Beta to theta power ratio in EEG periodic components as a potential biomarker in mild cognitive impairment and Alzheimer's dementia.
Alzheimer's dementia (AD) is associated with electroencephalography (EEG) abnormalities including in the power ratio of beta to theta frequencies. EEG studies in mild cognitive impairment (MCI) have been less consistent in identifying such abnormalities. One potential reason is not excluding the EEG aperiodic components, which are less associated with cognition than the periodic components. Here, we investigate whether aperiodic and periodic EEG components are disrupted differently in AD or MCI vs. healthy control (HC) individuals and whether a periodic based beta/theta ratio differentiates better MCI from AD and HC groups than a ratio based on the full spectrum. Data were collected from 44 HC (mean age (SD) = 69.1 (5.3)), 114 MCI (mean age (SD) = 72.2 (7.5)), and 41 AD (mean age (SD) = 75.7 (6.5)) participants. Aperiodic and periodic components and full spectrum EEG were compared among the three groups. Receiver operating characteristic curves obtained via logistic regression classifications were used to distinguish the groups. Last, we explored the relationships between cognitive performance and the beta/theta ratios based on the full or periodic spectrum. Aperiodic EEG components did not differ among the three groups. In contrast, AD participants showed an increase in full spectrum and periodic relative powers for delta, theta, and gamma and a decrease for beta when compared to HC or MCI participants. As predicted, MCI group differed from HC participants on the periodic based beta/theta ratio (Bonferroni corrected p-value = 0.036) measured over the occipital region. Classifiers based on beta/theta power ratio in EEG periodic components distinguished AD from HC and MCI participants, and outperformed classifiers based on beta/theta power ratio in full spectrum EEG. Beta/theta ratios were comparable in their association with cognition. In contrast to a full spectrum EEG analysis, a periodic-based analysis shows that MCI individuals are different on beta/theta ratio when compared to healthy individuals. Focusing on periodic components in EEG studies with or without other biological markers of neurodegenerative diseases could result in more reliable findings to separate MCI from healthy aging, which would be valuable for designing preventative interventions.


Surface imprinted core-shell nanorod for selective extraction of glycoprotein.
In this paper, combining phenylboronic affinity, surface imprinting, and magnetic Fe3O4, a novel surface imprinted core-shell nanorod (Fe3O4@SiO2/MIPs) was developed for glycoprotein extraction. The Fe3O4@SiO2/MIPs was prepared in water solution using dopamine as functional monomer. The Fe3O4@SiO2/MIPs showed high binding capacity (175.2 mg/g) and fast mass transfer rate (40 min) toward the template protein (ovalbumin, OVA). In addition, the successful extraction of OVA from egg white confirmed the outstanding selectivity of the obtained material. All these results demonstrated that the Fe3O4@SiO2/MIPs had broad application prospects in glycoprotein recognition, biomedical research and clinical diagnosis.


Ascending spinal pathways from sexual organs: effects of chronic spinal lesions.
A recent survey of paraplegics indicates that regaining sexual function is of the highest priority for both males and females (Anderson, K.D. (2004) Targeting recovery: priorities of the spinal cord-injured population J. Newrotrauma, 21: 1371-1383). Our understanding of the neural pathways and mechanisms underlying sexual behavior and function is limited at the present time. More studies are obviously needed to direct experiments geared toward developing effective therapeutic interventions. In this chapter, a review of studies on the processing of sensory inputs from the male and female reproductive organs is presented with a review of what is known about the location of ascending spinal pathways conveying this information. The effect of spinal cord injury on sexual function and the problems that ensue are discussed.


Elective Caesarean Delivery Associated with Infant Hospitalisation for Intestinal But Not Respiratory Infection.
We assessed the impact of caesarean delivery on offspring respiratory and intestinal infection. Data were extracted from all live births (n = 429,058) occurring in the Australian state of Queensland between January 2009 and December 2015, and followed for 12 months. Births were categorised as either non-medically indicated caesarean or vaginal delivery and each offspring had a record (present/absent) of respiratory and intestinal infection hospitalisation for each month from birth to 12 months. Infants delivered by non-medically indicated caesarean were more likely to experience respiratory infection [OR = 1.51 (1.15, 1.99)] and intestinal infection [OR = 1.74 (1.19, 2.55)] than those born by vaginal delivery. In the propensity score weighted analyses the estimate for respiratory infection was similar but non-significant [OR = 1.52 (0.99, 2.31)], while the association with intestinal infection strengthened [OR = 2.21 (1.25, 3.89)]. Our findings provide strong evidence for a specific and clinically meaningful link between non-medically indicated caesarean delivery and infant intestinal infection.


siRNA-mediated knockdown of sperm-associated antigen 11a (Spag11a) mRNA in epididymal primary epithelial cells affects proliferation: a transcriptome analyses.
Differential expression of a variety of proteins in the four major regions of the epididymis contributes to maturation of spermatozoa and region-specific cellular functions as well. Proliferation of epithelial cells of the epididymis is highly controlled and thus is one of the major reasons for the nonoccurrence of cancers in this organ system. The molecular mechanisms and the contribution of region-specific genes in epithelial cell proliferation are not yet fully understood. In this study, for the first time, we analyzed the role of sperm-associated antigen 11a (Spag11a), a caput-specific beta-defensin-like antimicrobial gene in governing epididymal cell proliferation and global gene expression. siRNA-mediated knockdown of Spag11a mRNA in epididymal primary epithelial cells resulted in increased cell proliferation. Out of the 68,842 genes analyzed, 4182 genes were differentially expressed (2154 upregulated and 2028 downregulated). A variety of genes that participate in different cellular processes and pathways were differentially regulated. Genes that are important for epithelial cell proliferation were found to be differentially regulated and these changes were confirmed by real-time PCR. Overexpression of Spag11a in immortalized rat caput epididymal cells resulted in decreased proliferation capacity. Results of this study indicate that Spag11a plays a crucial role in governing epididymal epithelial cell proliferation.


Enhanced acute antihypertensive effect of propranolol in the absence of circulating epinephrine in the rat.
beta-Adrenoceptor blocking agents might reduce blood pressure, in part, by blocking presynaptic beta-adrenoceptors. Absence of circulating epinephrine should then reduce the antihypertensive effect of propranolol. Biadrenalectomized Wistar-Kyoto rats were made hypertensive with methylprednisolone (20 mg/kg s.c. weekly), given for 2 weeks, and supplemented with deoxycorticosterone pivalate (10 mg/kg weekly). Sham-operated controls received the same treatment. Baseline weight, mean intraarterial blood pressure, and heart rate of the groups were the same. After propranolol (5 mg/kg s.c.) was administered to the unanesthetized rats, blood pressure fell within 90 min from 151 +/- 4 by 23 +/- 4 mm Hg (mean +/- SEM) in the adrenalectomized animals and from 153 +/- 4 by only 7 +/- 3 mm Hg in the sham-operated controls (p less than 0.001); heart rate fell by 91 +/- 13 beats/min in the adrenalectomized animals and by 40 +/- 11 beats/min in the controls (p less than 0.01). Propranolol's vehicle had no effect. At the end of the experiment, plasma epinephrine levels were less than 40 pg/ml for adrenalectomized rats, and 420 +/- 60 pg/ml for controls. Norepinephrine levels were approximately equal in the two groups. Since blood pressure fell despite virtual absence of circulating epinephrine, these results suggest that propranolol reduces blood pressure, at least in part, by mechanisms other than presynaptic beta-adrenoceptor blockade.


Altered temporal profile of visual-auditory multisensory interactions in dyslexia.
Recent studies have demonstrated that dyslexia is associated with deficits in the temporal encoding of sensory information. While most previous studies have focused on information processing within a single sensory modality, it is clear that the deficits seen in dyslexia span multiple sensory systems. Surprisingly, although the development of linguistic proficiency involves the rapid and accurate integration of auditory and visual cues, the capacity of dyslexic individuals to integrate information between the different senses has not been systematically examined. To test this, we studied the effects of task-irrelevant auditory information on the performance of a visual temporal-order-judgment (TOJ) task. Dyslexic subjects' performance differed significantly from that of control subjects, specifically in that they integrated the auditory and visual information over longer temporal intervals. Such a result suggests an extended temporal "window" for binding visual and auditory cues in dyslexic individuals. The potential deleterious effects of this finding for rapid multisensory processes such as reading are discussed.


Culture Directed Antibiotic Prophylaxis Reduces Post-Prostate Biopsy Infectious Complications in the Community: A "How-to" for Urologists in the Trenches.
The rate of post-prostate biopsy infection is increasing. We noted this trend in our practice and began using prebiopsy rectal swab cultures to direct antibiotic prophylaxis. Clinical investigation has shown that culture directed antibiotic prophylaxis is effective. We report our methods and results as validation that culture directed antibiotic prophylaxis works in the community. We retrospectively reviewed the charts of 686 consecutive patients who underwent transrectal prostate biopsy from March 2010 to April 2013. The electronic medical record was queried for the antibiotic prophylaxis used, rectal swab culture, post-biopsy infection, culture data and post-biopsy hospitalization if applicable. Prebiopsy rectal swab was incorporated into our practice in May 2012. Each patient received 3 days of fluoroquinolone prophylaxis or culture directed antibiotic prophylaxis. If antibiotic resistance to standard fluoroquinolone prophylaxis was identified, antibiotic prophylaxis was adjusted appropriately. Of 543 patients who received standard fluoroquinolone prophylaxis 17 (3.1%) had infectious complications. Eight patients were hospitalized for post-biopsy sepsis and 4 received outpatient treatment for urinary tract infection. A total of 143 patients underwent prebiopsy rectal swabs and received culture directed antibiotic prophylaxis. Compared to standard antibiotic prophylaxis no patient treated with culture directed antibiotic prophylaxis after a rectal swab had infectious complications (p = 0.03). However, 19.5% of the patients in this group had resistant bacteria requiring alternative antibiotic prophylaxis. A prebiopsy rectal swab to direct antibiotic prophylaxis decreased post-biopsy infectious complications in the community setting. The strategy is simple and it improves patient safety.


