Treating nicotine dependence.
This article reviews the biology of nicotine addiction and the most effective treatments for nicotine dependence. Nicotine elevates dopamine levels in the brain, which is associated with drug reinforcement and dependence. Nicotine abuse leads to nicotine dependence. The most effective pharmacological adjuncts for treating nicotine dependence are nicotine replacement therapy and bupropion SR. When these are combined with behavioral counseling, the best treatment outcomes are observed.


Physical attractiveness and sex as modulatory factors of empathic brain responses to pain.
Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI), and the anterior cingulate cortex (ACC). High empathy may lead people to undertake pro-social behavior. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behavior and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male) were studied using functional magnetic resonance imaging (fMRI) method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioral effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI) for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens' faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain.


Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1.
CC Chemokine Receptor 3 (CCR3), the major chemokine receptor expressed on eosinophils, binds promiscuously to several ligands including eotaxins 1, 2, and 3. Even though the only cells that consistently accumulate following eotaxin administration in vivo are myeloid cells (primarily eosinophils), other cell types have recently been shown to express CCR3. It is therefore important to elucidate the molecular mechanisms regulating receptor expression. In order to define regions responsible for CCR3 transcription, a DNAse hypersensitive site was identified in the vicinity of exon 1. Coupled with our previous data implicating exon 1 in CCR3 transcription, we hypothesized that transcription factors bind to exon-1. Electrophoretic mobility shift analysis revealed that nuclear proteins in eosinophilic cells bound to exon 1. Furthermore, antibody interference and mutation studies demonstrated GATA-1 binding to exon 1. In order to test the 1.6-kb CCR3 promoter element (that includes exon 1) for in vivo function, this region was used to generate transgenic mice that expressed a reporter protein. Strong transgene expression was achieved, with the pattern of expression suggesting a broad acting promoter. The transcription factor GATA-1 binds to CCR3 exon 1. The 1.6-kb CCR3 promoter element, that includes exon 1, is a strong promoter in vivo.


[Epidemiology and causes of Parkinson's disease].
Parkinson's disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (<5%) are monogenic, i. e. caused by mutations in single genes. At present, six genes have been established for the clinically classical form of parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1). In addition, there are a plethora of genes causing atypical forms of parkinsonism. In contrast, idiopathic PD is of a multifactorial nature. Genome-wide association studies have established a total of 26 genetic loci for this form of the disease; however, for most of these loci the underlying functional genetic variants have not yet been identified and the respective disease mechanisms remain unresolved. Furthermore, there are a number of environmental and life style factors that are associated with idiopathic PD. Exposure to pesticides and possibly a history of head trauma represent genuine risk factors. Other PD-associated factors, such as smoking and intake of coffee and alcohol may not represent risk factors per se and the cause-effect relationship has not yet been elucidated for most of these factors. A patient with a positive family history and/or an early age of disease onset should undergo counseling with respect to a possible monogenic form of the disease. Disease prediction based on genetic, environmental and life style factors is not yet possible for idiopathic PD and potential gene-specific therapies are currently in the development or early testing phase.


Modulation of microRNA Activity by Semi-microRNAs.
The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing the formation of 19-24-nucleotide (nt) long microRNAs. Subsequently incorporated into Argonaute 2 (Ago2) effector complexes, microRNAs are known to regulate messenger RNA (mRNA) translation. Whether shorter RNA species derived from microRNAs exist and play a role in mRNA regulation remains unknown. Here, we report the serendipitous discovery of a 12-nt long RNA species corresponding to the 5' region of the microRNA let-7, and tentatively termed semi-microRNA, or smiRNA. Using a smiRNA derived from the precursor of miR-223 as a model, we show that 12-nt long smiRNA species are devoid of any direct mRNA regulatory activity, as assessed in a reporter gene activity assay in transfected cultured human cells. However, smiR-223 was found to modulate the ability of the microRNA from which it derives to mediate translational repression or cleavage of reporter mRNAs. Our findings suggest that the 12-nt RNA species, generated along the microRNA pathway, may participate to the control of gene expression by regulating the activity of the related full-length mature microRNA in vivo.


A guide to biological skin substitutes.
The role of artificial skin substitutes in burn surgery and the treatment of chronic wounds is constantly evolving. New products are regularly being produced and approved for clinical use. Studies on existing products clarify their efficacy and effectiveness in different clinical scenarios. This review is aimed at busy clinicians in order to bring them up to date with the latest developments in the field of artificial skin substitutes. It examines the components, structure, performance and comparative costs of the main commercial skin substitutes, and reviews briefly technologies under development that have not yet become widely available.


Familial hypotrichosis of the scalp. Autosomal dominant inheritance in four generations.
We describe a Danish family of four generations suffering from hypotrichosis of the scalp. Age at onset was 6-17 years and almost total scalp alopecia was reached by the age of 14-21 years. No associated ectodermal defects were present. Nine of 22 persons covering four generations were affected. Growth of the scalp hair slowly decreased and was accompanied by a gradual, diffuse hair loss without regional variation. A scalp biopsy was performed, revealing a non-scarring alopecia with features of androgenetic alopecia. The pedigree was compatible with autosomal dominant inheritance.


Unravelling the grief of involuntary pregnancy loss: A meta-ethnography of midwives' and nurses' emotional experiences.
Parents who experience involuntary pregnancy loss encounter nurses and midwives when requiring care. But the environment in which this attention is provided turns it into a stressful and challenging event that favours the concealment of emotions. Literature supports the development of compassion in nurses and midwives who tend to parents who experience pregnancy losses. To synthesise the emotional experiences of midwives and nurses when caring for parents who have suffered an involuntary pregnancy loss. This is a synthesis of qualitative studies following Noblit and Hare's interpretive meta-ethnography. Eleven studies met the research objective and inclusion criteria. An overarching metaphor, 'Unravelling the grief of loss', accompanied by four major themes provided interpretive explanations to the experiences of midwives and nurses in caring for involuntary pregnancy losses: 'Pulling the thread' - looking for the meaning of loss; 'Yarn entanglement degree' - determinants for grief expression; 'Detangling tools' - focusing on the loss; and 'Fraying the thread' - moving away from the loss. The provision of whole care to these parents requires midwifery and nursing training and continued education. Furthermore, the organisational culture should prioritise the health and well-being of midwives and nurses. Midwives and nurses encounter the parents' loss in care and personally in various ways and give meaning to the loss conditioned by personal and professional determinants. They unravel the grief of loss by looking for the meaning, expressing their grief, focusing and moving away from the loss.


Differential diagnosis of parkinsonism by a combined use of diffusion kurtosis imaging and quantitative susceptibility mapping.
We investigated whether diffusion kurtosis imaging (DKI) and quantitative susceptibility mapping (QSM) could detect pathological changes that occur in Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P) or predominant cerebellar ataxia (MSA-C), and progressive supranuclear palsy syndrome (PSPS) and thus be used for differential diagnosis that is often difficult. Seventy patients (41 with PD, 6 with MSA-P, 7 with MSA-C, 16 with PSPS) and 20 healthy controls were examined using a 3.0 T MRI scanner. From DKI and QSM data, we automatically obtained mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values of the midbrain tegmentum (MBT), pontine crossing tract (PCT), and superior/middle cerebellar peduncles (CPs), which were used to calculate diffusion MBT/PCT ratios (dMPRs) and diffusion superior/middle CP ratios (dCPRs), as well as MS (magnetic susceptibility) values of the anterior/posterior putamen (PUa and PUp) and globus pallidus (GP). dMPRs of MK were significantly decreased in PSPS and increased in MSA-C compared with the other groups, while dCPRs of MK showed significant differences only between MSA-C and PD, PSPS, or control. MS values were significantly increased in the PUp of MSA-P and in the PUa and GP of PSPS compared with those in PD. The combined use of MK-dMPR and MS-PUp showed sensitivities of 83-100% and specificities of 81-100% for discriminating among the disease groups, respectively. A quantitative assessment using DKI and QSM analyses, particularly MK-dMPR and MS-PUp values, can readily identify patients with parkinsonism.


Phase shifts of synchronized oscillators and the systolic-diastolic blood pressure relation.
We study the phase-synchronization properties of systolic and diastolic arterial pressure in healthy subjects. We find that delays in the oscillatory components of the time series depend on the frequency bands that are considered, in particular we find a change of sign in the phase shift going from the very low frequency band to the high frequency band. This behavior should reflect a collective behavior of a system of nonlinear interacting elementary oscillators. We prove that some models describing such systems, e.g., the Winfree and the Kuramoto models, offer a clue to this phenomenon. For these theoretical models there is a linear relationship between phase shifts and the difference of natural frequencies of oscillators and a change of sign in the phase shift naturally emerges.


Physicians play important role in families' long-term care decisions. Choice of home care vs. nursing home.
Physicians are often involved in decisions about long-term care for the elderly and adults with disabilities. In Arkansas, some home and community-based services (HCBS) have been established for these Medicaid-eligible populations, as a nursing home alternative, but some are under-utilized. Unnecessary use of nursing home care burdens the state Medicaid budget. A recent study on service utilization suggests that physicians' lack of knowledge about HCBS may be a factor in their under-utilization. A number of programs that enable individuals to remain in their homes in Arkansas, including ElderChoices, Alternatives, the Developmental Disabilities Waiver and the Assisted Living Waiver are described.


