Accuracy, Reliability and Clinical Implications of Static Compared to Quantifiable Occlusal Indicators.
This literature review summarizes the properties, advantages, limitations, and clinical implications of employing static occlusal indicators compared to quantifiable digital occlusal indicators during occlusal adjustments. An electronic database search of dental literature was carried out in PubMed/MEDLINE using the key words Occlusal Indicators, Occlusal Assessment, Static, Reliability, Dynamic, Repeatability, Validity and Clinical Accuracy. A total of 231 papers were isolated, with 129 papers considered for review. The included papers were grouped by Static and Dynamic Occlusal indicators. The numbers of papers in the Static Group was extremely low (only 20 papers) compared to The Dynamic group (T-Scan: 89; Dental Prescale: 28; Intraoral Scanners:17). Little evidence supports the use of static occlusal indicators due to their high degree of subjectivity required during implementation. However, much scientific evidence supports the use of T-Scan, as it measures relative occlusal forces and timing objectively, accurately, and repeatedly. For the improvement of Occlusal Practice, Subjective Interpretation using Static occlusal indicators should be replaced with digital ones for objective measurements. The computerized occlusal analysis system is well studied and has the capacity to provide precise time and force sequencing information to objectively evaluate occlusal contacts for improved treatment outcome.


Estimated prevalence of helmet use while bicycling, rollerblading, and skateboarding among middle school students in selected U.S. States- Youth Behavior Risk Survey, 2013-2019.
Helmet use helps prevent severe and fatal head and brain injuries from bicycle, rollerblade, and skateboard crashes. This study explores the prevalence of self-reported helmet use among middle school students while bicycling, skateboarding, and rollerblading. Data from the Middle School Youth Risk Behavior Survey (YRBS) for selected states were analyzed. Self-reported prevalence (frequency) of helmet use while bicycling, rollerblading, or skateboarding and other variables (sex, grade level, and race/ethnicity) are reported. The overall prevalence of rarely or never wearing a helmet while bicycling among middle school students in selected states was 68.6%; decreasing from 71.7% in 2013 to 67.1% in 2019. The overall prevalence of rarely or never wearing a helmet while rollerblading or skateboarding in middle school students in selected states was 74.6%; decreasing from 76.4% in 2013 to 73.5% in 2019. Students in 7th and 8th grade and students of non-Hispanic race/ethnicity had significantly higher odds of rarely or never wearing a helmet while bicycling or while rollerblading and skateboarding than students in 6th grade and non-Hispanic White students. While helmet use among middle school students improved over time, overall helmet use during bicycling, rollerblading, and skateboarding remained low. These estimates illustrate the continued call for universal implementation of helmet use efforts among kids using established strategies. Future research on helmet use among youth who rollerblade and skateboard, as well as multi-pronged efforts to promote helmet use among middle schoolers who bicycle, skateboard, and rollerblade (inclusive of education, helmet distribution, and social marketing techniques, as well as the provision of helmets at no-cost) may be beneficial for addressing perceived risks for injury and other barriers.


Non-linear optical properties of gold quantum clusters. The smaller the better.
By developing a new method for synthesizing atomically monodisperse Au15 nanoclusters stabilized with glutathione molecules and using the current state-of-the-art methods for synthesizing monodisperse protected Au25 nanoclusters, we investigated their nonlinear optical (NLO) properties after two-photon absorption. The two-photon emission spectra and the first hyperpolarizabilities of these particles were obtained using, in particular, a hyper-Rayleigh scattering technique. The influence on NLO of the excitation wavelength, the size as well as the nature of the ligands is also explored and discussed. Au15, the smallest stable thiolated gold nanocluster, presents remarkable nonlinear properties with respect to two-photon processes. The two-photon absorption cross-section at 780 nm for Au15 is ∼65,700 GM. This experimental cross-section value points to a quantum yield for two-photon emission of about 3 × 10(-7) at 475 nm for Au15. The first hyperpolarizability β for Au15 clusters (509 × 10(-30) esu), as compared to Au25 clusters (128 × 10(-30) esu), is larger considering the difference in the number of gold atoms. Also, 10(30) β per atom values reported for Au15 and Au25 clusters are more than two orders of magnitude larger than the values reported for Au NPs in the size range 10-50 nm, outlining the quantum cluster regime.


Cosmetic concerns and management strategies to combat aging.
Multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Intervetions should be geared towards addressing the intrinsic and extrinsic signs of aging and can include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and soft tissue fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of the aging face and thus will provide the optimal aesthetic outcome.


The excess choice effect: The role of outcome valence and counterfactual thinking.
Contrary to economic theory, psychological research has demonstrated increased choice can undermine satisfaction. When and why this 'excess choice effect' (ECE) occurs remains unclear. Building on theories of counterfactual thinking we argue the ECE is more likely to occur when people experience counterfactual thought or emotion and that a key trigger is a negative versus positive task outcome. Participants either selected a drink (Experiment 1) or chocolate (Experiment 2) from a limited (6) versus extensive (24) selection (Experiment 1) or were given no choice versus extensive (24) choice (Experiment 2). In both experiments, however, the choice was illusory: Half the participants tasted a 'good' flavour, half a 'bad' flavour. As predicted, extensive choice was only detrimental to satisfaction when participants tasted the 'bad' drink or chocolate, and this was mediated by the experience of counterfactual thought (Experiment 1) or emotion (Experiment 2). When outcomes were positive, participants were similarly satisfied with limited versus extensive and no choice versus extensive choice. Implications for our theoretical understanding of the ECE and for the construction of choice architectures aimed at promoting individual satisfaction and well-being are discussed.


Surface binding of toxins and heavy metals by probiotics.
Removal of toxic metals and toxins using microbial biomass has been introduced as an inexpensive, new promising method on top of conventional methods for decontamination of food, raw material and concentrated. In this article the potential application of lactic acid bacteria and yeasts as the most familiar probiotics to eliminate, inactivate or reduce bioavailability of contamination in foods and feed has been reviewed. After fast glance to beneficial health effects and preservative properties of lactic acid bacteria, the mechanisms which explain antibacterial and antifungal efficiency as well as their antifungal metabolites are mentioned. Then the article has been focused on potential application of single strain or combination of lactic acid bacteria for removal of heavy metals (copper, lead, cadmium, chromium, arsenic), cyanotoxins (microcystin-LR, -RR, -LF) and mycotoxins (aflatoxin B1, B2, B2a, M1, M2, G1, G2, patulin, ochratoxin A, deoxynivalenol, fumonisin B1 and B2, 3-acetyldeoxynivalenol, deoxynivalenol, fusarenon, nivalenol, diacetoxyscirpenol, HT-2 and T-2 toxin, zearalenone and its derivative, etc) from aqueous solutions in vitro. Wherever possible the mechanism of decontamination and the factors influencing yield of removal are discussed. Some factors which can facilitate metal removal capacity of lactic acid bacteria including the strains, surface charge, pH, temperature, presence of other cations are introduced. The cell wall structure of lactic acid bacteria and yeasts are also introduced for further explanation of mechanism of action in complex binding of probiotic to contaminants and strength of mycotoxin- bacterium interaction.


[Model of the effect of the vestibular system on blood pressure during sleep].
A structural model of the effect of vestibular system on blood pressure during sleep is proposed. This model reflects joint action of the otolyth system and semicircular canal system, vestibular nuclei, vasomotor centre, vagus nuclei and of the central control mechanism of the state awakeness -- sleep. Anatomic and physiological prerequisites involved in the model are expressed by chains with transmission functions, signal generators, summators etc.