In vitro antibacterial activities of DQ-113, a potent quinolone, against clinical isolates.
The antibacterial activity of DQ-113, formerly D61-1113, was compared with those of antibacterial agents currently available. MICs at which 90% of the isolates tested are inhibited (MIC90s) of DQ-113 against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and methicillin-susceptible and -resistant coagulase-negative staphylococci were 0.03, 0.008, 0.03, and 0.06 microg/ml, respectively. Moreover, DQ-113 showed the most potent activity against ofloxacin-resistant and methicillin-resistant S. aureus, with a MIC90 of 0.25microg/ml. DQ-113 inhibited the growth of all strains of Streptococcus pneumoniae, including penicillin-resistant strains, and Streptococcus pyogenes at 0.06 microg/ml, and DQ-113 was more active than the other quinolones tested against Enterococcus faecalis and Enterococcus faecium with MIC90s of 0.25 and 2 microg/ml, respectively. Against vancomycin-resistant enterococci, DQ-113 showed the highest activity among the reference compounds, with a MIC range from 0.25 to 2 microg/ml. DQ-113 also showed a potent activity against Haemophilus influenzae, including ampicillin-resistant strains (MIC90, 0.015 microg/ml), and Moraxella catarrhalis (MIC90, 0.03 microg/ml). The activity of DQ-113 was roughly comparable to that of levofloxacin against all species of ENTEROBACTERIACEAE: The MICs of DQ-113 against ofloxacin-susceptible Pseudomonas aeruginosa ranged from 0.25 to 2 microg/ml, which were four times higher than those of ciprofloxacin. From these results, DQ-113 showed the most potent activity against gram-positive pathogens among antibacterial agents tested.


Quantitative autoradiography of [3H]indalpine binding sites in the rat brain: I. Pharmacological characterization.
The binding of [3H]indalpine (4-[2-(3-indolyl)]ethyl piperidine) to slide-mounted sections of rat brain has been characterized. This 5-hydroxytryptamine (5-HT) uptake blocker binds to sections with high affinity (KD approximately 1 nM). The binding is saturable, and can be displaced by the addition of clomipramine (1 microM). Other drugs inhibiting the uptake of 5-HT also have the capacity to inhibit the binding of [3H]indalpine. A significant correlation (r = 0.86) was found between the capacity of these compounds to inhibit the uptake of 5-HT and their potencies as inhibitors of [3H]indalpine binding. Binding was Na+ - and Cl- -dependent and was inhibited competitively by 5-HT. Furthermore, electrolytic lesions of the dorsal raphe or medial forebrain bundle, which cause a degeneration of 5-HT cell bodies and fibers, respectively, resulted in a 30-40% reduction in the binding of [3H]indalpine. [3H]Indalpine binds to the 5-HT uptake recognition sites in a different manner from imipramine-like compounds.


The work of worrying in children undergoing surgery.
This study examined the relationship involving children's level of anxiety, defensiveness, and play patterns 1 week prior to, during, and 1 week after hospitalization for minor surgery. A 7-month follow-up was also conducted in order to assess the children's recall for hospital events and coping style. The results suggested that two classes of children could be identified. The children in one group distinguished themselves in terms of their disposition to engage in the "work of worrying" (i.e., were low defensive prior to hospitalization, actively played with stress-related toys prior to hospitalization, and reported minimal distress and anxiety following surgery). Those in the second group were highly defensive, avoided playing with stress-related toys, and reported most anxiety following surgery. The parallel between children and adults patterns of dealing with surgery was considered in terms of Janis's (1978) model of coping with psychological stress.


Shock-induced modulation of lymphocyte responsiveness and natural killer activity: differential mechanisms of induction.
The present study was designed to determine the influence of signaled shock on splenic natural killer (NK) activity and nonspecific T-lymphocyte mitogenic responsiveness. Furthermore, experiments were conducted to examine possible mechanisms mediating this suppression. The results demonstrate that a single session of signaled shock induces suppression of splenic NK activity and T-cell response to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). However, the suppression of mitogenic responsiveness was attenuated after five daily sessions of shock, while NK activity remained suppressed. The suppression of NK function was prevented by administration of naltrexone prior to the shock session indicating mediation by opiate receptors. However, naltrexone did not prevent the shock induced suppression of mitogenic responsiveness to Con A or PHA. Diazepam was not effective in preventing the shock-induced suppression of mitogenic responses or NK activity. Collectively, these results demonstrate that mononuclear cell populations in the spleen are differentially affected by the same stressor and that the immune alterations are mediated via different pathways.


Otitis media and reading achievement: a review.
Nineteen studies on the relationship between otitis media (OM) or otitis media with effusion (OME) (secretory otitis media (SOM)) and reading achievement were reviewed. The result is that the children catch up in cognitive development when their ears and hearing become normal at about school age. The correlations that have been found between SOM and reading achievement are so small that they have no practical importance for the average child. At the present time we have no knowledge that justifies intervention against SOM as a general preventive task to ensure the cognitive development, or reading achievement. The absent or very small correlation between SOM and reading in the reviewed studies, 'explaining' only 2-4% of the variance, has no implications in comparison with other important factors. Reading achievement was more closely correlated with cognitive, language, and linguistic factors, and to a series of socioenvironmental and classroom related factors. The high frequency of SOM, with resulting hearing loss, and the long duration and high rate of occurrence of OM in 'otitis-prone' children, and clinical observations underlines the need for further research.


Impact of renal graft nephrectomy on second kidney transplant survival.
To determine the impact of non-functional renal graft nephrectomy on second kidney transplantation survival. We performed a retrospective study on patients managed in our department from April 1989 to April 2011. We compared the number of acute graft rejections and graft survival between patients undergoing second transplantation with (Group I) or without (Group II) prior graft nephrectomy. A total of ninety-one patients received a second renal graft: 43 underwent graft nephrectomy and 48 kept their non-functional renal graft. There were 5 episodes of acute graft rejection in Group I and 12 in Group II (p = 0.3). Six (13.9 %) grafts failed in Group I and eight (16.6 %) in Group II. Five and 10 years actuarial graft survival in Group I were, respectively, 91 and 85 %, while in Group II were 82.7 % and 69 % (p = 0.2). PRA level and number of acute rejection episodes did not have a statistically significant influence on graft survival, whether the patient had a nephrectomy or not (p = 0.2). Nephrectomy of a failed allograft did not significantly improve the survival of a subsequent graft. Graft nephrectomy should be indicated in case of graft-related pain or a chronic inflammation syndrome.


The short-term effect of fatty acids on glucagon secretion is influenced by their chain length, spatial configuration, and degree of unsaturation: studies in vitro.
The influence of fatty acids on beta cell function has been well established whereas little is known about the role of fatty acids on alpha cell function. The aim of our study was to investigate the short-term effects of chain length, spatial configuration, and degree of unsaturation of fatty acids on glucagon secretion from isolated mouse islets and alpha tumor cell 1 clone 6 cells (alpha TC1-6 cells). Glucagon release was measured with different saturated and unsaturated fatty acids as well as cis and trans isomers of fatty acids at low and high glucose. Palmitate (0.1-0.5 mmol/L) immediately stimulated glucagon release in a dose-dependent manner from both isolated islets and alpha TC 1-6 cells. The longer chain length of saturated fatty acids, the higher glucagon responses were obtained. The average fold increase in glucagon to saturated fatty acids (0.3 mmol/L) compared to control was octanoate 1.5, laurate 2.0, myristate 2.9, palmitate 5.4, and stearate 6.2, respectively. Saturated fatty acids were more effective than unsaturated fatty acids in stimulating glucagon secretion. At an equimolar concentration, trans-fatty acids were more potent than their cis isomers. Fatty acids immediately stimulate glucagon secretion from isolated mouse islets pancreatic alpha cells. The chain length, spatial configuration, and degree of unsaturation of fatty acids influence the glucagonotropic effect.


Double-time-scale non-probabilistic reliability-based controller optimization for manipulator considering motion error and wear growth.
Motion error and wear growth are two crucial factors that determine the performance of the manipulator system. The two factors are distinct from the sensitivity to time and respectively indicate its control performance and lifespan level. In this paper, a double-time-scale non-probabilistic reliability (DTSNPR)-based optimization method, which considers time-sensitive factor motion error as time-dependent reliability (TDR) and time-insensitive factor clearance wear growth as time-independent reliability (TIR), is proposed to comprehensively evaluate and optimize the controller of the manipulator system in consideration of these multi-scale factors. Meanwhile, for a highly nonlinear response problem of a manipulator system, the adaptive subinterval collocation method (ASICM) which transfers the highly nonlinear uncertainty propagation problem into a sequence of small subintervals, is adopted to obtain the response range more precisely. The proposed DTSNPR-based optimization method is applied to three numerical manipulator systems and ensures each of them under a predefined level of reliability upon both motion error and wear growth. The results also indicate that the proposed ASICM owns an advantage over computational cost and precision, with only 0.4% error and 1% computational cost compared with the Monte-Carlo methods.


Combined heat and power systems: economic and policy barriers to growth.
Combined Heat and Power (CHP) systems can provide a range of benefits to users with regards to efficiency, reliability, costs and environmental impact. Furthermore, increasing the amount of electricity generated by CHP systems in the United States has been identified as having significant potential for impressive economic and environmental outcomes on a national scale. Given the benefits from increasing the adoption of CHP technologies, there is value in improving our understanding of how desired increases in CHP adoption can be best achieved. These obstacles are currently understood to stem from regulatory as well as economic and technological barriers. In our research, we answer the following questions: Given the current policy and economic environment facing the CHP industry, what changes need to take place in this space in order for CHP systems to be competitive in the energy market? We focus our analysis primarily on Combined Heat and Power Systems that use natural gas turbines. Our analysis takes a two-pronged approach. We first conduct a statistical analysis of the impact of state policies on increases in electricity generated from CHP system. Second, we conduct a Cost-Benefit analysis to determine in which circumstances funding incentives are necessary to make CHP technologies cost-competitive. Our policy analysis shows that regulatory improvements do not explain the growth in adoption of CHP technologies but hold the potential to encourage increases in electricity generated from CHP system in small-scale applications. Our Cost-Benefit analysis shows that CHP systems are only cost competitive in large-scale applications and that funding incentives would be necessary to make CHP technology cost-competitive in small-scale applications. From the synthesis of these analyses we conclude that because large-scale applications of natural gas turbines are already cost-competitive, policy initiatives aimed at a CHP market dominated primarily by large-scale (and therefore already cost-competitive) systems have not been effectively directed. Our recommendation is that for CHP technologies using natural gas turbines, policy focuses should be on increasing CHP growth in small-scale systems. This result can be best achieved through redirection of state and federal incentives, research and development, adoption of smart grid technology, and outreach and education.


