Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis.
The role of resident cells such a synoviocytes and chondrocytes in intra-articular inflammation is well-characterized, however the in vivo gene expression patterns of cells (predominantly leukocytes) in the synovial fluid (SF) of an inflamed joint have never previously been investigated. The aim of this study was to investigate gene expression in SF leukocytes from the inflamed joint cavity after intra-articular lipopolysaccharide (LPS) injection in horses to improve our understanding of the temporal regulation of the intra-articular inflammatory response. Gene expression was investigated in SF samples available from six horses 2, 4, 8 16 and 24 h after experimental induction of inflammation in the radiocarpal joint by lipopolysaccharide (LPS) injection. Leukocytic expression of 43 inflammation-related genes was studied using microfluidic high throughput qPCR (Fluidigm®). Expression of 26 genes changed significantly over the 24 h study period, including pro- and anti-inflammatory genes such as interleukin (IL)1, IL6, tumor necrosis factor (TNF), cyclooxygenase 2 (COX2), IL1 receptor antagonist (IL1RN), IL10, and superoxide dismutase 2 (SOD2), chemokine genes, apoptosis-related genes, and genes related to cartilage turnover (matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1). The inflammatory responses appeared to be regulated, as an early increase (at 2 h) in expression of the pro-inflammatory genes IL1, IL6, TNF and COX2 was rapidly followed by increased expression (at 4 h) of several anti-inflammatory genes (IL10, IL1RN and SOD2). Similarly, both pro- and anti-apoptotic gene expression as well as expression of chondrodegenerative and chondroprotective genes were activated in SF leukocytes. Thus, the inflammatory response in leukocytes infiltrating the joint in the acute stage of arthritis was well orchestrated in this single-hit LPS-induced arthritis model. This study is the first to describe gene expression patterns in SF-derived leukocytes in vivo during severe joint inflammation, and the results thus expand our knowledge of basic inflammatory mechanisms in the early local response in an inflamed joint.


Dose response of various radiation detectors to synchrotron radiation.
Accurate dosimetry is particularly difficult for low- to medium-energy x-rays as various interaction processes with different dependences on material properties determine the dose distribution in tissue and radiation detectors. Monoenergetic x-rays from synchrotron radiation offer the unique opportunity to study the dose response variation with photon energy of radiation detectors without the compounding effect of the spectral distribution of x-rays from conventional sources. The variation of dose response with photon energies between 10 and 99.6 keV was studied for two TLD materials (LiF:Mg,Ti and LiF:Mg,Cu,P), MOSFET semiconductors, radiographic and radiochromic film. The dose response at synchrotron radiation energies was compared with the one for several superficial/orthovoltage radiation qualities (HVL 1.4 mm Al to 4 mm Cu) and megavoltage photons from a medical linear accelerator. A calibrated parallel plate ionization chamber was taken as the reference dosimeter. The variation of response with x-ray energy was modelled using a two-component model that allows determination of the energy for maximum response as well as its magnitude. MOSFET detectors and the radiographic film were found to overrespond to low-energy x-rays by up to a factor of 7 and 12 respectively, while the radiochromic film underestimated the dose by approximately a factor of 2 at 24 keV. The TLDs showed a slight overresponse with LiF:Mg, Cu, P demonstrating better tissue equivalence than LiF:Mg, Ti (maximum deviation from water less than 25%). The results of the present study demonstrate the usefulness of monoenergetic photons for the study of the energy response of radiation detectors. The variations in energy response observed for the MOSFET detectors and GAF chromic film emphasize the need for a correction for individual dosimeters if accurate dosimetry of low- to medium-energy x-rays is attempted.


Lactic acidosis transiently increases metabolic rate of turtle myocytes.
We measured O2 consumption as an estimate of metabolic rate in isolated calcium-tolerant ventricular myocytes of turtles (Chrysemys picta belli) at control pH 7.8 and in the same solution brought to pH 7.4 and 7.0 with additions of lactic acid. Our aim was to test the hypothesis that lactic acidosis caused metabolic depression by initiating downregulation of Na+ channels, and thus Na(+)-K(+)-ATPase (Na+ pump) activity, which we would measure as a decrease in O2 consumption. Myocyte O2 consumption was measured in reptilian N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid-buffered Ringer solution and in nomially Na(+)- and Ca(2+)-free solution, thus estimating the Na+ pump component of metabolic rate. Lowering extracellular pH from 7.8 to 7.0 resulted in a significant increase in metabolic rate of cells in Ringer solution but not those in Na(+)- and Ca(2+)-free solution. This result was unchanged by the addition of 2 mM Ca2+ to Na(+)-free cell suspensions, indicating that the difference was due to the presence of Na+. Addition of 100 microM amiloride to cells in Ringer solution at pH 7.0 abolished the increase in O2 consumption, suggesting that the apparent increase in Na(+)-K(+)-ATPase activity was secondary to Na(+)-H+ exchange. Intracellular pH was measured using 5,5-dimethyl[14C]oxazolidine-2,4-dione. Cells treated with amiloride and those in Na(+)- and Ca(2+)-free solution did not regulate intracellular pH following acidosis and maintained basal metabolic rate. These data suggest that the Na(+)-H+ exchanger is an important contributor to intracellular pH regulation in the myocyte but increases Na+ pump activity and metabolic rate immediately following acidosis.


[Risk factors to periventricular-intraventricular hemorrhage in newborns weighing less than 2000g]
OBJECTIVE: To study the incidence and analyze risk factors to neonatal periventricular-intraventricular hemorrhage; to suggest a working protocol for diagnosis in newborns at risk.METHODS: This is a cohort prospective study including 120 out of 129 children weighing less than 2000g born from May 18 th, 1994 to May 17 th,1995 at the Hospital das Clínicas da UFMG. The study group comprised 39 newborns with the ultrasound diagnosis of periventricular-intraventricular hemorrhage; the control group comprised 81 newborns who although submitted to the same evaluation protocol did not show any echographic signs of hemorrhage. The ultrasound examinations were all done by the same researcher who was not aware of the clinical history or the neurologic and laboratory examinations. The hemorrhage was classified according to Papilés criteria: grade I (13%); grade II (7%); grade III (9%) and grade IV (3%).RESULTS: Low gestational age, low birth weight, masculine sex, vaginal delivery, and neonatal sepsis were significantly associated (p < 0.05) with periventricular-intraventricular hemorrhage in univariate analysis. Apgar score in the first or fifth minute and Battagliás and Lubchenkós classification for the weight in relation to gestational age were not predisposing factors to the hemorrhage. Low gestational age (p = 0.002), vaginal delivery (p = 0.037), and masculine sex (p = 0.016) kept statistical significance after multivariate adjustment. Birth weight may substitute for gestational age in the multivariate model because they are highly associated. The best cutoff point to screen for periventricular-intraventricular hemorrhage was 1750 g instead of the traditionally adopted point of 1500 g. CONCLUSIONS: The incidence of neonatal periventricular-intraventricular hemorrhage was similar to those reported by other studies. Low gestational age or low birth weight, vaginal delivery and masculine sex were the most important risk factors to the hemorrhage. The screening cutoff point of 1750 g seems to be more adequate than the commonly used birth weight of 1500 g.


Accuracy of intraoral scanners in different complete arch scan patterns.
The accuracy (trueness and precision) of intraoral scanners and complete arch scans remains controversial. The purpose of this in vitro study was to compare the trueness and precision of 3 intraoral scanners with various scan patterns. Four standard metal spheres were installed on a dental maxillary cast according to American National Standard/American Dental Association (ANSI/ADA) specification no. 132. Six distances among the center of spheres were measured with a coordinate measuring machine and used as references. Four different scanning patterns were assigned: zigzag, occlusal-palatal-buccal, occlusal-buccal-palatal, and molar-to-canine. Dental Wings and TRIOS 3 applied to the first 3 scan patterns, while True Definition applied to all patterns (n=30). Six distances in the scan files were also measured and calculated for relative errors of trueness and precision. A ratio less than 0.0025 was considered acceptable and used for binary outcome analysis. Differences among scanners and scan patterns in terms of trueness and precision were analyzed with the chi-squared test, Fisher exact test, and logistic regression (α=.05). The zigzag scan pattern from TRIOS 3 and the occlusal-buccal-palatal pattern from True Definition exhibited 100% acceptable precision. TRIOS 3 revealed the highest number of acceptable trueness values in the occlusal-palatal-buccal scan (88.3%). The scan patterns from Dental Wings and TRIOS 3 were related to the trueness. TRIOS 3 and True Definition were 12.8 and 6.4 times more likely to obtain acceptable trueness than Dental Wings (P<.001). The zigzag scan pattern had the highest chance of obtaining acceptable trueness. The scan patterns influenced the trueness and precision of the intraoral scanners in different ways. For the best trueness, TRIOS 3 should be applied with an occlusal-palatal-buccal scan pattern, Dental Wings should be applied with a zigzag scan pattern, while True Definition can be used with any scan pattern.


[Evaluation of clinical efficacy and safety of cefpodoxime proxetil (CPDX-PR) in acute uncomplicated cystitis].
One hundred and fifty female patients with acute uncomplicated cystitis were given 200 mg of CPDX-PR twice daily for 3-7 days to evaluate both its overall clinical efficacy and its adverse effects. In 82 cases (Group I) in which it was administered for 3 days, the overall clinical efficacy, evaluated by the criteria proposed by the Japanese UTI committee, was excellent in 64 cases, moderate in 17 and poor in one, with the effective rate being 98.8%. In 35 cases (Group II) in which it was administered for 4-7 days, the overall clinical efficacy was excellent in 18 cases, moderate in 15 and poor in 2, with the effective rate being 94.3%. The overall clinical evaluation was not performed in another 33 cases because they were given CPDX-PR for more than 8 days or 300 mg/day. Subjective adverse effects such as hoarseness and lingual inflammation were observed in only one of the 150 cases, but they disappeared spontaneously after the cessation of administration of CPDX-PR. These findings suggest that CPDX-PR is one of the most effective and safe antibiotic in the treatment of acute uncomplicated cystitis.