Majority of women are influenced by nonprofessional information sources when deciding to consult a complementary and alternative medicine practitioner during pregnancy.
Up to 87% of women are using some form of complementary and alternative medicine (CAM) during their pregnancy, and this study was conducted to investigate the information sources that these women find influential in relation to such use. The study sample was obtained via the Australian Longitudinal Study on Women's Health. This article is based on a substudy of 1835 pregnant women who were surveyed in 2010. The women answered questions about CAM use, pregnancy-related health concerns, and influential information sources in relation to CAM use. Logistic regression models were used to determine the information sources that women reported as influential in their decision making regarding CAM use. Of the respondents (n=1835, 79.2% response rate), 48.1% (n=623) of the pregnant women consulted a CAM practitioner and 91.7% (n=1485) used a CAM product during pregnancy. The results show that, of the women who used CAM, nearly half (48%, n=493) were influenced by their own personal experience of CAM and 43% (n=423) by family and friends. Other popular sources of information were general practitioners 27% (n=263), the media (television, radio, books, magazines, newspapers) 22% (n=220), obstetricians 21% (n=208) and midwives 19% (n=190). Numerous statistically significant associations between influential information sources and pregnancy-related health conditions were identified. Women utilize a wide variety of information sources regarding their CAM use during pregnancy. Nonprofessional sources of information were found to be particularly influential, and maternity health care professionals need to have a nonjudgmental and open discussion with women about their CAM use during pregnancy in order to ensure safe and effective maternal outcomes.


Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania.
To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of fever. Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adolescents and adults, the remainder were infants and children. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adolescents and adults, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing an aetiologic diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections.


Tobacco use among students in Bihar (India).
Determination of the prevalence and attitudes toward tobacco use was assessed among 13-15 years school students in Bihar (India). Schools having grade 8-10 in Bihar. A two stage cluster sample design was used. SUDAAN and the C-sample procedure in Epi-Info was used for statistical analysis. Of the 2636 respondents, 71.8% (76.5% boys, 57.2% girls) were ever tobacco users; of them 48.9% had used tobacco before 10 years of age. Current use was reported by 58.9% (Boys 61.4%, Girls 51.2%); smokeless tobacco by 55.6% (Boys 57.6%, Girls 49.2%); and smoking by 19.4% (23.0% boys, 7.8% girls). Nearly one third (29%) students were exposed to ETS inside their homes and nearly half (48%) outside their homes. Almost all students reported watching cigarette and gutka advertisements in almost all kinds of media and events. Tobacco use by parents and friends, knowledge on harmful effects of chewing tobacco, smoking and environmental smoke, and attitudes on tobacco use by others were strongly associated with student tobacco use. Current tobacco use was reported significantly more by students who received pocket money/or were earning than by students who did not receive any pocket money/or did not earn (p value for trend <0.0001). Over half of current users (56%) bought their tobacco products from stores; of these, over 3/4th (77.2%) of them despite their age, had no difficulty in procuring these products. Teaching in schools regarding harmful effects of tobacco use was non-existent (3%). This urgently requires a comprehensive prevention program in schools and the community especially targeted towards girls.


Cardiac sarcoplasmic reticulum Ca2+-ATPase: heat production and phospholamban alterations promoted by cold exposure and thyroid hormone.
Short-term response to cold promotes a small but significant rise in serum T3 in euthyroid rabbits, where the heart is an important target of T3 action. In this work, we measured changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban (PLB) in hearts of hypo- and hyperthyroid rabbits and compared them with modifications induced by short- and long-term cold exposure. Short-term cold exposure promotes a small increase in T3 and, similar to hyperthyroidism, induces an increase of heart SERCA2a expression. The total PLB content does not change in hyperthyroidism, but short-term cold exposure promotes a significant decrease in total PLB and an increase in the ratio between phosphorylated and total PLB. The temperature of a given tissue depends on the balance between the heat provided by blood circulation and the rate of heat production by the tissue. In an attempt to evaluate the heat contribution of cardiac tissue, we measured mitochondrial respiration in permeabilized cardiac muscle and heat produced by cardiac sarcoplasmic reticulum (SR) during Ca(2+) transport. We observed that there was an increase in oxygen consumption and heat production during Ca(2+) transport by cardiac SR in both hyperthyroidism and short-term cold exposure. In contrast, both the mitochondrial respiration rate and heat derived from Ca(2+) transport were decreased in hypothyroid rabbits. The heart changes in oxygen consumption, SERCA2a-PLB ratio, and Ca(2+)-ATPase activity detected during short-term cold exposure were abolished after cold adaptation. We hypothesize that the transient rise in serum T3 contributes to the short-term response to cold exposure.


Kinetics of substrate inhibition of periplasmic nitrate reductase.
Periplasmic nitrate reductase catalyzes the reduction of nitrate into nitrite using a mononuclear molybdenum cofactor that has nearly the same structure in all enzymes of the DMSO reductase family. In previous electrochemical investigations, we found that the enzyme exists in several inactive states, some of which may have been previously isolated and mistaken for catalytic intermediates. In particular, the enzyme slowly and reversibly inactivates when exposed to high concentrations of nitrate. Here, we study the kinetics of substrate inhibition and its dependence on electrode potential and substrate concentration to learn about the properties of the active and inactive forms of the enzyme. We conclude that the substrate-inhibited enzyme never significantly accumulates in the EPR-active Mo(+V) state. This conclusion is relevant to spectroscopic investigations where attempts are made to trap a Mo(+V) catalytic intermediate using high concentrations of nitrate.


Shear thickening and migration in granular suspensions.
We study the emergence of shear thickening in dense suspensions of non-Brownian particles. We combine local velocity and concentration measurements using magnetic resonance imaging with macroscopic rheometry experiments. In steady state, we observe that the material is heterogeneous, and we find that the local rheology presents a continuous transition at low shear rate from a viscous to a shear thickening, Bagnoldian, behavior with shear stresses proportional to the shear rate squared, as predicted by a scaling analysis. We show that the heterogeneity results from an unexpectedly fast migration of grains, which we attribute to the emergence of the Bagnoldian rheology. The migration process is observed to be accompanied by macroscopic transient discontinuous shear thickening, which is consequently not an intrinsic property of granular suspensions.


Expression of RNA polymerase and ribosome component genes in Escherichia coli mutants having conditionally defective RNA polymerases.
The expression of the genes coding for the beta and beta' subunits of RNA polymerase, ribosomal RNA, ribosomal proteins, and beta-galactosidase was investigated in strains carrying conditionally lethal mutations affecting either RNA polymerase core assembly or RNA polymerase enzyme activity. The mutant strain XH56 produces a temperature-sensitive beta' subunit and at 42 degrees C is defective in RNA chain initiation; consequently, little or no transcription occurs at the restrictive temperature. A partial restriction, produced by shifting the strain to 39 degrees C, resulted in a rapid fivefold increase in the transcription of the rpoB and C genes and in the synthesis of the beta- and beta'-subunit proteins for which they code. The RNA polymerase assembly-defective strains A2R7 and TS4 exhibited a 1.5- to 2-fold increase in the transcription of the rpoB and C genes and in the synthesis of beta- and beta-subunit proteins after prolonged restriction. These results demonstrate (i) that regulation of the synthesis of the beta- and beta-RNA polymerase subunits is under these conditions primarily transcriptional rather than translational, and (ii) that a stimulation of rpoB and C gene expression results from a restriction on RNA synthesis caused by either RNA polymerase inactivation or inhibition of its assembly. During restriction of the mutant strains, the transcription of the ribosome component genes exhibited patterns which were similar to transcription of the rpoB and C genes, supporting the evidence that genes coding for RNA polymerase are cotranscribed with ribosomal protein genes; transcription of the lacZ gene was observed to decrease concomitant with the stimulation of the rpoB and C genes.