Associations between human herpesvirus-6, human papillomavirus and cervical cancer.
Cervical cancer (CxCa) is the second most common cancer among women globally. Human papillomavirus (HPV) infection is thought to be a necessary, but not sufficient, causal factor in CxCa development. Why some women are able to clear HPV infection with no adverse effects, whereas others develop cancer, remains unclear. HHV-6 has demonstrated transformative abilities and has been shown to be present in the genital tract. However, based on the current evidence, we cannot conclude that HHV-6 is a co-factor in HPV-associated carcinogenesis. Nonetheless, future research is warranted because of several crucial gaps in the literature.


Information transmission defect identified and localized in language learning impaired children by means of electrophysiology.
Children with language processing deficits have various learning impairments and poor scholastic performance. In 3-10% of all children a specific language processing deficit can be identified by the Sound Connecting Sub-Test of the Illinois Test of Psycholinguistic-Abilities (SC-ITPA). These children among which we drew our index group (AS-Group) suffer from the disability to recognize isolated sounds as parts of words. Following linguistic terminology this is known as an auditory sequential sound processing deficit (ASSPD) Eighteen children (AS-Group) and 21 controls (C-Group) were subjected to mapped P300 evoked potential analyses of cortical response to acoustic stimulation in the oddball paradigm. The data presented here show that there exists significant relation between the P300 amplitude reduction and ASSPD. The P300 amplitude decrease measured in the AS-Group is due to a reduced information transmission in accordance with Johnson's Triarchic Model of the P300 Amplitude. The cerebral structures involved in poor language processing are localized at the left temporo-parietal cortex. This supports the hypothesis that the underlying neuronal defect of ASSPD is localized in the language center and not in the auditory pathway. The P300 amplitude may serve as electrophysiological tool to identify ASSPD and to quantify the degree of improvement in the course of specific therapy.


Calcium store-mediated signaling in sustentacular cells of the mouse olfactory epithelium.
Sustentacular cells have structural features that allude to functions of secretion, absorption, phagocytosis, maintenance of extracellular ionic gradients, metabolism of noxious chemicals, and regulation of cell turnover. We present data detailing their dynamic activity. We show, using a mouse olfactory epithelium slice model, that sustentacular cells are capable of generating two types of calcium signals: intercellular calcium waves where elevations in intracellular calcium propagate between neighboring cells, and intracellular calcium oscillations consisting of repetitive elevations in intracellular calcium confined to single cells. Sustentacular cells exhibited rapid, robust increases in intracellular calcium in response to G-protein coupled muscarinic and purinergic receptor stimulation. In a subpopulation of sustentacular cells, oscillatory calcium transients were evoked. We pharmacologically characterized the properties of purinergic-evoked increases in intracellular calcium. Calcium transients were elicited by release from intracellular stores and were not dependent on extracellular calcium. BAPTA-AM, a cytosolic calcium chelator, and cyclopiazonic acid, an endoplasmic reticulum Ca(2+)-ATPase inhibitor irreversibly blocked the purinergic-induced calcium transient. Phospholipase C antagonist U73122 inhibited the purinergic-evoked calcium transient. 2-Aminoethoxydiphenyl borate, an inositol-1,4,5-trisphosphate (IP(3)) receptor antagonist, and the ryanodine receptor (RyR) antagonists tetracaine and ryanodine, inhibited the UTP-induced calcium transients. Collectively, these data suggest that activation of the phospholipase C pathway, IP(3)-mediated calcium release, and subsequent calcium-induced-calcium release is involved in ATP-elicited increases in intracellular calcium. Our findings indicate that sustentacular cells are not static support cells, and, like glia in the central nervous system, have complex calcium signaling.


Seasonal trends and retention of polycyclic aromatic compounds (PACs) in a remote sub-Arctic catchment.
Atmospheric deposition is the most dominant source of polycyclic aromatic hydrocarbons (PAHs) in remote and pristine areas. Despite low bioaccumulation potential, PAHs and their persistent transformation products (PAH-derivatives) are chemicals of concern as they can harm human and animal health through chronic low dose exposure. In this study, atmospheric deposition fluxes of polycyclic aromatic compounds (PACs) were measured on a seasonal basis (3-month periods) from 2012 to 2016 in a remote subarctic forest catchment in northern Europe. The target PACs included 19 PAHs and 15 PAH-derivatives (oxygenated, nitrogenated, and methylated PAHs). The deposition fluxes of ƩPAHs and ƩPAH-derivatives were in the same range and averaged 530 and 500 ng m2 day-1, respectively. The fluxes were found to be higher with a factor of 2.5 for ƩPAHs and a factor of 3 for ƩPAH-derivatives during cold (<0 °C) in comparison to warm (>10 °C) periods. PAHs and PAH-derivatives showed similar seasonal patterns, which suggests that these two compound classes have similar sources and deposition mechanisms, and that the source strength of the PAH-derivatives in air follows that of the PAHs. The terrestrial export of PACs via the outlet of the catchment stream was estimated to be 1.1% for ƩPAHs and 1.7% for ƩPAH-derivatives in relation to the annual amounts deposited to the catchment, which suggests that boreal forests are sinks for PACs derived from the atmosphere. Some individual PACs showed higher export than others (i.e. chrysene, cyclopenta(c,d)pyrene, carbazole, quinoline, and benzo(f)quinoline), with high export PACs mostly characterized by low molecular weight and low hydrophobicity (2-3 benzene rings; log Kow<6.0).


The Development of Helicopter Emergency Medical Services in the Republic of Ireland.
Helicopter emergency medical services (HEMS) have formed an integral component of the Irish health care system for the past decade; yet, the factors leading their commencement, their evolutions over this time, and the current model of service delivery have not been widely published. Aeromedical service provision may vary significantly from country to country and may also vary regionally within countries. A health system's necessities; capacity and maturity; the level of state, corporate, private, or community investment; and the capacity of the contracted service provider are all factors that influence the service provision. This research article describes the historic factors leading to a military and health system collaboration to HEMS during an era of health care reform. Over the past decade, the Irish health system has undergone significant reconfiguration and centralization of services, leading to increased demands on emergency medical ground and air medical services. Future advancements in aeromedical service provision require an innate understanding of the current model. This article adds to the knowledge base, informs policy makers, and supports decision making surrounding HEMS provision and the potential to explore military and health system collaborations and enhanced overall service provision.


Recruitment and the manpower crunch.
In summary, the signals are clear that current trends indicate a scarcity of pathologists not too many years hence. Recruiting efforts must be mounted now to bring to the attention of the appropriate medical students that pathology is a demanding, rewarding clinical discipline whose importance and satisfaction reach beyond basic science and the physical confines of the clinical laboratory.


Genetic mapping of Y-chromosomal DNA markers in Pacific salmon.
Sex chromosomes in fish provide an intriguing view of how sex-determination mechanisms evolve in vertebrates. Many fish species with single-factor sex-determination systems do not have cytogenetically-distinguishable sex chromosomes, suggesting that few sex-specific sequences or chromosomal rearrangements are present and that sex-chromosome evolution is thus at an early stage. We describe experiments examining the linkage arrangement of a Y-chromosomal GH pseudogene (GH-Y) sequence in four species of salmon (chum, Oncorhynchus keta; pink, O. gorbuscha; coho, O. kisutch; chinook, O. tshawytscha). Phylogenetic analysis indicates that GH-Y arose early in Oncorhynchus evolution, after this genus had diverged from Salmo and Salvelinus. However, GH-Y has not been detected in some Oncorhynchus species (O. nerka, O. mykiss and O. clarki), consistent with this locus being deleted in some lineages. GH-Y is tightly linked genetically to the sex-determination locus on the Y chromosome and, in chinook salmon, to another Y-linked DNA marker OtY1. GH-Y is derived from an ancestral GH2 gene, but this latter functional GH locus is autosomal or pseudoautosomal. YY chinook salmon are viable and fertile, indicating the Y chromosome is not deficient of vital genetic functions present on the X chromosome, consistent with sex chromosomes that are in an early stage of divergence.


Mutators and long-term molecular evolution of pathogenic Escherichia coli O157:H7.
It has been proposed that an increased mutation rate (indicated by the frequency of hypermutable isolates) has facilitated the emergence of Escherichia coli O157:H7. Analysis of the divergence of 12 genes shows no evidence that the pathogen has undergone an unusually high rate of mutation and molecular evolution.


Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child-Pugh B cirrhosis.
Patients with decompensated cirrhosis are excluded or underrepresented in clinical trials of systemic therapies for hepatocellular carcinoma (HCC) and comparisons of available therapies are lacking. We aimed to compare overall survival for patients with HCC and Child-Pugh B cirrhosis treated with nivolumab or sorafenib as first systemic treatment. We performed a retrospective cohort study in patients with HCC and Child-Pugh B cirrhosis treated at Veterans Affairs medical centers to compare overall survival, adverse events, and reason for discontinuation of therapy between patients treated with nivolumab or sorafenib as first systemic treatment. All statistical tests were 2-sided. Of those meeting inclusion criteria, 431 patients were treated with sorafenib and 79 with nivolumab. Median OS was 4.0 months (95% CI 3.5-4.8) in the sorafenib cohort and 5.0 months (95% CI 3.3-6.8) in the nivolumab cohort. In the multivariable Cox proportional hazards model, nivolumab was associated with a significantly reduced hazard of death compared to sorafenib (HR 0.69; 95% CI 0.52-0.91; p = 0.008). In a secondary analysis using propensity score methods, results did not reach statistical significance (HR 0.77; 95% CI 0.55-1.06; p = 0.11). Treatment was discontinued due to toxicity in 12% of patients receiving nivolumab compared to 36% receiving sorafenib (p = 0.001). In patients with HCC and Child-Pugh B cirrhosis, nivolumab treatment may be associated with improved overall survival and improved tolerability compared to sorafenib and should be considered for the first systemic treatment in this population.


