20 m-shuttle-run-test) was assessed by the European-PF test battery and MVPA by a physical activity (PA) questionnaire. Data on the frequency of TV-viewing was also collected. Between 1992/93 and 2006/07, there was a significant increase in all fitness tests in both genders (P<0.001) and in MVPA in boys (76.5 min/week vs. 38.7 min/week, P<0.001). Time spent watching TV on weekdays was significantly more in both genders in 2006/07, compared to 1992/93 (P<0.001). In 2006/07, active boys and active girls spent more time in MVPA than active boys and girls in 1992/93 (P<0.001). Significantly higher proportions of boys and girls engaged in vigorous activities in 2006/07, than 1992/93 (P<0.001 and P=0.027, respectively). A significant increase in physical and cardiorespiratory fitness in both genders and MVPA in boys was observed in children from Crete between 1992/93 and 2006/07. The increase in weekday TV-viewing, despite being parallel to an increase in leisure-time MVPA, could have an unfavorable effect on health and should be tackled in future interventions in this population. Dietary, anthropometric and biochemical indices should also be investigated to assess their impact on the secular changes in physical fitness and activity observed in this sample of children.


Behavioral predictors of household food-safety practices during the COVID-19 pandemic: Extending the theory of planned behavior.
The epidemiological scenario of COVID-19, social distancing, and business restrictions has increased food preparation and consumption at home. Food mishandling at home can significantly raise the risk of foodborne diseases. This study investigates food-mishandling behavior predictors by applying the extended theory of planned behavior (TPB), with the addition of knowledge and risk perception, to households during the COVID-19 pandemic. One thousand and sixty-eight consumers (n = 1068) in Brazil participated in this study before the COVID-19 vaccination period. Data were collected using an online questionnaire with 40 questions and different anchors; they were analyzed using structural equation modeling. The following original TPB factors positively affected the intention to implement safe food-handling practices: attitude (p < 0.001), perceived behavioral control (p < 0.001), and subjective norms (p < 0.001). More robust effects of attitude and perceived behavioral control on intention were also observed. Although food-safety knowledge did not affect intention (p = 0.30), it positively affected the other TPB factors. Perceived risk positively affected all TPB factors. The results of this study support the usefulness of TPB and its extension, providing evidence that public-health crises can contribute to changes in food-safety-related consumer behavior.


Classes, activity and chronicity indices, and alpha-smooth muscle actin expression as prognostic parameters in lupus nephritis outcome.
Renal biopsies of 86 patients with lupus nephritis were assessed according to the WHO classification, and according to activity and chronicity indices. The aim of the present study was to correlate clinical, and histological features (WHO class, activity and chronicity indices, and alpha-SM actin expression) with the progression of lupus nephritis, and identify the pathological role of alpha-SM actin in lupus nephritis. The median follow-up time was 75.5 +/- 57.3 months. Two patients were grouped as WHO class IIa lupus nephritis, eight patients as class IIb, 16 patients as class III, 25 patients as class IV, 15 patients as class V, and 19 patients as mixed pattern lupus nephritis. Sex, age, race, and the alpha-SM actin expression in glomeruli and tubulo-interstitial area in WHO class III and IV showed no correlation with clinical follow-up outcome of lupus nephritis. Unfavorable clinical outcome of lupus nephritis was correlated with WHO class IV compared to the other classes, and with the chronicity index in WHO class III patients.


Malignant mesenchymoma of the liver in children.
Four children, aged 5 to 13 years, were treated for malignant mesenchymoma of the liver. Two survived longer than 5 years with complete resection and adjuvant chemotherapy. Two children who had incomplete resection with microscopic residual mesenchymoma both had tumor recurrence and died of disease progression despite radiation therapy and chemotherapy. Although previous reports emphasize a poor prognosis for children with this tumor, our experience would indicate that long-term survival can be achieved using complete surgical extirpation and adjuvant chemotherapy.


Structural investigations by extended X-ray absorption fine structure spectroscopy of the iron center of mitochondrial aconitase in higher plant cells.
We have obtained iron K-edge extended x-ray absorption fine structure spectra of the plant mitochondrial aconitase in its active state, in the presence (aconitase (+)) and absence (aconitase (-)) of the substrate citrate. Analysis of the data indicates that oxygens are present in the first coordination shell, at an average Fe-O distance of 1.96/1.98 A (aconitase (+)/aconitase(-)). Part of these oxygens is provided by the citrate, which binds at 1.99 A from the iron in aconitase (+). The second shell (sulfur) contribution is split and is consistent with Fe-S distances of 2.30/2.29 and 2.56/2.59 A, and the third shell (iron) is consistent with an Fe-Fe distance of 2.83/2.84 A. Both Fe-S and Fe-Fe distances are longer than similar distances found in most Fe-S centers. A strong scattering at approximately 5 A has been identified as originating from an iron atom which is near to, but not part of, the Fe-S cluster. These data indicate that active plant mitochondrial aconitase contains a novel type of iron center.


Suppression of pacemaker activity by Ginkgo biloba extract and its main constituent, bilobalide in rat sino-atrial nodal cells.
Effects of Ginkgo biloba extract (GBE) and bilobalide (a main constituent) on the pacemaker activity and the underlying ionic currents in rat sino-atrial (SA) nodal cells were investigated using patch-clamp techniques. Both GBE and bilobalide depressed the pacemaker activity in a concentration-dependent manner. At both 0.03 mg/ml GBE and 0.3 microM bilobalide, a negative chronotropic effect was produced. Dysrhythmias often occurred. The L-type Ca(2+) current (I(Ca)) and the hyperpolarization-activated inward current (I(f)) decreased by 69.7+/-3.2% (n=6, P<0.001) and by 12.6+/-2.1% (n=7, P<0.05) at 0.03 mg/ml GBE, and by 51.2+/-3.3% (n=6, P<0.01) and by 19.8+/-2.2 % (n=6, P<0.05) at 0.3 microM bilobalide, respectively. The delayed rectifier K(+) current (I(K)) also decreased. The inhibition was 12.3+/-2.0% (n=6, P<0.05) at 0.03 mg/ml GBE, and was 28.0+/-2.9% (n=6, P<0.05) at 0.3 microM bilobalide. These results indicate that cardiac ionic channels contributing to the pacemaking are highly sensitive to GBE and bilobalide, which can sufficiently modify the spontaneous activity in rat SA nodal cells.


Construction of a constitutively expressed homo-fermentative pathway in Lactobacillus brevis.
Lactobacillus brevis is a promising lactic acid producing strain that simultaneously utilizes glucose and xylose from lignocellulosic hydrolysate without carbon catabolic repression and inhibition. The production of by-products acetic acid and ethanol has been the major drawback of this strain. Two genes, pfkA (fructose-6-phosphate kinase [PFK]) and fbaA (fructose-1,6-biphosphate aldolase [FBA]), that encode the key enzymes of the EMP/glycolytic pathway from Lactobacillus rhamnosus, were fused to the downstream of the strong promoter P32 and expressed in L. brevis s3f4 as a strategy to minimize the formation of by-products. By expressing the two enzymes, a homo-fermentative pathway for lactic acid production was constructed. The lactic acid yields achieved from glucose in the transformants were 1.12 and 1.16 mol/mol, which is higher than that of the native strain (0.74 mol/mol). However, the lactic acid yield from xylose in the transformants stayed the same as that of the native strain. Enzyme assay indicated that the activity of the foreign protein FBA in the transformants was much higher than that of the native strains, but was ten times lower than that in L. rhamnosus. This result was consistent with the metabolic flux analysis, which indicated that the conversion efficiency of the expressed PFK and FBA was somewhat low. Less than 20 % of the carbons accumulated in the form of fructose-6-phosphate were converted into glyceraldehyde-3-phosphate (GAP) by the expressed PFK and FBA. Metabolic flux analysis also indicated that the enzyme phosphoketolase (XPK) played an important role in splitting the carbon flow from the pentose phosphate pathway to the phosphoketolase pathway. This study suggested that the lactic acid yield of L. brevis could be improved by constructing a homo-fermentative pathway.