The glycine site of the N-methyl-D-aspartate receptor channel: differences between the binding of HA-966 and of 7-chlorokynurenic acid.
The mechanisms of action of three different glycine-site antagonists of the N-methyl-D-aspartate (NMDA)-receptor channel were analyzed employing [3H]glycine direct binding assays, as well as functional glycine- and glutamate-induced uncompetitive blocker binding assays. The latter assays measure apparent channel opening. All three antagonists tested, viz., 7-chlorokynurenic acid (7-Cl-KYNA), kynurenic acid (KYNA), and 1-hydroxy-3-aminopyrrolidone-2 (HA-966), inhibited the binding of [3H]glycine to the NMDA receptor in a dose-dependent manner. These antagonists also inhibited the glycine-induced increase in accessibility of the uncompetitive blocker [3H]N-[1-(2-thienyl)cyclohexyl]-piperidine ([3H]TCP) to the channel. 7-Cl-KYNA and KYNA, but not HA-966, completely blocked the glutamate-induced binding of [3H]TCP, in a manner similar to the non-competitive manner in which the selective NMDA antagonist D-(-)-2-amino-5-phosphonovaleric acid (AP-5) inhibited glycine-induced [3H]TCP binding. The inhibitory effects of HA-966 and of AP-5 on glutamate-induced [3H]TCP binding were overcome when glutamate concentrations were increased. Of the three antagonists, 7-Cl-KYNA appears to be the most potent (Ki = 0.4-1.0 microM) and the most selective glycine antagonist. KYNA was found to act at both the glycine (Ki = 40-50 microM) and the glutamate sites. In contrast, HA-966 (Ki = 6-17 microM) appears to act either on a domain distinct from the glutamate and the glycine sites, but tightly associated with the latter, or at the glycine site, but according to a mechanism distinct from that of 7-Cl-KYNA.(ABSTRACT TRUNCATED AT 250 WORDS)


Following the Birth, Life, and Death of mRNAs in Single Cells.
Recent advances in single-molecule imaging of mRNAs in fixed and living cells have enabled the lives of mRNAs to be studied with unprecedented spatial and temporal detail. These approaches have moved beyond simply being able to observe specific events and have begun to allow an understanding of how regulation is coupled between steps in the mRNA life cycle. Additionally, these methodologies are now being applied in multicellular systems and animals to provide more nuanced insights into the physiological regulation of RNA metabolism.


Angiographic Coronary Calcification: A Simple Predictor of Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction.
Coronary calcification detected by coronary angiography is a simple risk marker for long-term clinical outcomes in stable coronary artery disease. However, the significance of angiographic coronary calcification in the culprit lesion of acute myocardial infarction (AMI) has not been fully discussed. The purpose of this retrospective study was to assess the usefulness of angiographic coronary calcification as a risk marker for long-term clinical outcomes following percutaneous coronary intervention to the culprit lesions of AMI. We included 1209 patients with AMI and divided them into the none-mild calcification group (n=923) and the moderate-severe calcification group (n=286) according to angiographic coronary calcification in the culprit lesion of AMI. The primary endpoint was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, nonfatal MI, readmission for heart failure, and ischemia-driven target vessel revascularization. The median follow-up duration was 542 (Q1: 182, Q3: 990) days. A total of 345 MACE were observed during the study period. The occurrence of MACE was significantly greater in the moderate-severe calcification group than in the none-mild calcification group (43.4% vs. 23.9%, p<0.001). In the multivariate Cox hazard model, moderate-severe calcification was significantly associated with MACE (hazard ratio 1.302, 95% confidence interval 1.011-1.677, p=0.041) after controlling multiple confounding factors. Angiographically moderate to severe calcification in AMI culprit lesion was associated with long-term worse clinical outcomes. Angiographic coronary calcification can be a simple risk marker in patients after AMI.


Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family.
SENPs [Sentrin/SUMO (small ubiquitin-related modifier)-specific proteases] include proteases that activate the precursors of SUMOs, or deconjugate SUMOs attached to target proteins. SENPs are usually assayed on protein substrates, and for the first time we demonstrate that synthetic substrates can be convenient tools in determining activity and specificity of these proteases. We synthesized a group of short synthetic peptide fluorogenic molecules based on the cleavage site within SUMOs. We demonstrate the activity of human SENP1, 2, 5, 6, 7 and 8 on these substrates. A parallel positional scanning approach using a fluorogenic tetrapeptide library established preferences of SENPs in the P3 and P4 positions that allowed us to design optimal peptidyl reporter substrates. We show that the specificity of SENP1, 2, 5 and 8 on the optimal peptidyl substrates matches their natural protein substrates, and that the presence of the SUMO domain enhances catalysis by 2-3 orders of magnitude. We also show that SENP6 and 7 have an unexpected specificity that distinguishes them from other members of the family, implying that, in contrast to previous predictions, their natural substrate(s) may not be SUMO conjugates.


Analysis of incidence and prevalence of cardiovascular risk factors and evaluation of their control in epidemiological survey in the Czech Republic.
The aim of this analysis was to analyze the presence of the most important cardiovascular (CV) risk factors and to discuss patterns of LDL cholesterol management in the population studied. We enrolled 961 males, average age of 42.9 ± 4.7, and 851 females, average age of 51.2 ± 3.6. Data on personal, pharmacological and family history, and laboratory examinations were collected. Cardiovascular (CV) risk was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm with modifications according to the guidelines. The distribution of CV risk in the observed cohort was as follows: 24% of the subjects had low, 51% moderate, 17% high and 8% very high risk. The percentage of patients who reached target values of LDL cholesterol was dramatically lower in the groups with very high (1%) and high (3%) risk than in the groups with moderate (14%) or low risk (59%). Dyslipidemia was newly identified in 20% of both sexes. Arterial hypertension was newly diagnosed in 8% of males and 5% of females, and type 2 diabetes mellitus was newly diagnosed in 3% of both the males and females. Dyslipidemia was present in 39% of males and 41% of females; arterial hypertension in 43% of males and 45% of females, and type 2 diabetes mellitus was diagnosed in 11% of the subjects of both sexes. 49% of males and 31% of females were overweight and 32% of both genders were obese. There were 36% of male smokers and 22% of female smokers. 48% of the participants were pharmacologically treated. Non-pharmacological treatment was recommended to 62% of male and to 65% of female participants. Pharmacological intervention was started in 53% of males and 51% of females. In both gender antihypertensive treatment with angiotensin-converting enzyme (ACE) inhibitors (29% of males and 27% of females) and lipid lowering therapy with a statin (28% of males, 27% of females) were the most commonly initiated treatments. In the subgroup of the 101 patients with LDL cholesterol levels > 5 mmol/L 56% were not treated with a statin. The analysis of relationship between the positive family history of any of the followed CV risks showed significant increases of the risk for arterial hypertension, type 2 diabetes mellitus and dyslipidemia. European guidelines suggest general screening for risk factors, including analysis of lipid profiles in the population of 40-year-old males and 50-year-old or postmenopausal women. Our study documents high prevalence and incidence of CV risk factors together with insufficient control of the risk factors in Czech patients of this age range. This finding suggests that preventive examinations should be undertaken earlier (e.g., in 30-year-old males and 40-year-old women). Exact timing of the preventive check-ups to yield the best cost-benefit ratio needs to be verified.


A two-dimensional mixed-valence Cu(II)/Cu(I) coordination polymer constructed from 2-(pyridin-3-yl)-1H-imidazole-4,5-dicarboxylate.
Coordination polymers are a thriving class of functional solid-state materials and there have been noticeable efforts and progress toward designing periodic functional structures with desired geometrical attributes and chemical properties for targeted applications. Self-assembly of metal ions and organic ligands is one of the most efficient and widely utilized methods for the construction of CPs under hydro(solvo)thermal conditions. 2-(Pyridin-3-yl)-1H-imidazole-4,5-dicarboxylate (HPIDC(2-)) has been proven to be an excellent multidentate ligand due to its multiple deprotonation and coordination modes. Crystals of poly[aquabis[μ3-5-carboxy-2-(pyridin-3-yl)-1H-imidazole-4-carboxylato-κ(5)N(1),O(5):N(3),O(4):N(2)]copper(II)dicopper(I)], [Cu(II)Cu(I)2(C10H5N3O4)2(H2O)]n, (I), were obtained from 2-(pyridin-3-yl)-1H-imidazole-4,5-dicarboxylic acid (H3PIDC) and copper(II) chloride under hydrothermal conditions. The asymmetric unit consists of one independent Cu(II) ion, two Cu(I) ions, two HPIDC(2-) ligands and one coordinated water molecule. The Cu(II) centre displays a square-pyramidal geometry (CuN2O3), with two N,O-chelating HPIDC(2-) ligands occupying the basal plane in a trans geometry and one O atom from a coordinated water molecule in the axial position. The Cu(I) atoms adopt three-coordinated Y-shaped coordinations. In each [CuN2O] unit, deprotonated HPIDC(2-) acts as an N,O-chelating ligand, and a symmetry-equivalent HPIDC(2-) ligand acts as an N-atom donor via the pyridine group. The HPIDC(2-) ligands in the polymer serve as T-shaped 3-connectors and adopt a μ3-κ(2)N,O:κ(2)N',O':κN''-coordination mode, linking one Cu(II) and two Cu(I) cations. The Cu cations are arranged in one-dimensional -Cu1-Cu2-Cu3- chains along the [001] direction. Further crosslinking of these chains by HPIDC(2-) ligands along the b axis in a -Cu2-HPIDC(2-)-Cu3-HPIDC(2-)-Cu1- sequence results in a two-dimensional polymer in the (100) plane. The resulting (2,3)-connected net has a (12(3))2(12)3 topology. Powder X-ray diffraction confirmed the phase purity for (I), and susceptibilty measurements indicated a very weak ferromagnetic behaviour. A thermogravimetric analysis shows the loss of the apical aqua ligand before decomposition of the title compound.