Abolition of exercise induced ST depression after exercise training and its recurrence after beta blockade.
Exercise training can improve angina. A patient whose exercise tolerance test became normal after a year on an exercise programme nevertheless had a positive exercise test when he was taking a beta blocker. These results suggest that it may be undesirable to use beta blockers in patients with angina who are on exercise programmes.


Reduction of adipose tissue lipoprotein lipase activity as a result of in vivo administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the guinea pig.
Within 1 hr of intraperitoneal administration of 1 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, lipoprotein lipase (LPL) activity was reduced 38% from initial levels in the adipose tissue of the guinea pig. Maximal depression was observed after 2 days and persisted throughout the 10-day observation period. Oral administration of glucose restored LPL activity in TCDD-treated animals after 1 day but only partially after 2 and 5 days, and had no effect after 10 days of exposure. Although initial (2-day) serum insulin levels were depressed, the inability of glucose to restore LPL activity after prolonged exposure was not due to malabsorption of glucose nor to changes in serum thyroxine or insulin concentration. TCDD also inhibited the lipolytic pathway in the adipocyte, but had no effect on hormone sensitive lipase (HSL). Since HSL and LPL are reciprocally regulated, it was concluded that TCDD acts on the adipocyte to uncouple HSL-LPL reciprocity as well as to reduce LPL production.


Active increase in cardiolipin synthesis in the stationary growth phase and its physiological significance in Escherichia coli.
Activity of the Escherichia coli cardiolipin synthase, encoded by cls, increased about 10-fold in the stationary growth phase, while other committed-step enzymes in phospholipid biosynthesis rather decreased. A null cls mutant lost viability to 10(-4) of the wild-type cells during the prolonged incubation for 5 days. Cardiolipin was most stable among membrane phospholipids during the incubation. Accordingly, cardiolipin should play a role in survival of the cell and E. coli employs a sophisticated way to form cardiolipin according to need even under non-growing conditions.


Ablation of prion protein immunoreactivity by heating in saturated calcium hydroxide.
Prions, the infectious agents that cause transmissible spongiform encephalopathies (TSEs), are relatively resistant to destruction by physical, enzymatic, and chemical treatments. Hydrolysis in boiling saturated calcium hydroxide (limewater) utilizes inexpensive chemicals to digest protein components of offal. The purpose of this work was to determine if incubating brain material from scrapie-infected sheep in near-boiling saturated calcium hydroxide solution (Ca(OH)2) would abolish immunoreactivity of the infectious prion (PrPSc) as determined by western blot. After incubating for as few as 10 minutes in saturated calcium hydroxide at 99 degrees C, immunoreactivity of protease resistant bands by western blot analysis is completely lost. Boiling in limewater may offer an alternative for disposal of carcasses and enable alternative uses for rendered products from potentially infected carcasses.


On the therapy of urolithiasis in chronic renal failure.
A resigning attitude in respect to patients suffering from nephrolithiasis and manifest renal failure is not justified anymore in view of the advances in diagnosis and therapy. During the period 1964-1975, at the urological clinic of the hospital Friedrichshain 188 patients suffering from nephrolithiasis and renal failure have been treated: 120 surgically and 68 conservatively. The operative-therapeutical conception is outlined. The pre- and postoperative hemodialysis therapy is described in detail and the different indications of hemodialysis according to the stage of renal failure are elaborated. Tabulated data demonstrate the fate of all surgically treated patients.


Rapidly adhering cells in two cases of anencephaly.
We report the successful use of a new method described by Gosden and Brock (1977) in two cases of anencephaly; according to this method 'rapidly adhering cells' are identified as neural cells of a specific morphology. Although the original method described adherence of cells during the first 20 h, we were able to identify a considerable number of such cells after a delay of three days due to mailing of the amniotic fluid.


Focal motor seizures mimicking hemifacial spasm.
A young female patient, who presented acutely with an unusual movement disorder characterized by hyperkinetic facial movements, was referred to us for hemifacial spasm. The only abnormality on neurological examination was myoclonus of the left perioral and bilateral periorbital muscles, exacerbated by mental tasks. A week later, the patient also presented two generalized tonic-clonic seizures on awakening and was successfully treated with antiepileptic drugs. Laboratory and neuroimaging investigations yielded normal findings. Although we were unable to identify a cortical generator, the concomitant occurrence of generalized seizures, the disappearance of symptoms after treatment and the topography of the myoclonus support an epileptic origin of this myoclonus.


Modulation of key signal transduction molecules by a novel peptide combination effective for the treatment of gastrointestinal carcinomas.
We have reported earlier a novel combination of four structurally designed synthetic neuropeptide analogs of vasoactive intestinal peptide (VIP), bombesin, substance P and somatostatin, code-named DRF 7295 which have anti-tumor efficacy for adenocarcinomas in vitro and in vivo (Jaggi et al., Invest New Drugs, 2008). The discovery, synthesis, in vitro and in vivo efficacy was reported (Jaggi et al., Invest New Drugs, 2008). Gastrointestinal tumor cells of the colon, pancreas and duodenum were found to most sensitive to DRF7295 in vitro and in vivo (Jaggi et al., Invest New Drugs, 2008). We have further investigated and report here the modulation of cellular signaling in gastrointestinal carcinomas by DRF 7295, which may be mediating its observed anticancer activity in these cancer types. DRF 7295 inhibits the binding of specific neuropeptides initiating a cascade of cellular signaling events leading to programmed cell death. It down regulates the second messenger cAMP, epidermal growth factor (EGF) dependent proliferation and the phosphorylated MAP Kinase pERK1/2 in gastrointestinal carcinomas, thus depriving the tumour cells of critical pro-proliferative cellular signals. It triggers bcl2 and Caspase 3 dependent apoptotic cell death and induces p53 tumor suppressor protein in the treated carcinoma cells in vitro. It has significant anti-angiogenic potential as reflected in the inhibition of tube like formation in the endothelial cells and down regulation of VEGF levels. Tumour xenograft studies confirmed the in vivo efficacy of DRF 7295 for gastrointestinal carcinomas (Jaggi et al., Invest New Drugs, 2008). The Phase I clinical trials have shown DRF 7295 to be well tolerated and devoid of systemic toxicities of the conventional cytotoxics (Mukherjee et al., Phase I dose escalating study of DRF7295: a new class of peptide based drugs. "Abstract" ASCO ID:948, 2003). The drug may have a promising role in disease stabilization in colorectal and other cancers. Thus DRF 7295 is a novel targeted drug in the class of signal transduction modulators, with potential for treatment of gastrointestinal carcinomas.


Accelerated one-step generation of full-color holographic videos using a color-tunable novel-look-up-table method for holographic three-dimensional television broadcasting.
A color-tunable novel-look-up-table (CT-NLUT) for fast one-step calculation of full-color computer-generated holograms is proposed. The proposed method is composed of four principal fringe patterns (PFPs) such as a baseline, a depth-compensating and two color-compensating PFPs. CGH patterns for one color are calculated by combined use of baseline-PFP and depth-compensating-PFP and from them, those for two other colors are generated by being multiplied by the corresponding color-compensating-PFPs. color-compensating-PFPs compensate for differences in the wavelength between two colors based on their unique achromatic thin-lens properties, enabling transformation of one-color CGH pattern into those for other colors. This color-conversion property of the proposed method enables simultaneous generation of full color-CGH patterns, resulting in a significant reduction of the full color-CGH calculation time. Experimental results with test scenario show that the full color-CGH calculation time of the proposed CT-NLUT has been reduced by 45.10%, compared to the conventional NLUT. It has been further reduced by 96.01% when a data compression algorithm, called temporal redundancy-based NLUT, was used together, which means 25-fold reduction of its full color-CGH calculation time. Successful computational and optical reconstructions of full color-CGH patterns confirm the feasibility of the proposed method.


Analysis of the prognostic factors and evaluation of surgical treatment for synchronous liver metastases from gastric cancer.
Whether or not a synchronous resection of liver metastases from gastric cancer provides a survival benefit has been a key issue. We identify the significant prognostic factors and clarify the beneficial effect on the survival of liver surgical treatment. We reviewed 72 patients who underwent a gastrectomy for gastric cancer with synchronous liver metastases and classified the liver metastases into three grades, such as H1: metastases were limited to one of the lobes, H2: there were a few scattered metastases in both lobes, and H3: there were numerous scattered metastases. H1, 2 metastases, and an absence of peritoneal dissemination (P0) were significantly independent prognostic factors for liver metastases of gastric cancer. In addition, the cumulative 1 and 5-year survival rates of liver surgical treatment (hepatic resection and/or microwave coagulation therapy) were 80.0% and 60.0%, whereas the survival rates for non-hepatic surgical treatment were 36.4% and 0% in 26 patients with H1, 2, and P0. In those patients, the radical operation, the solitary metastatic liver tumor, and no-distant lymph node metastases were independent prognostic determinants of survival. The radical operation including the surgical treatment for metastatic liver tumors should be performed to improve the prognosis in gastric cancer patients with synchronous H1, 2, and P0.


Diimidazo[1,2-c:4',5'-e]pyrimidines: N6-N1 conformationally restricted adenosines.
Tethering the N6-substituents of N6-substituted adenosines to N1 has resulted in a series of conformationally restricted adenosine analogues. The resultant diimidazo[1,2-c:4',5'-e]pyrimidines were shown to be adenosine A1 selective.