A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity.
Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.


Prevalence, Correlates and Management of Hyperglycemia in Diabetic Non-critically Ill Patients at a Tertiary Care Center in Lebanon.
Diabetes Mellitus is a chronic metabolic disease that affects 387 million people around the world. Episodes of hyperglycemia in hospitalized diabetic patients are associated with poor clinical outcomes and increased morbidity and mortality. Therefore, prevention of hyperglycemia is critical to decrease the length of hospital stay and to reduce complications and readmissions. The study aims to examine the prevalence of hyperglycemia and assess the correlates and management of hyperglycemia in diabetic non-critically ill patients. The study was conducted on the medical wards of a tertiary care teaching hospital in Lebanon. A retrospective chart review was conducted from January 2014 until September 2015. Diabetic patients admitted to Internal Medicine floors were identified. Descriptive analysis was first carried out, followed by a multivariable analysis to study the correlates of hyperglycemia occurrence. A total of 235 medical charts were reviewed. Seventy percent of participants suffered from hyperglycemia during their hospital stay. The identified significant positive correlates for inpatient hyperglycemia, were the use of insulin sliding scale alone (OR=16.438 ± 6.765-39.941, p=0.001) and the low frequency of glucose monitoring. Measuring glucose every 8 hours (OR= 3.583 ± 1.506-8.524, p=0.004) and/or every 12 hours (OR=7.647 ± 0.704-79.231, p=0.0095) was associated with hyperglycemia. The major factor perceived by nurses as a barrier to successful hyperglycemia management was the lack of knowledge about appropriate insulin use (87.5%). Considerable mismanagement of hyperglycemia in diabetic non-critically ill patients exists; indicating a compelling need for the development and implementation of protocol-driven insulin order forms a comprehensive education plan on the appropriate use of insulin.


Analysis of gender perspective in the use of NANDA-I nursing diagnoses: A systematic review.
To identify, describe and analyse the gender perspective in the use of the diagnoses contained in the NANDA-I taxonomy in observational studies published in the scientific literature. A systematic review has been conducted spanning from 2002 to 2020. The most frequent NANDA-I nursing diagnoses in care plans reported in observational studies, and the defining characteristics and related factors identified for men and women have been described. The Preferred Reporting Items for Systematic Reviews (PRISMA-P) have guided our research. The main findings have been summarized using a descriptive narrative synthesis approach. Forty-one articles were included in our study. With regard to gender analysis, the percentage of men and women that make up the sample were not specified in all articles, and half of the studies did not identify gender either in the diagnosis label or in their defining characteristics or related factors. Based on the reviewed articles, gender perspectives are not systematically incorporated in the use of the NANDA-I diagnosis. Therefore, gender biases in its use in the scientific literature may exist. This situation poses barriers to determine the health responses that are different and unequal between women and men.


Site- and horizon-specific patterns of microbial community structure and enzyme activities in permafrost-affected soils of Greenland.
Permafrost-affected soils in the Northern latitudes store huge amounts of organic carbon (OC) that is prone to microbial degradation and subsequent release of greenhouse gasses to the atmosphere. In Greenland, the consequences of permafrost thaw have only recently been addressed, and predictions on its impact on the carbon budget are thus still highly uncertain. However, the fate of OC is not only determined by abiotic factors, but closely tied to microbial activity. We investigated eight soil profiles in northeast Greenland comprising two sites with typical tundra vegetation and one wet fen site. We assessed microbial community structure and diversity (SSU rRNA gene tag sequencing, quantification of bacteria, archaea and fungi), and measured hydrolytic and oxidative enzyme activities. Sampling site and thus abiotic factors had a significant impact on microbial community structure, diversity and activity, the wet fen site exhibiting higher potential enzyme activities and presumably being a hot spot for anaerobic degradation processes such as fermentation and methanogenesis. Lowest fungal to bacterial ratios were found in topsoils that had been relocated by cryoturbation ("buried topsoils"), resulting from a decrease in fungal abundance compared to recent ("unburied") topsoils. Actinobacteria (in particular Intrasporangiaceae) accounted for a major fraction of the microbial community in buried topsoils, but were only of minor abundance in all other soil horizons. It was indicated that the distribution pattern of Actinobacteria and a variety of other bacterial classes was related to the activity of phenol oxidases and peroxidases supporting the hypothesis that bacteria might resume the role of fungi in oxidative enzyme production and degradation of phenolic and other complex substrates in these soils. Our study sheds light on the highly diverse, but poorly-studied communities in permafrost-affected soils in Greenland and their role in OC degradation.


Genetic Variation in POU4F3 and GRHL2 Associated with Noise-Induced Hearing Loss in Chinese Population: A Case-Control Study.
Noise-induced hearing loss (NIHL) is an important occupational disease worldwide resulting from interactions between genetic and environmental factors. The purpose of this study was to examine whether genetic variations in POU4F3 and GRHL2 may influence susceptibility to NIHL in the Chinese population. A matched case-control study was carried out among 293 hearing loss individuals and 293 normal hearing workers drawn from a population of 3790 noise-exposed workers. Ten single-nucleotide polymorphisms (SNPs) in POU4F3 and GRHL2 were selected and genotyped. Logistic regression was performed to analyze the main effects of SNPs and the interactions between noise exposure and SNPs. Moreover, the interactions between predictor haplotypes and noise exposure were also analyzed. Analysis revealed that the CC genotype of rs1981361 in the GRHL2 gene was associated with a higher risk of NIHL (adjusted OR = 1.59; 95% CI: 1.08-2.32, p = 0.018). Additionally, the GG genotype of rs3735715 in the GRHL2 gene was also a risk genotype (adjusted OR = 1.48; 95% CI: 1.01-2.19, p = 0.046). Significant interactions were found between rs3735715, rs1981361 (GRHL2), rs1368402 as well as rs891969 (POU4F3) and noise exposure in the high-level exposure groups. Furthermore, the protective haplotype CA in the POU4F3 gene and the risk haplotype GCCG in the GRHL2 gene were identified combined with noise exposure. These results indicated that GRHL2 might be an NIHL susceptibility gene, but the effect of POU4F3 on NIHL could only be detected when taking noise exposure into account, and their effects were enhanced by higher levels of noise exposure. However, the differences were not significant after the Bonferroni correction was applied. These results should be seen as suggestive.


Individual versus Standardized Running Protocols in the Determination of VO2max.
The purpose of this study was to determine whether an individually designed incremental exercise protocol results in greater rates of oxygen uptake (VO2max) than standardized testing. Fourteen well-trained, male runners performed five incremental protocols in randomized order to measure their VO2max: i) an incremental test (INCS+I) with pre-defined increases in speed (2 min at 8.64 km·h(-1), then a rise of 1.44 km·h(-1) every 30 s up to 14.4 km·h(-1)) and thereafter inclination (0.5° every 30 s); ii) an incremental test (INCI) at constant speed (14.4 km·h(-1)) and increasing inclination (2° every 2 min from the initial 0°); iii) an incremental test (INCS) at constant inclination (0°) and increasing speed (0.5 km·h(-1) every 30 s from the initial 12.0 km·h(-1)); iv) a graded exercise protocol (GXP) at a 1° incline with increasing speed (initially 8.64 km·h(-1) + 1.44 km·h(-1) every 5 min); v) an individual exercise protocol (INDXP) in which the runner chose the inclination and speed. VO2max was lowest (-4.2%) during the GXP (p = 0.01; d = 0.06-0.61) compared to all other tests. The highest rating of perceived exertion, heart rate, ventilation and end-exercise blood lactate concentration were similar between the different protocols (p < 0.05). The time to exhaustion ranged from 7 min 18 sec (INCS) to 25 min 30 sec (GXP) (p = 0.01).The VO2max attained by employing an individual treadmill protocol does not differ from the values derived from various standardized incremental protocols. Key pointsThe mean maximum oxygen uptake during the GXP was lower than for all other tests.Differences in the maximum rate of oxygen uptake between the various protocols exhibited considerable inter-individual variation.From the current findings, it can be concluded that well trained athletes are able to perform an individually designed treadmill running protocol.


Translation and Psychometric Testing of the Healthcare Environment Survey in Turkey.
This study aimed to translate and psychometrically test the Healthcare Environment Survey, describe the strengths and needs of job satisfaction for nurses in Turkey, and advance an international discussion across countries that used Healthcare Environment Survey. The Healthcare Environment Survey was the only instrument found that measured multiple facets of nurses' satisfaction in caring for patients. Healthcare Environment Survey has been psychometrically tested in Jamaica, Scotland, and the USA. This study was a methodological design. A convenience sample of 400 nurses from 2 hospitals in Antalya, Turkey, was asked to complete the Healthcare Environment Survey. A total of 241 nurses (60.3%) responded to all 57 items. Factor analysis revealed all items loaded into 10 facets, with all factor loadings greater than 0.40, except 1 item regarding executive leadership. Kaiser-Meyer-Olkin measure of 0.91 revealed a good model fit. The Healthcare Environment Survey explained 75% of the variance in nurse job satisfaction. The Cronbach alpha coefficient for the 10 facets ranged from 0.83-0.90. A comparison of these results with the other 3 countries that used the Healthcare Environment Survey revealed that caring for patients had a high factor loading in Turkey, Scotland, and the USA but a low one in Jamaica. The Healthcare Environment Survey -Turkish form was found to be a valid and reliable tool, which could be used by nurse managers to evaluate satisfied and unsatisfied areas. It provides new opportunities for national/international benchmark, cooperation, and research with others.


Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries.
The incidence of the two main clinical subentities of testicular germ cell cancer (seminoma and nonseminoma) is increasing throughout Europe. Most studies have revealed little variation in risk factors between the two subtypes. This study compared generation-specific trends in eight European countries, hypothesizing that similar temporal pattern by birth cohort implied that seminoma and nonseminoma had a largely comparable etiology. The results are presented using the age-period-cohort model and the nonidentifiability problem highlighted by partitioning the age, period, and cohort effects in terms of their linear and curvature component parts, assuming a priori that cohort effects predominated. Despite uniform overall increases by calendar period, declining rates of nonseminoma but not pure seminoma were observed in the majority of countries during the 1990s. The subtype trends were, however, largely analogous on a birth cohort scale. Notable observations were a decline in rates of both subtypes among recent birth cohorts in Switzerland and a short-term wartime effect in several countries, involving an attenuation of increasing risk of both subtypes in men born in 1940 to 1945. Departures from the steady increases in testicular cancer over time were likely to occur for nonseminomas some years ahead of seminoma on a period scale. The importance of birth cohort coincided with the view that given a short time interval of susceptibility to exposures earlier in life and a biologically constant time to diagnosis, all temporal changes in rate-limiting exposures should appear as generational effects. Trends in seminoma and nonseminoma conform to largely the same temporal patterns on this scale, implying that they share important etiologic factors.


Interventions for primary prevention of suicide in university and other post-secondary educational settings.
Suicide is a leading cause of death among post-secondary students worldwide. Suicidal thoughts and planning are common among post-secondary students. Previous reviews have examined the effectiveness of interventions for symptomatic individuals; however, many students at high risk of suicide are undiagnosed and untreated. We evaluated the effect on suicide and suicide-related outcomes of primary suicide prevention interventions that targeted students within the post-secondary setting. We searched the following sources up to June 2011: Specialised Registers of two Cochrane Groups, Cochrane Central Register of Controlled Trials, and nine other databases, trial registers, conference proceedings, and websites of national and international organizations. We screened reference lists and contacted authors of included studies to identify additional studies. We updated the search in November 2013; we will include these results in the review's next update. We included studies that tested an intervention for the primary prevention of suicide using a randomized controlled trial (RCT), controlled before-and-after (CBA), controlled interrupted time series (CITS), or interrupted time series (ITS) study design. Interventions targeted students within the post-secondary setting (i.e. college, university, academy, vocational, or any other post-secondary educational institution) without known mental illness, previous suicide attempt or self-harm, or suicidal ideation. Outcomes included suicides, suicide attempts, suicidal ideation, changes in suicide-related knowledge, attitudes and behavior, and availability of means of suicide. We used standardized electronic forms for data extraction, risk of bias and quality of evidence determination, and analysis. We estimated standardised mean differences (SMD) with 95% confidence intervals (CIs). We analysed studies by intervention type and study design. We summarized RCT effect sizes using random-effects models meta-analyses; and analysed statistical heterogeneity using the Chi(2) test and I(2) statistic. We described narratively the results from studies that used other study designs. Eight studies met inclusion criteria. They were heterogeneous in terms of participants, study designs, and interventions. Five of eight studies had high risk of bias. In 3 RCTs (312 participants), classroom-based didactic and experiential programs increased short-term knowledge of suicide (SMD = 1.51, 95% CI 0.57 to 2.45; moderate quality evidence) and knowledge of suicide prevention (SMD = 0.72, 95% CI 0.36 to 1.07; moderate quality evidence). The effect on suicide prevention self-efficacy in one RCT (152 participants) was uncertain (SMD = 0.20, 95% CI -0.13 to 0.54; low quality evidence). One CBA analysed the effects of an institutional policy that restricted student access to laboratory cyanide and mandated professional assessment for suicidal students. The incidence of student suicide decreased significantly at one university with the policy relative to 11 control universities, 2.00 vs. 8.68 per 100,000 (Z = 5.90; P < 0.05). Four CBAs explored effects of training 'gatekeepers' to recognize and respond to warning signs of emotional crises and suicide risk in students they encountered. The magnitude of effect sizes varied between studies. Gatekeeper training enhanced short-term suicide knowledge in students, peer advisors residing in student accommodation, and faculty and staff, and suicide prevention self-efficacy among peer advisors. There was no evidence of an effect on participants' suicide-related attitudes or behaviors. One CBA found no evidence of effects of gatekeeper training of peer advisors on suicide-related knowledge, self-efficacy, or gatekeeper behaviors measured four to six months after intervention. We found insufficient evidence to support widespread implementation of any programs or policies for primary suicide prevention in post-secondary educational settings. As all evaluated interventions combined primary and secondary prevention components, we were unable to determine the independent effects of primary preventive interventions. Classroom instruction and gatekeeper training increased short-term suicide-related knowledge. We found no studies that tested the effects of classroom instruction on suicidal behavior or long-term outcomes. Limited evidence suggested minimal longer-term effects of gatekeeper training on suicide-related knowledge, while no evidence was found evaluating its effect on suicidal behavior. A policy-based suicide intervention reduced student suicide, but findings have not been replicated. Our findings are limited by the overall low quality of the evidence and the lack of studies from middle- and low-income countries. Rigorously designed studies should test the effects of preventive interventions on important health outcomes, including suicidal ideation and behavior, in varying post-secondary settings.


Asthma, Family History of Drug Allergy, and Age Predict Amoxicillin Allergy in Children.
Suspected adverse reactions to amoxicillin are common, but there are no known factors that can predict amoxicillin allergy in children. In addition, methods used for the diagnosis of amoxicillin allergy are not standardized and their role in diagnosis is not clear. To identify predictive factors and to assess the role of skin test in the diagnosis of amoxicillin allergy in children. Children with a history of immediate (excluding anaphylaxis) or nonimmediate reactions to amoxicillin were tested by skin prick test, followed by oral graded challenge with amoxicillin. Clinical characteristics of the reaction before and after the challenge were recorded, and data of personal and relatives' drug allergies and atopy were collected for statistical analysis. Skin prick tests followed by an oral graded challenge with amoxicillin were performed on 133 children. The skin test result was not of clinical value because it was negative in all children. Three children (2%) had an immediate reaction and 7 children (5%) had a nonimmediate reaction. Asthma (odds ratio [OR], 0.12; 95% CI, 0.017-0.869; P = .03), family history of drug allergy (OR, 0.12; 95% CI, 0.026-0.613; P = .01), older age at reaction (OR, 0.837; 95% CI, 0.699-1; P = .05), and angioedema (OR, 0.22; 95% CI, 0.043-1.12; marginally significant at P = .069) were associated with reduced chance to pass the oral challenge. Skin prick test did not contribute to the diagnosis of amoxicillin allergy. The presence of asthma, family history of drug allergy, and older age at reaction can be used as predictive factors for true amoxicillin allergy in children.


The charge distribution in the rough endoplasmic reticulum/Golgi complex transitional area investigated by microinjection of charged tracers.
The distribution of microinjected ferritin, ranging in charge from anionic to highly cationic, has been used to indicate differences in surface charge on the rough endoplasmic reticulum and the Golgi complex of intact cells. Highly cationic ferritins (HCF)(HCF1, pI 7.9-9.1; HCF2, pI 8.5-9.4; and HCF3.pI 9.5-10.1) were mostly bound and caused swelling of the rough endoplasmic reticulum. Cationic ferritin (CF) (pI 7.0-8.0) and anionic ferritin (AF) (pI 4.0-4.4) caused no changes in morphology. The distribution of these ferritins in the cytoplasmic space varied with their charge. Significantly more CF was bound to surfaces than was found in the free cytoplasmic space. Conversely, there was significantly more AF in the free cytoplasmic space than close to surfaces. Therefore, the intracellular surfaces are negatively charged. Comparison of the structures in the secretory pathway showed no differences in ferritin binding to transition vesicles, rough endoplasmic reticulum, Golgi saccules or secretory vesicles. The Golgi complex beads are not distinguished by their charge. It is therefore unlikely that charge differences play a role in regulating membrane-membrane interactions in this region of the secretory pathway.


Comparison of prostaglandin and hypertonic saline for termination of pregnancy.
The abortifacient efficacy and complication rate of the administration of hypertonic saline intraamniotically to 796 women were compared with those following administration of various prostaglandins by several routes to 3783 women. Intraamniotic administration of 2.5 mg 15-methyl-PGF2alpha or repeated vaginal administration of 15-methyl PGF2alpha methyl ester were both highly effective. The interval from treatment to abortion following prostaglandin administration was significantly shorter than that following hypertonic saline. The frequency of complications varied with prostaglandin compound and route of administration but was generally of the same magnitude as that following hypertonic saline administration. None of the prostaglandin-treated patients experienced epileptic seizures, and no maternal deaths occurred.


Caffeic acid phenethyl ester exerts apoptotic and oxidative stress on human multiple myeloma cells.
Caffeic acid phenethyl ester (CAPE) is a phenolic compound initially identified in bee glue. CAPE is reported to exhibit antitumor activity in many cancer models. However, the effect of CAPE on multiple myeloma (MM) is not well studied. We investigated the anti-myeloma effect of CAPE, and the data showed that CAPE inhibited the growth of human MM cells in a dose (1 ~ 30 μM) and time (24 ~72 h) dependent manner without altering the viability of normal human peripheral blood B cells. Stress and toxicity pathway analysis demonstrated that CAPE, in a dose- and time-related fashion, induced the expression of apoptotic and oxidative stress-response genes including growth arrest and DNA-damage inducible, alpha and gamma (GADD45A and GADD45G) and heme oxygenase-1. Apoptosis of MM cells by CAPE was further confirmed through flow cytometric analysis with up to 50% apoptotic cells induced by 50 μM CAPE within 24 h. Western blot analysis revealed the CAPE-induced activation of apoptosis executioner enzyme caspase-3, and corresponding cleavage of its downstream target poly(ADP-ribose)polymerase (PARP). The oxidative stress caused by CAPE cytotoxicity in MM cells was evaluated through measurement of reactive oxygen species (ROS) level, antioxidant intervention and glutathione depletion. The intracellular ROS level was not elevated by CAPE, but the pretreatment of antioxidant (N-acetyl cysteine) and glutathione synthesis inhibitor (buthionine sulfoximine) suggested that CAPE may cause oxidative stress by decrease of intracellular antioxidant level rather than over production of ROS. These data suggest that CAPE promotes apoptosis through oxidative stress in human multiple myeloma cells.