Domestic Factors as Determinant of Sickness Absence with Psychiatric Disorders: A Scoping Review of Nordic Research Published between 2010-2019.
Uneven division of domestic factors may contribute to sex differences in sickness absence with psychiatric disorders. The aim of this scoping review was to compile current Nordic research on domestic factors and sickness absence with psychiatric disorders. A systematic search was performed to identify studies from the Nordic countries published between 1 January 2010 and 31 December 2019. Twelve studies were included. Marital status, family situation, work-home interference (in both directions), social affiliation, and loss of child/young adult (suicide, accident, or natural death) were identified as measures of domestic factors. In 8 of the 12 studies, domestic factors were used as co-variates, while four used them as the main exposure. Social affiliation, home-to-work conflict, and total workload were not associated with the outcome. One study found that parents with children older than two years, widows/widowers, and those divorced or unmarried had an increased risk of sickness absence with psychiatric disorders. One study found that work-to-home conflict was associated with sickness absence with stress-related diagnoses in men, and with other mental disorders in women. Finally, one study found that losing a son or daughter aged 16-24 years increased the risk of future sickness absence with a psychiatric disorder regardless of the cause of death. Future studies need to develop concepts, study designs, and measurements to move this research area further. In particular, the concept of "unpaid domestic work" needs theoretical and empirical development.


Hepatolithiasis: epidemiology and classification.
Hepatolithiasis or intrahepatic stone is more common among East Asian countries than in Western world. The relative incidence (i.e. hepatolithiasis cases against all cases with gallstone disease) in the Western countries is approximately 1% whereas in Taiwan, South Korea, the People's Republic of China it has been reported to be 20%, 18% and 38-45% respectively. There are two types of hepatolithiasis and in East Asian countries one usually finds pigmented stone. The disease appears to be more common among people with low socio-economic status. No single worldwide accepted classification of hepatolithiasis exists at present.


Geographically Related Variation in Epicuticular Wax Traits of Pinus nigra Populations from Southern Carpathians and Central Balkans - Taxonomic Considerations.
The chemical composition of epicuticular waxes of nine populations from three Pinus nigra J. F. Arnold subspecies (namely subsp. nigra, subsp. banatica (Borbás) Novák, and subsp. pallasiana (Lamb.) Holmboe) from Southern Carpathians and central Balkan Peninsula were analyzed using GC/MS and GC/FID chromatography, and multivariate statistical techniques with respect to biogeography and taxonomy. In the needle waxes, four primary alcohols and 14 n-alkanes ranging from C21 to C33 were identified, and the most abundant compounds were the four odd-numbered n-alkanes C27 , C25 , C23 , and C29. Multivariate statistical analyses (CDA and CA) have shown existence of three P. nigra groups and suggested clinal differentiation as a mechanism of genetic variation across a geographic area: the first group consisted of the southernmost populations of subsp. pallasiana from Macedonia, the second consisted of the northernmost subsp. banatica populations from Romania, while all populations in Serbia described as three different subspecies (nigra, banatica, and pallasiana) formed the third group together with subsp. nigra population from Bosnia and Herzegovina. According to simple linear regression, geographic latitude and four bioclimatic parameters were moderately correlated with the contents of epicuticular wax compounds that are important in population discrimination, while stepwise multiple regression showed that latitude participated in most of the regression models for predicting the composition of the epicuticular waxes. These results agree with CDA and CA analysis, and confirmed the possibility of recognition of fine geographic differentiation of the analyzed P. nigra populations.


Generalized occurrence of the broadly antiviral substance UTI beta in mammalian sera.
This study compares the characteristics of naturally occurring antiviral activities in nonhuman mammalian sera to UTI beta (University of Texas virus inhibitor beta), an innate, non-specific viral inhibitor found in human serum. The antiviral agent in sera from four different species appears to possess properties similar to those of UTI beta, e.g. molecular weight of 60 +/- 10 kDa, broad spectrum antiviral activity, glycoprotein structure with antiviral oligosaccharide moiety(s) attached to a carrier protein, and inhibition of most viruses by preventing their attachment to target cells. These findings suggest that UTI beta or UTI beta-like virus inhibitors are a normal component of the non-specific immune defenses of mammals.


[Optimization of the invasive strategy for acute coronary syndrome in patients of the older age group.]
A study is presented on the effectiveness and safety of various anticoagulants used in patients of an older age group with acute coronary syndrome during percutaneous coronary interventions. Bivalirudin was shown to be highly effective in comparison with unfractionated heparin and monafram in relation to the amount of bleeding that occurs in the postoperative period and adverse cardiovascular complications.


COMPARISON OF SURFACE, ESOPHAGEAL, AND CLOACAL TEMPERATURES IN DIFFERENT REPTILE SPECIES.
The objective of this study was to compare surface, esophageal, and cloacal temperatures in awake iguanas, chameleons, and snakes at two different ambient temperatures and in alligators at one ambient temperature. Surface, esophageal, and cloacal temperatures were measured in all animals twice, with exception of the alligators, where temperatures were taken once. The first set of temperature readings was done at lower environmental temperature. An analysis of variance (ANOVA) with a mixed-effect model was used to analyze the temperature difference between esophageal and cloacal temperature against each other, and against surface temperature. Significance was set at P < 0.05. In all animals, surface, esophageal, and cloacal temperatures increased significantly (P < 0.0001) with increased ambient temperature. Esophageal and cloacal temperature were not significantly different from each other in iguanas and chameleons at lower environmental temperature or in snakes and chameleons at high ambient temperature. In snakes, esophageal temperature 26.1 ± 1.6°C was significantly higher than cloacal temperature 25.2 ± 0.9°C (P = 0.0016) at lower ambient temperature. In alligators no difference between esophageal and cloacal temperature was observed at the given ambient temperature. Surface temperature was significantly lower than esophageal and cloacal temperature in all species investigated, except iguanas at lower ambient temperature. The results of this study suggest that in healthy awake iguanas and chameleons at any ambient temperature and in snakes at high ambient temperature, cloacal temperatures are reflective of esophageal temperature in the species evaluated. In alligators, rectal temperature reflected esophageal temperature at the given ambient temperature. Surface temperature in contrast was underestimating esophageal temperature in all species investigated.


[Advance in studies on antitumor and immunomodulatory effects of wogonin].
Wogonin is a kind of natural flavonoid compound. According to findings in the latest studies, wogonin shows a wide range of antitumor effects, with the characteristics of multi-pathway, multi-link and multi-target, such as promoting tumor cell apoptosis through ROS or Ca(2+)-mediated signal paths, enhancing tumor cytotoxicity by TNF-α and TRAIL, blocking tumor cell cycle, inhibiting tumor angiogenesis and resisting cancer synergistically with chemotherapeutic drugs. Moreover, Wogonin could enhance body immune function by enhancing immune cell infiltration, regulating the immune cell phenotype and promoting relevant cytokine secretion. In this paper, the authors summarized the advance in studies on wogonin's antitumor and immunomodulatory effects.


Control of steroid receptor dynamics and function by genomic actions of the cochaperones p23 and Bag-1L.
Molecular chaperones encompass a group of unrelated proteins that facilitate the correct assembly and disassembly of other macromolecular structures, which they themselves do not remain a part of. They associate with a large and diverse set of coregulators termed cochaperones that regulate their function and specificity. Amongst others, chaperones and cochaperones regulate the activity of several signaling molecules including steroid receptors, which upon ligand binding interact with discrete nucleotide sequences within the nucleus to control the expression of diverse physiological and developmental genes. Molecular chaperones and cochaperones are typically known to provide the correct conformation for ligand binding by the steroid receptors. While this contribution is widely accepted, recent studies have reported that they further modulate steroid receptor action outside ligand binding. They are thought to contribute to receptor turnover, transport of the receptor to different subcellular localizations, recycling of the receptor on chromatin and even stabilization of the DNA-binding properties of the receptor. In addition to these combined effects with molecular chaperones, cochaperones are reported to have additional functions that are independent of molecular chaperones. Some of these functions also impact on steroid receptor action. Two well-studied examples are the cochaperones p23 and Bag-1L, which have been identified as modulators of steroid receptor activity in nuclei. Understanding details of their regulatory action will provide new therapeutic opportunities of controlling steroid receptor action independent of the widespread effects of molecular chaperones.


Improvement in uniformity of emission by ZrO₂ nano-particles for white LEDs.
The high luminous efficiency and superior uniformity of angular-dependent correlated color temperature (CCT) white light-emitting diodes have been investigated by ZrO₂ nano-particles in a remote phosphor structure. By adding ZrO₂ nano-particles with silicone onto the surface of the phosphor layer, the capability of light scattering could be enhanced. In particular, the intensity of blue light at large angles was increased and the CCT deviations could be reduced. Besides, the luminous flux was improved due to the ZrO₂ nano-particles with silicone providing a suitable refractive index between air and phosphor layers. This novel structure reduces angular-dependent CCT deviations from 1000 to 420 K in the range of -70° to 70°. Moreover, the enhancement of lumen flux was increased by 2.25% at a driving current 120 mA, compared to a conventional remote phosphor structure without ZrO₂ nano-particles. Consequently, the ZrO₂ nano-particles in a remote phosphor structure could not only improve the uniformity of lighting but also increase the light output.


[Nasolabioplasty after rupture of the nasal ring in cattle].
In 25 cases of muzzle and nasal septum injuries operative treatment was performed by different methods. In conventional nasolabioplasty (n = 23) horizontal mattress sutures were used, the free parts of the thread passing through pieces of rubber tube. In two bulls, suffering from such a rupture the second time, a new surgical technique was applied. To prevent stenosis of the nostrils, the nasal septum was reconstructed by cutaneous pedicle graft. The techniques of both methods are described and illustrated. Healing was observed in all cases.