Promoting Social Connection and Deepening Relations Among Older Adults: Design and Qualitative Evaluation of Media Parcels.
Being socially connected is related to well-being, and one way of avoiding social isolation is to deepen existing relationships. Even though existing relationships can be reinforced by regular and meaningful communication, state-of-the-art communication technologies alone do not increase the quality of social connections. Thus, there is a need for the involvement of a trained human facilitator in a network of older adults, preferably for a short period, to promote the deepening of their relationships. This study aimed to evaluate the hypothesis that a human-facilitated, media-sharing social networking system can improve social connection in a small group of older people, who are more vulnerable to social isolation than most, and deepen their relationships over a period of a few weeks. We conducted the design and evaluation of Media Parcels, a novel human-facilitated social networking system. Media Parcels is based on the metaphor of a facilitator collecting and delivering parcels in the physical mail. Extending the metaphor, the system supports a facilitator in designing time-based dialogue requesting parcels from participants that bring out their memories and feelings, in collecting the parcels, wrapping them in annotations that communicate the corresponding requests, and delivering the wrapped parcel to a target person. Qualitative evaluation was carried out in two trials with a group of three people each, one with family members (children and father; aged 55, 56, and 82 years old) and the other with a group of friends (aged 72, 72, and 74 years old), over two weeks. In each trial, data were collected in three interviews (pre-, mid-, and posttrial) and via system logging. Collected data indicate positive social effects for deepening and developing relationships. The parcel metaphor was easily understood and the computational system was readily adopted. Preferences with regard to media production or consumption varied among participants. In the family group, children preferred receiving media parcels (because of their sentimental value) to producing them, whereas the father enjoyed both. In the friendship group, preferences varied: one friend enjoyed both producing and receiving, while the other two preferred one over the other. In general, participants reported a preference for the production of items of a certain type depending on the associated content. Apart from having a strong engagement with the system, participants reported feeling closer to each other than usual. For both groups, Media Parcels was effective in promoting media sharing and social connections, resulting in the deepening of existing relationships. Its design informs researchers who are attempting to promote social connection in older adults.


Injury-related emergency department use among assisted living residents with Alzheimer's disease and related dementias.
Injuries are a leading cause of emergency department (ED) visits among older adults, and individuals with Alzheimer's disease and related dementias (ADRD) may be at particular risk. We compared injury-related ED use among assisted living (AL) residents with and without ADRD and assessed differences in the risk of injury-related ED visits among individuals with ADRD residing in ALs with memory care designation versus general AL. Using Medicare claims, we identified a cohort of fee-for-service beneficiaries who lived in AL in 2018 and resided in one of 20 states with site-specific information on memory care designation (n = 116,754). Outcomes included all injury-related ED visits and injury-related ED visits resulting in hospitalization in the calendar year 2018. We fit multilevel models of the association between ADRD and outcomes, adjusting for resident demographic characteristics and chronic conditions, license type characteristics, and AL characteristics, with random intercepts at the AL and license type levels. Among residents with ADRD, we examined whether memory care licensure was associated with injury-related ED visits. The adjusted risk of injury-related ED use during the year was 20.1% (95% CI: 19.6%, 20.6%) for residents with ADRD compared to 16.1% for residents without ADRD (95% CI: 15.7%, 16.5%; p < 0.001). The adjusted risk of injury-related ED use ending in hospitalization was 4.9% (95% CI: 4.6%, 5.1%) for AL residents with ADRD and 3.9% for residents without ADRD (95% CI: 3.8%, 4.1%; p < 0.001). There were no significant differences in injury-related ED visits between residents with ADRD in ALs with memory care designation and residents in general AL. Injury-related ED visits are common among AL residents with ADRD and residents in memory care, but residents in memory care AL experienced similar risks of injury as those in general AL. Further research should identify modifiable factors that can prevent injury among AL residents with ADRD.


Unsuccessful Host Stinging by Aphelinus asychis (Hymenoptera: Aphelinidae) Impacts Population Parameters of the Pea Aphid (Hemiptera: Aphididae).
The biocontrol values of natural enemies are strongly correlated to their ability to regulate the density of their host/prey. For parasitoids, apart from parasitism and host feeding, unsuccessful host stinging (i.e., stings that were aborted, abandoned, or discontinued without oviposition or host feeding) can also negatively affect their hosts and host populations. Although several studies have reported unsuccessful host stinging and its impacts on hosts, the effects of this type of attack on host life table parameters are still unclear. In the present study, we used the parasitoid Aphelinus asychis Walker (Hymenoptera: Aphelinidae) and its host Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae) to investigate the influence of unsuccessful host stinging on host populations under laboratory conditions at. Biological parameters of A. pisum were analyzed using an age stage, two-sex life table. The results of this study showed that unsuccessful host stinging was prevalent under laboratory conditions, and the frequency of this type of attack on third- and fourth-instar hosts was higher than the frequencies of parasitism and host feeding. Unsuccessful host stinging adversely impacted aphid populations, by decreasing aphid survival and reproduction, and impacts were greatest in hosts attacked at the first and fourth instars. These results indicate that unsuccessful host stinging enhances the biological control impact of A. asychis attacking A. pisum, and its effect on host populations should also be considered when selecting and mass rearing of parasitoids for biological control.


Chemically resolved interface structure of epitaxial graphene on SiC(0001).
Atomic-layer 2D crystals have unique properties that can be significantly modified through interaction with an underlying support. For epitaxial graphene on SiC(0001), the interface strongly influences the electronic properties of the overlaying graphene. We demonstrate a novel combination of x-ray scattering and spectroscopy for studying the complexities of such a buried interface structure. This approach employs x-ray standing wave-excited photoelectron spectroscopy in conjunction with x-ray reflectivity to produce a highly resolved chemically sensitive atomic profile for the terminal substrate bilayers, interface, and graphene layers along the SiC[0001] direction.


Evaluation of commercially available reagents for diagnosis of histoplasmosis infection in immunocompromised patients.
Urinary histoplasma antigen measurement can be useful for diagnosing systemic histoplasmosis and for monitoring treatment response, especially in immunocompromised patients. However, testing has traditionally been limited to specialized reference laboratories, as immunoassay reagents for the antigen were not widely available. Recently, a polyclonal-antibody-based in vitro diagnostic (IVD) kit for histoplasma antigen detection was released, as well as monoclonal-antibody reagents against the target. We evaluated the analytical and clinical performance of the two reagents. Both assays were capable of detecting histoplasma antigen in urine samples over a wide dynamic range, although the monoclonal assay showed improved precision and analytical sensitivity relative to the polyclonal IVD. In a test set of clinically characterized patient samples, the monoclonal laboratory-developed test (LDT) demonstrated 90.5% sensitivity and 96.3% specificity versus 61.9% sensitivity and 79.3% specificity for the polyclonal IVD, with areas under the curve (AUCs) of 0.987 and 0.754, respectively. The major differences between the two assays were higher background reactivity in healthy donors with the polyclonal assay and an increased signal response in positive samples for the monoclonal assay. The impact of these differences on monitoring treatment response was evaluated in a series of patients undergoing treatment for histoplasmosis. While all the assays gave similar qualitative estimates of treatment response, responses were more evident using the monoclonal assay. In summary, we conclude that while multiple assays are available for measuring histoplasma antigen in urine, a monoclonal-antibody-based assay appears to provide improved analytical performance for management of immunocompromised histoplasmosis patients.


A Knowledge-based and Data-driven Approach for Predicting Acute Kidney Injury in Patients with Heart Failure.
It has great potential to integrate medical knowledge and electronic health record data for diagnosis prediction. However, present studies only utilized information from knowledge graphs, omitting potentially significant global graph structural features. In this study, we proposed a knowledge and data integrating modeling approach to reconstruct patient electronic health record data with graph structure and use medical knowledge as internal information of patient data to build a risk prediction model for acute kidney injury in patients with heart failure based on graph neural networks. Experimental results based on the MIMIC III data showed that the method proposed was superior to other baseline models in predicting the risk of acute kidney injury in heart failure patients, with an accuracy of 0.725 and an F1 score of 0.755. This study provides a novel approach to the disease risk prediction models that integrates medical knowledge and data.