An Ultra-Area-Efficient 1024-Point In-Memory FFT Processor.
Current computation architectures rely on more processor-centric design principles. On the other hand, the inevitable increase in the amount of data that applications need forces researchers to design novel processor architectures that are more data-centric. By following this principle, this study proposes an area-efficient Fast Fourier Transform (FFT) processor through in-memory computing. The proposed architecture occupies the smallest footprint of around 0.1 mm 2 inside its class together with acceptable power efficiency. According to the results, the processor exhibits the highest area efficiency ( FFT / s / area ) among the existing FFT processors in the current literature.


Function and pharmacology of spinally-projecting sympathetic pre-autonomic neurones in the paraventricular nucleus of the hypothalamus.
The paraventricular nucleus (PVN) of the hypothalamus has been described as the "autonomic master controller". It co-ordinates critical physiological responses through control of the hypothalamic-pituitary-adrenal (HPA)-axis, and by modulation of the sympathetic and parasympathetic branches of the central nervous system. The PVN comprises several anatomical subdivisions, including the parvocellular/ mediocellular subdivision, which contains neurones projecting to the medulla and spinal cord. Consensus indicates that output from spinally-projecting sympathetic pre-autonomic neurones (SPANs) increases blood pressure and heart rate, and dysfunction of these neurones has been directly linked to elevated sympathetic activity during heart failure. The influence of spinally-projecting SPANs on cardiovascular function high-lights their potential as targets for future therapeutic drug development. Recent studies have demonstrated pharmacological control of these spinally-projecting SPANs with glutamate, GABA, nitric oxide, neuroactive steroids and a number of neuropeptides (including angiotensin, substance P, and corticotrophin-releasing factor). The underlying mechanism of control appears to be a state of tonic inhibition by GABA, which is then strengthened or relieved by the action of other modulators. The physiological function of spinally-projecting SPANs has been subject to some debate, and they may be involved in physiological stress responses, blood volume regulation, glucose regulation, thermoregulation and/or circadian rhythms. This review describes the pharmacology of PVN spinally-projecting SPANs and discusses their likely roles in cardiovascular control.


Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice.
To investigate whether ivermectin, a semi-synthetic derivative of a family of macrocyclic lactones could inhibit lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. C57BL/6 mice were administered ivermectin (or saline) orally and challenged intraperitoneally with LPS at a lethal dose of 32 mg/kg. RAW 264.7 murine macrophages were stimulated with LPS at 1 microg/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss (IL-1ss) and interleukin-6 (IL-6) in serum from mice and supernatants from cells were measured by ELISA. Nuclear factor-kB (NF-kB) translocation with subunit p65 was evaluated by immunocytochemical analysis. Ivermectin improved mouse survival rate induced by a lethal dose of LPS. In addition, ivermectin significantly decreased the production of TNF-alpha, IL-1ss and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB translocation induced by LPS. The results indicate that ivermectin may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB pathway and improve LPS-induced survival in mice. This finding might provide a new strategy for the treatment of endotoxemia and associated inflammation.


Ginger and Garlic Extracts Enhance Osteogenesis in 3D Printed Calcium Phosphate Bone Scaffolds with Bimodal Pore Distribution.
Natural medicines have long been used to treat physiological ailments where both ginger (gingerol) and garlic (allicin) are key players in immune system promotion, reduction in blood pressure, and lowering inflammation response. With their efficacy in bone healing, these compounds have great value as medicinal additives in bone scaffolds for localized treatment to support tissue formation, along with providing their natural therapeutic benefits. Utilization of 3D-printed (3DP) bone tissue engineering scaffolds as drug delivery vehicles for ginger and garlic extracts enables patient specificity in bone defect applications with enhanced osseointegration. Our objective is to understand their combined efficacy on osteogenesis when released from 3DP calcium phosphate bone scaffolds designed with a bimodal pore distribution. With a porous core and dense exterior, the resulting scaffolds have good mechanical integrity with 10 ± 1 MPa compressive strengths. Results show that ginger + garlic extracts released from bone scaffolds enhance their osteogenic potential through on site drug delivery. Both compounds exhibit exponential drug release profiles which fit Weibull distribution equations. The release of ginger extract also increases osteoblast proliferation by 59%. Both compounds show decreased osteoclast resorption activity, with a greater than 20% reduction in pit area on sample surfaces. Ginger + garlic extract induces a twofold increase in early osteoid tissue formation in vivo at week 4, in addition to a 30% increase in total bone area and a 90% increase in osteocytes with respect to control 3DP tricalcium phosphate scaffolds. Late-stage bone healing at week 10 reveals healthy angiogenic tissue, a twofold higher bone mineralization, and significant enhancement of type I collagen formation in the presence of ginger and garlic extracts. Naturally sourced ginger and garlic extracts provide osteogenic promotion and improved bone tissue in-growth in a patient-specific 3DP scaffold biomedical device for low load-bearing bone tissue engineering and dental applications.


Breast Cancer Awareness and Barriers to Early Presentation in the Gaza-Strip: A Cross-Sectional Study.
Timely detection of breast cancer (BC) is important to reduce its related deaths. Hence, high awareness of its symptoms and risk factors is required. This study aimed to assess the awareness level of BC among females in Gaza. A cross-sectional study was performed during September and October 2017 in Gaza, Palestine. Stratified sampling was used to recruit patients from four hospitals and seven high schools. The validated Breast Cancer Awareness Measure (BCAM) was used to assess confidence and behavior in relation to breast changes, awareness of BC symptoms and risk factors, barriers to seek medical help, and knowledge of BC screening. Women (age ≥ 18 years) visiting or admitted to any of the four hospitals, and female adolescents (age 15 to 17 years) in any of the seven schools, were recruited for face-to-face interviews to complete the BCAM. Of 3,055 women approached, 2,774 participants completed the BCAM questionnaire (response rate, 90.8%); 1,588 (57.2%) were adults, and 1,186 (42.8%) were adolescents. Of these, 1,781 (64.2%) rarely (or never) checked their breasts, and 909 (32.8%) were not confident to notice changes. In total, 1,675 (60.4%) were aware of the availability of BC screening programs. The overall mean ± standard deviation score for awareness of BC symptoms was 5.9 ± 2.9 of 11, and that of risk factors 7.5 ± 3.1 of 16. Feeling scared was the most reported barrier to seeking advice reported among women (n = 802; 50.2%), whereas feeling embarrassed was the most reported in adolescents (n = 745; 62.8%). Awareness of BC symptoms, risk factors, and screening programs is suboptimal in Gaza. Educational interventions are necessary to increase public awareness of BC and to train local female breast surgeons to address barriers to early detection.


Blending of soluble corn fiber with pullulan, sorbitol, or fructose attenuates glycemic and insulinemic responses in the dog and affects hydrolytic digestion in vitro.
The objective of these experiments was to measure in vitro hydrolytic digestion and glycemic and insulinemic responses of select carbohydrate blends, all containing the novel carbohydrate soluble corn fiber (SCF). Two SCF that varied in their method of production were used to formulate the carbohydrate blends. One set of blends contained a SCF that was spray dried (SCFsd) and then blended with different amounts of either pullulan, sorbitol, or fructose. The other set of blends contained a SCF produced using longer evaporation time (SCF) and then blended with different ratios of pullulan, sorbitol, and fructose. Free sugar concentrations found in the individual SCFsd and SCF substrates were low but varied. Spray-dried soluble corn fiber had a reduced free sugar concentration compared with SCF (2.8 vs. 14.2%). Glucose was the main free sugar found in both SCFsd and SCF but at different concentrations (2.7 vs. 12.7%, respectively). The majority of the SCFsd blends were completely hydrolyzed to their monosaccharide components. Glucose accounted for most of the hydrolyzed monosaccharides for SCFsd and all the SCFsd blends. Hydrolyzed monosaccharide concentrations for the SCF:pullulan:sorbitol:fructose blends followed similar trends to the SCFsd blends where greater percentages of fructose and sorbitol resulted in decreased (P < 0.05) hydrolyzed monosaccharide concentrations. The SCFsd blends had intermediate to high amounts of monosaccharides released as a result of in vitro hydrolytic digestion. The SCFsd:pullulan blends were more digestible in vitro (approximately 91%; P < 0.05) than SCFsd:fructose or SCFsd:sorbitol. Total released monosaccharides were high in SCFsd blends containing either 50% fructose or sorbitol, but the combination resulted in reduced concentrations of glucose released (P < 0.05). The SCF:pullulan:sorbitol:fructose blends also had intermediate to high released monosaccharides as a result of in vitro hydrolytic digestion. All SCF blends resulted in decreased glycemic and insulinemic responses compared with the maltodextrin control (P < 0.05) using a canine model. The addition of pullulan reduced the glycemic response compared with maltodextrin at all concentrations, but only 50:50 SCFsd:pullulan resulted in a reduction of the glycemic response compared with SCFsd alone (P < 0.05). The addition of fructose and sorbitol in the blends had the greatest impact on glycemic and insulinemic responses, even at concentrations as low as 5% of the blends. Overall, SCF and their blends may prove beneficial as components of low glycemic foodstuffs.


Osteosclerosis (punctate form) in multiple myeloma.
Generalized punctate and nodular osteosclerosis associated with multiple myeloma is reported with review of the literature and differential diagnoses. This patient differs from some others reported earlier in the absence of any recognized osteolytic lesions either during life or at autopsy.