The hypothalamus.
The hypothalamus is an integral part of the neuroendocrine system. The anatomy, embryologic development, and normal function of the hypothalamus are described here. Pathophysiology of congenital abnormalities and brain injury is discussed and a case study examined. In addition, nursing implications of caring for such an infant are addressed.


Benzo(a)pyrene induced structural and functional modifications in lung cystatin.
Cystatins are thiol proteinase inhibitors ubiquitously present in the mammalian body. They serve a protective function to regulate the activities of endogenous proteinases, which may cause uncontrolled proteolysis and damage. In the present study, the effect of benzo(a)pyrene [BaP] on lung cystatin was studied to explore the hazardous effects of environmental pollutant on structural and functional integrity of the protein. The basic binding interaction was studied by UV-absorption, FT-IR, and fluorescence spectroscopy. The enhancement of total protein fluorescence with a red shift of 5 nm suggests structural scratch of lung cystatin by benzo(a)pyrene. Further, ANS binding studies reaffirm the unfolding of the thiol protease inhibitor (GLC-I) after treating with benzo(a)pyrene. The results of FT-IR spectroscopy reflect perturbation of the secondary conformation (alpha-helix to β-sheet) in goat lung cystatin on interaction with BaP. Finally, functional inactivation of cystatin on association with BaP was checked by its papain inhibitory activity. Benzo(a)pyrene (10 μM) caused complete inactivation of goat lung cystatin. Benzo(a)pyrene-induced loss of structure and function in the thiol protease inhibitor could provide a caution for lung injury caused by the pollutants and smokers.


Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia.
Ph-positive leukemias are caused by the aberrant fusion of the BCR and ABL genes. Nilotinib is a selective Bcr/Abl tyrosine kinase inhibitor related to imatinib, which is widely used to treat chronic myelogenous leukemia. Because Ph-positive acute lymphoblastic leukemia only responds transiently to imatinib therapy, we have used mouse models to test the efficacy of nilotinib against lymphoblastic leukemia caused by the P190 form of Bcr/Abl. After transplant of 10,000 highly malignant leukemic cells into compatible recipients, untreated mice succumbed to leukemia within 21 days, whereas mice treated with 75 mg/kg nilotinib survived significantly longer. We examined cells from mice that developed leukemia while under treatment for Bcr/Abl kinase domain point mutations but these were not detected. In addition, culture of such cells ex vivo showed that they were as sensitive as the parental cell line to nilotinib but that the presence of stromal support allowed resistant cells to grow out. Nilotinib also exhibited impressive anti-leukemia activity in P190 Bcr/Abl transgenic mice that had developed overt leukemia/lymphoma masses and that otherwise would have been expected to die within 7 days. Visible lymphoma masses disappeared within six days of treatment and leukemic cell numbers in peripheral blood were significantly reduced. Treated mice survived more than 30 days. These results show that nilotinib has very impressive anti-leukemia activity but that lymphoblastic leukemia cells can become unresponsive to it both in vitro and in vivo through mechanisms that appear to be Bcr/Abl independent.


Serum levels of corticosterone and 18-hydroxy-11-deoxycorticosterone in the female rat at the high and low points of the circadian rhythm.
Serum corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-hydroxy-DOC) levels were determined in female rats at the high (1800 h) and low (0600 h) points of the circadian rhythm. In order to carry out these studies, a rapid and accurate non-chromatographic radioimmunoassay method was developed for the measurement of 18-hydroxy-DOC in peripheral blood and similar methodology was used for the B assay. In quiescent rats both steroids were dramatically elevated at 1800 h as compared to 0600 h. The serum levels of B and 18-hydroxy-DOC determined at 1800 h fifteen minutes following stress did not differ significantly from the levels determined following a similar stress at 0600 h. There was a good correlation (r = 0.91) between the levels of B and 18-hydroxy-DOC and it appears that both steroids are regulated by ACTH.


Application of time-resolved fluoroimmunoassay (TR-FIA) for the diagnosis of invasive amoebiasis.
A development of solid-phase immunoassay, time-resolved fluoroimmunoassay (TR-FIA), was used for anti-amoebic antibodies. The test used a chelate of the lanthanide europium as label. The long fluorescent life-time and large Stoke's shift of europium chelates permit sensitive detection in a time-resolved fluorimeter. The TR-FIA was compared with counterimmunoelectrophoresis (CIEP), indirect haemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) using 61 sera from patients with invasive amoebiasis, 344 sera submitted routinely for amoebic serology without clinical data, 125 sera from patients with diseases other than amoebiasis, and 86 sera from "healthy" individuals. Overall agreement between TR-FIA and ELISA was 97.1%, between TR-FIA and IHA 93.2%, and between TR-FIA and CIEP 94.0%. Sensitivity, specificity and positive and negative predictive values were calculated to compare the 4 diagnostic methods in invasive amoebiasis. TR-FIA showed a higher validity than other methods. The application of such highly detectable labels in immunometric assays promises to open up entirely new areas of research.


[Study on the pharmacokinetics Oxytropis falcate total flavonoids ointment in rats].
To study the pharmacokinetics of Oxytropis falcate total flavonoids ointment after transdermal administration in rats. The content of 2',4'-dihydroxychalcone (TFC) in plasma was determined by high performance liquid chromatography. The concentration was determined at various time and the data was processed by 3P97. TFC behaved as a one-compartment and a two-compartment model after transdermal administration of total Oxytropis falcate total flavonoids ointment and solution, respectively. And the C(max) of ointment was improved about 3 times compared with that of the solution. The results show that the ointment possesses sustained release property and significantly prolong the degradation half life of TFC. The ointment is benefit to improve the analgesic and anti-inflammatory activity after transdermal administration.


CDC25-dependent induction of inositol 1,4,5-trisphosphate and diacylglycerol in Saccharomyces cerevisiae by nitrogen.
The addition of ammonium sulfate to starved yeast cells leads to a 3- to 4-fold rapid increase of the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), the products of phosphoinositide-specific phospholipase C (PI-PLC). This response is reduced by dissecting the RAS-activating Cdc25 protein, and is completely abolished by the cdc25-1 mutation even at permissive temperature. Starved cdc25-1 mutant cells have a strongly reduced IP3 content, but an at least 10-fold increased DAG level compared to the isogenic wild-type strain. NH4 does not stimulate cAMP synthesis, and glucose does not induce IP3 and DAG. Our data suggest that the Cdc25 protein controls a nitrogen-specific signalling pathway involving the effector PI-PLC, in addition to the glucose-induced activation of adenylyl cyclase (AC).