A monsoon-related 174-year relative humidity record from tree-ring δ18O in the Yaoshan region, eastern central China.
The authors present a time series of tree-ring cellulose stable oxygen isotope ratios (δ18O) constructed using a numerical mixing method, from five Pinus tabulaeformis from Yaoshan, eastern central China. The time series is synchronous with the observed April-to-September precipitation δ18O time series records from surrounding stations, implying that the tree-ring δ18O signals reflect Asian summer monsoon-related precipitation. Moreover, significant correlations were detected between the tree-ring δ18O records and central-eastern Pacific sea surface temperature (SSTs)/Asian summer monsoon indices. This suggests that the Yaoshan tree-ring δ18O time series offers a promising means to study past Asian summer monsoons and ENSO variability. The time series is significantly correlated with the mean relative humidity from April to September (RHAS) (r=-0.638, n=52, p<0.0001) over the Yaoshan region. The authors assign a transfer function to the reconstruct the RHAS time series from 1835 to 2008. The mean value of RHAS over the period 1870-1890 is the lowest observed value during the past 174years, implying severe drought at that time. From 1930 to 2008, an obvious drying trend in the Yaoshan region is observed. Particularly from 1985 to 2008, frequent, extremely dry years occurred, with few extremely wet years. The drying trend is consistent with decreasing Asian summer monsoon precipitation over the Loess Plateau over the past 60years. The acidification implied by this data extends well beyond the vicinity of Yaoshan and may be expected to impact the entire monsoonal region in northern China. A multi-taper spectral analysis and an ensemble empirical mode decomposition EEMD of the time series indicate 14.6-12.4 and 6.4-2.3 year cycles in the reconstructed RHAS time series during the past 174years, which correspond with solar cycles and ENSO cycles, respectively.


Prediction of Hopeless Peptides Unlikely to be Selected for Targeted Proteome Analysis.
In targeted proteomics using liquid chromatography-tandem triple quadrupole mass spectrometry (LC/MS/MS) in the selected reaction monitoring (SRM) mode, selecting the best observable or visible peptides is a key step in the development of SRM assay methods of target proteins. A direct comparison of signal intensities among all candidate peptides by brute-force LC/MS/MS analysis is a concrete approach for peptide selection. However, the analysis requires an SRM method with hundreds of transitions. This study reports on the development of a method for predicting and identifying hopeless peptides to reduce the number of candidate peptides needed for brute-force experiments. Hopeless peptides are proteotypic peptides that are unlikely to be selected for targets in SRM analysis owing to their poor ionization characteristics. Targeted proteomics data from Escherichia coli demonstrated that the relative ionization efficiency between two peptides could be predicted from sequences of two peptides, when a multivariate regression model is used. Validation of the method showed that >20% of the candidate peptides could be successfully eliminated as hopeless peptides with a false positive rate of less than 2%.


Water and electrolyte status in children with acute asthma.
The water and electrolyte status was studied in 26 children with acute asthma, 8 of whom required hospital admission. Patients were evaluated before therapy, during hospital management, and at least 10 days after symptoms had subsided. Laboratory evaluation included serum electrolytes, BUN, sOsmo, urinalysis, and uOsmo. Data were analyzed for the manifestations of SI-ADH. Mild serum hyposmolarity was noted initially in only two patients and during the hospital stay in one patient for a short time, but none of the patients fulfilled the criteria of SIADH. At the time of presentation at the emergency room, none of the 26 patients had clinical signs of dehydration, yet some degree of hypertonicity seemed to be present in most patients. This study shows that children with acute asthma are ordinarily not at high risk of SIADH and fluid therapy should be included in the management. Nevertheless, because such patients may be at risk of pulmonary edema, vigorous fluid administration should be discouraged, except to correct dehydration.


The interaction of dietary fatty acid and cholesterol on catecholamine-stimulated adenylate cyclase activity in the rat heart.
Diets supplemented with high levels of saturated or unsaturated fatty acids supplied by addition of sheep kidney fat or sunflower seed oil, respectively, were fed to rats with or without dietary cholesterol. The effects of these diets on cardiac membrane lipid composition, catecholamine-stimulated adenylate cyclase and beta-adrenergic receptor activity associated with cardiac membranes, were determined. The fatty acid-supplemented diets, either with or without cholesterol, resulted in alterations in the proportion of the (n-6) to (n-3) series of unsaturated fatty acids, with the sunflower seed oil increasing and the sheep kidney fat decreasing this ratio, but did not by themselves significantly alter the ratio of saturated to unsaturated fatty acids. However, cholesterol supplementation resulted in a decrease in the proportion of saturated and polyunsaturated fatty acids and a dramatic increase in oleic acid in cardiac membrane phospholipids irrespective of the nature of the dietary fatty acid supplement. The cholesterol/phospholipid ratio of cardiac membrane lipids was also markedly increased with dietary cholesterol supplementation. Although relatively unaffected by the nature of the dietary fatty acid supplement, catecholamine-stimulated adenylate cyclase activity was significantly increased with dietary cholesterol supplementation and was positively correlated with the value of the membrane cholesterol/phospholipid ratio. Although the dissociation constant for the beta-adrenergic receptor, determined by [125I](-)-iodocyanopindolol binding, was unaffected by the nature of the dietary lipid supplement, the number of beta-adrenergic receptors was dramatically reduced by dietary cholesterol and negatively correlated with the value of the membrane cholesterol/phospholipid ratio. These results indicate that the activity of the membrane-associated beta-adrenergic/adenylate cyclase system of the heart can be influenced by dietary lipids particularly those altering the membrane cholesterol/phospholipid ratio and presumably membrane physico-chemical properties. In the face of these dietary-induced changes, a degree of homeostasis was apparent both with regard to membrane fatty acid composition in response to an altered membrane cholesterol/phospholipid ratio, and to down regulation of the beta-adrenergic receptor in response to enhanced catecholamine-stimulated adenylate cyclase activity.


[Long-term malaria prophylaxis with mefloquine: a study of adverse drug reactions].
To estimate the relative frequency of reported adverse drug reactions during the malaria chemoprophylactic period of the Moroccan contingent in Democratic Republic of Congo (DRC). The transversal survey involved all military personnel of the Moroccan contingent and was carried out using a questionnaire to be filled out by a multidisciplinary medical team. It was performed in all the military sites and the advanced posts accessible during the period of the study. The study involved 362 male military subjects. Ninety-four adverse drug reactions were described: neuropsychiatric (anxiety, irritability, dizziness...) [n=76], digestive (anorexia, diarrhea, nausea...) [n=42], cardiovascular (tachycardia, palpitation, precordialgia...) [n=5], musculoskeletal (arthralgia, cramps) [n=4], cutaneous (redness, purpura) [n=2], and other (n=13). No "unexpected" or "serious" adverse drug reaction was reported. The causality assessment score was determined in 94 cases. Two of these reports were rated "likely", 12 "possible" and 80 doubtful. More adverse drug reactions were reported by subjects having medical and paramedical functions. During our study, mefloquine induced adverse drug reactions in a quarter of the treated subjects. Most of the adverse drug reactions were neuropsychiatric. No "serious" adverse drug reactions were reported underlying the interest of its use, even for long-term chemoprophylaxis.


Rubisco is not really so bad.
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the most widespread carboxylating enzyme in autotrophic organisms. Its kinetic and structural properties have been intensively studied for more than half a century. Yet important aspects of the catalytic mechanism remain poorly understood, especially the oxygenase reaction. Because of its relatively modest turnover rate (a few catalytic events per second) and the competitive inhibition by oxygen, Rubisco is often viewed as an inefficient catalyst for CO2 fixation. Considerable efforts have been devoted to improving its catalytic efficiency, so far without success. In this review, we re-examine Rubisco's catalytic performance by comparison with other chemically related enzymes. We find that Rubisco is not especially slow. Furthermore, considering both the nature and the complexity of the chemical reaction, its kinetic properties are unremarkable. Although not unique to Rubisco, oxygenation is not systematically observed in enolate and enamine forming enzymes and cannot be considered as an inevitable consequence of the mechanism. It is more likely the result of a compromise between chemical and metabolic imperatives. We argue that a better description of Rubisco mechanism is still required to better understand the link between CO2 and O2 reactivity and the rationale of Rubisco diversification and evolution.


Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo.
Efficient and safe delivery of the CRISPR/Cas system is one of the key challenges for genome-editing applications in humans. Herein, we designed and synthesized a series of biodegradable lipidlike compounds containing ester groups for the delivery of mRNA-encoding Cas9. Two lead materials, termed N-methyl-1,3-propanediamine (MPA)-A and MPA-Ab, showed a tunable rate of biodegradation. MPA-A with linear ester chains was degraded dramatically faster than MPA-Ab with branched ester chains in the presence of esterase or in wild-type mice. Most importantly, MPA-A and MPA-Ab demonstrated efficient delivery of Cas9 mRNA both in vitro and in vivo. Consequently, these biodegradable lipidlike nanomaterials merit further development as genome-editing delivery tools for biological and therapeutic applications.


Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets.
Human milk (HM) is rich in oligosaccharides (HMO) that exert prebiotic and anti-infective activities. HM feeding reduces the incidence of rotavirus (RV) infection in infants. Herein, the anti-RV activity of oligosaccharides was tested in an established in vitro system for assessing cellular binding and viral infectivity/replication, and also tested in a newly developed, acute RV infection, in situ piglet model. For the in vitro work, crude HMO isolated from pooled HM, neutral HMO (lacto-N-neotetraose, LNnT; 2'-fucosyllactose) and acidic HMO (aHMO, '-sialyllactose, 3'-SL; -sialyllactose, -SL) were tested against the porcine OSU strain and human RV Wa strain. The RV Wa strain was not inhibited by any oligosaccharides. However, the RV OSU strain infectivity was dose-dependently inhibited by sialic acid (SA)-containing HMO. 3'-SL and 6'-SL concordantly inhibited (125)I-radiolabelled RV cellular binding and infectivity/replication. For the in situ study, a midline laparotomy was performed on 21-d-old formula-fed piglets and six 10 cm loops of ileum were isolated in situ. Briefly, 2 mg/ml of LNnT, aHMO mixture (40% 6'-SL/10 % 3'-SL/50 % SA) or media with or without the RV OSU strain (1 x 10(7) focus-forming units)were injected into the loops and maintained for 6 h. The loops treated with HMO treatments þ RV had lower RV replication, as assessed by non-structural protein-4 (NSP4) mRNA expression, than RV-treated loops alone. In conclusion, SA-containing HMO inhibited RV infectivity in vitro; however, both neutral HMO and SA with aHMO decreased NSP4 replication during acute RV infection in situ.