The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency.
During herpes simplex virus type 1 (HSV-1) neuronal latency, the only viral RNA detected is from the latency-associated transcript (LAT) gene. We have made a LAT deletion mutant of McKrae, an HSV-1 strain with a very high in vivo spontaneous reactivation rate. This mutant (dLAT2903) lacks the LAT promoter and the first 1.6 kb of the 5' end of LAT. dLAT2903 was compared with its parental virus and with a rescued virus containing a restored LAT gene (dLAT2903R). Replication of the LAT mutant in tissue culture, rabbit eyes, and rabbit trigeminal ganglia was similar to that of the rescued and parental viruses. On the basis of semiquantitative PCR analysis of the amount of HSV-1 DNA in trigeminal ganglia, the LAT mutant was unimpaired in its ability to establish latency. In contrast, spontaneous reactivation of dLAT2903 in the rabbit ocular model of HSV-1 latency and reactivation was decreased to approximately 33% of normal. This decrease was highly significant (P < 0.0001) and demonstrates that in an HSV-1 strain with a high spontaneous reactivation rate, deletion of LAT can dramatically decrease in vivo spontaneous reactivation. We also report here that deletion of LAT appeared to eliminate rather than just reduce in vivo induced reactivation.


Mutational spectrum and risk stratification of intermediate-risk acute myeloid leukemia patients based on next-generation sequencing.
Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. Although several mutations have been identified, the heterogeneity of AML is uncertain because novel mutations have yet to be discovered. Here we applied next generation sequencing (NGS) platform to screen mutational hotspots in 410 genes relevant to hematological malignancy. IR-AML samples (N=95) were sequenced by Illumina Hiseq and mutations in 101 genes were identified. Only seven genes (CEBPA, NPM1, DNMT3A, FLT3-ITD, NRAS, IDH2 and WT1) were mutated in more than 10% of patients. Genetic interaction analysis identified several cooperative and exclusive patterns of overlapping mutations. Mutational analysis indicated some correlation between genotype and phenotype. FLT3-ITD mutations were identified as independent factors of poor prognosis, while CEBPA mutations were independent favorable factors. Co-occurrence of FLT3-ITD, NPM1 and DNMT3A mutations was identified with associated with specific clinical AML features and poor outcomes. Furthermore, by integrating multiple mutations in the survival analysis, 95 IR-AML patients could be stratified into three distinct risk groups allowing reductions in IR-AML by one-third. Our study offers deep insights into the molecular pathogenesis and biology of AML and indicated that the prognosis of IR-AML could be further stratified by different mutation combinations which may direct future treatment intervention.


Rhox in mammalian reproduction and development.
Homeobox genes play essential roles in embryonic development and reproduction. Recently, a large cluster of homeobox genes, reproductive homeobox genes on the X chromosome (Rhox) genes, was discovered as three gene clusters, α, β, and γ in mice. It was found that Rhox genes were selectively expressed in reproduction-associated tissues, such as those of the testes, epididymis, ovaries, and placenta. Hence, it was proposed that Rhox genes are important for regulating various reproductive features, especially gametogenesis in male as well as in female mammals. It was first determined that 12 Rhox genes are clustered into α (Rhox1-4), β (Rhox5-9), and γ (Rhox10-12) subclusters, and recently Rhox13 has also been found. At present, 33 Rhox genes have been identified in the mouse genome, 11 in the rat, and three in the human. Rhox genes are also responsible for embryonic development, with considerable amounts of Rhox expression in trophoblasts, placenta tissue, embryonic stem cells, and primordial germ cells. In this article we summarized the current understanding of Rhox family genes involved in reproduction and embryonic development and elucidated a previously unreported cell-specific expression in ovarian cells.


Pyrene fluorescence probing of unsaturated lipids in Phytophthora infestans zoospores.
Pyrene rapidly penetrates into isolated zoospores of phytopathogenic fungus Phytophthora infestans localizing predominantly in lipid bodies. An analysis of steady-state monomer and excimer fluorescence spectra, as well as of vibronic structure has suggested a considerable part of the fluorescent probe to be located in a lipid environment. Pyrene partition into hydrophilic phase was observed at its high concentrations. Catalytic hydrogenation of unsaturated lipids in zoospores in situ reduced excimer production. The kinetics of changes of pyrene excimerization suggest that hydrogenation affects both the surface and the intrinsic lipids of the zoospores. The usefulness of pyrene as a fluorescent probe for unsaturated lipids in membranes and lipid bodies of intact cells, and the possible role of eicosapolyunsaturated fatty acids in induction of immune response in potato plants are discussed.


Linking alternative reproductive tactics and habitat selection in Northern chamois.
In polygynous ungulates, males may achieve fertilization through the use of alternative reproductive tactics (ARTs), discrete phenotypic variations evolved to maximize fitness. ARTs are often associated with different male spatial strategies during the rut, from territoriality to female-following. Although variation in space use patterns of rutting male ungulates is known to be largely affected by the spatial distribution of females, information on the year-round habitat selection of alternative reproductive types is scant. Here, we investigate the seasonal variation in habitat choice of a large mammal with ARTs (territoriality and nonterritoriality), the Northern chamois Rupicapra rupicapra. Global Positioning System (GPS) data on 28 adult males were collected between February 2010 and December 2013 in the Gran Paradiso National Park (Italy) and used to fit resource selection functions to explore the ART-specific use of key topographic features, such as elevation, aspect, and slope, and vegetation phenology expressed as NDVI values. Territorial and nonterritorial chamois profoundly differed in their habitat selection not only during the rutting season. Compared to nonterritorial males, territorial males used lower elevations in summer and autumn, preferred southern slopes in spring and summer, and used steeper areas in summer but not in winter. We found no difference in seasonal selection of NDVI values between males adopting ARTs. Our results suggest that territorial males tend to occupy warmer, lower-food-quality habitats in late spring and summer, whereas nonterritorial males are free to follow and exploit vegetation phenology and more favorable temperatures. Different patterns of habitat selection may reflect different trade-offs between the optimization of energy balances throughout the year and the increase of mating opportunities during the rut in males adopting alternative reproductive tactics.


Evaluating the Height of Biomass Burning Smoke Aerosols Retrieved from Synergistic Use of Multiple Satellite Sensors over Southeast Asia.
This study evaluates the height of biomass burning smoke aerosols retrieved from a combined use of Visible Infrared Imaging Radiometer Suite (VIIRS), Ozone Mapping and Profiler Suite (OMPS), and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) observations. The retrieved heights are compared against spaceborne and ground-based lidar measurements during the peak biomass burning season (March and April) over Southeast Asia from 2013 to 2015. Based on the comparison against CALIOP, a quality assurance (QA) procedure is developed. It is found that 74% (81-84%) of the retrieved heights fall within 1 km of CALIOP observations for unfiltered (QA-filtered) data, with root-mean-square error (RMSE) of 1.1 km (0.8-1.0 km). Eliminating the requirement for CALIOP observations from the retrieval process significantly increases the temporal coverage with only a slight decrease in the retrieval accuracy; for best QA data, 64% of data fall within 1 km of CALIOP observations with RMSE of 1.1 km. When compared with Micro-Pulse Lidar Network (MPLNET) measurements deployed at Doi Ang Khang, Thailand, the retrieved heights show RMSE of 1.7 km (1.1 km) for unfiltered (QA-filtered) data for the complete algorithm, and 0.9 km (0.8 km) for the simplified algorithm.


Preparing the male urethra for transurethral procedures.
The antiseptic and analgesic effectiveness of different preparations of lignocaine gel used prior to flexible cystoscopy were studied in patients recruited over a 12-month period. This random study involved 106 patients in four groups. There appeared to be no difference in bacterial colonisation of the urethra between the groups. Urethral analgesia was improved when higher volumes of gel were used. It was concluded that high-volume gel preparations (> 20 ml) with no antiseptic provided optimal conditions for flexible cystoscopy.


Adult-onset adrenoleukodystrophy presenting as a psychiatric disorder: MRI findings.
A 35-year-old, previously healthy man presented psychiatric symptoms lasting four years, receiving treatment with neuroleptics. One year later he evolved with gait disequilibrium. After a further six months, cognitive symptoms were characterized with rapid evolution to a profound demented state. MRI showed signal changes in cerebral white matter and very long-chain fatty acids were detected in blood.


Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker.
Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM. A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI). Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively. Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker's diagnostic and prognostic value should be further investigated in future studies.


Hemodynamic and gas transfer properties of a compliant thoracic artificial lung.
A compliant thoracic artificial lung (TAL) has been developed for acute respiratory failure or as a bridge to transplantation. The development goal was to increase TAL compliance, lower TAL impedance, and improve right ventricular function during use. Prototypes were tested in vitro and in vivo in eight pigs between 67 and 79 kg to determine hemodynamic and gas transfer properties. The in vitro compliance was 16.2 +/- 4.4 ml/mm Hg at pressures < 7.8 mm Hg and 4.3 +/- 1.1 ml/mm Hg above 7.8 mm Hg. In vivo, this compliance significantly reduced blood flow pulsatility from 1.7 at the inlet to 0.36 at the outlet. Device resistance was 1.9 and 1.8 mm Hg/(L/min) at a flow rate of 4 L/min in vitro and in vivo, respectively. Approximately 75% of the resistance was at the inlet and outlet. In vivo TAL O2 and CO2 transfer rates were 188 and 186 ml/min, respectively, at 4 L/min of blood and gas flow, and average outlet O2 saturations exceeded 98% for average flow rates up to and including the maximum tested, 5.3 L/min. The new design has a markedly improved compliance and excellent gas transfer but also possesses inlet and outlet resistances that must be reduced in future designs.


[Echocardiography in coronary heart disease].
Coronary heart disease can be detected via echocardiography, if myocardial ischemia or infarction are present leading to segmental abnormalities of left ventricular function. The capability to demonstrate these regional changes is limited as far as TM echocardiography is concerned, whereas 2D echocardiography is more reliable. For this purpose, cross-sectional imaging of all segments in several planes is necessary. The complex mosaic of findings obtained in this way is best documented by means of a segmental scheme of representative sections. Infarct size then can be estimated by a segmental score. Depressed wall motion and systolic wall thickening are used as criteria for ischaemia and infarction. In the chronic phase, morphological changes can be identified additionally: Thinning, expansion and increased reflectivity of the infarcted areas. In acute myocardial infarction, echocardiography is mainly used if the course is complicated, in the chronic phase, if ECG-changes are questionable, or to evaluate residual ventricular function after large infarcts. Even the TM echocardiogram reliably estimates the ventricular damage caused by the infarct in the chronic phase.