Novel and reported APC germline mutations in Chinese patients with familial adenomatous polyposis.
Familial adenomatous polyposis (FAP) is mainly caused by germline mutations in the adenomatous polyposis coli (APC) gene. This study aimed to detect pathogenic variants in five Chinese FAP families and review all previously reported pathogenic variants of APC gene in Chinese population. Five non-consanguineous FAP families and 100 unrelated ethnicity-matched controls were included in the study. Sanger sequencing was performed to screen for APC coding and splicing variants. Chinese and English literature on APC germline mutations were reviewed to compile the mutation spectrum of APC gene in Chinese FAP patients. One pathogenic variant was detected in each family for the five pedigrees we tested. Three variants (c.3183_3187delACAAA, c.2626C>T and c.1312+1G>A) were previously reported as pathogenic. The other two variants were novel: c.794_795insG/p.Val266SerfsTer11 and c.2142_2143insG/p.His715AlafsTer19. They are absent from public databases (1000 Genomes, dbSNP, ESP and ExAC) and 100 normal controls, and are classified as pathogenic based on the new ACMG/AMP variant classification guidelines. Literature review and current study revealed a total of 82 different pathogenic variants from 127 Chinese FAP families. Among these families, 83 families had frameshift variants (65.35%), 26 with nonsense variants (20.47%), six with splice site variants (4.72%), three with missense variants (2.36%) and nine with large deletion or duplication variants (7.09%). Apart from the two previously reported mutation hotspots c.3927_3931delAAAGA (20.47%) and c.3183_3187delACAAA (7.09%), c.847C>T/p.Arg283Ter variant occurred with a frequency of 3.15% (4 out of 127) in Chinese FAP patients. We reported two novel pathogenic variants. The comprehensive compilation of variants and comparison revealed largely similar mutation spectrum between Chinese and Western patient populations. Some unique features noticed in Chinese patient population may help to better understand the pathogenesis of FAP.


Long-term outcome of combined trabeculotomy-trabeculectomy by a single surgeon in patients with primary congenital glaucoma.
PurposeAssess long-term outcome of combined trabeculotomy-trabeculectomy (CTT) in primary congenital glaucoma (PCG).MethodsData of PCG patients treated with CTT by a single surgeon between 1976 and 1993 were reviewed for reduction in intraocular pressure (IOP), visual acuities, surgical success rates, and need for repeat surgeries at last follow-up (FU). At the last FU, IOP<21 mm Hg without any topical antiglaucoma medication (TAM) was complete success and with 1-2 TAMs was qualified success. IOP reduction ≥30% without any TAM was modified complete success and with 1-2 TAMs was modified qualified success. IOP>21 mm Hg, IOP reduction <30%, or use of >2 TAM at last FU, or need for additional surgery was considered as failure.ResultsTwo hundred thirty eyes of 121 patients had been followed up for 21.5-38 years (mean 28.87±2.77 years). Eyes that were pthisical (3), had immeasurable IOP (2), or IOP<6 mm Hg (3) were excluded from the success analysis. At last FU, mean IOP reduction was 22.71±11.28 mm Hg and TAM score was 1.71 (0-4). Complete success was achieved in 14 (6.3%), modified complete success in 14 (6.3%), qualified success in 148 (66.7%), and modified qualified success in 140 (63.1%). Success probability was 95% till 25 years and 92, 90, 85, 79 and 68% at 26, 27, 28, 29, and 30 years, respectively. Severe visual impairment or functional blindness was found in only 13 (10.7%) patients.ConclusionCTT shows long-term success in PCG patients. All patients must be monitored for IOP control to avoid need for repeat surgeries.


Rebamipide protects against experimentally induced intestinal ischemia/reperfusion-promoted liver damage: Impact on SIRT1/β-catenin/FOXO1and NFκB signaling.
Rebamipide (Reba) is a well-known gastroprotective agent. However, its potential protective efficacy against intestinal ischemia/reperfusion (I/R)-induced liver injury remains elusive. Therefore, this study aimed to assess the modulatory effect of Reba on SIRT1/β-catenin/FOXO1-NFκB signaling cascade. Thirty-two male Wistar albino rats were randomized into four groups: G1 (sham): rats were subjected to surgical stress without I/R, GII (I/R): rats were subjected to 60 min/4-h I/R, GIII (Reba + I/R): rats received Reba 100 mg/kg/day, p.o. for three weeks, then were subjected to 60 min/4-h I/R, and GIV (Reba + EX527 + I/R): rats received Reba (100 mg/kg/day p.o.) + EX527 (10 mg/kg/day, ip) for three weeks before I/R. Reba pretreatment decreased the serum levels of ALT and AST, improved I/R-induced histological alterations of both intestine and liver, increased hepatic Silent information regulator 1 (SIRT1) expression/content, β-catenin expression/immunoreactivity, and FOXO1 expression, while suppressed NF-κB p65 expression/protein content. In addition, Reba increased hepatic total antioxidant capacity (TAC), while suppressed malondialdehyde (MDA), tumor necrosis factor (TNFα), and caspase-3 activity. Furthermore, Reba inhibited BAX expression, while upregulated Bcl-2 expression. Reba exhibited a plausible protective effect against intestinal I/R-mediated liver injury by modulating SIRT1/β-catenin/FOXO1-NFκB signaling mechanisms.


Improved Description of Stereoelectronic Effects in Hydrocarbons Using Semilocal Density Functional Theory.
Serious and systematic errors with popular density functionals occur for isodesmic stabilization energies of n-alkanes, isomerization, and dimerization energies of hydrocarbons and geometries of sterically overcrowded aromatic systems. These functionals are too biased toward the correct description of free atoms. Changing two parameters within the Perdew-Burke-Ernzerhof approximation leads to a new nonempirical functional, PBEsol, that improves the description of large organic systems.


Human proteolipid protein (PLP) mediates winding and adhesion of phospholipid membranes but prevents their fusion.
Proteolipid protein (PLP or lipophilin) is a highly conserved, strongly hydrophobic, integral membrane protein, and is the major protein component of central nervous system myelin. Although PLP has been implicated in many functions, its in vivo role is still uncertain. Here, we report the investigation of PLP's putative adhesive function using purified PLP and reconstituted phospholipid vesicles made of either 100% phosphatidylcholine (PC), or a mixture of 92% PC and 8% phosphatidylserine (PS), by weight. PLP-induced changes in the phospholipid bilayer surfaces were directly examined by transmission electron microscopy. We found that upon the introduction of PLP, larger lipid vesicles became smaller and unilamellar. At the PLP:lipid molar ratio of 1:20, vesicle membranes rolled onto themselves forming 'croissant'-like structures that subsequently adhered to each other. The phenomena of PLP-induced bilayer rolling and adhesion were dependent on the concentration of PLP and the period of incubation, but were independent of the presence of calcium and types of phospholipids (PC or PC:PS). Furthermore, the presence of PLP in the lipid bilayers prevented the fusion of membranes. These findings show that PLP can induce membrane 'winding' while preventing the fusion of adjacent lipid bilayers. Hence, our data provide direct evidence for PLP's suspected function of membrane adhesion, and also suggest that PLP could potentially play a role in the formation of the myelin sheath.


Treatment of MOPP-refractory Hodgkin's disease with vinblastine, doxorubicin, bleomycin, CCNU, and dacarbazine.
Eighteen patients with advanced Hodgkin's disease, refractory to combination chemotherapy with nitrogen mustard, vincristine, prednisone, and procarbazine (MOPP), were treated with vinblastine, doxorubicin (Adriamycin), bleomycin, CCNU, and dacarbazine (DTIC) (VABCD). Fifteen patients had Stage IV disease and 11 had systemic symptoms. Although hematologic toxicity was considerable, there was no drug related mortality. Eight patients achieved a complete remission (CR), and five are currently in a continuous CR of five, 24, 30, 34, and 36 months duration, respectively. An additional patient had a 30-month CR and relapsed with localized lymphadenopathy and is currently disease-free following involved-field radiotherapy 46 months from initiation of VABCD. This study suggests that long-term disease-free survival and potential cure can be achieved with VABCD in MOPP-refractory Hodgkin's disease.


Assessment of the air quality in 20 public indoor swimming pools located in the Northern Region of Portugal.
Air exposures occurring in indoor swimming pools are an important public health issue due to their popularity and regular use by the general population, including vulnerable groups such as children and elderly people. More comprehensive information on indoor air quality (IAQ) in swimming pools is thus needed in order to understand health risks, establish appropriate protective limits and provide evidence-based opportunities for improvement of IAQ in these facilities. In this context, twenty public indoor swimming pools located in the Northern Region of Portugal were examined in two sampling campaigns: January-March and May-July 2018. For each campaign, a comprehensive set of environmental parameters was monitored during the entire period of the facilities' operating hours of a weekday, both indoors and outdoors. In addition, four air (1-h samplings) and water samples were collected. Findings show that comfort conditions, ultrafine particles number concentrations and exposure to substances in the indoor air (concentration and composition) is likely to vary greatly from one public indoor swimming pool to another. Trihalomethanes (THM) and dichloroacetonitrile were the predominant disinfection by-products identified in the indoor air but other potentially hazardous volatile organic compounds, such as limonene, 1,2,4-trimethylbenzene, 2,2,4,4,6,8,8-heptamethylnonane, 2- and 3-methylbutanenitrile, acetophenone, benzonitrile, and isobutyronitrile were found to have relevant putative emission sources in the environment of the swimming pools analyzed. Furthermore, indicators of poor ventilation conditions (namely carbon dioxide, relative humidity and existence of signs of condensation in windows) and some water-related parameters (THM levels, conductivity and salinity) were found to be determining factors of the measured airborne THM concentrations that appeared to significantly potentiate the exposure. In summary, this work provides evidence for the need to establish adequate standards for the comprehensive evaluation of IAQ in public swimming pools, in order to guide further development of evidence-based prevention/remediation strategies for promoting healthy environments in swimming pools.


Medical students' beliefs and attitudes towards schizophrenia before and after undergraduate psychiatric training in Greece.
The aim of the present study was to explore medical students' beliefs and attitudes towards people with schizophrenia (PwS) prior to receiving any training in psychiatry and to assess the impact of the psychiatric placement on changing them. A questionnaire addressing beliefs, attitudes and desired social distance from PwS was distributed to all final year medical students before the beginning of their 4-week undergraduate psychiatric placement and upon its completion. Students did not endorse stereotypes commonly attached to PwS, such as being dangerous, lazy or of lower intelligence, but they held the view that PwS are unpredictable and suffer from split personality. Furthermore, the baseline level of desired social distance was found to increase as the intimacy of the interaction increased, and the only variable associated with it was personal experience of serious mental illness. Moreover, the placement was found to have either no influence at all or in a negative direction. Upon its completion more students were found to believe that PwS cannot recover, have no insight into their condition, cannot make reasonable decisions, cannot work in regular jobs and are dangerous to the public. No difference was recorded in social distance scores. A close and critical examination of the various elements of the undergraduate placement in psychiatry is needed in order to develop an evidence-based, fully rounded education with an anti-stigma orientation.