LncRNA NEAT1/microRNA-129-5p/SOCS2 axis regulates liver fibrosis in alcoholic steatohepatitis.
Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to play an essential role in non-alcoholic fatty liver disease. However, the role of NEAT1 in regulation of alcoholic steatohepatitis (ASH) remains largely unknown. This study aims to explore the role of NEAT1 in ASH by mediating microRNA-129-5p (miR-129-5p) targeting suppressor of cytokine signaling 2 (SOCS2). NEAT1, miR-129-5p and SOCS2 expression in serum of ASH patients were assessed. In the in vitro cellular experiment, we transfected siRNAs, oligonucleotides or plasmids into ethanol-induced AML-12 mouse hepatocytes to alter NEAT1 and miR-129-5p expression, and inflammatory factors and lipid content were determined. In the in vivo animal experiment, we injected lentiviruses carrying siRNAs, oligonucleotides or plasmids onto ASH mice (ASH induced by feeding mice a Lieber-DeCarli ethanol diet) to alter NEAT1 and miR-129-5p expression through the tail vein. Serum liver function, blood lipids and inflammatory factors were detected; liver histopathology, liver cell apoptosis, and fibrosis were observed. The relationship between NEAT1 and miR-129-5p, or between miR-129-5p and SOCS2 was verified. MiR-129-5p was reduced while NEAT1 and SOCS2 were elevated in ASH. Inhibited NEAT1 or elevated miR-129-5p suppressed the elevated lipid metabolism and restrained inflammation reaction in ethanol-stimulated AML-12 cells. The promoted miR-129-5p and inhibited NEAT1 could improve the liver function and repress blood lipid, inflammation reaction, hepatocyte apoptosis and liver fibrosis in ethanol-induced ASH mice. Furthermore, NEAT1 could negatively regulate miR-129-5p to target SOCS2. We have found that the inhibited NEAT1 could suppress liver fibrosis in ASH mice by promoting miR-129-5p and restraining SOCS2, thereby decelerating the development of ASH.


A double dealing tale of p63: an oncogene or a tumor suppressor.
As a member of tumor suppressor p53 family, p63, a gene encoding versatile protein variant, has been documented to correlate with cancer formation and progression, though it is rarely mutated in cancer patients. However, it has long been controversial on whether p63 is an oncogene or a tumor suppressor. Here, we comprehensively reviewed reports on roles of p63 in development, tumorigenesis and tumor progression. According to data from molecular cell biology, genetic models and clinic research, we conclude that p63 may act as either an oncogene or a tumor suppressor gene in different scenarios: TA isoforms of p63 gene are generally tumor-suppressive through repressing cell proliferation, survival and metastasis; ΔN isoforms, however, may initiate tumorigenesis via promoting cell proliferation and survival, but inhibit tumor metastasis and progression; effects of p63 on tumor formation and progression depend on the context of the whole p53 family, and either amplification or loss of p63 gene locus can break the balance to cause tumorigenesis.


Immune responses of sheep to the parasitic nematode Trichostrongylus colubriformis: infections in Thiry-Vella loops.
Some aspects of the local immune response to nematode infection were examined by introducing fourth-stage Trichostrongylus colubriformis larvae into Thiry-Vella loops in worm-free and T. colubriformis-resistant sheep. Approximately 15% of the larvae introduced into the worm-free sheep survived and matured into adult worms, whereas less than 1% survival in resistant sheep. The amount of IgG1, IgG2, IgM and albumin discharged from loops in worm-free but not resistant sheep all increased following infection with larvae. Secretions from resistant sheep contained approximately three times as much IgA as secretions from the worm-free group and, in addition, their plasma IgG1 level was significantly higher. Antibodies against T. columbriformis were found in both plasma and intestinal secretions, the highest titres being found in the resistant sheep. During worm expulsion from loops in the resistant sheep neither immunoglobulin levels nor antibody titres in the secretions increased significantly.


Electrophysiologic changes in the lateral and basal amygdaloid nuclei in temporal lobe epilepsy: an in vitro study in epileptic rats.
The functional consequences of neuronal loss during epileptogenesis in the lateral and basal amygdaloid nuclei are poorly understood. The present study tested the hypothesis that electrical responsiveness varies in different amygdaloid nuclei in the chronically epileptic amygdala. Further, we examined the amygdaloid region most prone to seizure initiation. Epileptogenesis was triggered in 20 rats by inducing status epilepticus (SE) with electrical stimulation of the lateral nucleus of the amygdala. Electrode-implanted non-stimulated rats served as controls. The occurrence and duration of spontaneous seizures were monitored with video-electroencephalography (EEG) at 8-9 weeks after SE. Thereafter, animals were killed and extracellular recordings were made from slices of both amygdalas. In the lateral nucleus of epileptic animals, the frequency of spontaneous responses was reduced compared with controls (P < 0.05). The amplitudes of evoked field responses were reduced (P < 0.01), whereas paired pulse (PP) facilitation was enhanced (P < or = 0.05). In the basal nucleus of the epileptic animals, PP facilitation was enhanced (P < 0.05) and sensitivity to 4-aminopyridine (4-AP)-induced epileptiform activity was increased compared with controls (P < 0.05). In the epileptic animals, the basal nucleus was also more sensitive than the lateral nucleus to 4-AP-induced epileptiform activity (P < 0.05). Correlation analysis indicated that longer SE duration was associated with longer half widths (P = 0.001) and smaller slopes (P < 0.05) of evoked responses as well as with attenuated PP facilitation (P<0.01). Moreover, a higher frequency of spontaneous seizures was associated with longer half widths (P < 0.05) and smaller slopes (P < 0.05) of evoked responses as well as with enhanced PP facilitation (P < 0.05). These data suggest that there is a reduced release of glutamate and reduced inhibition in the lateral and basal amygdaloid nuclei in epileptic animals. Further, the basal nucleus is more prone to epileptic activity than the lateral nucleus. Finally, the severity of SE and spontaneous seizures in vivo is associated with electrophysiologic alterations in vitro.


Target search and recognition mechanisms of glycosylase AlkD revealed by scanning FRET-FCS and Markov state models.
DNA glycosylase is responsible for repairing DNA damage to maintain the genome stability and integrity. However, how glycosylase can efficiently and accurately recognize DNA lesions across the enormous DNA genome remains elusive. It has been hypothesized that glycosylase translocates along the DNA by alternating between a fast but low-accuracy diffusion mode and a slow but high-accuracy mode when searching for DNA lesions. However, the slow mode has not been successfully characterized due to the limitation in the spatial and temporal resolutions of current experimental techniques. Using a newly developed scanning fluorescence resonance energy transfer (FRET)-fluorescence correlation spectroscopy (FCS) platform, we were able to observe both slow and fast modes of glycosylase AlkD translocating on double-stranded DNA (dsDNA), reaching the temporal resolution of microsecond and spatial resolution of subnanometer. The underlying molecular mechanism of the slow mode was further elucidated by Markov state model built from extensive all-atom molecular dynamics simulations. We found that in the slow mode, AlkD follows an asymmetric diffusion pathway, i.e., rotation followed by translation. Furthermore, the essential role of Y27 in AlkD diffusion dynamics was identified both experimentally and computationally. Our results provided mechanistic insights on how conformational dynamics of AlkD-dsDNA complex coordinate different diffusion modes to accomplish the search for DNA lesions with high efficiency and accuracy. We anticipate that the mechanism adopted by AlkD to search for DNA lesions could be a general one utilized by other glycosylases and DNA binding proteins.