Microsurgical training: vascular control and intraoperative vessel rupture in the human placenta infusion model.
Microsurgery is a challenging discipline. Regular lab training under the operating microscope has been the environment where most surgeons have mastered the skills and techniques inherent to most microneurosurgical procedures. However, some critical scenarios remain difficult to master or simulate. We describe a step-by-step method for how to build a low-cost, feasible, and widely available model that allows residents to familiarize themselves with demanding critical situations such as intraoperative rupture of major vessels. After delivery, nine fresh human placentas were transferred to the lab. The umbilical vein was cannulated for normal saline infusion. Several hands-on procedures were performed under direct microscope vision. Operating microscope setup, allantoic membrane splitting, vascular dissection and vessel injury, and repair exercises were simulated and video recorded. Indocyanine green was administered to simulate intraoperative angiography. The model can be setup in less than 15 min, with minimal cost and infrastructure requirements. All the exercises described above can be conducted with a single placenta. Umbilical vein cannulation adds realism and allows quantification of the volume of saline required to complete the exercise. The final check with indocyanine green simulates intraoperative angiography and allows the assessment of distal vessel patency. Minimal infrastructure requirements, simplicity, and easy setup models provide a suitable environment for regular training. The human placenta is inexpensive and widely available, making it a feasible model for residents training. Neurosurgery residents may benefit from this model to familiarize with microsurgery and critical scenarios in a risk-free environment without time or resource constraints.


The effects of supplementation of the diet with highly palatable foods upon energy balance in the rat.
Full energy balance studies have been performed for 9 weeks on four groups of four adult female rats housed in a continuously running indirect calorimeter; for four weeks two of the groups received highly palatable foods in addition to a standard pelleted diet. A further sixteen groups, of which eight received the palatable foods, provided additional carcass composition data. All practicable precautions were taken to measure energy exchange accurately. Comparison of 'start-to-finish' apparent energy balance with carcass composition changes showed a systematic error of approx. +3% of energy throughput. This was most probably caused by losses of energy in food and excreta, which led to over-estimation of energy intake. Variations among individual balance periods added a standard error of approx. +/- 1%: the source of error here was probably imperfect matching of animals analysed at intermediate stages. The rats offered the palatable foods increased their metabolizable energy (m.e.) intake by 106 kJ/day, 51% of the control groups' intake, in the first week of supplementation. Over the whole 4 weeks of supplementation the increase was 64 kJ/day, or 31%. Withdrawal of the palatable foods led to an immediate fall in intake to about two-thirds of control level, and a return to control level over the next 2-3 weeks. Energy expenditure rose more slowly than intake, reaching a fairly steady level ca. 5 days after introduction of the palatable foods. Expenditure was then ca. 22 kJ/day above control level; an increase of 12% above control expenditure or, allowing for systematic and random errors, 33-37% of the additional m.e. intake. Expenditure returned to control level over the 2 weeks after ceasing supplementation. The experimental groups gained weight at a declining rate throughout the period of supplementation. The gain in live body weight at the end was ca. 32 g, but this comprised a carcass weight gain of 37 g and a loss of 5 g gastrointestinal tract contents. The carcass weight gain comprised 27 g fat (i.e. ca. 70% of the weight gained), 9 g lean tissue and 1 g additional water. The gain of carcass energy was 1100 kJ. There was a small increase in body length, an increase in liver weight, and an increase in the weight of the interscapular brown adipose tissue pad. Regression analysis showed that the increase in the weight of the interscapular brown adipose tissue pad reflected the increase in total body fat.(ABSTRACT TRUNCATED AT 400 WORDS)


Activation of a relaxation cascade in isolated coronary arteries by brief electrical pulses.
Superfused cattle coronary artery rings contracted with endothelin or with a thromboxane A2 mimetic respond to transmural stimulation with relaxation. These relaxations are not reduced by denudation of the endothelium, or by combined pretreatment with quanethidine, atropine and propranolol, nor do they involve free radicals. Stimulation at 0.5 Hz with an increasing number of pulses, from 1 to 50, each of 500 microseconds in duration, produced progressively greater and more prolonged relaxations. Human coronary arteries, denuded and pretreated with guanethidine or tetrodotoxin, also showed prominent relaxations of both spontaneous and induced contractions with minimal transmural stimulation at 0.5 Hz. The delivery of 10 pulses briefly depressed near-maximal contractions to combinations of two or even three spasmogens in the cattle preparations. Reduction of extracellular potassium to near zero did not reduce stimulation-induced relaxations, but decreases in extracellular calcium did. The participation of ATP-sensitive potassium channels in stimulation-induced relaxations was unlikely because glibencamide did not reduce them, although it antagonized the relaxation produced by the potassium channel opener pinacidil. Tetraethylammonium blocked the relaxations to stimulation, indicating the involvement of calcium-dependent potassium channels, but block of small to moderate conductance SK channels with apamin was ineffective in antagonizing relaxations, making it likely that activation of large conductance SK channels or maxi-K channels was involved. Blockade of stimulation-induced relaxation in low sodium Krebs', but not by vanadate (1 mM), indicated the likely involvement of the Na+/Ca++ exchanger rather than a Ca(++)-ATPase as the calcium extrusion component of the relaxation process. Restoration of prestimulation tone required calcium influx through nifedipine-sensitive channels. It is concluded that a highly effective relaxation cascade is initiated by the delivery of one to five 0.5-msec pulses at 0.5 Hz, whose effects long outlast the stimulation parameters. The significance of this finding for coronary pathophysiology and as a means of selectively activating a relaxation cascade in an intact coronary artery segment is discussed.


Concreteness effects in different tasks: implications for models of short-term memory.
This study investigates concreteness effects in tasks requiring short-term retention. Concreteness effects were assessed in serial recall, matching span, order reconstruction, and free recall. Each task was carried out both in a control condition and under articulatory suppression. Our results show no dissociation between tasks that do and do not require spoken output. This argues against the redintegration hypothesis according to which lexical-semantic effects in short-term memory arise only at the point of production. In contrast, concreteness effects were modulated by task demands that stressed retention of item versus order information. Concreteness effects were stronger in free recall than in serial recall. Suppression, which weakens phonological representations, enhanced the concreteness effect with item scoring. In a matching task, positive effects of concreteness occurred with open sets but not with closed sets of words. Finally, concreteness effects reversed when the task asked only for recall of word positions (as in the matching task), when phonological representations were weak (because of suppression), and when lexical semantic representations overactivated (because of closed sets). We interpret these results as consistent with a model where phonological representations are crucial for the retention of order, while lexical-semantic representations support maintenance of item identity in both input and output buffers.


[The use of computer technology in a tuberculosis control institution].
Program complexes that are being developed at the laboratory of the Research Institute of Tuberculosis (USSR Ministry of Public Health) are directed to the employment of the IBM-compatible personal computers of a diverse configuration in antituberculosis institutions of a various level. In this respect the routine work of a doctor of an out- and in-patient department supplied by the appropriate modules can be replaced by work on computers which will enable the attending doctor to fill in medical records according to the scheme of the out- and in-patient departments. A program complex was also developed for the employment of computer technology in control over the antituberculosis service. These systems operate in a dialogue regimen. All the data can be put on a display and (or) printers in the form of texts, tables, diagrams and curves.


Ocean acidification increases the toxic effects of TiO2 nanoparticles on the marine microalga Chlorella vulgaris.
Concerns about the environmental effects of engineered nanoparticles (NPs) on marine ecosystems are increasing. Meanwhile, ocean acidification (OA) has become a global environmental problem. However, the combined effects of NPs and OA on marine organisms are still not well understood. In this study, we investigated the effects of OA (pH values of 7.77 and 7.47) on the bioavailability and toxicity of TiO2 NPs to the marine microalga Chlorella vulgaris. The results showed that OA enhanced the growth inhibition of algal cells caused by TiO2 NPs. We observed synergistic interactive effects of pH and TiO2 NPs on oxidative stress, indicating that OA significantly increased the oxidative damage of TiO2 NPs on the algal cells. Importantly, the elevated toxicity of TiO2 NPs associated with OA could be explained by the enhanced internalization of NPs in algal cells, which was attributed to the slighter aggregation and more suspended particles in acidified seawater. Overall, these findings provide useful information on marine environmental risk assessments of NPs under near future OA conditions.


Community Health Workers as Influential Health System Actors and not "Just Another Pair Of Hands".
Over the last 20 years, community health workers (CHWs) have become a mainstay of human resources for health in many low- and middle-income countries (LMICs). A large body of research chronicles CHWs' experience of their work. In this study we focus on 2 narratives that stand out in the literature. The first is the idea that social, economic and health system contexts intersect to undermine CHWs' experience of their work, and that a key factor underpinning this experience is that LMIC health systems tend to view CHWs as just an 'extra pair of hands' to be called upon to provide 'technical fixes.' In this study we show the dynamic and evolving nature of CHW programmes and CHW identities and the need, therefore, for new understandings. A qualitative case study was carried out of the Indian CHW program (CHWs are called accredited social health activists: ASHAs). It aimed to answer the research question: How do ASHAs experience being CHWs, and what shapes their experience and performance? In depth interviews were conducted with 32 purposively selected ASHAs and key informants. Analysis was focused on interpreting and on developing analytical accounts of ASHAs' experiences of being CHWs; it was iterative and occurred throughout the research. Interviews were transcribed verbatim and transcripts were analysed using a framework approach (with Nvivo 11). CHWs resent being treated as just another pair of hands at the beck and call of formal health workers. The experience of being a CHW is evolving, and many are accumulating substantial social capital over time - emerging as influential social actors in the communities they serve. CHWs are covertly and overtly acting to subvert the structural forces that undermine their performance and work experience. CHWs have the potential to be influential actors in the communities they serve and in frontline health services. Health systems and health researchers need to be cognizant of and consciously engage with this emerging global social dynamic around CHWs. Such an approach can help guide the development of optimal strategies to support CHWs to fulfil their role in achieving health and social development goals.