MTNR1B gene variations and high pre-pregnancy BMI increase gestational diabetes mellitus risk in Chinese women.
To investigate the association of melatonin receptor 1B (MTNR1B) gene variations and pre-pregnancy body mass index (BMI) with gestational diabetes mellitus (GDM). In this study, 1566 Chinese Han pregnant women were enrolled and multiple genetic models were used to evaluate the association between MTNR1B gene polymorphisms and the risk of GDM. The clinical value of pre-pregnancy BMI in predicting GDM was analyzed and evaluated using receiver operating characteristic (ROC) curves. Several methods of analysis were used to examine the impact of gene-gene and gene-BMI interactions on the incidence of GDM influence. For the MTNR1B gene, rs1387153 (C > T), rs10830962 (C > G), rs4753426 (T > C), and rs10830963 (C > G) are all risk mutations associated with the susceptibility of GDM. The ROC curve analysis indicated that the BMI demonstrated an area under the curve (AUC) of 0.595. Alongside, the sensitivity and specificity stood at 0.676 and 0.474 respectively. The maximum Joden index was found to be 0.150, with a corresponding critical BMI value of 20.5691 kg/m2. Interaction analysis revealed that gene-gene and gene-BMI interactions had no significant effect on GDM occurrence. MTNR1B genetic variations confers the risk to GDM in Chinese women. Furthermore, the high pre-pregnancy BMI (≥20.5691 kg/m2) significantly increases the risk of GDM in Chinese women.


Human podocytes adhere to the KRGDS motif of the alpha3alpha4alpha5 collagen IV network.
Podocyte adhesion to the glomerular basement membrane is required for proper function of the glomerular filtration barrier. However, the mechanism whereby podocytes adhere to collagen IV networks, a major component of the glomerular basement membrane, is poorly understood. The predominant collagen IV network is composed of triple helical protomers containing the alpha3alpha4alpha5 chains. The protomers connect via the trimeric noncollagenous (NC1) domains to form hexamers at the interface. Because the NC1 domains of this network can potentially support integrin-dependent cell adhesion, it was determined whether individual NC1 monomers or alpha3alpha4alpha5 hexamers support podocyte adhesion. It was found that, although human podocytes did not adhere to NC1 domains proper, they did adhere via integrin alphavbeta3 to a KRGDS motif located adjacent to alpha3NC1 domains. Because the KRGDS motif is a site of phosphorylation, its interactions with integrin alphavbeta3 may play a critical role in cell signaling in physiologic and pathologic states.


New and improved vaccines. Promising weapons against varicella, hepatitis A, and typhoid fever.
The initial motives behind development of vaccines were to protect against life-threatening infections (eg, rabies, diphtheria), to eradicate sweeping outbreaks of serious diseases (eg, paralytic poliomyelitis, smallpox), and to prevent diseases in a vulnerable population by the immunization of surrogates (eg, rubella immunization to prevent congenital rubella syndrome). Now a fourth motive emerges: prevention of less serious infections to improve quality of life. The advantages of new vaccines and immunization programs should no longer be measured exclusively in terms of the number of lives saved but should take into account direct and indirect cost savings and overall benefit to individual and societal health and well-being. Although varicella and hepatitis A infections can be life-threatening, most cases are self-limited and have no significant sequelae. Immunization is more likely to improve quality of life than to save lives. Vaccination against typhoid remains a potentially lifesaving act in developing nations, but even the newer typhoid vaccines were developed primarily to reduce the frequency and severity of adverse reactions to immunization rather than to improve the protective efficacy of the original heat-phenol inactivated vaccine. Varicella virus vaccine, hepatitis A virus vaccines, and the typhoid polysaccharide Vi capsular vaccine represent important additions to immunization agents. These vaccines are immunogenic, clinically effective, and generally safe, with infrequent and usually mild adverse reactions. Their favorable benefit-risk ratio should encourage their appropriate use. The Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians have already recommended varicella vaccine for universal immunization of children. Formal recommendations that hepatitis A vaccine also be routinely used for all children may be forthcoming in the next few years; in the meantime, persons at high risk should be immunized. Typhoid vaccination will likely continue to be used selectively for those who have significant contact with the organism or those who travel to typhoid-endemic countries.


N-alpha-acetylation of α-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation.
A switch in the conformational properties of α-synuclein (αS) is hypothesized to be a key step in the pathogenic mechanism of Parkinson's disease (PD). Whereas the beta-sheet-rich state of αS has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to β-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian αS. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human αS to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced α-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of αS with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated αS enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of αS-membrane interaction, and for a protective function of N-terminal-acetylation against αS aggregation mediated by GM1.


Minimally invasive ileal pouch-anal anastomosis for patients with obesity: a propensity score-matched analysis.
Obesity is a risk factor for failure of pouch surgery completion. However, little is known about the impact of obesity on short-term outcomes after minimally invasive (MIS) ileal pouch-anal anastomosis (IPAA). This study aimed to assess short-term postoperative outcomes in patients undergoing MIS total proctocolectomy (TPC) with IPAA in patients with and without obesity. All adult patients (≥ 18 years old) who underwent MIS IPAA as reported in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participant User Files 2007 to 2018 were included. Patients were divided according to their body mass index (BMI) into two groups (BMI ≥ 30 kg/m2 vs. BMI < 30 kg/m2). Baseline demographics, preoperative risk factors including comorbidities, American Society of Anesthesiologists Class, smoking, different preoperative laboratory parameters, and operation time were compared between the two groups. Propensity score matching (1:1) based on logistic regression with a caliber distance of 0.2 of the standard deviation of the logit of the propensity score was used to overcome biases due to different distributions of the covariates. Thirty-day postoperative complications including overall surgical and medical complications, surgical site infection (SSI), organ space infection, systemic sepsis, 30-day mortality, and length of stay were compared between both groups. Initially, a total of 2158 patients (402 (18.6%) obese and 1756 (81.4%) nonobese patients) were identified. After 1:1 matching, 402 patients remained in each group. Patients with obesity had a higher risk of postoperative organ/space infection (12.9%; vs. 6.5%; p-value 0.002) compared to nonobese patients. There was no difference between the groups regarding the risk of postoperative sepsis, septic shock, need for blood transfusion, wound disruption, superficial SSI, deep SSI, respiratory, renal, major adverse cardiovascular events (myocardial infarction, stroke, cardiac arrest requiring cardiopulmonary resuscitation), venous thromboembolism, 30-day mortality, and length of stay. MIS IPAA can be safely performed in patients with obesity. However, patients with obesity have a 2-fold risk of organ space infection compared to patients without obesity. Loss of weight before MIS IPAA is recommended not only to allow for pouch creation but also to decrease organ space infections.


Neural correlates of processing situational relationships between a part and the whole: an fMRI study.
Daily situations involve many objects and behaviors. To comprehend the meaning of situations, the relationships between objects, behaviors, and the situational context are important. To reveal the cortical networks involved in processing these relationships we used functional magnetic resonance imaging to compare brain activation during processing of behavior-situation and object-situation relationships. Each session examined two aspects of situational relationship processing: monitoring of the situational relationship and responses to irrelevant relationships. Monitoring was analyzed by comparing cortical activation during a situational relevance judgment task with that during a physical appropriateness judgment task. Responses were analyzed by comparing neural responses to situationally irrelevant and situationally relevant components. The left medial frontal cortex, fusiform gyrus, inferior frontal gyrus, calcarine sulcus, right anterior middle temporal gyrus, orbitoinsular junction, and occipito-temporo-parietal junction were commonly activated while monitoring relationships of both types. The right anterior middle temporal gyrus and orbitoinsular junction were considered to have roles in implicit monitoring because they were more deactivated during physical judgment tasks than during the resting state; this deactivation seemed to reflect unconscious situational monitoring in the resting state. Other regions seemed to be linked to explicit conscious monitoring. Responses to irrelevance were linked to separate and category-specific cortical activation in the left medial frontal cortex and frontal pole for behavioral irrelevance and in the left orbitofrontal cortex for irrelevant objects. We demonstrated that the hierarchical structure of processing situational relationships consisted of implicit monitoring, explicit monitoring, and category-specific responses to irrelevance.