Costing the cascade: estimating the cost of increased obstetric intervention in childbirth using population data.
To estimate the cost of "the cascade" of obstetric interventions introduced during labour for low risk women. A cost formula derived from population data. New South Wales, Australia. All 171,157 women having a live baby during 1996 and 1997. Four groups of interventions that occur during labour were identified. A cost model was constructed using the known age-adjusted rates for low risk women having one of three birth outcomes following these pre-specified interventions. Costs were based on statewide averages for the cost of labour and birth in hospital. The outcome measure is an "average cost unit per woman" for low risk women, predicted by the level of intervention during labour. Obstetric care is classified as either private obstetric care in a private or public hospital, or routine public hospital care. The relative cost of birth increased by up to 50% for low risk primiparous women and up to 36% for low risk multiparous women as labour interventions accumulated. An epidural was associated with a sharp increase in cost of up to 32% for some primiparous low risk women, and up to 36% for some multiparous low risk women. Private obstetric care increased the overall relative cost by 9% for primiparous low risk women and 4% for multiparous low risk women. The initiation of a cascade of obstetric interventions during labour for low risk women is costly to the health system. Private obstetric care adds further to the cost of care for low risk women.


Comparison of the subgingival temperature of smokers and nonsmokers in healthy and diseased sites of gingiva in association with sublingual body temperature.
To compare the subgingival temperature in healthy and diseased sites of gingiva in smokers and non-smokers using a modified digital thermometer. To also find whether subgingival temperature measurements can be used as reliable indicator of periodontal disease activity. Participants for this study comprised 50 males, 25 smokers and 25 non-smokers with mild to moderate periodontitis, aged 25-40 years and had four maxillary incisor teeth (12, 11, 21, 22) intact. For each participant, six sites around each tooth were examined. Hence, a total of 24 sites for each participant were examined. The clinical parameters used were probing pocket depth and gingival bleeding index. Sublingual and subgingival temperature was found to be warmer in smokers compared to non-smokers. Subgingival temperature was more in diseased sites than healthy sites in both smokers and non-smokers. The mean temperature differential of diseased sites in smokers was more compared to non-smokers. Mean probing pocket depth was higher in smokers, but bleeding sites were less. Subgingival temperature measurement was found to be a good indicator of periodontal disease activity.


Association between platelet distribution width and poor outcome of acute ischemic stroke after intravenous thrombolysis.
The platelet distribution width (PDW) reflects the status of platelet activity and may be useful for early predictions of the clinical outcome of stroke patients. The purpose of the study was to determine the associations between PDW and clinical outcomes after intravenous thrombolysis in stroke patients. Acute ischemic stroke patients who received intravenous treatment with recombinant tissue-type plasminogen activator were selected for inclusion in the retrospective cohort of this study. The relations between PDW at admission and clinical outcomes were analyzed, including a poor outcome as assessed using the modified Rankin Scale at 3 months, early neurological improvement, and any hemorrhage. The effect of PDW at admission on a poor outcome at 3 months was analyzed using a multivariable logistic regression model with adjustment for potential confounders. The optimal PDW cutoff for predicting poor outcome at 3 months was determined by analyzing the receiver operating characteristics curve. PDW was significantly higher for a good outcome than a poor outcome (p=0.005), with median (interquartile range) values of 16.2 (13.2-17.2) and 13.6 (12.5-15.9), respectively. PDW was also higher in patients with early neurological improvement than in patients without improvement (p=0.020) and did not differ between hemorrhage and nonhemorrhage patients. The association between PDW <16.05% and poor outcome remained in a multivariable logistic regression analysis, with an OR of 6.68 and a 95% CI of 1.69-26.49 (p=0.007). Results suggest a novel hypothesis that a lower PDW may be related with a poor outcome at 3 months after intravenous thrombolysis in acute ischemic stroke patients.


The CHAIN program: forging evolutionary links to underlying mechanisms.
Proteins evolve new functions by modifying and extending the molecular machinery of an ancestral protein. Such changes show up as divergent sequence patterns, which are conserved in descendent proteins that maintain the divergent function. After multiply-aligning a set of input sequences, the CHAIN program partitions the sequences into two functionally divergent groups and then outputs an alignment that is annotated to reveal the selective pressures imposed on divergent residue positions. If atomic coordinates are also provided, hydrogen bonds and other atomic interactions associated with various categories of divergent residues are graphically displayed. Such analyses establish links between protein evolutionary divergence and functionally crucial atomic features and, as a result, can suggest plausible molecular mechanisms for experimental testing. This is illustrated here by its application to bacterial clamp-loader ATPases.


Hyaluronic acid in the pulmonary secretions of patients with alveolar proteinosis.
Hyaluronic acid was the only glycosaminoglycan found in the pulmonary secretions of patients with alveolar proteinosis. The compound gave a hexouronate/hexosamine molar ratio of about 1:1. Glucosamine constituted over 98% of the hexosamines, the remaining being galactosamine. It moved as a single spot with the mobility of standard hyaluronic acid on cellulose acetate electrophoresis, and this spot disappeared after digestion with hyaluronidase. It was associated with small amounts of proteins, the major amino acids of which are aspartic acid, glutamic acid, glycine, alanine, and leucine.


Mechanism of phospholipase A2 action toward mixed micelles of detergent and phospholipids.
Phospholipase A2 from cobra venom (Naja naja naja) is a homogeneous, heat-stable enzyme that has a monomer molecular weight of only 11,000 and contains one histidine and one tryptophan residue. This enzyme acts optimally on phospholipids contained in mixed micelles with the nonionic detergent Triton X-100; the interactions of this detergent with phospholipid in the mixed micelles have been elucidated with 1H- and 13C-NMR. In reacting, the enzyme first associates with the mixed micelle and then exhibits "surface dilution kinetics" in its reaction with substrate. Recent studies show that various reagents completely inactivate this phospholipase A2 resulting in the modification of the histidine in only one-half of the enzyme molecules. These results suggest that the histidine residue, which is essential for activity, exhibits "half-site reactivity." These and other experiments are interpreted in terms of a model that suggests that the monomeric enzyme forms an asymmetric dimer or higher order aggregate at the lipid-water interface. The studies which are described on the interaction of the phospholipase A2 with mixed micelles serve as a general model system for understanding detergent effects on the assay of lipid enzymes.


Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab.
The type I interferon (IFN) signaling pathway is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Anifrolumab is a monoclonal antibody that targets the type I IFN receptor subunit 1. Anifrolumab is approved in several countries for patients with moderate to severe SLE receiving standard therapy. The approved dosing regimen of anifrolumab is a 300-mg dose administered intravenously every 4 weeks; this was initially based on the results of the Phase 2b MUSE and further confirmed in the Phase 3 TULIP-1 and TULIP-2 trials, in which anifrolumab 300-mg treatment was associated with clinically meaningful improvements in disease activity with an acceptable safety profile. There have been several published analyses of the pharmacokinetic and pharmacodynamic profile of anifrolumab, including a population-pharmacokinetic analysis of 5 clinical studies of healthy volunteers and patients with SLE, in which body weight and type I IFN gene expression were significant covariates identified for anifrolumab exposure and clearance. Additionally, the pooled Phase 3 SLE population has been used to evaluate how serum exposure may be related to clinical responses, safety risks, and pharmacodynamic effects of the 21-gene type I IFN gene signature (21-IFNGS). The relevance of 21-IFNGS with regard to clinical efficacy outcomes has also been analyzed. Herein, the clinical pharmacokinetics, pharmacodynamics, and immunogenicity of anifrolumab as well as results of population-pharmacokinetics and exposure-response analyses are reviewed.