[The Importance of Vagus Nerve Afferent in the Formation of Emotions in Attention-Deficit Hyperactivity Disorder Model Rat].
It is of interest to know how environmental stimuli contribute to the formation of emotion during development. In a rat model of attention-deficit hyperactivity disorder, monosodium L- glutamate (MSG), a taste substance of umami, was administered for 5 weeks during developmental period, followed by emotional behavior tests such as open-field test and social interaction test in adulthood. Although no significant change was observed in anxiety-like behavior, MSG intake caused a reduction in aggressive behavior. Vagotomy under the level of diaphragm resulted in eliminating the MSG effect on aggression, indicating the importance of neuronal activity of the vagus nerve in this effect. Futher studies will focus on futher questions regarding the gut-brain axis such as the change of microbiota and the mechanism of the axis in the brain.


Hypochlorous acid generated by neutrophils inactivates ADAMTS13: an oxidative mechanism for regulating ADAMTS13 proteolytic activity during inflammation.
ADAMTS13 is a plasma metalloproteinase that cleaves large multimeric forms of von Willebrand factor (VWF) to smaller, less adhesive forms. ADAMTS13 activity is reduced in systemic inflammatory syndromes, but the cause is unknown. Here, we examined whether neutrophil-derived oxidants can regulate ADAMTS13 activity. We exposed ADAMTS13 to hypochlorous acid (HOCl), produced by a myeloperoxidase-H2O2-Cl(-) system, and determined its residual proteolytic activity using both a VWF A2 peptide substrate and multimeric plasma VWF. Treatment with 25 nm myeloperoxidase plus 50 μm H2O2 reduced ADAMTS13 activity by >85%. Using mass spectrometry, we demonstrated that Met(249), Met(331), and Met(496) in important functional domains of ADAMTS13 were oxidized to methionine sulfoxide in an HOCl concentration-dependent manner. The loss of enzyme activity correlated with the extent of oxidation of these residues. These Met residues were also oxidized in ADAMTS13 exposed to activated human neutrophils, accompanied by reduced enzyme activity. ADAMTS13 treated with either neutrophil elastase or plasmin was inhibited to a lesser extent, especially in the presence of plasma. These observations suggest that oxidation could be an important mechanism for ADAMTS13 inactivation during inflammation and contribute to the prothrombotic tendency associated with inflammation.


Wellness School Assessment Tool Version 3.0: An Updated Quantitative Measure of Written School Wellness Policies.
Schools play an important role in promoting student wellness. As directed by the Healthy Hunger-Free Kids Act, the US Department of Agriculture updated the requirements for written school wellness policies in 2016. The WellSAT (Wellness School Assessment Tool) is an online tool that provides a quantitative score for wellness policy comprehensiveness and strength. The WellSAT has been updated 3 times over the past decade to remain current with federal law and best practices. In this article, we describe the process of updating to WellSAT 3.0. The steps included: reviewing the language of each item linked to a federal provision; adding and deleting items based on frequencies from the National Wellness Policy Study and the empirical support for specific policies; gathering feedback from a survey of experts (N = 77) about best practices and measure usability; and establishing intercoder reliability in a national sample (N = 50) of policies. We conclude with recommendations and guidance for the use of WellSAT 3.0.


Emotional and neurocognitive deficits in fragile X.
We have studied the neurocognitive deficit in premutation and full mutation women as compared to control women and to explore the relationship between those deficits and the incidence of emotional problems. Four groups of women were examined: two fragile X (fra(X)) negative control groups, one of which grew up in fra(X) families and one not; and two DNA positive groups, one with a premutation (CGG repeats < 200) and one with an expanded mutation (CGG repeats > 200). All women were assessed using the MMPI-2, the SADS-L, and a battery of neuropsychological tests. Full mutation women had lower scores on composite measures of executive function and nonverbal function. There was no difference between the groups in terms of the lifetime incidence of depressive and anxiety disorders on the SADS-L. Full mutation women displayed Lie scales higher than the other groups on the MMPI-2. Neurocognitive measures were not related to SADS-L diagnoses but were related to the Lie scale on the MMPI-2. Finally, number of CGG repeats was related to the neuropsychological variables and the Lie scale.


In Vivo Confocal Microscopy Morphometric Analysis of Meibomian Glands in Patients With Graves Ophthalmopathy.
To characterize meibomian glands (MGs) features in patients with Graves ophthalmopathy (GO) by in vivo confocal microscopy (IVCM) and to further investigate possible correlations with ocular surface characteristics. Consecutive patients with GO and controls were enrolled. The following ocular surface parameters were measured: tear break-up time, Schirmer test, and corneal fluorescein staining (Oxford score) were performed on each subject. IVCM of MGs was performed, and the scans were analyzed with ImageJ software for the calculation of the following: acinar unit density, total gland area, total lumen area (TLA), acinar longest diameter, and acinar shortest diameter. A nonparametric Mann-Whitney U test was used to compare variables between patients with GO and controls. The Spearman correlation analysis was used to evaluate the correlations between ocular surface and IVCM parameters. Twenty-one patients with GO and 24 sex- and age-matched healthy controls were included. Acinar unit density was significantly lower in patients with GO compared with controls (24.5 ± 8.1 vs. 34.2 ± 7.5 U/mm; P < 0.001). In addition, patients with GO showed significantly higher values of TLA, acinar longest diameter, and acinar shortest diameter compared with controls (respectively, 3104.7 ± 1713.3 vs. 1393.8 ± 448.0 μm, 94.4 ± 21.2 vs. 64.3 ± 10.1 µm and 56.6 ± 15.3 vs. 42.2 ± 12.3 μm; always P < 0.05). In patients with GO, TLA showed a significant inverse correlation with Schirmer test (Rs = -0.467; P = 0.038). IVCM allowed to detect distinctive features of MGs in patients with GO and could represent a surrogate tool for the assessment of MG status in these patients.


Lichen planus with predominant plasma cell infiltrate.
We herein report the case of a patient with lichenoid plaques on the lower extremities and anonychia of all toenails. Histologically, the eruption showed typical features of lichen planus, with the exceptional finding of a lichenoid infiltrate composed mostly of plasma cells. Only two other similar cases have been reported. The explanation for the numerous plasma cells remains unknown although such cases may represent a new histologic variant.


Maternal hypothyroidism and its effect on placental histopathology in singleton live births resulting from in vitro fertilization treatment.
We aimed to examine the impact of maternal hypothyroidism on placental pathology and perinatal outcomes in singleton live births resulting from IVF, using medical records of IVF births between 2009 and 2017 at a tertiary hospital. The primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included foetal, maternal, perinatal, and delivery complications. There were 1,057 live births, of which 103 (9.7%) and 954 (90.3%) were in the study and control groups, respectively. Patients in the study group were more likely to have diabetes mellitus, polycystic ovarian syndrome, gestational diabetes mellitus, and non-reassuring foetal heart rate (NRFHR) tracing during delivery. After adjustment for potential confounding factors, hypothyroidism was significantly associated with the bilobed placenta (aOR 4.1; 95% CI 1.2-14.3), retroplacental haematoma (aOR 2.4; 95% CI 1.2-4.9), decidual arteriopathy (aOR 2.0; 95% CI 1.2-4.1) and subchorionic thrombi (aOR 2.4; 95% CI 1.3-5.0). Additionally, there was a statistically significant relationship with NRFHR tracing. The incidence of acute chorioamnionitis and severe foetal inflammatory response was higher in the study group. In conclusion, the placental histopathology patterns of singleton IVF live births show that maternal hypothyroidism has a significant impact on adverse perinatal outcomes.


Isolating Discriminant Neural Activity in the Presence of Eye Movements and Concurrent Task Demands.
A growing number of studies use the combination of eye-tracking and electroencephalographic (EEG) measures to explore the neural processes that underlie visual perception. In these studies, fixation-related potentials (FRPs) are commonly used to quantify early and late stages of visual processing that follow the onset of each fixation. However, FRPs reflect a mixture of bottom-up (sensory-driven) and top-down (goal-directed) processes, in addition to eye movement artifacts and unrelated neural activity. At present there is little consensus on how to separate this evoked response into its constituent elements. In this study we sought to isolate the neural sources of target detection in the presence of eye movements and over a range of concurrent task demands. Here, participants were asked to identify visual targets (Ts) amongst a grid of distractor stimuli (Ls), while simultaneously performing an auditory N-back task. To identify the discriminant activity, we used independent components analysis (ICA) for the separation of EEG into neural and non-neural sources. We then further separated the neural sources, using a modified measure-projection approach, into six regions of interest (ROIs): occipital, fusiform, temporal, parietal, cingulate, and frontal cortices. Using activity from these ROIs, we identified target from non-target fixations in all participants at a level similar to other state-of-the-art classification techniques. Importantly, we isolated the time course and spectral features of this discriminant activity in each ROI. In addition, we were able to quantify the effect of cognitive load on both fixation-locked potential and classification performance across regions. Together, our results show the utility of a measure-projection approach for separating task-relevant neural activity into meaningful ROIs within more complex contexts that include eye movements.


Friedel-Crafts acylation with amides.
Friedel-Crafts acylation has been known since the 1870s, and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually performed with carboxylic acid chlorides or anhydrides, while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55-96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations.


The regulation and function of the NUAK family.
AMP-activated protein kinase (AMPK) is a critical regulator of cellular and whole-body energy homeostasis. Twelve AMPK-related kinases (ARKs; BRSK1, BRSK2, NUAK1, NUAK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4, and MELK) have been identified recently. These kinases show a similar structural organization, including an N-terminal catalytic domain, followed by a ubiquitin-associated domain and a C-terminal spacer sequence, which in some cases also contains a kinase-associated domain 1. Eleven of the ARKs are phosphorylated and activated by the master upstream kinase liver kinase B1. However, most of these ARKs are largely unknown, and the NUAK family seems to have different regulations and functions. This review contains a brief discussion of the NUAK family including the specific characteristics of NUAK1 and NUAK2.