Neonatal septicemia caused by pneumococci.
Pneumococci (Streptococcus pneumoniae) infrequently cause neonatal septicemia. An increased number of cases have been reported in recent years, but no increase in the relative incidence among neonatal infections has been noted. On the basis of two cases of our own and a review of 40 recently published case reports, the clinical characteristics of pneumococcal septicemia are described and the pathogenesis is discussed. The presenting clinical picture in early-onset pneumococcal septicemia is dominated by respiratory distress, frequently accompanied by leukopenia, and is indistinguishable from that seen in septicemia caused by Group B Streptococci (GBS). The onset is preceded by prelabor rupture of the fetal membranes in almost half of the instances. The mortality is 50%, twice the figure given in recent GBS reports.


Cortical neurons with collateral projections to both the caudate nucleus and the centromedian-parafascicular thalamic complex: a fluorescent retrograde double labeling study in the cat.
The retrograde fluorescent technique was used to label cortical neurons which project to both the caudate nucleus and also to the centromedian-parafascicular (CM-Pf) thalamic nuclear complex. After experimentation with many other pairs of fluorescent tracers, Evans Blue (EB) and Fast Blue (FB) were chosen as the best combination for studying the systems involved. Following injections of EB into the caudate nucleus and FB into the CM-Pf complex, doubly labeled medium-sized pyramidal neurons were present within layer V and VI of specific cortical regions. These cells were found on the inferior bank of the cruciate sulcus, in the anterior limbic area, in the cingulate and anterior sylvian gyri and within the buried cortex of the presylvian sulcus. The doubly labeled cells were relatively few in number compared to the more numerous singly labeled FB (corticothalamic) cells found in layers V and VI, and the very numerous singly labeled EB (corticostriatal) neurons, located in layers II, III, V, and VI.


Saccade Preparation Reshapes Sensory Tuning.
Human observers make large rapid eye movements-saccades-to bring behaviorally relevant information into the fovea, where spatial resolution is high. In some visual tasks [1-4], performance at the location of a saccade target improves before the eyes move. Although these findings provide evidence that extra-retinal signals evoked by saccades can enhance visual perception, it remains unknown whether and how presaccadic modulations change the processing of feature information and thus modulate visual representations. To answer this question, one must go beyond the use of methods that only probe performance accuracy (d') in different tasks. Here, using a psychophysical reverse correlation approach [5-8], we investigated how saccade preparation influences the processing of orientation and spatial frequency-two building blocks of early vision. We found that saccade preparation selectively enhanced the gain of high spatial frequency information and narrowed orientation tuning at the upcoming saccade landing position. These modulations were time locked to saccade onset, peaking right before the eyes moved (-50-0 ms). Moreover, merely deploying covert attention within the same temporal interval without preparing a saccade did not alter performance. The observed presaccadic tuning changes may correspond to the presaccadic enhancement [9-11] and receptive field shifts reported in neurophysiological studies [12-14]. Saccade preparation may support transaccadic integration by reshaping the representation of the saccade target to be more fovea-like just before the eyes move. The presaccadic modulations on spatial frequency and orientation processing illustrate a strong perception-action coupling by revealing that the visual system dynamically reshapes feature selectivity contingent upon eye movements.


Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.
Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known. All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection. Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy. Ustekinumab could be a promising option for the treatment of POR of CD.


Universal health coverage in India and health technology assessment: current status and the way forward.
In India, there is a renewed emphasis on Universal Health Coverage (UHC). Alongside this, Health Technology Assessment (HTA) is an important tool for advancing UHC. The development and application of HTA in India, including capacity building and establishing institutional mechanisms. We emphasized using the HTA approach within two components of the Ayushman Bharat programme, and the section concludes with lessons learned and the next steps. The UHC has increased the importance of selecting and implementing effective technologies and interventions within national health systems, particularly in the context of limited resources. To maximize the use of limited resources and produce reliable scientific assessments, developing and enhancing national capacity must be based on established best practices, information exchange between different sectors, and collaborative approaches. A more potent mechanism and capacity for HTA in India would accelerate the country's progress toward UHC.


Using corpora to reveal style in translation: The case of The Song of Everlasting Sorrow.
This article reports on a corpus-based study of the English translation of Wang Anyi's award-winning novel, The Song of Everlasting Sorrow [, Chang Hen Ge] from the perspective of style. Using the keyword and concordance functions of corpus software packages AntConc and ParaConc, this research focuses on how the translator's style reveals itself in the target text (TT) as well as how the style of the source text (ST) is represented in the TT. Findings show that the translators have a preference for contracted negative verb forms and expressions such as "bit" over "little," making the text more colloquial. In general, the rendering of the ST style tends not to be entirely faithful. A distinction between reader-centered and text-centered keywords is made. While the reader-centered ST keywords are, as expected, largely altered, the translation of text-centered ST keywords is also rewritten, contrary to expectations. Presumably, the translators tended to reduce the ambiguity of the ST, resulting in a more explicit TT. The article argues that the translators chose to rewrite the translation to make it more understandable for the target audience since it concerned a work from a source culture very different from the target culture.


Risk factors of avascular necrosis in the treatment of congenital dislocation of the hip.
We examined the causes of iatrogenic avascular necrosis of the femoral head in 254 hips with congenital dislocation (CDH) treated conservatively. The influence of the age of the child, the height of the displacement of the femoral head, the extent of acetabular dysplasia, and the method of treatment on the frequency and degree of necrosis were estimated. The investigation showed that children are at the highest risk of iatrogenic necrosis in the following cases: (a) age less than 6 months, (b) severe acetabular dysplasia, (c) use of an abduction apparatus such as the Frejka pillow for outpatients, and (d) "frog-leg" position after reduction.


Characterization of polysorbate 80 with liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy: specific determination of oxidation products of thermally oxidized polysorbate 80.
The polysorbate species in polysorbate 80 (PS 80) have been characterized with (1)H NMR, LC-UV/MS and MS/MS. The MS was operated with both negative and positive electrospray ionization (ESI). PS 80 was found to contain mono- and di-fatty acid esters of polyoxyethylene (POE) sorbitan, POE isosorbide and of POE. In addition, the same species were also present without fatty acid esters. The polysorbate species were esterified with C12:0, C14:0, C16:1, C16:0, C18:2, C18:1 and C18:0 fatty acids. The main species were polysorbate esters of C18:1. The C18:2 polysorbate species were shown, by (1)H NMR, to have a large component of fatty acids with a conjugated double bond of ZE and/or EZ configuration. The positive ESI mass spectra of the polysorbate species displayed a specific in-source fatty acid fragment for each fatty acid ester. The mass chromatograms of the in-source fatty acid fragments were used to determine the degradation of specific polysorbate species in PS 80. The C18:2 polysorbate species were completely degraded after 8 weeks at 40°C under an atmosphere of air, while the main C18:1 polysorbate species were reduced to ca. 80-86% accompanied by an increase of short-chain POE C18:1 species. Polysorbate species esterified with C18:1-OH, C18:1 keto and C18:0 epoxy acids were found as degradation products of PS 80 stored at 40°C for 8 weeks under air. C18:1-OH, C18:1 keto and C18:0 epoxy acids were believed to be oxidation products of C18:1. With the present conditions, the positive ESI mass spectra of C18:1-OH and C18:0 epoxy polysorbate species displayed identical ions to the C18:2 polysorbate species due to a facile in-source loss of H(2)O from the protonated molecules. The presence of polysorbate esters of C18:1-OH and C18:0 epoxy acids were established using negative ESI MS. The presence of oxidized fatty acids in degraded PS 80 was also confirmed by saponification and extraction followed by negative ESI LC-MS analysis of the free fatty acids.


[Practice-relevant autoimmune diseases of the central nervous system in pediatrics: early diagnosis and adequate initiation of treatment].
Pediatric autoimmune diseases affecting the central nervous system have recently come into the the focus of attention. Important advances have been made in the field of children with multiple sclerosis (MS), which led to a better understanding of the clinical characteristics and treatment options. Furthermore, new autoantibodies against target antigens of neurons, peripheral nerves and the myelin sheath have been detected. This article summarizes new advances in children with MS and addresses the differences to their adult counterparts. In addition, the most important forms of autoimmune encephalitis, such as N‑methyl D‑aspartate receptor (NMDA-R) or myelin oligodendrocyte glycoprotein (MOG) encephalitis in children are described together with the diagnostic algorithm and therapeutic approach in the event of a suspected autoimmune encephalitis. Lastly, the clinical spectrum of MOG antibody-associated diseases (MOGAD) is detailed.


MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951.
The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others. We conducted genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status. We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 3.8 years, both P < 0.0001 for CIMP and MGMT-STP27 status, respectively]. Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex, performance score, and review diagnosis in the model. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years, respectively (P = 0.0033); for MGMT-STP27 methylated samples, it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P = 0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response. MGMT-STP27 may be used to guide treatment decisions in this tumor type.


A new series of C3-aza carbocyclic influenza neuraminidase inhibitors: synthesis and inhibitory activity.
The synthesis and influenza neuraminidase inhibitory activity of a new series of C3-aza carbocyclic neuraminidase inhibitors are described. Analogues 3c and 3j, bearing a 3-pentyl group, exhibit influenza A inhibitory activities comparable to that of 1.


Myocyte enhancer factor 2 (MEF2) is a key modulator of the expression of the prothoracicotropic hormone gene in the silkworm, Bombyx mori.
Prothoracicotropic hormone (PTTH) plays a central role in controlling molting, metamorphosis, and diapause termination in insects by stimulating the prothoracic glands to synthesize and release the molting hormone, ecdysone. Using Autographa californica nucleopolyhedrovirus (AcNPV)-mediated transient gene transfer into the central nervous sytem (CNS) of the silkworm, Bombyx mori, we identified two cis-regulatory elements that participate in the decision and the enhancement of PTTH gene expression in PTTH-producing neurosecretory cells (PTPCs). The cis-element mediating the enhancement of PTTH gene expression binds the transcription factor Bombyx myocyte enhancer factor 2 (BmMEF2). The BmMEF2 gene was expressed in various tissues including the CNS. In brain, the BmMEF2 gene was expressed at elevated levels in two types of lateral neurosecretory cells, namely PTPCs and corazonin-like immunoreactive lateral neurosecretory cells. Overexpression of BmMEF2 cDNA caused an increase in the transcription of PTTH. Therefore, BmMEF2 appears to be particularly important in the brain where it is responsible for the differentiation of lateral neurosecretory cells, including the enhancement of PTTH gene expression. This is the first report to identify a target gene of MEF2 in the invertebrate nervous system.