Global induced motion and visual stability in an optic flow illusion.
When an expansion flow field of moving dots is overlapped by planar motion, observers perceive an illusory displacement of the focus of expansion (FOE) in the direction of the planar motion (Duffy and Wurtz, Vision Research, 1993;33:1481-1490). The illusion may be a consequence of induced motion, wherein an induced component of motion relative to planar dots is added to the motions of expansion dots to produce the FOE shift. While such a process could be mediated by local 'center-surround' receptive fields, the effect could also be due to a higher level process which detects and subtracts large-field planar motion from the flow field. We probed the mechanisms underlying this illusion by adding varying amounts of rotation to the expansion stimulus, and by varying the speed and size of the planar motion field. The introduction of rotation into the stimulus produces an illusory shift in a direction perpendicular to the planar motion. Larger FOE shifts were perceived for greater speeds and sizes of planar motion fields, although the speed effect saturated at high speeds. While the illusion appears to share a common mechanism with center-surround induced motion, our results also point to involvement of a more global mechanism that subtracts coherent planar motion from the flow field. Such a process might help to maintain visual stability during eye movements.


State-dependent attention modulation of human primary visual cortex: a high density ERP study.
Converging electrophysiological and brain-imaging results show that sensory processing in V1 can be modulated by attention. In this study, we tested the prediction that this early filtering effect depends on the current affective state of the participant. We recorded visual evoked potentials (VEPs) to visual peripheral distractors while participants performed a demanding task at fixation, whose perceptual load was manipulated in a parametric fashion. Crucially, levels of negative affect were either increased or decreased independently of changes in perceptual load. Concurrent psychophysiological measurements and self-report scales confirmed that changes in emotional state were effective. In the control condition, ERP results showed that the C1 component generated in response to the exact same peripheral distractors systematically varied in amplitude with the amount of perceptual load imposed at fixation, being larger when perceptual load decreased. However, this early modulatory effect in V1 was disrupted when participants transiently experienced increased state anxiety, resulting in a decreased C1 amplitude even though task load at fixation remained low. These results suggest that early bottom-up processing in V1 is not only influenced by the amount of attention resources available, but also by the current internal state of the participant.


Which exposure stage (gestation or lactation) is more vulnerable to atrazine toxicity? Studies on mouse dams and their pups.
Either during gestation or lactation, the experimental mouse dams received one of the following treatments: (a) diet free of pesticide; (b) diet enriched with atrazine (ATZ); 31.0 μg kg-1; (c) diet free of pesticide + oral vitamin E (α-tocopherol; 200 mg kg-1 per mouse); and (d) diet enriched with ATZ (31.0 μg kg-1) + oral vitamin E (200 mg kg-1 per mouse). At the weaning, pups and dams were killed and selected organs and blood samples were collected for analyses. Compared with the control results, ATZ induced alteration in a number of biochemical and histopathological parameters either in the dams or their offspring. The ameliorative effect of vitamin E, based on estimating the "Ameliorative Index; AI" to malondialdehyde (MDA) and superoxide dismutase (SOD) ranged between 0.95 and 1.06 (≈1.0) for the dams and the pups either in gestational or lactational exposure routes. In general, the mouse pups were more vulnerable to ATZ toxicity than their mothers and exposure during gestation was suggested to be more effective than during lactation. The findings may support the need to further investigating the adverse effects of exposure to low doses of commonly used pesticides, especially during pregnancy and breast-feeding as well as effects on newborn child.


Decreased adiposity and enhanced glucose tolerance in shikonin treated mice.
Obesity represents a major public health problem, and identifying natural compounds that modulate energy balance and glucose homeostasis is of interest for combating obesity and its associated disorders. The naphthoquinone shikonin has diverse beneficial properties including anti-inflammatory, anti-oxidant, and anti-microbial effects. The objective of this study is to investigate the effects of shikonin on adiposity and glucose homeostasis. The metabolic effects of shikonin treatment on mice fed regular chow or challenged with a high-fat diet (HFD) were determined. Shikonin treated mice fed regular chow exhibited improved glucose tolerance compared with controls. In addition, shikonin treated mice fed HFD displayed decreased weight gain and resistance to HFD-induced glucose intolerance. Further, shikonin treatment decreased HFD-induced hepatic dyslipidemia. These findings correlated with enhanced hepatic insulin signaling in shikonin treated mice as evidenced by increased tyrosyl phosphorylation of the insulin receptor and enhanced downstream signaling. These studies identify shikonin as a potential regulator of systemic glucose tolerance, energy balance, and adiposity in vivo.


Ultra-sensitive and fast optical detection of the spike protein of the SARS-CoV-2 using AgNPs/SiNWs nanohybrid based sensors.
Severe acute respiratory syndrome SARS-CoV-2 virus led to notable challenges amongst researchers in view of development of new and fast detecting techniques. In this regard, surface-enhanced Raman spectroscopy (SERS) technique, providing a fingerprint characteristic for each material, would be an interesting approach. The current study encompasses the fabrication of a SERS sensor to study the SARS-CoV-2 S1 (RBD) spike protein of the SARS-CoV-2 virus family. The SERS sensor consists of a silicon nanowires (SiNWs) substrate decorated with plasmonic silver nanoparticles (AgNPs). Both SiNWs fabrication and AgNPs decoration were achieved by a relatively simple wet chemical processing method. The study deliberately projects the factors that influence the growth of silicon nanowires, uniform decoration of AgNPs onto the SiNWs matrix along with detection of Rhodamine-6G (R6G) to optimize the best conditions for enhanced sensing of the spike protein. Increasing the time period of etching process resulted in enhanced SiNWs' length from 0.55 to 7.34 µm. Furthermore, the variation of the immersion time in the decoration process of AgNPs onto SiNWs ensued the optimum time period for the enhancement in the sensitivity of detection. Tremendous increase in sensitivity of R6G detection was perceived on SiNWs etched for 2 min (length=0.90 µm), followed by 30s of immersion time for their optimal decoration by AgNPs. These SiNWs/AgNPs SERS-based sensors were able to detect the spike protein at a concentration down to 9.3 × 10-12 M. Strong and dominant peaks at 1280, 1404, 1495, 1541 and 1609 cm-1 were spotted at a fraction of a minute. Moreover, direct, ultra-fast, facile, and affordable optoelectronic SiNWs/AgNPs sensors tuned to function as a biosensor for detecting the spike protein even at a trace level (pico molar concentration). The current findings hold great promise for the utilization of SERS as an innovative approach in the diagnosis domain of infections at very early stages.


Editorial: What to Do About Rigid, Repetitive Behaviors in Autism Spectrum Disorder?
Rigid, repetitive behaviors (RRBs) as a part of autism spectrum disorder (ASD) are perplexing and challenging to treat effectively. First, how is it that they associate with deficits in social communication and social interaction to create a strong symptomatic association for the DSM-5 diagnosis of ASD?1 Deficits in social communication make sense in how they define a developmental disorder, but what is the mechanism by which social interaction and RRBs connect to define the classification of ASD? Perhaps it is that, rather than by neurotransmitters or linked structural brain regions, ASD is a neural systems condition mediated by abnormalities in regionally distributed cortical networks.2.