Aberrations of diffracted wave fields: distortion.
Near-field diffraction patterns are merely aberrated Fraunhofer diffraction patterns. These aberrations, inherent to the diffraction process, provide insight and understanding into wide-angle diffraction phenomena. Nonparaxial patterns of diffracted orders produced by a laser beam passing through a grating and projected upon a plane screen exhibit severe distortion (W311). This distortion is an artifact of the configuration chosen to observe diffraction patterns. Grating behavior expressed in terms of the direction cosines of the propagation vectors of the incident and diffracted orders exhibits no distortion. Use of a simple direction cosine diagram provides an elegant way to deal with nonparaxial diffraction patterns, particularly when large obliquely incident beams produce conical diffraction.


Daily behavioral measures recorded by precision technology devices may indicate bovine respiratory disease status in preweaned dairy calves.
Precision technology devices can measure and detect relative changes in an animal's behavior to possibly create alerts to intervene and to administer treatments. However, the association of relative changes in daily feeding and activity behaviors in calves with bovine respiratory disease (BRD) status is still largely unexplored. The objective of this case-control study was to determine if daily behavioral patterns of preweaning dairy calves (measured by precision technologies) change before BRD diagnosis. This case-control study enrolled 33 pairs of calves (33 BRD calves matched by age, sex, and birthdate to 33 controls) health scored daily for BRD for the preweaning period (until 50 d on the automated feeder). A pedometer (IceQube, Ice Robotics) was attached to the left rear leg to track activity (lying time, lying bouts, total steps, and acceleration activity index). At 3.0 ± 2.0 d of age, calves were trained to use the automated feeder, which recorded milk and calf starter intake, drinking speed, and feeder visits. Calves were allotted a maximum 10 L/d of milk replacer (Cow's Match, Land O'Lakes Animal Milk Products Co.; 140 g/L) and starter (Special Calf Starter and Grower, Baghdad Feeds), ad libitum. Calves were scored daily for signs of BRD using the Wisconsin scoring system, and their lungs were scored with ultrasonography twice weekly. Outward signs of BRD as defined by the Wisconsin scoring system and an area of consolidated lung ≥3.0 cm2 was identified as BRD (d 0). Relative changes in daily behaviors were calculated using d -5 before BRD diagnosis as the baseline for each calf for each behavior. Linear mixed models were used to investigate the association of BRD status with feeding behaviors, activity, and relative changes in calf behavior over a 5-d period before diagnosis, as well as the BRD status × day interaction. Calves with a BRD bout were diagnosed at an average age of 33.0 ± 9.0 d (mean ± standard deviation) and weighed 56.1 ± 9.7 kg. Over the period, BRD calves had reduced milk and starter intake, greater lying times, and fewer lying bouts, step counts, and activity indices when compared with healthy calves. Furthermore, there was a BRD status × day interaction for relative changes in unrewarded visits, and relative changes in calf starter intake. Specifically, BRD calves had a decline in relative changes in their unrewarded visits on d -4, -2, -1, and 0 compared with healthy calves. This study suggests that there is the potential to use feeding and activity behaviors to identify BRD development in preweaning calves. However, utilization of an animals' daily behavioral patterns in real time is fundamental for developing disease detection algorithms, thus we suggest relative changes in unrewarded visits may be useful for algorithm development when d -5 is used as a baseline. Future research should investigate the potential of feeding behavior and activity levels collectively to indicate BRD status in calves using machine learning techniques.


N4BP1 is a newly identified nucleolar protein that undergoes SUMO-regulated polyubiquitylation and proteasomal turnover at promyelocytic leukemia nuclear bodies.
A number of proteins can be conjugated with both ubiquitin and the small ubiquitin-related modifier (SUMO), with crosstalk between these two post-translational modifications serving to regulate protein function and stability. We previously identified N4BP1 as a substrate for monoubiquitylation by the E3 ubiquitin ligase Nedd4. Here, we describe Nedd4-mediated polyubiquitylation and proteasomal degradation of N4BP1. In addition, we show that N4BP1 can be conjugated with SUMO1 and that this abrogates N4BP1 ubiquitylation. Consistent with this, endogenous N4BP1 is stabilized in primary embryonic fibroblasts from mutants of the desumoylating enzyme SENP1, which show increased steady-state sumoylation levels. We have localized endogenous N4BP1 predominantly to the nucleolus in primary cells. However, a small fraction is found at promyelocytic leukemia (PML) nuclear bodies (NBs). In cells deficient for SENP1 or in wild-type cells treated with the proteasome inhibitor MG132, there is considerable accumulation of N4BP1 at PML NBs. These findings suggest a dynamic interaction between subnuclear compartments, and a role for post-translational modification by ubiquitin and SUMO in the regulation of nucleolar protein turnover.


Factors Associated With Early Discharge in Pediatric Trauma Patients Transported by Rotor: A Retrospective Analysis.
Helicopter emergency medical services (HEMS) play a crucial role in providing timely transport for pediatric trauma patients. This service carries the highest risk of any mode of medical transport and a high financial burden, and patient outcomes are seldom investigated. This study evaluated the characteristics of pediatric trauma patients discharged within 24 hours after transport by HEMS. This was a single-center, retrospective analysis on pediatric trauma patients transported by HEMS from 2019 to 2022. Analyses were performed to identify factors associated with discharge within 24 hours. Factors analyzed included vital signs, Shock Index, Pediatric Age-Adjusted scores, management details, and clinical outcomes. A total of 466 pediatric trauma patients were transported by HEMS, including 171 patients (36.7%) who were discharged within 24 hours. There were no differences in the rates of blunt and penetrating injury (P = .583). Patients discharged within 24 hours were more likely to have a higher Glasgow Coma Scale score (14 vs. 11, P < .001) and a lower Injury Severity Score (4.9 vs. 14.7, P < .001), required less prehospital fluid resuscitation (5.5 vs. 11.7 mL/kg, P = .039), and had higher levels of serum calcium (9.3 vs. 8.9 mg/dL, P < .001). They were also less likely to meet criteria for level 1 trauma activation (13.0% vs. 40%, P < .001) or to require prehospital respiratory support of any kind (4.1% vs. 31.1%, P < .001). After arrival at the hospital, they were less likely to require blood transfusions (2.9% vs. 29.8%, P < .001) or tranexamic acid (2.9% vs. 11.5%, P = .001). Trauma patients with a high Glasgow Coma Scale score and a low Injury Severity Score who do not require critical care or meet the criteria for high-level trauma activation may be suitable for transportation with lower acuity. Further studies aimed at improving triage and implementing improved criteria for the use of HEMS are paramount.


An evaluation of adherence to society of pharmacists' standards care in pharmacy information systems in Iran.
Pharmacy information system (PIS) is a complex computerized system used for collecting, storing, and managing the medication therapy data in the course of patients' care. The purpose of this study was to evaluate the level of adherence to the standards established by the societies of pharmacists in the PISs employed in the hospitals in Isfahan, Iran. The present study was an applied, descriptive-analytical study conducted on the PISs of 19 teaching, private and social insurance hospitals in Isfahan in 2011. Study population consisted of the PISs available in the hospitals under study. Study sample was the same as the study population. The data collection instrument was a self-developed checklist based on the guidelines of the American Society of Health-System Pharmacists and Pharmaceutical Society of Australia, whose validity was assessed and confirmed by expert professors' views. Having been collected by observation and interview methods, data were analyzed by SPSS 18 software using Mann-Whitney statistical test. The findings of the study revealed that the highest rank in adherence to the standards of societies of pharmacists was obtained by social services hospitals (32.75%), while the private hospitals obtained the lowest rank (23.32%). Based on the findings, in the PISs in the hospitals under study, some standards of the society of pharmacists were ignored. Hence, prior to designing and implementing PIS, a needs analysis is required to increase its users' motivation to identify the system potentialities and to allow the system development in compliance with the world technology advancement.


Atmospheric pressure photoionization coupled to porous graphitic carbon liquid chromatography for the analysis of globotriaosylceramides. Application to Fabry disease.
Globotriaosylceramides (Gb(3)) are biological compounds implicated in Fabry disease, a lysosomal storage disease due to the deficient activity of alpha-D-galactosidase A, which results in an accumulation of Gb(3) in many organs. The naturally occurring samples are composed of mixtures of several molecular species differing by the structure of the alkyl chains and the nature of the sphingoid base. Atmospheric pressure photoionization mass spectrometry (APPI-MS) proved to be an efficient method for the analysis of globotriaosylceramide molecular species, both in direct injection and by coupling with liquid chromatography (LC). In the positive ion mode, in-source fragmentations yield very precious information that can be used to determine the structure of the alkyl chains. In the negative ion mode, the chloroform solvent participates to the analyte ionization by forming an adduct with chloride ions generated in situ. Combination of LC on a Porous Graphitic Carbon stationary phase and APPI-MS allowed the detection of a great number of species from biological samples isolated from Fabry patients. This method could be an interesting analytical tool for the biochemical investigation of (sphingo) lipid metabolism.


Altered human voice processing in the frontal cortex and a developmental language delay in 3- to 5-year-old children with autism spectrum disorder.
The inferior frontal and superior temporal areas in the left hemisphere are crucial for human language processing. In the present study, we investigated the magnetic mismatch field (MMF) evoked by voice stimuli in 3- to 5-year-old typically developing (TD) children and children with autism spectrum disorder (ASD) using child-customized magnetoencephalography (MEG). The children with ASD exhibited significantly decreased activation in the left superior temporal gyrus compared with the TD children for the MMF amplitude. If we classified the children with ASD according to the presence of a speech onset delay (ASD - SOD and ASD - NoSOD, respectively) and compared them with the TD children, both ASD groups exhibited decreased activation in the left superior temporal gyrus compared with the TD children. In contrast, the ASD - SOD group exhibited increased activity in the left frontal cortex (i.e., pars orbitalis) compared with the other groups. For all children with ASD, there was a significant negative correlation between the MMF amplitude in the left pars orbitalis and language performance. This investigation is the first to show a significant difference in two distinct MMF regions in ASD - SOD children compared with TD children.