Herpes simplex virus seroprevalence and seroconversion among active duty US air force members with HIV infection.
Herpes simplex virus (HSV) infection is associated with an increased risk of both HIV transmission and acquisition. We evaluated longitudinal HSV serology and sexually transmitted infections (STIs) among active duty US Air Force (USAF) members with HIV infection. USAF members diagnosed with HIV between 1996 and 2012 were included and divided into 2 groups: 1996-2004 (n=131) and 2005-2012 (n=266). HSV-1 and -2 serology was evaluated at HIV diagnosis. Longitudinal HSV-1 and -2 serology and ICD-9 codes for HSV and non-HSV STIs were also examined for those with ≥ 1 year of follow-up. Patients were most commonly Caucasian (44.2%) or African American (43.4%) men with a median age of 28 years at HIV diagnosis. HSV-2 seroprevalence at HIV diagnosis decreased from the period of 1996-2004 (48.8%) to 2005-2012 (30.1%; P<0.01). Odds of HSV-2 seropositivity was significantly greater for non-Caucasians (OR 2.19, 95% CI 1.33-3.60) and for HIV diagnosis between 1996 and 2004 (OR 2.06, 95% CI 1.29-3.27), with a trend observed for those age >30 years at HIV diagnosis (OR 1.73, 95% CI 0.94-3.18). A total of 81 (20.4%) patients developed STIs by ICD-9 codes, including 24 (6.1%) new genital herpes diagnoses, during a median follow-up of 4.6 years. HSV-2 seroconversion occurred in 33 of 253 (13.0%) with an incidence rate of 5.07 per 100 person-years (95% CI 4.76-5.37). Although HSV-2 seroprevalence at HIV diagnosis decreased over time, high-risk sexual behaviors were ongoing as evidenced by the high proportion of new STI diagnoses and HSV-2 seroconversions. Continued education to reduce risk behaviors is warranted to prevent acquisition and transmission of STIs in HIV-infected persons.


Effect of Diet Composition on Excreta Composition and Ammonia Emissions from Growing-Finishing Pigs.
This study aimed to investigate the impact of decreased crude protein (CP) levels (by 2% units) or acidifying diets (by adding 10 g benzoic acid/kg diet in combination with replacing a part of CaCO3 by about 10 g Ca-formate/kg diet) on urine, feces and manure composition and ammonia emissions from growing and finishing pig houses. Yorkshire x F1(Landrace x Yorkshire) pigs (n = 576) with an initial body weight of 24.9 ± 3.4 kg were randomly allocated to four treatments of (i) a control diet with normal protein content and no acidifying components added; (ii) a diet with 2% units CP reduction; (iii) a diet with an acidifying effect on the manure; (iv) or a diet consisting of a combination of diet (ii) and (iii). Pigs were housed in four mechanically ventilated and temperature-controlled rooms. Results showed that decreasing the dietary CP levels by 2% units reduced the ammonia emission from the floor by 46% (p = 0.06) and from the pig house by 31% (p = 0.08). Decreased CP diets reduced the total N in feces and in manure and NH4-N in the manure, as well as the ammonia concentration at 1 cm and 10 cm above the manure surface (p < 0.05). However, acidifying diets failed to reduce ammonia emissions from the floor and the pig house (p > 0.05). Reducing dietary crude protein is, therefore, a solution to reducing ammonia emissions from pig houses.


Molecular diagnosis of Pneumocystis pneumonia.
The detection of Pneumocystis DNA in clinical specimens by using PCR assays is leading to important advances in Pneumocystis pneumonia (PcP) clinical diagnosis, therapy and epidemiology. Highly sensitive and specific PCR tools improved the clinical diagnosis of PcP allowing an accurate, early diagnosis of Pneumocystis infection, which should lead to a decreased duration from onset of symptoms to treatment, a period with recognized impact on prognosis. This aspect has marked importance in HIV-negative immunocompromised patients, who develop often PcP with lower parasite rates than AIDS patients. The specific amplification of selected polymorphous sequences of Pneumocystis jirovecii genome, especially of internal transcribed spacer regions of the nuclear rRNA operon, has led to the identification of specific parasite genotypes which might be associated with PcP severity. Moreover, multi-locus genotyping revealed to be a useful tool to explore person-to-person transmission. Furthermore, PCR was recently used for detecting P. jirovecii dihydropteroate synthase gene mutations, which are apparently associated with sulfa drug resistance. PCR assays detected Pneumocystis-DNA in bronchoalveolar lavage fluid or biopsy specimens, but also in oropharyngeal washings obtained by rinsing of the mouth. This non-invasive procedure may reach 90%-sensitivity and has been used for monitoring the response to treatment in AIDS patients and for typing Pneumocystis isolates.


Time course of histone deacetylase 1 and acetylated H3 and H4 histones in the brain of rats treated with ladasten.
We studied the effects of single intragastric administration of ladasten in a dose of 50 mg/kg on the time course of histone deacetylase 1 (HDAC1) and levels of acetylated histones H3 (Lys9) and H4 (Lys8) in the striatum, hippocampus, and hypothalamus. Ladasten reduced HDAC1 level in rat striatum and hippocampus and modified H3acK9 and H4acK8 levels in various structures of rat brain.


Pattern of Uveitic Hypotony in a Tertiary Eye Hospital in India.
To report pattern of uveitic patients with hypotony in Indian population. Retrospective medical record review of 30 eyes of 21 consecutive patients with uveitic hypotony. Patient demographics, ocular findings and systemic association were recorded. Mean age of the patients was 29.5 years (range 7-71 years) and 80.9%(17 patients) were below the age of 40 years. Most common complaint associated with the development of hypotony was diminution of vision (26 eyes; 86.6%), and cells in anterior vitreous (25 eyes, 83.3%) were the most common slit-lamp finding. Most common type of ocular inflammation causing hypotony was panuveitis (14, 46.6%), and ocular tuberculosis (5; 23.8%) was the most common cause of uveitis in these patients. Ocular hypotony is a rare but dreaded complication of uveitis. The etiology of uveitic hypotony is not uniform across the world, and tuberculosis remains an important cause of uveitic hypotony in tuberculosis endemic country like India.


Psychological outcomes of the systematic interventions based on the stress-induced situation, affective, bodily, and cognitive reactions framework for patients with lung cancer: A randomized clinical trial.
Psychological distress is a multi-factorial unpleasant experience of a psychological, social, spiritual, and/or physical nature that may interfere with one's ability to cope effectively with cancer, physical symptoms and treatment. Psychological distress is common and affects the prognosis of cancer patients. Lung cancer accounted for 11.4 % of all new cancer cases and 18 % of all cancer mortality for 36 cancers in 185 countries. The prevalence of distress among Chinese lung cancer patients ranged from 10.1 % to 61.29 %. However, the existing intervention studies on the psychological distress in lung cancer patients are limited and intervention results may be different. To explore the psychological outcomes of a nurse-led systematic intervention program based on the stress-induced situation, affective, bodily, and cognitive reactions framework for patients with lung cancer undergoing operation at anxiety and depression. A randomized clinical trial. Thoracic surgery ward in a tertiary hospital in China. Lung cancer patients undergoing surgery. This is a 12-month longitudinal randomized controlled study in a tertiary hospital in China. A total of 240 lung cancer patients were randomly divided into either the control group or the intervention group. The nurse-led systematic intervention contents include psychological education, intervention measures based on the stress-induced situation, affective, bodily, and cognitive reactions framework, issuance of daily lifestyle cards, and regular follow-ups. The Hospital Anxiety and Depression Scale, Functional Assessment of Chronic Illness Therapy-Fatigue Scale, and Satisfaction with Life Scale were used for the baseline assessment within 48 h upon admission. The same assessment was performed respectively at 1, 3, 6 and 12 months after the intervention started. The effects of the systematic interventions on depression, anxiety, fatigue, and life satisfaction were tested by a linear mixed effects model. Overall time-by-group interaction effects were significantly different with regard to anxiety, depression, and fatigue after controlling for the covariates, while a significant time-by-group interaction effect was not found for life satisfaction. Changes for anxiety and depression scores at 6 and 12 months after initiation of the intervention were significantly greater in the intervention group compared with those in the control group (t = 3.046, p = 0.002, t = 3.190, p = 0.001; t = 3.735, p = 0.000, t = 2.979, p = 0.002), whereas scores for fatigue were significantly higher in the intervention group at 6 and 12 months (t = -3.096, p = 0.002, t = -2.784, p = 0.005). The systematic intervention program based on the stress-induced situation, affective, bodily, and cognitive reactions framework may effectively relieve anxiety, depression, and fatigue in lung cancer patients undergoing surgery. This study was registered on December 22, 2019 with the registration number ChiCTR1900028487, and the date of first recruitment was Jan 5, 2020.


Acoustic Parameters for Optimal Ultrasound-Triggered Release from Novel Spinal Hardware Devices.
Post-operative infection is a catastrophic complication of spinal fusion surgery, with rates as high as 10%, and existing preventative measures (i.e., peri-operative antibiotics) are only partially successful. To combat this clinical problem, we have designed a drug delivery system around polyether ether ketone clips to be used for prophylactic post-surgical release of antibiotics upon application of ultrasound. The overall hypothesis is that antimicrobial release from this system will aggressively combat post-surgical bacterial survival. This study investigated a set of acoustic parameters optimized for in vitro ultrasound-triggered coating rupture and subsequent release of encapsulated prophylactic antibiotics. We determined that a transducer frequency of 1.7 MHz produced the most consistent burst release and that, at this frequency, a pulse repetition frequency of 6.4 kHz and acoustic output power of 100% (3.41 MPa) produced the greatest release, representing an important proof of principle and the basis for continued development of this novel drug delivery system.