Combination of Anterior Acetabular Coverage and Femoral Head Shape Predicts Femoroacetabular Impingement After Periacetabular Osteotomy.
Femoroacetabular impingement (FAI) after periacetabular osteotomy (PAO) may be affected by both anterior acetabular coverage and femoral head shape. This study aimed to radiographically evaluate the relationship of the combination of acetabular coverage and femoral head shape with the occurrence of FAI after curved PAO. In this study, 76 hip joints from patients with symptomatic developmental dysplasia of the hip underwent curved PAO. The relationship between the combined postoperative anterior center-edge and alpha angles (ie, the combination angle) and the occurrence of postoperative FAI was evaluated. Clinical factors and the preoperative and postoperative 3-dimensional center-edge angles, acetabular versions, femoral versions, radiographic alpha angles of the femoral head, and the combination angle were measured and compared to clinical outcomes. The modified Harris Hip Scores, University of California, Los Angeles activity scores, and acetabular coverage angles were significantly improved following curved PAO. Receiver operator characteristic curve analysis demonstrated that the combination angle over 108° may be a predictive factor for the occurrence of FAI after curved PAO. Multivariate analysis demonstrated that an age <40 years (odds ratio 6.6, 95% confidence interval 1.2-36.4, P = .037) and a combination angle <108° (odds ratio 9.2, 95% confidence interval 1.7-50.0, P = .010) were significantly associated with modified Harris Hip Scores ≧90 points. A combination angle >108° may be a predictive factor for the occurrence of FAI after curved PAO and impaired clinical outcomes. To avoid postoperative FAI, we propose that osteochondroplasty of the femoral head should be performed for patients with preoperative combination angles >90°.


Schimmelpenning syndrome: a case report and literature review.
We report a case of a male newborn with Schimmelpenning syndrome, which presented as diffuse sebaceous nevi covering the left side of the body, from the lower chin midface to the lower leg; cardiac-ocular comorbidities were also present. We present photographs of this patient's sebaceous nevi, which may assist physicians in the early diagnosis of this condition and prevent unnecessary examinations and inadequate therapies.


Pharmacokinetics of 2-methyl-9-hydroxyellipticinium acetate (NSC-264137) in cancer patients (phase I study).
In 12 cancer patients we studied the pharmacokinetics of a new antitumor compound, elliptinium, which is a quaternary ammonium derivative of ellipticine, after i.v. infusion. The main parameters were calculated by means of the ADAPT program based upon plasma concentrations and urinary elimination determined by a high performance liquid chromatographic assay and fluorescence detection. The mean apparent volume of distribution for the central compartment, V1, is 2.8 l, the total plasma clearance is 971 ml/min, with a renal clearance of 127 ml/min. The mean elimination half-life, t1/2, z, is 23.7 hr, but shows a large interindividual variation. Urinary elimination is quite low (16%), with the main part (12%) excreted in the first 24 hr. In vitro plasma protein binding (78%) was found to be independent of the concentration (0.1-5.0 micrograms/ml).


Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate.
Novel lipophilic platinum(II) complexes (LSPt-1-3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH(3) or 1R,2R-diaminocyclohexane or (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient logP was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% (T/C) at a dose of 30 mg/kg following i.p. administration. LD(50) for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.


Risk factors for healthcare-associated infection in light of two years of experience with the ECDC point prevalence survey of healthcare-associated infection and antimicrobial use in Poland.
Healthcare-associated infection (HAI) and antimicrobial resistance are two of the most important threats in contemporary medicine. The aim of this study was to evaluate independent risk factors associated with higher prevalence of HAI in a population of patients hospitalized in acute care hospitals in Poland. This study was conducted in accordance with the protocol of the European Centre for Disease Prevention and Control (ECDC) point prevalence survey of HAI and antimicrobial use. Data for 16,598 patients were collected from 50 hospitals. Independent risk factors assessed included: hospital size and type; consumption of alcohol hand rub; isolation capacity; number of beds per full-time-equivalent (FTE) infection control doctor/nurse; sex; age; hospitalization specialty; exposure to invasive procedures; and McCabe score. The highest prevalence of HAI was observed in large and teaching hospitals (6.7% and 7.4%, respectively), in children aged less than one (13.3%) and among males (7.2%). With regard to invasive procedures, the strongest association was observed for central venous catheterization (30.2%), intubation (41.6%) and urinary catheterization (17.5%). The highest prevalence of HAI was observed among patients in intensive care units (adult 39.8%, paediatric 30.8%). The lowest prevalence of HAI was observed in hospitals with one FTE infection control nurse per <200 beds (4.1%). A high prevalence of HAI combined with high exposure to risk factors among patients in paediatric and adult ICUs should result in the introduction of an HAI prevention programme across Poland.


Identification of circular RNAs in the ovarian follicles of Meishan and Duroc sows during the follicular phase.
Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that play an important role in growth and development by regulating gene expression and participating in a variety of biological processes. However, the role of circRNAs in porcine follicles remains unclear. Therefore, this study examined middle-sized ovarian follicles obtained from Meishan and Duroc sows at day 4 of the follicular phase. High-throughput RNA sequencing (RNA-seq) was utilized to construct circRNAs, and differential expression was identified. The findings were validated using reverse transcription PCR (RT-PCR) and DNA sequencing, GO and KEGG analyses were performed, and potential miRNA targets were identified. The RNA-seq identified a total of 15,866 circRNAs, with 244 differentially expressed in the Meishan relative to the Duroc (111 up-regulated and 133 down-regulated). The RT-PCR finding confirmed the RNA-seq results, and quantitative real-time PCR (qPCR) analysis examining a subset of the circRNAs showed that they are resistant to RNase R digestion. Bioinformatics analysis (GO and KEGG) showed that the host genes associated with the differentially expressed circRNAs are involved in reproduction and follicular development signaling pathways. Furthermore, many of the circRNAs were found to interact with miRNAs that are associated with follicular development. This study presents a new perspective for studying circRNAs and provides a valuable resource for further examination into the potential roles of circRNAs in porcine follicular development.


The transfer of heavy chains from bikunin proteins to hyaluronan requires both TSG-6 and HC2.
Tumor necrosis factor-stimulated gene-6 protein (TSG-6) is involved in the transfer of heavy chains (HCs) from inter-alpha-inhibitor (IalphaI), pre-alpha-inhibitor, and as shown here HC2.bikunin to hyaluronan through the formation of covalent HC.TSG-6 intermediates. In contrast to IalphaI and HC2.bikunin, pre-alpha-inhibitor does not form a covalent complex in vitro using purified proteins but needs the presence of another factor (Rugg, M. S., Willis, A. C., Mukhopadhyay, D., Hascall, V. C., Fries, E., Fülöp, C., Milner, C. M., and Day, A. J. (2005) J. Biol. Chem. 280, 25674-25686). In the present study we purified the required component from human plasma and identified it as HC2. Proteins containing HC2 including IalphaI, HC2.bikunin, and free HC2 promoted the formation of HC3.TSG-6 and subsequently HC3.hyaluronan complexes. HC1 or HC3 did not possess this activity. The presented data reveal that both HC2 and TSG-6 are required for the transesterification reactions to occur.