The lion's mane sign: surgical results using the bilateral fronto-orbito-nasal approach in large and giant anterior skull base meningiomas.
Concerns about extreme peritumoral edema and its ensuing surgical and perioperative complications led the authors to use the bilateral fronto-orbito-nasal approach to remove midline anterior skull base meningiomas that were larger than 4 cm. The authors hypothesize that extreme vasogenic edema exemplified by finger-like hyperintensities extending into the bifrontal white matter and external capsule and/or the extreme capsule, coined the lion's mane sign (LMS), would help identify patients with a challenging postoperative course. They hypothesize that the LMS would better predict symptomatic postoperative cerebral edema than the edema index (EI). This is an observational case series of 9 patients. The authors noted the grade, pathology, tumor volume, EI, and the presence or absence of the LMS in all tumors. They used the intensive unit care (ICU) length of stay as a nonspecific measure reflecting postoperative symptomatic cerebral edema. Comparisons of edema-related postoperative complications and the EI were made between patients with and without an LMS. Bifrontal hyperintensities, extending into at least three-eighths of the length of the external capsules on T2-weighted MRI, seen in 4 of 9 patients, portended a longer postoperative ICU stay. The presence of an LMS better predicted postoperative complications related to cerebral edema than tumor grade, pathology, volume, or EI. The LMS predicts an increased duration of stay in the ICU after a bilateral fronto-orbito-nasal approach for resection of large and giant anterior skull base meningiomas. Furthermore, the LMS better predicted increased length of stay in the ICU than did the EI.


A high-performance brain-computer interface.
Recent studies have demonstrated that monkeys and humans can use signals from the brain to guide computer cursors. Brain-computer interfaces (BCIs) may one day assist patients suffering from neurological injury or disease, but relatively low system performance remains a major obstacle. In fact, the speed and accuracy with which keys can be selected using BCIs is still far lower than for systems relying on eye movements. This is true whether BCIs use recordings from populations of individual neurons using invasive electrode techniques or electroencephalogram recordings using less- or non-invasive techniques. Here we present the design and demonstration, using electrode arrays implanted in monkey dorsal premotor cortex, of a manyfold higher performance BCI than previously reported. These results indicate that a fast and accurate key selection system, capable of operating with a range of keyboard sizes, is possible (up to 6.5 bits per second, or approximately 15 words per minute, with 96 electrodes). The highest information throughput is achieved with unprecedentedly brief neural recordings, even as recording quality degrades over time. These performance results and their implications for system design should substantially increase the clinical viability of BCIs in humans.


Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis.
Cardiomyocyte apoptosis is an important remodeling event contributing to heart failure and adiponectin may mediate cardioprotective effects at least in part via attenuating apoptosis. Here we used hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cells to examine the effect of adiponectin and cellular mechanisms of action. We first used TUNEL labeling in combination with laser scanning cytometry to demonstrate that adiponectin prevented H/R-induced DNA fragmentation. The anti-apoptotic effect of adiponectin was also verified via attenuation of H/R-induced phosphatidylserine exposure using annexin V binding. H/R-induced apoptosis via the mitochondrial-mediated intrinsic pathway of apoptosis as assessed by cytochrome c release into cytosol and caspase-3 activation, both of which were attenuated by adiponectin. Mechanistically, we demonstrated that adiponectin enhanced anti-oxidative potential in these cells which led to attenuation of the increase in intracellular reactive oxygen species (ROS) caused by H/R. To further address the mechanism of adiponctins anti-apoptotic effects we used siRNA to efficiently knockdown adiponectin receptor (AdipoR1) expression and found that this attenuated the protective effects of adiponectin on ROS production and caspase 3 activity. Knockdown of APPL1, an important intracellular binding partner for AdipoR, also significantly reduced the ability of adiponectin to prevent H/R-induced ROS generation and caspase 3 activity. In summary, H/R-induced ROS generation and activation of the intrinsic apoptotic pathway was prevented by adiponectin via AdipoR1/APPL1 signaling and increased anti-oxidant potential.


[Electroglottography - an objective method for the evaluation of the vocal function in the children: reliability and validity].
The objective of the present study was to estimate the relevance and validity of the electroglottographic technique as a method for diagnostics of voice disorders in children. The authors analyse the normative data on the vocal disorders in the children obtained by electroglottography (EGT) and assess the value of this technique for the control of treatment of dysphonia of different etiology. It is shown that that dynamics of these findings (before and after the treatment including their comparison with age-related normative data) attains statistical significance . It is concluded that the results of EGT can be regarded as the important diagnostic criteria for the effectiveness and quality of the treatment of dysphonia of different origin in children.


O-Arm Stereotactic Imaging in Deep Brain Stimulation Surgery Workflow: A Utility and Cost-Effectiveness Analysis.
Deep brain stimulation (DBS) surgery is an established treatment for movement disorders. Advances in neuroimaging techniques have resulted in improved targeting accuracy that may improve clinical outcomes. This study aimed to evaluate the safety and feasibility of using the Medtronic O-arm device for the acquisition of intraoperative stereotactic imaging, targeting, and localization of DBS electrodes compared with standard stereotactic MRI or computed tomography (CT). Patients were recruited prospectively into the study. Routine frame-based stereotactic DBS surgery was performed. Intraoperative imaging was used to facilitate and verify the accurate placement of the intracranial electrodes. The acquisition of coordinates and verification of the position of the electrodes using the O-arm were evaluated and compared with conventional stereotactic MRI or CT. Additionally, a systematic review of the literature on the use of intraoperative imaging in DBS surgery was performed. Eighty patients were included. The indications for DBS surgery were dystonia, Parkinson's disease, essential tremor, and epilepsy. The globus pallidus internus was the most commonly targeted region (43.7%), followed by the subthalamic nucleus (35%). Stereotactic O-arm imaging reduced the overall surgical time by 68 min, reduced the length of time of acquisition of stereotactic images by 77%, reduced patient exposure to ionizing radiation by 24.2%, significantly reduced operating room (OR) costs per procedure by 31%, and increased the OR and neuroradiology suite availability. The use of the O-arm in DBS surgery workflow significantly reduced the duration of image acquisition, the exposure to ionizing radiation, and costs when compared with standard stereotactic MRI or CT, without reducing accuracy.