Linking emotional intelligence to safety performance: The roles of situational awareness and safety training.
Safety outcomes in the workplace require individual employees to perform (behave) safely in everyday duties. While the literature suggests that emotional management capabilities or traits can be positively related to individual performance in certain conditions, it is not clear how they can influence safety-related performance in high-risk work contexts. Drawing upon trait activation theory, this paper aims to examine when emotional intelligence (EI) benefits employees' safety performance. We propose that when employees receive inadequate safety training, EI is more likely to trigger their situational awareness and consequently promote their safety performance. We collected time-lagged data from 133 full-time airplane pilots working in commercial aviation industry. Hierarchical moderated regression analysis was conducted to test the moderating effect of safety training inadequacy on the EI-situational awareness relationship. The moderated mediation model, which involves conditional indirect effects of EI on safety performance via situational awareness across different levels of safety training inadequacy, was tested using the PROCESS-based bootstrap confidence interval. Safety training inadequacy negatively moderated the relationship between EI and situational awareness, such that EI was significantly related to situational awareness only when safety training inadequacy was more salient. The more inadequate safety training was, the greater the indirect effect of EI on safety performance via situational awareness was. Inadequate safety training, as a negative situational cue, can activate individuals' EI to drive their safety-related cognitions (e.g., situational awareness) and behaviors. Effective safety training may be able to complement employees' low EI in shaping their situational awareness and safety behaviors. Practical Applications: Aviation managers should monitor the adequacy and effectiveness of safety training; this could make pilots' situational awareness and safety performance depend less on personal attributes (e.g., EI), which organizations are less able to control. When training capacity is temporarily limited, priority might be given to those with low EI.


Clinical presentation and follow up of children with congenital toxoplasmosis in Brazil.
We evaluated the clinical presentation and determined the ocular and neurologic sequelae in children with congenital toxoplasmosis in Brazil, taking into consideration the shortage of national publications on this disease. Follow-up evaluations were made of 43 children with congenital toxoplasmosis referred to Santa Casa de São Paulo, during a period of at least five years. Selection of the cases was based in clinical and laboratory criteria. A clear predominance of children with subclinical presentation of the disease at birth (88%) was found. Of the 43 children, 22 (51%) developed neurological manifestations. Using skull radiography, we detected neuroradiologic alterations in seven children (16%) and with tomography in 33 children (77%). Neurological sequelae were identified in 15 children (54%) in the group with cerebral calcifications and in 7 (47%) in the group without cerebral calcifications. We observed chorioretinitis in 95% of the cases. Reactivation of cicatricial lesions and the emergence of new ocular lesions were observed in five cases. The most frequent neurological manifestation was a delay in neuropsychomotor development. Most remarkable was the finding that cerebral calcifications were not associated with a higher incidence of neurological sequelae among the children. Chorioretinitis was the main ocular sequel of the infection, found in nearly all children; it can manifest years from birth, even in children submitted to specific therapy druing the first year of life, highlighting the importance of a follow-up of these children.


Dysbiosis in the Neonatal Period: Role of Cesarean Section.
From epidemiological studies and studies done evaluating microbiomes in infants, there is a strong signal that the infants born by elective cesarean section (C-section) develop microbiota that differs from those babies born by vaginal delivery. Epidemiological studies show increased odds ratios for the development of immunological disorders such as type 1 diabetes, celiac disease, asthma, allergic diseases as well as metabolic diseases such as obesity in babies born by C-section. These are interesting associations, and if supported by additional studies that rigorously control for confounding factors, they will have major public health implications. Such studies represent major challenges because the confounding factors are numerous. The fact that provision of vaginal bacteria to C-section-delivered babies using a mouth swab that may actually transmit these bacteria to the infant is of interest and supports the concept that this can be done to alter the infant microbiota. However, significant caution needs to be taken, and alternative approaches that are safe as well as effective need to be considered; follow-up studies showing efficacy as well as safety need to be evaluated in the long term.


Smoking prevention in childhood cancer survivors.
In the year 2000, there may be 220,000 adult survivors of childhood cancer. This creates new emphasis on the health of long-term survivors. The oncology team is responsible for educating patients about methods of modifiable risk reduction for the development of cancer. Smoking is the single most avoidable risk factor implicated in the development of cancer, yet survivors of childhood cancer have been found to smoke at the same rate as their peers. Nurses play a key role in developing patients' knowledge, beliefs and skills to avoid smoking behaviors.


LC-ESI-MS/MS analysis and pharmacokinetics of jolkinolide B, a potential antitumor active component isolated from Euphorbia fischeriana, in rat plasma.
A simple, specific and reproducible liquid chromatography-electrospray ionization mass spectrometry was developed and validated for the determination of jolkinolide B, a potential antitumor active component isolated from Euphorbia fischeriana, in rat plasma. Chromatographic separation was achieved on a Venusil MP-C18 column using an isocratic elution. Jolkinolide B and osthole (internal standard) were monitored by positive electrospray ionization in the selected reaction monitoring mode. Good linearity (r(2) > 0.996) was achieved by a weighted (1/x(2) ) linear least-squares regression over a concentration range of 6.50-2600 ng/mL. The accuracy and precision of the assay were satisfactory and the method proved to be applicable to pharmacokinetics following a single intravenous bolus injection of jolkinolide B to rats.


Difficulties in conducting a randomized controlled trial of health service interventions in intellectual disability: implications for evidence-based practice.
In an era of evidence-based medicine, practice is constantly monitored for quality in accordance with the needs of clinical governance (Oyebode et al. 1999). This is likely to lead to a dramatic change in the treatment of those with intellectual disability (ID), in which evidence for effective intervention is limited for much that happens in ordinary practice. As Fraser (2000, p. 10) has commented, the word that best explains "the transformation of learning disability practice in the past 30 years is 'enlightenment'." This is not enough to satisfy the demands of evidence, and Fraser exhorted us to embrace more research-based practice in a subject that has previously escaped randomized controlled trials (RCTs) of treatment because of ethical concerns over capacity and consent, which constitute a denial of opportunity which "is now at last regarded as disenfranchising". The present paper describes the difficulties encountered in setting up a RCT of a common intervention, i.e. assertive community treatment, and concludes that a fundamental change in attitudes to health service research in ID is needed if proper evaluation is to prosper.


Availability of Adequate Photoprotection for Skin of Color.
The impact of ultraviolet (UV) light on the skin is well-established to have both immediate and delayed effects with increasing awareness of the impact of visible light (VL) on the skin with regard to photoaging and dyspigmentation. The effects of VL disproportionately impact the skin of color with regard to discoloration of the skin leading to guidelines for photoprotection that include the use of iron oxides in sunscreen products that impart a tint. Commercially available sunscreen products found in the suncare and sun protection displays at local stores, pharmacies, and grocery stores were cataloged, and ingredients were reviewed for the presence of iron oxides. Of the 410 commercially available sunscreen products cataloged, 1.7% of facial sunscreen products available offered iron oxides, and 0.5% of non-lip products offered shade matching. With only 1.7% of commercially available facial sunscreen products offering iron oxides in addition to traditional broad-spectrum UV protection, there is a clear gap in the market for iron oxide-containing sunscreen products to meet the photoprotection needs for the skin of color.


Postural flexibility during quiet standing in healthy elderly and patients with Parkinson's disease.
Postural instability is one of the predominant symptoms of Parkinson's disease (PD). Despite its significant impact on the deterioration in quality of life in PD patients, mechanistic causes of the instability have not been clarified. Joint inflexibility at ankle and hip joints might be such a major cause, leading to small variability in the center of pressure (CoP) during quiet stance. However, this conjecture is still controversial. Thus, quantitative characterization of CoP patterns during quiet stance in PD patients remains a matter of research. Here we performed a linear discriminant analysis for CoP data in PD patients and age-matched healthy elderly during quiet stance, and showed that CoP variations in PD patients and those in healthy elderly could be well distinguished with an accuracy of about 90%, to which appropriately selected sway indices characterizing aspects of power spectrum for the CoP variations contributed. Specifically, major factors responsible for the discrimination were all associated with increase in the power at a high-frequency band (near and over 1 Hz) along with reduction at the low-frequency regime (lower than about 0.7 Hz). Then, the power-ratio, defined as the relative spectral power in a band around 1 Hz, was examined, since the power in this band reflects postural sway with anti-phase coordinated motions of the ankle and hip joints. We showed that the power-ratio values were significantly smaller in the PD patients than those in the healthy subjects. This difference as well as the results of the linear discriminant analysis suggest joint inflexibility in PD patients, particularly at hip joint, which diminished anti-phase coordination between trunk and lower extremity, leading to postural instability in PD patients.


Malocclusions in guinea pigs, chinchillas and rabbits.
The types of malocclusions encountered in rodents and lagomorphs are classified. Diagnosis, treatment, and prognosis are reviewed. Some malocclusions are curable, whereas others can only be controlled. The need to perform a complete oral examination and to find a cause for the condition is stressed, as it will seriously affect the prognosis.