Synergy between Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma (KS), which is the most common AIDS-associated malignancy. KS is characterized by neovascularization and spindle cell proliferation. The interaction between HIV-1 and KSHV has a central role in promoting the aggressive manifestations of KS in AIDS patients; however, the pathogenesis underlying AIDS-related KS (AIDS-KS) remains unknown. Herein, we examined the potential of HIV-1 negative factor (Nef) to impact KSHV viral interleukin-6 (vIL-6)-induced angiogenesis and tumorigenesis. In vitro experiments showed that exogenous Nef penetrated vIL-6-expressing endothelial cells. Both internalized and ectopic expression of Nef in endothelial cells and fibroblasts synergized with vIL-6 to promote vascular tube formation and cell proliferation. Using a chicken chorioallantoic membrane (CAM) model, we demonstrated that Nef synergistically promotes vIL-6-induced angiogenesis and tumorigenesis. Animal experiments further showed that Nef facilitates vIL-6-induced angiogenesis and tumor formation in athymic nu/nu mice. Mechanistic studies indicated that Nef synergizes with vIL-6 to enhance angiogenesis and tumorigenesis by activating the AKT pathway in the CAM model, as well as nude mice. LY294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly impaired the ability of Nef to promote vIL-6-induced tumorigenesis in an allograft model of nude mice. Our data provide first-line evidence that Nef may contribute to the pathogenesis underlying AIDS-KS in synergy with vIL-6. These novel findings also suggest that targeting the PI3K/AKT signal may be a potentially effective therapeutic approach in AIDS-KS patients.


Multimodal signaling in the Small Torrent Frog (Micrixalus saxicola) in a complex acoustic environment.
Many animals use multimodal (both visual and acoustic) components in courtship signals. The acoustic communication of anuran amphibians can be masked by the presence of environmental background noise, and multimodal displays may enhance receiver detection in complex acoustic environments. In the present study, we measured sound pressure levels of concurrently calling males of the Small Torrent Frog (Micrixalus saxicola) and used acoustic playbacks and an inflatable balloon mimicking a vocal sac to investigate male responses to controlled unimodal (acoustic) and multimodal (acoustic and visual) dynamic stimuli in the frogs' natural habitat. Our results suggest that abiotic noise of the stream does not constrain signal detection, but males are faced with acoustic interference and masking from conspecific chorus noise. Multimodal stimuli elicited greater response from males and triggered significantly more visual signal responses than unimodal stimuli. We suggest that the vocal sac acts as a visual cue and improves detection and discrimination of acoustic signals by making them more salient to receivers amidst complex biotic background noise.


Erratum: Correction of Affiliations in the Article "Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019".
This corrects the article on p. e413 in vol. 35, PMID: 33258333.


[Hydroalcoholic, prophylenic, hydropropylenic and glycerinated solutions of PMCF. Their use in endodontics. "In vitro" and "in vivo" study].
This work aims to test the efficiency of hand instrumentation allied to paramonochlorophenol dressing in cases of pulp necrosis, when this substance is diluted in water and alcohol, propylenoglicol and glycerin. Superficial pression and pH were verified to test them afterwards facing to bacteria that could be found in infected root canals and avaible to study in our bacteria lab. Solution more effective "in vitro" and of less cytotoxicity "in vivo" were selected to be employed in patients from the Dental Clinics at School of Dentistry--Federal University of Minas Gerais. It was concluded that: 1. the relationship between cytotoxicity and bacterial activity was proportionally the reverse to superficial pression, except to Hydropropylenic solution of PMCF 5% and 10%; 2. in the study with patients (40 cases) the growth anaerobic microorganisms were present in 97.5% of examined teeth; 3. from solutions used for intracanal dressing hydroalcoholic solution of PMCF at 5% was the on which showed more effectiveness; 4. studies must be carried out on glycerin solution of PMCF, to turn viable its employment in Endodontia.


Experiences of First-Time Mothers With Persistent Pelvic Girdle Pain After Childbirth: Descriptive Qualitative Study.
Pelvic girdle pain (PGP) is common during pregnancy and negatively affects women's lives. When PGP persists after the birth, the way it affects women's lives may change, particularly for first-time mothers as they adjust to motherhood, yet the experiences of women with persistent PGP remain largely unexplored. The objective of this study was to explore primiparous women's experiences of persistent PGP and its impact on their lives postpartum, including caring for their infant and their parental role. This was a descriptive qualitative study. Following institution ethical approval, 23 consenting primiparous women with PGP that had started during pregnancy and persisted for at least 3 months postpartum participated in individual interviews. These interviews were recorded, transcribed, and analyzed using thematic analysis. Four themes emerged: (1) "Putting up with the pain: coping with everyday life," in which women put up with the pain but had to balance activities and were grateful for support from family and friends to face everyday challenges; (2) "I don't feel back to normal," in which women's feelings of physical limitations, frustration, and a negative impact on their mood were described; (3) "Unexpected," in which persistent symptoms were unexpected for women due to a lack of information given about PGP; and (4) "What next?," in which the future of women's symptoms was met with great uncertainty, and they expressed worry about having another baby. For first-time mothers, having persistent PGP postpartum affects their daily lives in many ways. These findings provide important information for health care providers, which will improve their understanding of these women's experiences, will enhance rapport, and can be used to provide information and address concerns to optimize maternity care during pregnancy and beyond.


Photobehavior of the antipsychotic drug cyamemazine in a supramolecular gel protective environment.
In this work, a molecular hydrogel made of gelator (S)-4-((3-methyl-1-(nonylamino)-1-oxobutan-2-yl)amino)-4-oxobutanoic acid (SVN) has been employed as soft container to modify the photochemical and photophysical behavior of the antipsychotic drug cyamemazine (CMZ). The interaction of CMZ with the gel network has been evidenced by fluorescence spectroscopy through a hypsochromic shift of the emission band (from λmax = 521 nm in solution to λmax = 511 nm in the gel) and an increase of the fluorescence lifetime (5.6 ns in PBS vs. 7.2 ns in the gel). In the laser flash photolysis experiments on CMZ/SVN systems, the CMZ triplet excited state (3CMZ*), monitored at λ = 320 nm, has been more efficiently generated and became much longer-lived than in solution (2.7 μs vs. 0.7 μs); besides, photochemical ionization leading to the radical cation CMZ+• was disfavored. In the steady-state experiments, photooxidation of CMZ to afford the N,S-dioxide derivative CMZ-SONO has been retarded in the gel, which provides a more lipophilic and constrained microenvironment. Both the photophysical properties and the photoreactivity are in agreement with CMZ located in a less polar domain when entrapped in the supramolecular gel, as result of the interaction of the drug with the fibers of the supramolecular SVN gel.