NTP Toxicology and Carcinogenesis Studies of Vinyl Toluene (Mixed Isomers) (65%-71% meta-isomer and 32-35% para-isomer) (CAS No. 25013-15-4) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).
Vinyl Toluene is used as a monomer in the plastics and surface-coating industries. NTP Toxicology and Carcinogenesis studies were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to vinyl toluene (mixed isomers: 65%-71% meta and 32%-35% para) by inhalation 6 hours per day, 5 days per week, for 15 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse L5178Y cells, and Chinese hamster ovary (CHO) cells. Fifteen-Day Studies: Rats were exposed to 0, 200, 400, 800, or 1,300 ppm vinyl toluene, and mice were exposed to 0, 10, 25, 50, 100, or 200 ppm. All rats lived to the end of the studies. The mean body weights at necropsy of rats exposed to 400-1,300 ppm were 13%-19% lower than that of controls for males and 9%-13% lower for females. Most male rats exposed to 1,300 ppm had centrilobular necrosis and focal inflammatory cell infiltration of the liver, whereas minimal centrilobular vacuolization of the liver was seen in all female rats exposed to 1,300 ppm. Dysplasia of the bronchial epithelial lining, chronic bronchitis, and lymphoid hyperplasia of the lung were observed in all rats exposed to 1,300 ppm. Three of five male mice exposed to 200 ppm vinyl toluene died before the end of the studies. Four of five male mice exposed to 200 ppm had moderate-to-severe hepatocellular necrosis; all female mice exposed to 200 ppm had hyperplasia of the epithelium of the intrapulmonary bronchi and centrilobular necrosis, vacuolization, and inflammatory cell infiltrates in the liver. Thirteen-Week Studies: Rats were exposed to 0, 25, 60, 160, 400, or 1,000 ppm vinyl toluene. All rats lived to the end of the studies. The final mean body weights of rats exposed to 400-1,000 ppm were 8%-19% lower than that of controls for males and 6%-12% lower for females. Relative liver weights for rats at 1,000 ppm were significantly greater than those for controls. The severity of nephropathy was increased in male rats exposed to 160, 400, or 1,000 ppm. Compound-related lesions were not observed in female rats. Mice were exposed to 0, 10, 25, 60, or 160 ppm vinyl toluene. The final mean body weights of mice exposed to 25-160 ppm were 12%-20% lower than that of controls for males and 13%-16% lower for females. Inflammation of the lung was observed in 5/10 male and 3/9 female mice exposed to 160 ppm. Metaplasia of the nasal turbinates was seen in all exposed groups. Based on these results, 2-year studies were conducted by exposing groups of 49 or 50 rats of each sex to 0, 100, or 300 ppm vinyl toluene by inhalation, 6 hours per day, 5 days per week for 103 weeks. Groups of 50 mice of each sex were exposed to 0, 10, or 25 ppm on the same schedule. Body Weights and Survival in the Two-Year Studies: Mean body weights of male rats exposed to 300 ppm vinyl toluene and those of female rats exposed to 100 and 300 ppm were generally 4%-11% lower than those of controls. No significant differences in survival were seen between any groups of rats of either sex (male: control, 19/49; low dose, 17/50; high dose, 19/50; female: 31/50; 28/50; 26/50). Mean body weights of mice exposed to 25 ppm were 10%-23% lower than those of controls after week 8, whereas mice exposed to 10 ppm showed a weight decrement that was generally less than 10%. The survival of male mice exposed to 25 ppm was significantly greater than that of controls. No other significant differences in survival were seen between any groups of mice of either sex (male: 33/50; 30/50; 41/50; female: 36/50; 37/50; 34/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Degenerative and nonneoplastic proliferative lesions of the nasal mucosa were observed at increased incidences in exposed rats. These lesions included diffuse hyperplasia (goblet cell) of the respiratory epithelium with intraepithelial mucous cysts and focal erosion of the olfactory epithelium with cystic dilation (cysts) of the Bowman's glands. Focal respiratory epithelial metaplasia of the olfactory epithelium was seen in some exposed males, and cells with homoge) of the Bowman's glands. Focal respiratory epithelial metaplasia of the olfactory epithelium was seen in some exposed males, and cells with homogeneous eosinophilic cytoplasm in the olfactory epithelium occurred at increased incidences in exposed female rats. Neoplasms of the nasal mucosa were not seen in male or female rats. There were no chemically related increases in neoplasm incidence in exposed male or female rats. Degenerative and inflammatory lesions of the nasal mucosa were observed at increased incidences in exposed mice. These lesions included focal chronic active inflammation and diffuse hyperplasia of the respiratory epithelium. Chronic active inflammation of the bronchioles occurred in many exposed mice but not in controls. Neoplasms of the nasal passage were not observed in mice. There were no chemically related increases in neoplasm incidence in exposed male or female mice. Exposure-related decreased incidences included alveolar/bronchiolar neoplasms (control, 12/50; 10 ppm, 5/49; 25 ppm, 2/49) and malignant lymphomas (7/50; 3/50; 0/50) in males and hepatocellular neoplasms (9/48; 5/16; 2/49) in females. Genetic Toxicology: Vinyl toluene did not induce gene mutations in S. typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation (S9). Vinyl toluene was positive in the mouse lymphoma assay for induction of trifluorothymidine resistance in L5178Y/TK cells in the absence of S9; it was not tested with S9. Vinyl toluene did not induce sister chromatid exchanges or chromosomal aberrations in CHO cells with or without S9. Conclusions: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity for male or female F344/N rats exposed to 100 or 300 ppm vinyl toluene and no evidence of carcinogenic activity for male or female B6C3F1 mice exposed to 10 or 25 ppm. There was evidence of chemical-related toxicity to the nasal passage in both rats and mice. Synonyms: 3-vinyl toluene and 4-vinyl toluene (mixed isomers)


Absence of MMP2 expression correlates with poor clinical outcomes in rectal cancer, and is distinct from MMP1-related outcomes in colon cancer.
Treatments for colorectal cancer (CRC) are primarily disease stage based. However, heterogeneity in outcome within even a single stage highlights its limitations in predicting disease behavior. Recently, the role of gene expression as predictive and prognostic markers has been explored. Our objectives were to identify consistently differentially expressed genes through meta-analysis of high-throughput gene-expression studies, and evaluate their predictive and prognostic significance in colon (CC) and rectal (RC) cancers. Publications applying high-throughput gene- expression technologies to specific CRC stages were identified. A vote counting strategy was used to identify the most significant differentially expressed genes. Their predictive and prognostic values were independently assessed in a tissue microarray of 191 cases of stage II-IV CC/RC from two tertiary care centers. Their biological effects were also examined in vitro. MMP1 and MMP2 were identified as consistently underexpressed in liver metastasis compared with primary CRC. Shorter time to distant metastasis and overall survival occurred in stage III CC lacking MMP1 expression, and in stage III RC lacking MMP2. MMP1 levels in stage II and III CC were associated with increased likelihood of distant metastasis, whereas the risk of local recurrence in stage III RC could be stratified by MMP2. Promotion of cell invasion of CRC cell lines exposed to MMP1/2 inhibitors were confirmed in vitro. MMP1 and MMP2 may be useful biomarkers that can help stratify patients at higher risk of developing recurrence in colorectal cancer, and guide individualized treatment decisions to achieve better outcomes.


Experimental Verification of a Coordinated Path-Following Strategy for Underactuated Marine Vehicles.
This work presents the results of an experimental verification of a coordinated path following strategy for underactuated marine vehicles. The coordinated path following strategy is presented, and is then experimentally verified using three autonomous underwater vehicles. The vehicles are required to coordinate their motion along spatially separated straight-line paths to obtain a desired formation. The vehicles are steered to the paths using an integral line-of-sight guidance approach that allows the vehicles to reject constant ocean currents. Simultaneously, the coordination is achieved by adjusting the velocity based on the along-path distance. First, simulation results are presented, which serve as benchmarks for the experimental results. Furthermore, the simulations are used to show the effect of changing different parameters. The simulation results are performed using high-fidelity hardware simulation models. The results obtained from experiments in the harbor of Porto are then presented and compared with the results of the simulation.


[Indications for surgical treatment of hard scarring gastric ulcers].
It was done the comparative analysis of the morphofunctional state of the upper gastrointestinal tract between 350 patients with effective conservative treatment and 104 patients with hard scarring gastric ulcers. The analysis identified the predictors of ineffective medical treatment and led to deliver the indications for timely surgical treatment. It was identified the next indications for planned organ-preserving surgical treatment of patients with hard scarring gastric ulcers: penetrating and non-healing ulcers with large or gigantic size in case of the adequate medical therapy, high-grade dysplasia and colonic metaplasia of the gastric epithelium in the borders or fundus of the ulcer,ulcers combination with fixed cardio-fundal or fundo-corporal hiatal hernias; hypotonic-hypokinetic type of the gastric and duodenal activity with the development of gastrostasis and pronounced duodenogastric reflux.


Abnormal small airways function in children with mild asthma.
Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects. The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy children (n=35) and children with asthma (n=31) at baseline and in children with asthma after bronchodilation. Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results were found for SDTG (≤-2 z scores) in 11; forced expiratory flow, midexpiratory phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2, FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline, 36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively). Abnormal acinar ventilation heterogeneity in one-third of the children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.