Stage-specific expression of surface molecules by the larval stages of Haemonchus contortus.
Three monoclonal antibodies, Hc2, Hc22 and Hc6, were produced against a surface extract of L3 Haemonchus contortus and screened against both free living and parasitic stages of the parasite. Hc2 and Hc22 were of IgG2c isotype and their target epitopes were insensitive to periodate treatment. Hc6 was of IgM isotype and its reactivity was sensitive to periodate treatment of the antigen, suggesting that Hc6 is specific for a carbohydrate epitope. Western blotting of larval extracts and staining of live worms demonstrated that Hc2 was specific for the surface of second stage larvae and that the epitope was still present on the protective sheath of third stage larvae but absent from the L3 cuticle itself. Hc22 was found to be specific for a 70-90 kDa antigen on the surface of third stage infective larvae and cross reacted with a higher molecular weight species present on the surface of third stage Teladorsagia circumcincta. Hc6 showed strong binding to three high molecular weight proteins on immunoblots of third stage larvae only, but in contrast to Hc2 and Hc22, showed no binding to the surface of live larvae. These studies demonstrate unique expression patterns of stage specific antigens on the surface of free living and parasitic H. contortus larvae.


In Vitro and In Vivo Comparison of Bone Growth Characteristics in Additive-Manufactured Porous Titanium, Nonporous Titanium, and Porous Tantalum Interbody Cages.
Autogenous bone grafts are the gold standard for interbody fusion implant materials; however, they have several disadvantages. Tantalum (Ta) and titanium (Ti) are ideal materials for interbody cages because of their biocompatibility, particularly when they are incorporated into a three-dimensional (3D) porous structure. We conducted an in vitro investigation of the cell attachment and osteogenic markers of self-fabricated uniform porous Ti (20%, 40%, 60%, and 80%), nonporous Ti, and porous Ta cages (n = 6) in each group. Cell attachment, osteogenic markers, and alkaline phosphatase (ALP) were measured. An in vivo study was performed using a pig-posterior-instrumented anterior interbody fusion model to compare the porous Ti (60%), nonporous Ti, and porous Ta interbody cages in 12 pigs. Implant migration and subsidence, determined using plain radiographs, were recorded before surgery, immediately after surgery, and at 1, 3, and 6 months after surgery. Harvested implants were assessed for bone ingrowth and attachment. Relative to the 20% and 40% porous Ti cages, the 60% and 80% cages achieved superior cellular migration into cage pores. Among the cages, osteogenic marker and ALP activity levels were the highest in the 60% porous Ti cage, osteocalcin expression was the highest in the nonporous Ti cage, and the 60% porous Ti cage exhibited the lowest subsidence. In conclusion, the designed porous Ti cage is biocompatible and suitable for lumbar interbody fusion surgery and exhibits faster fusion with less subsidence compared with porous Ta and nonporous Ti cages.


Improving treatment outcome assessment in a mouse tuberculosis model.
Preclinical treatment outcome evaluation of tuberculosis (TB) occurs primarily in mice. Current designs compare relapse rates of different regimens at selected time points, but lack information about the correlation between treatment length and treatment outcome, which is required to efficiently estimate a regimens' treatment-shortening potential. Therefore we developed a new approach. BALB/c mice were infected with a Mycobacterium tuberculosis Beijing genotype strain and were treated with rifapentine-pyrazinamide-isoniazid-ethambutol (RpZHE), rifampicin-pyrazinamide-moxifloxacin-ethambutol (RZME) or rifampicin-pyrazinamide-moxifloxacin-isoniazid (RZMH). Treatment outcome was assessed in n = 3 mice after 9 different treatment lengths between 2-6 months. Next, we created a mathematical model that best fitted the observational data and used this for inter-regimen comparison. The observed data were best described by a sigmoidal Emax model in favor over linear or conventional Emax models. Estimating regimen-specific parameters showed significantly higher curative potentials for RZME and RpZHE compared to RZMH. In conclusion, we provide a new design for treatment outcome evaluation in a mouse TB model, which (i) provides accurate tools for assessment of the relationship between treatment length and predicted cure, (ii) allows for efficient comparison between regimens and (iii) adheres to the reduction and refinement principles of laboratory animal use.


Mobility of secondary structure units of horse-muscle acylphosphatase. Relation to antigenicity.
The antigenic properties of acylphosphatase are compared with its various sequential characteristics (hydrophobicity, chemical shift of the main-chain 1H-NMR resonances, numbers and intensities of the nuclear Overhauser enhancements, hydrogen-deuterium exchange and sequential arrangement of the secondary structure units). The discussion is based on the complete sequential assignment of the 1H-NMR spectrum and the knowledge of the three-dimensional fold of the protein obtained by NMR spectroscopy from distance geometry calculations. Regions with very different degrees of mobility can be distinguished. It is found that all major antigenic sites are located in the most mobile surface loops.


The first fossil leaf insect: 47 million years of specialized cryptic morphology and behavior.
Stick and leaf insects (insect order Phasmatodea) are represented primarily by twig-imitating slender forms. Only a small percentage ( approximately 1%) of extant phasmids belong to the leaf insects (Phylliinae), which exhibit an extreme form of morphological and behavioral leaf mimicry. Fossils of phasmid insects are extremely rare worldwide. Here we report the first fossil leaf insect, Eophyllium messelensis gen. et sp. nov., from 47-million-year-old deposits at Messel in Germany. The new specimen, a male, is exquisitely preserved and displays the same foliaceous appearance as extant male leaf insects. Clearly, an advanced form of extant angiosperm leaf mimicry had already evolved early in the Eocene. We infer that this trait was combined with a special behavior, catalepsy or "adaptive stillness," enabling Eophyllium to deceive visually oriented predators. Potential predators reported from the Eocene are birds, early primates, and bats. The combination of primitive and derived characters revealed by Eophyllium allows the determination of its exact phylogenetic position and illuminates the evolution of leaf mimicry for this insect group. It provides direct evidence that Phylliinae originated at least 47 Mya. Eophyllium enlarges the known geographical range of Phylliinae, currently restricted to southeast Asia, which is apparently a relict distribution. This fossil leaf insect bears considerable resemblance to extant individuals in size and cryptic morphology, indicating minimal change in 47 million years. This absence of evolutionary change is an outstanding example of morphological and, probably, behavioral stasis.


Peer review of the pesticide risk assessment of the active substance captan.
The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Austria and co-rapporteur Member State Italy for the pesticide active substance captan are reported and the confirmatory data following the Article 12 of Regulation (EC) No 396/2005 as well. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of captan as a fungicide on pome fruit, peaches and nectarines, plums, cherry, tomato, strawberries (field use) and strawberries (greenhouse application). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.


Identification of allelic variants of pendrin (SLC26A4) with loss and gain of function.
Pendrin is a multifunctional anion transporter that exchanges chloride and iodide in the thyroid, as well as chloride and bicarbonate in the inner ear, kidney and airways. Loss or reduction in the function of pendrin results in both syndromic (Pendred syndrome) and non-syndromic (non-syndromic enlarged vestibular aqueduct (ns-EVA)) hearing loss. Factors inducing an up-regulation of pendrin in the kidney and the lung may have an impact on the pathogenesis of hypertension, chronic obstructive pulmonary disease (COPD) and asthma. Here we characterize the ion transport activity of wild-type (WT) pendrin and seven of its allelic variants selected among those reported in the single nucleotide polymorphisms data base (dbSNPs), some of which were previously identified in a cohort of individuals with normal hearing or deaf patients belonging to the Spanish population. WT and mutated pendrin allelic variants were functionally characterized in a heterologous over-expression system by means of fluorometric methods evaluating the I(-)/Cl(-) and Cl(-)/OH(-) exchange and an assay evaluating the efflux of radiolabeled iodide. The transport activity of pendrin P70L, P301L and F667C is completely abolished; pendrin V609G and D687Y allelic variants are functionally impaired but retain significant transport. Pendrin F354S activity is indistinguishable from WT, while pendrin V88I and G740S exhibit a gain of function. Amino acid substitutions involving a proline always result in a severe loss of function of pendrin. Two hyperfunctional allelic variants (V88I, G740S) have been identified, and they may have a contributing role in the pathogenesis of hypertension, COPD and asthma.


Glossopharyngeal neuralgia caused by arachnoid cyst in the cerebellopontine angle.
Glossopharyngeal neuralgia is a relatively rare condition characterized by severe, paroxysmal episodes of lancinating pain in the tongue, throat, ear, and tonsil. This disorder is assumed to be due to compression of the glossopharyngeal nerve by vascular structures. A 47-year-old woman complaining of sharp and lancinating pain in the right periauricular and submandibular areas visited our hospital. Swallowing, chewing, and lying on her right side triggered the pain. Her neurologic examination revealed no specific abnormalities. The results of routine hematologic and blood chemistry studies were all within normal limits. Carbamazepine and gabapentin were given, but her symptoms persisted. Her pain was temporarily relieved only by narcotic pain medication. MRI showed an arachnoid cyst located in the right cerebellomedullary cistern extending to the cerebellopontine cistern. Cyst removal was performed via a right retrosigmoid approach. Lateral suboccipital craniotomy was performed using the right park-bench position. After opening the dura and cerebellopontine angle, the arachnoid cyst was exposed. The arachnoid cyst was compressing the flattened lower cranial nerves at the right jugular fossa. Her symptoms resolved postoperatively. Two months after the operation, she was completely free from her previous symptoms.


Structural determination of NSC 670224, synthesis of analogues and biological evaluation.
Follow my lead! NSC 670224, previously shown to be toxic to Saccharomyces cerevisiae at low micromolar concentrations, potentially acts via a mechanism of action related to that of tamoxifen (NSC 180973), breast cancer drug. The structure of NSC 670224, previously thought to be a 2,4-dichloro arene, was established as the 3,4-dichloro arene, and a focused library of analogues were synthesized and biologically evaluated.