Molecular ammonia sensing of PEDOT:PSS/nitrogen doped MXene Ti3C2Txcomposite film at room temperature.
The irrational NH3emission routinely poses a significant threat to human health and environmental protection even at low dose. In addition, high miniaturization and low power-consumption has been the critical requirements of Internet of Things. To meet these demands, it is greatly pressing to develop a novel gas sensor with the capability to detect trace NH3without external heating or light-irradiation elements. In this work, the organic conducting conjugated polymer PEDOT:PSS was combined with inorganic nitrogen-doped transition metal carbides and nitrides (N-MXene Ti3C2Tx) for chemiresistive NH3sensing at room temperature (20oC). By means of the organic-inorganicn-pheterojunctions via the synergistic effect, the results show that the composite film sensor with the optimal mass ratio of 1:0.5 between N-MXene and PEDOT:PSS components delivered favorable NH3sensing performance than individual N-MXene or PEDOT:PSS counterparts in terms of higher response and quicker response/recovery speeds under 20oC@36%RH air. Besides, decent repeatability, stability and selectivity were demonstrated. The incorporated N atoms served as excellent electron donors to promote the electron-transfer reactions and augment the sorption sites. Simultaneously, partial oxidation of MXene brought about some TiO2nanoparticles which acted as spacers to widen the interlayer spacing and probably suppress the MXene restacking during the film deposition, thus favoring the gas diffusion/penetration within the sensing layer and then a quick reaction kinetic. The modulation of consequent build-in field within the heterojunctions was responsible for the reversible NH3sensing. In addition, pre-adsorbed water molecules facilitated to establish a swift adsorption/desorption balance. The proposed strategy expanded the application range of MXene based composite materials and enrich the current sensing mechanisms of NH3gas sensors.


An ultracentrifugation-based approach to the detection of hepatitis A virus in soft fruits.
A method was developed for detection of hepatitis A virus (HAV) in soft fruits (raspberries and strawberries). After washing the sample in 1 M sodium bicarbonate with added soya protein, fruits were removed by slow speed centrifugation, then particulate material and residual pectin were removed from the supernatant by flocculation and pectinase treatment during another slow speed centrifugation. Virus particles were then sedimented by ultracentrifugation. RNA was extracted from the virus particles, and nested RTPCR was performed on the nucleic acid extract. Nested RTPCR comprised an RTPCR, followed by PCR to amplify sequences within the amplicon. Internal amplification controls (IACs) were constructed for both the RTPCR and the PCR. The sensitivity of the nested RTPCR was approximately 10 RTPCRU. The overall method was shown to be able to detect 10(4) RTPCRU HAV in 90 g fresh strawberries, and 10(3) RTPCRU HAV in 60 g fresh raspberries. It is estimated that the lowest possible limit of detection of the method should be between 40 and 400 RTPCRU HAV per fruit sample. The method can be performed within one day, in suitably equipped microbiological laboratories, and is suitable for routine screening of food samples, and for analysis of suspected samples, e.g. during outbreak investigations.


Role of CXC chemokine ligand 13, CC chemokine ligand (CCL) 19, and CCL21 in the organization and function of nasal-associated lymphoid tissue.
Nasal-associated lymphoid tissue (NALT) orchestrates immune responses to Ags in the upper respiratory tract. Unlike other lymphoid organs, NALT develops independently of lymphotoxin-alpha (LTalpha). However, the structure and function of NALT are impaired in Ltalpha(-/-) mice, suggesting a link between LTalpha and chemokine expression. In this study we show that the expression of CXCL13, CCL19, CCL21, and CCL20 is impaired in the NALT of Ltalpha(-/-) mice. We also show that the NALT of Cxcl13(-/-) and plt/plt mice exhibits some, but not all, of the structural and functional defects observed in the NALT of Ltalpha(-/-) mice. Like the NALT of Ltalpha(-/-) mice, the NALT in Cxcl13(-/-) mice lacks follicular dendritic cells, BP3(+) stromal cells, and ERTR7(+) lymphoreticular cells. However, unlike the NALT of Ltalpha(-/-) mice, the NALT of Cxcl13(-/-) mice has peripheral node addressin(+) high endothelial venules (HEVs). In contrast, the NALT of plt/plt mice is nearly normal, with follicular dendritic cells, BP3(+) stromal cells, ERTR7(+) lymphoreticular cells, and peripheral node addressin(+) HEVs. Functionally, germinal center formation and switching to IgA are defective in the NALT of Ltalpha(-/-) and Cxcl13(-/-) mice. In contrast, CD8 T cell responses to influenza are impaired in Ltalpha(-/-) mice and plt/plt mice. Finally, the B and T cell defects in the NALT of Ltalpha(-/-) mice lead to delayed clearance of influenza from the nasal mucosa. Thus, the B and T cell defects in the NALT of Ltalpha(-/-) mice can be attributed to the impaired expression of CXCL13 and CCL19/CCL21, respectively, whereas impaired HEV development is directly due to the loss of LTalpha.


Effect of pH-Regulation on the Capture of Lipopolysaccharides from E. coli EH100 by Four-Antennary Oligoglycines in Aqueous Medium.
Bacterial lipopolysaccharides (LPS) are designated as endotoxins, because they cause fever and a wide range of pathologies in humans. It is important to develop effective methodologies to detect trace quantities of LPS in aqueous systems. The present study develops a fine-tuning procedure for the entrapment of trace quantities of LPS from E. coli EH100. The capture agents are self-assemblies (tectomers) formed by synthetic four-antennary oligoglycine (C-(CH2-NH-Gly7)4, T4). Based on previously performed investigations of bulk and adsorption-layer properties of aqueous solutions containing T4 and LPS, the optimal conditions for the entrapment interactions are further fine-tuned by the pH regulation of aqueous systems. A combined investigation protocol is developed, including dynamic light scattering, profile analysis tensiometry, microscopic thin-liquid-film techniques, and transmission electron microscopy. The key results are: (1) two types of complexes between T4 and LPS are generated-amphiphilic species and "sandwich-like" hydrophilic entities; the complexes are smaller at lower pH, and larger at higher pH; (2) an optimum range of pH values is established within which the whole quantity of the LPS is entrapped by the tectomers, namely pH = 5.04-6.30. The obtained data substantiate the notion that T4 may be used for an effective capture and the removal of traces of endotoxins in aqueous systems.


Effects of sampling context on spontaneous expressive language in males with fragile X syndrome or Down syndrome.
In this study, the authors examined the impact of sampling context on multiple aspects of expressive language in male participants with fragile X syndrome in comparison to male participants with Down syndrome or typical development. Participants with fragile X syndrome ( n = 27), ages 10-17 years, were matched groupwise on nonverbal mental age to adolescents with Down syndrome ( n = 15) and typically developing 3- to 6-year-olds ( n = 15). Language sampling contexts were an interview-style conversation and narration of a wordless book, with scripted examiner behavior. Language was assessed in terms of amount of talk, mean length of communication unit (MLCU), lexical diversity, fluency, and intelligibility. Participants with fragile X syndrome had lower MLCU and lexical diversity than did participants with typical development. Participants with Down syndrome produced yet lower MLCU. A differential effect of context among those with fragile X syndrome, Down syndrome, and typical development emerged for the number of attempts per minute, MLCU, and fluency. For participants with fragile X syndrome, autism symptom severity related to the number of utterances produced in conversation. Aspects of examiner behavior related to participant performance. Sampling context characteristics should be considered when assessing expressive language in individuals with neurodevelopmental disabilities.


Renal participation in cardiovascular risk in essential hypertension.
Renal damage as a consequence of uncontrolled hypertension is well recognized. Antihypertensive therapy has been proved to significantly decrease the vascular damage in the kidneys of hypertensive patients. However, prevalence of mild renal insufficiency remains present in a significant proportion of the hypertensive population. This is accompanied by a marked increase in cardiovascular risk, as a consequence of the clustering of other cardiovascular risk factors and of insufficiently controlled blood pressure. Prevention and protection of renal and cardiovascular damage in these patients will be one of the most relevant healt care tasks in the future.