Urine sulfatides and the diagnosis of metachromatic leukodystrophy.
A deficiency of the lysosomal enzyme arylsulfatase A (ASA) causes the lysosomal storage disorder metachromatic leukodystrophy (MLD). The diagnosis of MLD is straightforward in cases with deficient leukocyte or fibroblast ASA activity and a typical clinical history. However, several atypical and late-onset forms of MLD have been described. The diagnosis is also complicated by the high frequency of presumably benign polymorphisms at the ASA gene locus that are associated with markedly diminished in vitro ASA activity. Additional diagnostic tools are needed in the clinically and (or) enzymatically atypical cases. Although analyses of urinary sulfatides have been reported to be helpful in the diagnosis of MLD, previously described methods are complex and incompletely characterized and validated. We developed an improved method for determining urinary sulfatides and applied it to a cohort of individuals with MLD. The sulfatides are extracted from urine, separated from glycerol-based lipids by alkaline hydrolysis, isolated by ion-exchange chromatography, and hydrolyzed to galactosylceramide, which is then perbenzoylated and quantified by HPLC. This assay provides excellent resolution of sulfatides from other lipids and good analytical precision. In addition, the urinary sulfatide concentrations of healthy controls (mean +offSD: 0.16 +/- 0.07 nmol/mg creatinine; range: 0.07-0.34; n = 18) are clearly distinguished from those of individuals with MLD (7.6 +/- 6.1 nmol/mg creatine; 1.2-24.2; n = 20).


Association between executive attention and physical functional performance in community-dwelling older women.
Executive functions supervise the contents of working memory, where information from long-term memory is integrated with information in the immediate present. This study examined whether executive attentional abilities were uniquely associated with the performance of complex, instrumental activities of daily living (IADLs) in cognitively intact and physically high-functioning older women. Participants were 406 community-residing, older women aged 70-80 years in the Women's Health and Aging Study (WHAS) II, screened to be physically high functioning and cognitively intact using the Mini-Mental State Exam. Hierarchical regression models, adjusted for demographic and disease variables, were used to evaluate the association of cognitive domains, including executive attention, memory, psychomotor speed, and spatial ability with summary measures of IADL (e.g., looking up and dialing a telephone number) and mobility-based ADL (e.g., walking 4 meters) function. Tests of executive attention were associated with performance on IADLs (6.6%) and, to a lesser degree, mobility-based ADLs (1%), adjusting for demographic and disease variables. In particular, the mental flexibility component of the Trail Making Test accounted for the majority of attentional variance in IADL performance. Older age, lower education, and African American race were also associated with poorer physical test performances. Executive difficulties in flexibly planning and initiating a course of action were selectively associated with slower performance of higher-order IADL tests, relative to other domains of cognition, in a high-functioning, community-based older cohort. These results suggest that executive functions may be important in mediating the onset and progression of physical functional declines.


Serum identification of At-Risk MASH: The Metabolomics-Advanced steatohepatitis fibrosis score (MASEF).
Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or "at-risk MASH" is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH. We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for MASLD. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by transient elastography (VCTE). The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, positive and negative predictive values of 0.76 (95% CI 0.72-0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75-0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FAST performance in the validation cohort was 0.74 (95% CI 0.68-0.79; p = 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4 + MASEF showed similar overall performance compared to FIB-4 + LSM by VCTE ( p = 0.69) to identify at-risk MASH. MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.


Sire contribution to pregnancy loss and pregnancy-associated glycoprotein production in Nelore cows.
Pregnancy loss is a major contributing factor to reproductive inefficiency in both the beef and dairy industries. Sires can have a significant influence on the amount of pregnancy loss; however, this relationship is still poorly investigated. The primary objective of this study was to identify sires associated with high or low incidence of pregnancy loss (between d 30 and 100 of gestation) and investigate their effect on concentration of circulating pregnancy-associated glycoproteins (PAGs). Postpartum multiparous Nelore cows were inseminated artificially at a fixed time (FTAI, d 0) after synchronization of ovulation. A total of 736 cows were assigned randomly to be inseminated with semen from either of 6 Angus sires, whereas a separate subset of 492 cows were inseminated randomly with semen from either of 3 Nelore (n = 235) or either of 2 Angus sires (n = 257). Estrus expression was evaluated on d 0 using Estrotect Heat Detector patches. Blood samples were collected on d 30 of gestation for quantification of PAGs and pregnancy diagnosis was performed by ultrasound on d 30 and 100 after FTAI. Cows diagnosed pregnant at the first examination but not pregnant at the second were defined to have pregnancy loss. Overall pregnancy rate at d 30 was 54% (660/1,228) and pregnancy loss was 6.21% (41/660). Cows receiving semen from Nelore sires had greater (P < 0.001) pregnancy rate, greater (P = 0.014) pregnancy loss, and lesser (P = 0.002) PAG concentrations at d 30 of gestation compared with cows receiving Angus semen. Circulating PAG concentrations were lower (P = 0.008) in cows that had pregnancy loss (9.76 ± 0.25 vs. 7.41 ± 1.02 ng/mL). Angus sires were retrospectively classified according to percentage of pregnancy loss as either high pregnancy loss (mean of 7.25% or 67% of total) or low pregnancy loss (mean of 3.93% or 33% of total). Cows receiving semen from high pregnancy loss sires had 1.9 times greater (P = 0.123) rate of pregnancy loss and had lower (P = 0.059) PAG concentrations at d 30 of gestation compared with cows mated to low pregnancy loss sires. In summary, PAG concentrations reflected probability of pregnancy maintenance and were influenced by both sire and sire breed used at FTAI. Variation in the incidence of pregnancy loss was detected among sires that could not be predicted with standard semen fertility evaluations. Exploring the relationship of sire and PAG production might be promising to improve sire selection with regard to pregnancy loss.


Picosecond nonlinear optical properties of SrTiO3 composite films doped with gold and nickel nanoparticles.
Nanoparticles composite thin films formed by nanometer-sized gold and nickel particles embedded in SrTiO3 matrices were fabricated on MgO single-crystal substrates by co-depositing the metal and ceramic targets using the pulsed laser deposition technique. The linear optical absorption properties were measured from 350 to 800 nm, and the absorption peak due to the surface plasmon resonance of Au metal particles was observed around 557 nm. The ultra-fast third-order nonlinear optical properties of the films were determined by a single-beam z-scan method at a wavelength of 532 nm with laser duration of 55 ps. The nonlinear refractive index n2 and the nonlinear absorption coefficient β were determined, respectively, and the figure of merit χ(3)/α (with χ(3) being the third-order nonlinear susceptibility and α the linear optical absorption coefficient) was discussed. Whether gold or nickel, metal particles have little effect on the figure of merit, but significantly affect the ratio of the real part to the imaginary part of χ(3) [Reχ(3)/Imχ(3)]. The obtained Reχ(3)/Imχ(3) of Au/SrTiO3 is 1.43, which is more than 3 times as large as that of Ni/SrTiO3.


Species D Adenoviruses as Oncolytic Viral Vectors.
Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.


Process for deposition of AlF3 thin films.
We fabricated aluminum fluoride (AlF(3)) thin films by pulsed DC magnetron sputtering with various CF(4) flow rates and sputtering powers. Our method is distinct from the conventional deposition process in that we used inexpensive Al (99.99% purity) as the target instead of an expensive fluoride compound. The optical properties and microstructure of the thin films were examined. The optical quality of AlF(3) thin films deposited at a 20 W sputtering power and injected 110 SCCM (SCCM denotes cubic centimeters per minute at standard temperature and pressure) CF(4) flow at room temperature showed improvement with an extinction coefficient of less than 7 x 10(-4) at 193 nm. The deposition of AlF(3) thin films at different substrate temperatures and annealed by UV light was also investigated.