In vivo incorporation of [14C]leucine into brain protein of mice treated with methylmercury and thiol complexes of methylmercury.
The effect of methylmercury and thiol complexes of methylmercury on inhibition of protein synthesis was evaluated. Mice were injected (i.p.) with the following treatments: methylmercuric chloride, methylmercury-glutathione, methylmercury-cysteinylglycine and control (vehicle) for 10 days. Ten animals from each group were injected with [14C]leucine 90 min prior to death. The brains were removed and the extracted protein was subjected to liquid scintillation analysis. Mice receiving the methylmercury and methylmercury-glutathione treatments exhibited significantly greater weight loss than the control while the methylmercury-cysteinylglycine treatment was not significantly different than the control. Incorporation of [14C]leucine into brain protein was significantly depressed in the methylmercury (81% of control) and the methylmercury-glutathione (79% of control) treatments. Protein synthesis in mice receiving the methylmercury-cysteinylglycine complex although not significantly different than the methylmercury treatments was only 92% of the control mice.


Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice.
The NAD(+)-dependent protein deacetylase sirtuin (SIRT)1 is thought to be a key regulator of skeletal muscle metabolism. However, its precise role in the regulation of insulin sensitivity is unclear. Accordingly, we sought to determine the effect of skeletal muscle-specific overexpression of SIRT1 on skeletal muscle insulin sensitivity and whole-body energy metabolism. At 10 weeks of age, mice with muscle-specific overexpression of SIRT1 and their wild-type littermates were fed a standard diet with free access to chow or an energy-restricted (60% of standard) diet for 20 days. Energy expenditure and body composition were measured by indirect calorimetry and magnetic resonance imaging, respectively. Skeletal muscle insulin-stimulated glucose uptake was measured ex vivo in soleus and extensor digitorum longus muscles using a 2-deoxyglucose uptake technique with a physiological insulin concentration of 360 pmol/l (60 μU/ml). Sirt1 mRNA and SIRT1 protein levels were increased by approximately 100- and 150-fold, respectively, in skeletal muscle of mice with SIRT1 overexpression compared with wild-type mice. Despite this large-scale overexpression of SIRT1, body composition, whole-body energy expenditure, substrate oxidation and voluntary activity were comparable between genotypes. Similarly, skeletal muscle basal and insulin-stimulated glucose uptake were unaltered with SIRT1 overexpression. Finally, while 20 days of energy restriction enhanced insulin-stimulated glucose uptake in skeletal muscles of wild-type mice, no additional effect of SIRT1 overexpression was observed. These results demonstrate that upregulation of SIRT1 activity in skeletal muscle does not affect whole-body energy expenditure or enhance skeletal muscle insulin sensitivity in young mice on a standard diet with free access to chow or in young mice on energy-restricted diets.


Risk factors for vertebral fractures and bone loss after denosumab discontinuation: A real-world observational study.
Denosumab discontinuation without subsequent bisphosphonates (BPs) is associated with bone loss and multiple vertebral fractures. Identifying risk factors for bone loss and vertebral fractures after denosumab discontinuation. This retrospective study measured the outcome of 219 women with osteoporosis who discontinued denosumab treatment and received subsequent treatment with zoledronate, other BPs or a selective estrogen receptor modulator (SERM), or no therapy. Fracture rate, longitudinal bone mineral density (BMD) changes and bone turnover markers (BTMs) within 2 years after denosumab discontinuation were analysed. Linear regression analysis evaluated loss of BMD and age, BMI (kg/m2), denosumab treatment duration, pre-treatment, prior fracture state, baseline T-scores, use of glucocorticoids or aromatase inhibitors and BMD gains under denosumab therapy. 171 women received zoledronate after denosumab discontinuation, 26 had no subsequent treatment and 22 received other therapies (other BPs or a SERM). Zoledronate was associated with the fewest vertebral fractures (hazard ratio 0.16, p = 0.02) and all subsequent therapies retained BMD at all sites to some extent. Higher BMD loss was associated with younger age, lower BMI, longer denosumab treatment, lack of prior antiresorptive treatment and BMD gain under denosumab treatment. BTM levels correlated with denosumab treatment duration and bone loss at the total hip, but not the lumbar spine. Compared to no subsequent therapy, zoledronate was associated with fewer vertebral fractures after denosumab. Further, BMD loss depended on denosumab treatment duration, age, prior BP therapy and BMD gain under denosumab therapy, whereas BTM levels were associated with bone loss at the total hip and denosumab treatment duration.


A Novel Selective Deep Eutectic Solvent Extraction Method for Versatile Determination of Copper in Sediment Samples by ICP-OES.
In the present study, a simple, mono step deep eutectic solvent (DES) extraction was developed for selective extraction of copper from sediment samples. The optimization of all experimental parameters, e.g. DES type, sample/DES ratio, contact time and temperature were performed with using BCR-280 R (lake sediment certified reference material). The limit of detection (LOD) and the limit of quantification (LOQ) were found as 1.2 and 3.97 µg L-1, respectively. The RSD of the procedure was 7.5%. The proposed extraction method was applied to river and lake sediments sampled from Serpincik, Çeltek, Kızılırmak (Fadl and Tecer region of the river), Sivas-Turkey.


Stability of transplanted murine tumour systems after storage of cells at -196 degrees C for up to 13 years.
Two murine lymphomas of spontaneous origin were stored in liquid N2 as cell suspensions in DMSO for 8 and 13 years respectively. Isogenic transplantation assays done some years before freezing and immediately after thawing indicated no measurable loss of clonogenic cells during freezing, storage or thawing; the number of cells required for 50% successful transplantation remained close to unity in both cases. The overall data revealed no evidence of an alteration of the receptivity of the mouse colonies over a period of 13 or 20 years. We attribute this remarkable stability to close supervision of the systems within a single laboratory.


Research Hotspots and Trends of Bone Xenograft in Clinical Procedures: A Bibliometric and Visual Analysis of the Past Decade.
Bone defect therapy is a common clinical challenge for orthopedic and clinical physicians worldwide, and the therapeutic effect affects the physiological function and healthy life quality of millions of patients. Compared with traditional autogenous bone transplants, bone xenografts are attracting attention due to their advantages of unlimited availability and avoidance of secondary damage. However, there is currently a lack of bibliometric analysis on bone xenograft. This study aimed to use bibliometric methods to analyze the literature on bone xenograft from 2013 to 2023, to explore the current status, hotspots, and future trends of research in this field, and to promote its development and progress. Using the Web of Science Core Collection database, we retrieved and collected publication data related to xenogeneic bone grafting materials worldwide from January 2013 to March 2023. Origin (2021), CiteSpace (6.2.R2 standard), and an online bibliometric platform were used for bibliometric analysis and data visualization. A total of 3395 documents were retrieved, and 686 eligible papers were selected. The country and institutions with the highest number of publications and centrality were the United States (125 papers, centrality = 0.44) and the University of Zurich (29 papers, centrality = 0.28), respectively. The most cited author was Araujo MG (163 times), and the author with the most significant centrality was Froum SJ (centrality = 0.09). The main keyword clusters were "tissue engineering", "sinus floor elevation", "dental implants", "tooth extraction", and "bone substitutes". The most significant bursting keywords in the last three years were "platelet rich fibrin". Research on bone xenograft is steadily growing and will continue to rise. Currently, research hotspots and directions are mainly focused on dental implants related to bone-augmentation techniques and bone tissue engineering. In the future, research hotspots and directions may focus on decellularization technology and investigations involving platelet-rich fibrin.


Hafnium carbide nanoparticles for noninflammatory photothermal cancer therapy.
Photothermal therapy (PTT) effectively suppresses tumor growth with high selectivity. Nevertheless, PTT may cause an inflammatory response that leads to tumor recurrence and treatment resistance, which are the main disadvantages of PTT. Herein, monodisperse hafnium carbide nanoparticles (HfC NPs) were successfully prepared for noninflammatory PTT of cancer. HfC NPs possessed satisfactory near-infrared (NIR) absorption, good photothermal conversion efficiency (PTCE, 36.8 %) and photothermal stability. Furthermore, holding large surface areas and intrinsic redox-active sites, HfC NPs exhibited excellent anti-inflammatory properties due to their antioxidant and superoxide dismutase (SOD) enzymatic activities. In vitro and in vivo experiments confirmed that HfC NPs converted light energy into heat energy upon NIR laser irradiation to kill cancer cells through PTT and achieved a better therapeutic effect by anti-inflammatory effects after PTT. This work highlights that multifunctional HfC NPs can be applied in noninflammatory PTT with outstanding safety and efficacy.


Auricular acupuncture and biomedical research--A promising Sino-Austrian research cooperation.
Treatment by auricular acupuncture has a long history. Ear-acupoint research has been advancing step by step in China and also in Europe. Auricles are rich in nerves, therefore a close relationship with different functions of the human body has been proved by the research teams of the two main authors of this article from China and Austria. In recent years, great progress has been made in the research of regulating human body functions through electroacupuncture at the auricular branch of the vagus nerve, which is part of auricular acupuncture therapy. It is well known that the auricular branch of the vagus nerve is the only peripheral pathway to the cerebral cortex. Studies of the Chinese team on hypertension, diabetes, epilepsy and depression have shown that the mechanism of auricular vagus nerve stimulation (VNS) may be comparable with cervical VNS in terms of pathways. Auricular VNS has a broad clinical application prospect.


Hippocampal lesions, contextual retrieval, and autoshaping in pigeons.
Both pigeons and rats with damage to the hippocampus are slow to acquire an autoshaped response and emit fewer overall responses than control animals. Experiment 1 explored the possibility that the autoshaping deficit was due to an impairment in contextual retrieval. Pigeons were trained for 14 days on an autoshaping task in which a red stimulus was followed by reinforcement in context A, and a green stimulus was followed by reinforcement in context B. On day 15, the subjects were given a context test in which the red and green stimuli were presented simultaneously in context A and then later in context B. Both control and hippocampal animals showed context specificity, that is, they responded more to the red stimulus in context A and to the green stimulus in context B. In Experiment 2 we video-recorded the control and hippocampal animals performing the autoshaping task. Hippocampal animals tended to miss-peck the key more often than control animals. In addition, the number of missed pecks increased across days for hippocampal animals but not for control animals, suggesting that while the control animals increased their pecking accuracy, the hippocampal animals actually decreased their pecking accuracy. Our findings suggest that impairments in moving through space may underlie the hippocampal autoshaping deficit.