Comprehensive breast reconstruction in an academic surgical practice: an evaluation of the financial impact.
This study assessed the financial implications of providing all forms of breast reconstruction at a single academic institution with insurance as the primary mode of reimbursement. Billing records of 152 patients who underwent postmastectomy breast reconstruction offered at the University of Michigan for the 2012 fiscal year were reviewed. Professional and facility revenue, cost, and earnings for the first stage of reconstruction were calculated by applying actual collections and charges. Similar financial data were compiled for a subset of 49 patients who went on to complete reconstruction. The professional revenue and expenses allocated to breast reconstruction were $647,437 and $591,184, respectively (8.7 percent margin). Health care system facility revenue and costs were $2,762,797 and $2,773,131, respectively (-0.4 percent margin). Physician reimbursement by surgical time was highest for delayed tissue expander placement ($3505 per operating room hour). Abdominal free flap reconstructions resulted in greater professional revenue for the first stage of reconstruction ($7801 versus $2961) and for completed reconstructions ($14,943 versus $7703) relative to implant reconstructions. The facility also did better fiscally after the first stage of abdominally based reconstruction compared with implant reconstructions (10 percent versus -10.4 percent margin). Postmastectomy breast reconstruction for this academic surgical practice remains fiscally profitable. Implant-based reconstruction compared with abdominal flap reconstruction produces greater revenue per operative hour but ultimately generates less total revenue and results in financial losses for the facility. Abdominally based perforator flap reconstruction reimbursed through standard insurance plans can be financially advantageous for the academic surgical practice and health care system.


[The cytogenetic assay as a measure of genetic instability induced by genotoxic agents].
Human genetic integrity is compromised by the intense industrial activity, which emphasizes the importance to determine an "acceptable" genetic damage level and to carry out routine genotoxicity assays in the populations at risk. Micronuclei are cytoplasmatic bodies of nuclear origin which correspond to genetic material that is not correctly incorporated in the daughter cells in the cellular division; they reflect the existence of chromosomal aberrations and are originated by chromosomal breaks, replication errors followed by cellular division of the DNA and/or exposure to genotoxic agents. There are several factors able to modify the number of micronuclei present in a given cell, among them are age, gender, vitamins, medical treatments, daily exposure to genotoxic agents, etc. The cytogenetic assay for the detection of micronuclei (CBMN: cytokinesis-block micronucleus) is based on the use of a chemical agent, cytochalasin-B, which is able to block cytocinesis but allowing the nuclear division, therefore yielding binucleated and monodivided cells. The micronuclei scoring is performed on 1000 binucleated cells and the starting sample may vary, although most studies are performed on peripheral blood lymphocytes. The micronuclei assay is considered a practical, universally validated and technically feasible protocol which is useful to evaluate the genetic instability induced by genotoxic agents.


[Weightlessness and elementary biological processes].
This book gives comprehensive review of the role of gravity in fundamental biological processes. The book surveys the results of experiments on precellular and unicellular organisms, plant and animal cultured cells and tissues, fungi and actinomycetes, higher plants, and insects. The book discusses essentially every experiment performed in real flights, including those in which the combined effect of microgravity and ionizing radiation was investigated, as well as many clinostat and centrifuge studies. In orbital flights unicellular organisms exhibited no gravity-dependent processes. The maximum size and basic morphology of unicellular organisms developed obeying the second law of thermodynamics do not therefore depend on space or time. Fungi retained all their properties except for gravitational ordering. Higher plants developed normally through seed-to-seed cycles: from the stage of seed germination to that of maturation of next generation seeds. Plants changed all their gravity-dependent movements. Since plant movements are irreversible, this affected their final shape, although the basic structure and size remained unaltered. The frequency of spontaneous and radiation--induced mutations changed insignificantly. The rotation of generations of plants and animals taken under study developed in a normal way. The morphological, physiological and genetic status of present-day organisms has developed under the effect of the gravity force that plays three different parts: as the creator and transformer of the abiotic environment, as the factor of natural selection, and as the factor of environmental physiology eliciting stable mechanical stresses. The effects of these gravity roles are implemented by different mechanisms and actualized in different time scales. The uneventful development of the basic biological processes in microgravity is an important factor that makes possible long-term space missions. From this point of view, the road to outer space is open to man in terms of his biology.


A Comparison of Immune Responses Exerted Following Syngeneic, Allogeneic, and Xenogeneic Transplantation of Mesenchymal Stem Cells into the Mouse Brain.
Due to their multifactorial aspects, mesenchymal stem cells (MSCs) have been widely established as an attractive and potential candidate for the treatment of a multitude of diseases. A substantial number of studies advocate that MSCs are poorly immunogenic. In several studies, however, immune responses were observed following injections of xenogeneic donor MSCs. In this study, the aim was to examine differences in immune responses exerted based on transplantations of xenogeneic, syngeneic, and allogeneic MSCs in the wild-type mouse brain. Xenogeneic, allogeneic, and syngeneic MSCs were intracerebrally injected into C57BL/6 mice. Mice were sacrificed one week following transplantation. Based on immunohistochemical (IHC) analysis, leukocytes and neutrophils were expressed at the injection sites in the following order (highest to lowest) xenogeneic, allogeneic, and syngeneic. In contrast, microglia and macrophages were expressed in the following order (highest to lowest): syngeneic, allogeneic, and xenogeneic. Residual human MSCs in the mouse brain were barely detected after seven days. Although the discrepancy between leukocytes versus macrophages/microglia infiltration should be resolved, our results overall argue against the previous notions that MSCs are poorly immunogenic and that modulation of immune responses is a prerequisite for preclinical and clinical studies in MSC therapy of central nervous system diseases.


Surface changes in oviduct, uterus and vaginal cells of neonatal mice after estradiol-17 beta and the insecticide chlordecone (Kepone) treatment: a scanning electron microscopic study.
Surface changes in cells lining the oviduct, uterus and vagina of a neonatal mouse were studied after treatment with estradiol-17 beta (E2) or the insecticide chlordecone. One-day-old mice received daily intraperitoneal injections of 1 of 6 injection mixtures (0.05 ml) for 10 days. The daily dosages per animal were as follows: sesame oil only, 10 microgram E2, 15, 30, 60 and 125 microgram chlordecone suspended in sesame oil. Estradiol-treated mice were terminated after 5 and 10 injections, whereas all other mice were terminated at the end of 10 injections. After 5 and 10 estradiol injections, accelerated ciliation was recorded in the oviduct and increased secretory activity in the uterus or uterine glands. In the vagina, epithelial mucification proceeded to complete cornification with the cornified cell surfaces showing a prominent and complex pattern of microridges. Chlordecone treatments produced dose-dependent cell surface changes in the reproductive tract that were either characteristic of estrogenic stimulation or atypical responses. Chlordecone stimulatory action mimicked estrogen in the form of accelerated ciliation, secretory activity in oviductal and uterine cells as well as mucification leading to complete cornification of vaginal epithelium. Chlordecone doses of 60 microgram or higher produced atypical cellular expansions or swelling in the nonciliated cells of the oviduct and uterus in the mucified vaginal epithelial cells. Also, cornified vaginal cells of chlordecone-treated mice exhibited smoother cell surfaces with decreased microridge patterns when compared to estradiol-treated mice. The stimulatory mechanism of chlordecone action and the probable cause of cellular abnormality are discussed in the text.


Low-dose Nicotine Exposure Induced the Oxidative Damage of Reproductive Organs and Altered the Sperm Characteristics of Adolescent Male Rats.
Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague-Dawley rats. Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated. Chronic nicotine treatment significantly (P < 0.05) altered the sperm count, motility, viability, and morphology, and remarkably increased the malondialdehyde (P < 0.001) and advanced oxidation protein product (P < 0.05) levels in the testes and prostate of nicotine-treated group compared to control group. Moreover, nicotine caused a significant decrease (P < 0.05) in the superoxide dismutase activity of the testes. No significant differences were observed in the reduced glutathione level in both of the testes and prostate of nicotine group compared with control group. Nicotine also induced histopathological alteration in the testes. A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate.


Roles of I(f) and intracellular Ca2+ release in spontaneous activity of ventricular cardiomyocytes during murine embryonic development.
In recent years, the contribution of I(f), an important pacemaker current, and intracellular Ca(2+) release (ICR) from sarcoplasmic reticulum to pacemaking and arrhythmia has been intensively studied. However, their functional roles in embryonic heart remain uncertain. Using patch clamp, Ca(2+) imaging, and RT-PCR, we found that I(f) regulated the firing rate in early and late stage embryonic ventricular cells, as ivabradine (30 µM), a specific blocker of I(f), slowed down action potential (AP) frequency. This inhibitory effect was even stronger in late stage cells, though I(f) was down-regulated. In contrast to I(f), ICR was found to be indispensable for the occurrence of APs in ventricular cells of different stages, because abolishment of ICR with ryanodine and 2-aminoethoxydiphenyl borate (2-APB), specific blockers of ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), completely abolished APs. In addition, we noticed that RyR- and IP3R-mediated ICR coexisted in early-stage ventricular cells and RyRs functionally dominated. While at late stage RyRs, but not IP3Rs, mediated ICR. In both early and late stage ventricular cells, Na-Ca exchanger current (I(Na/Ca)) mediated ICR-triggered depolarization of membrane potential and resulted in the initiation of APs. We also observed that different from I(f), which presented as the substantial component of the earlier diastolic depolarization current, application of ryanodine, and/or 2-APB slowed the late phase of diastolic depolarization. Thus, we conclude that in murine embryonic ventricular cells I(f) regulates firing rate, while RyRs and IP3Rs (early stage) or RyRs (late stage)-mediated ICR determines the occurrence of APs.


Laparoscopic or open liver resection for intrahepatic cholangiocarcinoma: A meta-analysis and systematic review.
Although laparoscopic hepatectomy has been widely used in the treatment of benign and malignant liver diseases, its applicability in intrahepatic cholangiocarcinoma (ICC) is controversial. We conducted a meta-analysis to compare the short-term and long-term outcomes of laparoscopic hepatectomy (Lap-ICC) and open hepatectomy (Open-ICC) in ICC patients. The PubMed, Web of science, Cochrane Library, China National Knowledge Infrastructure and other databases were searched for the relevant literature. The research data were extracted according to the inclusion and exclusion criteria. Seventeen studies, including 3975 ICC patients, were selected for the meta-analysis. Compared to Open-ICC, Lap-ICC had lower rates of lymph node dissection (OR=0.44, P=0.01) and metastasis (OR=0.58, P=0.03), along with less intraoperative bleeding (MD=-128.43 ml, P<0.01) lower blood transfusion rate (OR=0.43, P<0.01), shorter hospital stay (MD=-2.75 day, P<0.01), higher R0 resection rate (OR=1.60, P<0.01), and lower tumor recurrence rate (OR=0.67, P=0.01). However, there was no difference between the two groups in terms of operation time, number of lymph node dissection, incision margin distance, overall complications rate, severe complications rate, and the 1-, 3- and 5-year DFS and OS rates. Laparoscopic hepatectomy is partially superior to open hepatectomy in terms of less bleeding, shorter hospital stay and higher R0 resection rate, while the long-term efficacy of the two approaches is similar.


Racial Disparity in Stroke Awareness in the US: An Analysis of the 2014 National Health Interview Survey.
Stroke is a leading cause of premature death and disability, and increasing the proportion of individuals who are aware of stroke symptoms is a target objective of the Healthy people 2020 project. We used data from the 2014 Supplement of the National Health Interview Survey (NHIS) to assess the prevalence of stroke symptom knowledge and awareness. We also tested, using a logistic regression model, the hypothesis that individuals who have knowledge of all 5 stroke symptoms will be have a greater likelihood to activate Emergency Medical Services (EMS) if a stroke is suspected. From the 36,697 participants completing the survey 51% were female. In the entire sample, the age-adjusted awareness rate of stroke symptoms/calling 911 was 66.1%. Knowledge of the 5 stroke symptoms plus importance of calling 911 when a stroke is suspected was higher for females, Whites, and individuals with health insurance. Stroke awareness was lowest for Hispanics, Blacks, and survey participants from Western US region. The findings allude to continuing differences in the knowledge of stroke symptoms across race/ethnic and other demographic groups. Further research will confirm the importance of increased health literacy for Stroke management and prevention in minority communities.


Identification of drugs in pharmaceutical dosage forms by X-ray powder diffractometry.
A simple X-ray powder diffractometric (XRD) method was developed for the identification of the active ingredient in a variety of dosage forms. The method was successfully used to unambiguously identify the active ingredient(s) in tablet, capsule, suppository and ointment formulations. The unique feature of the method is that it provides information about the solid-state of the drug. Thus, a capsule formulation containing anhydrous ampicillin was readily distinguished from that containing ampicillin trihydrate. The USP stipulates the use of the beta-polymorphic form of anhydrous carbamazepine in carbamazepine tablets. Contamination by the alpha-polymorph (down to a level of 1.4% w/w of the formulation) could be detected. In some of the multicomponent formulations, there was a pronounced overlap of the powder patterns of ingredients which made identification difficult. This problem was solved by using a pattern subtraction technique, which permitted selective subtraction of the XRD pattern of the constituents of the formulation from the overall XRD pattern. Such an approach enabled identification of the drug even when it constituted only 5% w/w of the formulation. The method also permitted simultaneous identification of the multiple active ingredients in trimethoprim-sulfamethoxazole and acetaminophen-aspirin-caffeine formulations.


A magnetic particle time-of-flight (MagPTOF) diagnostic for measurements of shock- and compression-bang time at the NIF (invited).
A magnetic particle time-of-flight (MagPTOF) diagnostic has been designed to measure shock- and compression-bang time using D(3)He-fusion protons and DD-fusion neutrons, respectively, at the National Ignition Facility (NIF). This capability, in combination with shock-burn weighted areal density measurements, will significantly constrain the modeling of the implosion dynamics. This design is an upgrade to the existing particle time-of-flight (pTOF) diagnostic, which records bang times using DD or DT neutrons with an accuracy better than ±70 ps [H. G. Rinderknecht et al., Rev. Sci. Instrum. 83, 10D902 (2012)]. The inclusion of a deflecting magnet will increase D(3)He-proton signal-to-background by a factor of 1000, allowing for the first time simultaneous measurements of shock- and compression-bang times in D(3)He-filled surrogate implosions at the NIF.


Analysing culture methods of frozen human ovarian tissue to improve follicle survival.
In vitro follicle growth is a potential fertility preservation method for patients for whom current methods are contraindicated. Currently, this method has only been successful using fresh ovarian tissue. Since many patients who may benefit from this treatment currently have cryopreserved ovarian tissue in storage, optimising in vitro follicle growth (IVG) for cryopreserved-thawed tissue is critical. This study sought to improve the first step of IVG by comparing different short-term culture systems for cryopreserved-thawed human ovarian tissue, in order to yield a higher number of healthy multilayer follicles. We compared two commonly used culture media (αMEM and McCoy's 5A), and three plate conditions (300 µL, 1 mL on a polycarbonate membrane and 1 mL in a gas-permeable plate) on the health and development of follicles after 6 days of culture. A total of 5797 follicles from three post-pubertal patients (aged 21.3 ± 2.3 years) were analysed across six different culture conditions and non-cultured control. All culture systems supported follicle development and there was no difference in developmental progression between the different conditions tested. Differences in follicle morphology were evident with follicles cultured in low volume conditions having significantly greater odds of being graded as morphologically normal compared to other conditions. Furthermore, culture in a low volume of αMEM resulted in the highest proportion of morphologically normal primary and multilayer follicles (23.8% compared to 6.3-19.9% depending on condition). We, therefore, recommend culturing cryopreserved human ovarian tissue in a low volume of αMEM to support follicle health and development. Ovaries contain a large number of follicles, each containing an immature egg and other important cells. Cancer treatments can lead to long-lasting negative side effects to the ovaries including the destruction of follicles, resulting in infertility. One strategy to preserve fertility is freezing of ovaries or ovarian tissue in girls and women undergoing cancer treatment. The long-term aim is to thaw and grow their ovarian tissue in the laboratory to obtain mature eggs, which can then be fertilised. In this study, we compared six different methods of growing previously frozen human ovarian tissue in order to best support follicle growth and health. We found that using the lowest amount of αMEM medium (a specific type of nutrient-rich growth solution) resulted in the highest proportion of healthy follicles. Improving the methods used to grow ovarian tissue, particularly frozen tissue, is important for future fertility preservation.


Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate.
The mechanism by which late asthmatic reactions are induced by toluene diisocyanate (TDI), a low molecular weight chemical that causes occupational asthma in exposed subjects, is unknown. We investigated whether early and late asthmatic reactions induced by TDI are associated with changes in airway responsiveness to methacholine and airway inflammation as determined by bronchoalveolar lavage. We measured FEV1 before and at regular intervals after exposure to TDI, and performed dose-response curves to methacholine and bronchoalveolar lavage at 8 h after TDI in a group of 6 subjects with late asthmatic reactions and in 6 subjects with only early asthmatic reactions. The same procedure was followed 2 h after TDI in a group of 6 subjects with previously documented late asthmatic reactions and in a group of 6 subjects without any previously documented asthmatic reaction after TDI. In subjects with late asthmatic reactions, neutrophils were increased at both 2 and 8 h, and eosinophils and airway responsiveness were increased only at 8 h. By contrast, neutrophils, eosinophils and airway responsiveness were not increased at 8 h after TDI in subjects with an early asthmatic reaction or at 2 h after TDI in normal control subjects. These results suggest that late asthmatic reactions to TDI, and the associated increase in airway responsiveness, may be caused by airway inflammation.


Are You Still a Postdoc? How My Scientific Identity Intersects with My Immigrant Status.
Academics in non-tenure-track positions encounter a unique set of challenges on the road toward tenure. Institutionalized policies and lack of mentors are additional burdens for foreign scientists, resulting in representation differences. Becoming a scientist has been a personal and moving journey in which my multiple selves intersect and clash every now and again. My identity as a scientist is a life project and has intersected with my other identities: a young Latina immigrant in Western Europe. This crossroad has molded, and at times, challenged my participation in science.


Muscle strength and serum testosterone, cortisol and SHBG concentrations in middle-aged and elderly men and women.
Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44-57; n = 9), F50 years (range 43-54; n = 9), M70 years (range 64-73; n = 11) and F70 years (range 63-73; n = 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 +/- 452 N in M50 was greater (P < 0.05) than that of 2627 +/- 752 N recorded for F50 as well as the force of 2787 +/- 843 in M70 was greater (P < 0.001) than that of 1849 +/- 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.01) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r = 0.66; P < 0.01) and in the elderly subjects (r = 0.69; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Safety and Efficacy of Brolucizumab in the Treatment of Diabetic Macular Edema and Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
To investigate the efficacy and safety of brolucizumab in diabetic macular edema (DME) and diabetic retinopathy (DR). In this systematic review and meta-analysis, an electronic search was done to acquire all articles describing brolucizumab use in patients with DME and DR. The review was prospectively registered on PROSPERO (CRD42022382625). Collected articles were filtered through two stages by independent reviewers. Data were extracted from the included articles and then analyzed accordingly. Brolucizumab induced significant improvement in best-corrected visual acuity and was either better or non-inferior to other types of anti-VEGF (MD -0.64 mu, 95% CI [-1.15, -0.13], P = .01); the same observation was noted with regards to central subfield macular thickness (CSMT) (MD -138.6 mu, 95% CI [-151.9, -125.3], P = .00001). Brolucizumab was reported to be relatively safe for use in diabetic patients, with few adverse events observed, with a higher frequency of adverse events in relation to the 3 mg dose compared to the 6 mg dose. Brolucizumab is a new drug that has potential advantages in efficacy over other anti-VEGF agents in the treatment of DME and DR. It showed significant improvement in BCVA and CSMT with the possibility of a lower dosing schedule compared to other agents. Although observed in low frequency, sight-threatening adverse effects appear to occur more frequently compared to other anti-VEGF agents. The main observed adverse event was retinal vasculitis which was seen more commonly with the 3 mg dose versus the 6 mg dose.