New Developments in Clinical Bacteriology Laboratories.
There are a number of changes underway in modern clinical bacteriology laboratories. Panel-based molecular diagnostics are now available for numerous applications, including, but not limited to, detection of bacteria and select antibacterial resistance markers in positive blood culture bottles, detection of acute gastroenteritis pathogens in stool, and detection of selected causes of acute meningitis and encephalitis in the cerebrospinal fluid. Today, rapid point-of-care nucleic acid amplification tests are bringing the accuracy of sophisticated molecular diagnostics closer to patients. A proteomic technology, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, is enabling rapid, accurate, and cost-effective identification of bacteria, as well as fungi, recovered in cultures. Laboratory automation, common in chemistry laboratories, is now available for clinical bacteriology laboratories. Finally, there are several technologies under development, such as rapid phenotypic antimicrobial susceptibility testing, whole-genome sequencing, and metagenomic analysis for the detection of bacteria in clinical specimens. It is helpful for clinicians to be aware of the pace of new development in their bacteriology laboratory to enable appropriate test ordering, to enable test interpretation, and to work with their laboratories and antimicrobial stewardship programs to ensure that new technology is implemented to optimally improve patient care.


A role for heterochromatin protein 1γ at human telomeres.
Human telomere function is mediated by shelterin, a six-subunit complex that is required for telomere replication, protection, and cohesion. TIN2, the central component of shelterin, has binding sites to three subunits: TRF1, TRF2, and TPP1. Here we identify a fourth partner, heterochromatin protein 1γ (HP1γ), that binds to a conserved canonical HP1-binding motif, PXVXL, in the C-terminal domain of TIN2. We show that HP1γ localizes to telomeres in S phase, where it is required to establish/maintain cohesion. We further demonstrate that the HP1-binding site in TIN2 is required for sister telomere cohesion and can impact telomere length maintenance by telomerase. Remarkably, the PTVML HP1-binding site is embedded in the recently identified cluster of mutations in TIN2 that gives rise to dyskeratosis congenita (DC), an inherited bone marrow failure syndrome caused by defects in telomere maintenance. We show that DC-associated mutations in TIN2 abrogate binding to HP1γ and that DC patient cells are defective in sister telomere cohesion. Our data indicate a novel requirement for HP1γ in the establishment/maintenance of cohesion at human telomeres and, furthermore, may provide insight into the mechanism of pathogenesis in TIN2-mediated DC.


[THE INFLUENCE OF SMOKING ON THE LUNG VENTILATION FUNCTION IN YOUNG SUBJECTS].
The aim of the work was to evaluate effect of smoking on the lung ventilation function in young subjects. The study included 1552 subjects (808 men and 744 women) of the mean age 31.6 ± 4.7 and 29.27 ± 5.3 years respectively divided into 3 groups: smokers (n = 568), ex-smokers (n = 103), and non-smokers (n = 881). A sample of the general population contained 36.6% smokers, 6.6% ex-smokers, and 56.8% non-smokers; it showed significant correlation of smoking habits with the gender and the education level. Functional studies revealed lower spirographic and higher whole-body plethysmographic parameters in the smokers and ex-smokers. Also, they more frequently suffered obstructive disorders. These data suggest negative effect of tobacco smoke on the respiratory system in practically healthy young subjects revealed by the studying external respiratory function with the use of spirographic and whole-body plethysmographic methods.


Social support needs in adjustment to stroke.
Persons experiencing recent onset of stroke show wide variation in their adjustment process. This study evaluates how much these individual differences are a function of interpersonal needs for social contact after the rehabilitation process. Subjective needs for social relations are measured and compared with adjustment to stroke. Variation in the expression of and desire for social support appears to be related to outcome of rehabilitation and adjustment to chronic physical limitations.


[Testicular tumor presenting as acute scrotum with infection caused by gas-producing bacteria].
A 46-year-old male patient visited our hospital with the chief complaint of a right scrotal swelling and pain. The enlarged scrotum was 8 cm in diameter with redness of the skin of the right scrotum. There was a firm mass in the scrotum with marked tenderness. The patient's body temperature was 38.0C, and blood tests showed increased inflammatory markers. The results of computed tomography and magnetic resonance imaging showed that the enlarged scrotum was filled with gas and there was a mass partially composed of fat inside it. The patient was treated with antibiotics, but the fever persisted and the inflammatory markers further increased. The size of the right scrotum gradually increased. A right high inguinal orchiectomy was performed to control the inflammation and makea diagnosis. Thehistopathological diagnosis was necrosis of seminoma, and culture of thene crotic tissuewas positivefor Clostridium. Thepre sent caseappe ars to bethefirst caseof a testicular tumor associated with acute scrotum due to tumor growth, necrosis and infection caused by gas-producing bacteria.


Marketing cardiovascular services: the new paradigms.
In this first of three articles dealing with how to market cardiovascular services in today's healthcare environment, the groundwork is laid for understanding what those changes are, what effects they can have on how those services should be marketed, and the market strategy planning process.


Occult periprosthetic fractures of the acetabulum in THA using an elliptic cup design have no adverse impact on outcome.
Occult periprosthetic fractures have been defined as a fracture only visible on postoperative CT scans but not on postoperative plain radiography after an uneventful surgery without intraoperative fracture. The fracture rate for hemispherical and peripheral self-locking cups has been described as 8.4%. We retrospectively analyzed postoperative CT scans after primary THA to clear the question whether such occult periprosthetic fractures of the acetabulum require particular treatment strategy. Between 2014 and 2018 we identified 115 CT scans of 114 patients after primary cementless THA with elliptical cups using a direct anterior approach. The CT scans were obtained as part of other investigations. Localization of the fracture, patients demographics, clinical (WOMAC, Harris Hip Score) and radiological outcome were analyzed. Fracture and non-Fracture group were compared with regard to demographics and short-term outcome after 1 year. Four occult fractures (3.5%) were identified. Three fractures involved the posterior wall. All patients had an uneventful routine postoperative rehabilitation. Patients with occult fractures showed similar post- operative HHS and WOMAC scores at 3 (HHS p = 0.576, WOMAC p = 0.128) and 12 (HHS p = 0.479, WOMAC p = 0.588) months. There were no cup loosening nor radiolucent lines at latest follow-up (mean FU 22 months, range 12-34 months). Clinical and radiological short-term outcome was not impaired by the occurrence of an occult periprosthetic fracture of the acetabulum. The incidental detection of an occult periprosthetic fracture of the acetabulum does not seem to oblige the surgeon to adapt the postoperative regime.


Epidemiological analysis of Trueperella abortisuis isolated from cases of pig abortion of a single farm.
The present study was designed to characterize six Trueperella (T.) abortisuis strains, cultured over a period of 5 months from fetus and abortion material of six pigs of a single farm in Mecklenburg-West Pomerania federal state, Germany. It was of interest to investigate the epidemiological relationships of the six strains among each other and whether a single bacterial clone was responsible for the abortion situation of the single farm. All six strains were identified phenotypically, by MALDI-TOF MS analysis and by phylogenetic analysis based on 16S rRNA gene and gap (encoding the glyceraldehyde 3-phosphate dehydrogenase) and tuf (encoding elongation factor tu) gene sequencing. Further genotypic comparison was performed using different genomic DNA fingerprint methods including BOX-PCR, (GTG)5-PCR, and three RAPD-PCRs. The sequence analysis of the genes gap and tuf and the genomic DNA fingerprinting results revealed, as noval findings, that the six T. abortisuis strains cultured from a single farm represent six different bacterial clones showing a genetic variability of this bacterial species in the pig population. All six T. abortisuis strains were isolated in mixed culture with several other bacterial species. However, the T. abortisuis strain, generally found in high numbers, seemed to be responsible for the abortion situation in the farm.


Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells.
Complex co-cultures of organoids with immune cells provide a versatile tool for interrogating the bi-directional interactions that underpin the delicate balance of mucosal homeostasis. These 3D, multi-cellular systems offer a reductionist model for addressing multi-factorial diseases and resolving technical difficulties that arise when studying rare cell types such as tissue-resident innate lymphoid cells (ILCs). This article describes a murine system that combines small intestine organoids and small intestine lamina propria derived helper-like type-1 ILCs (ILC1s), which can be readily extended to other ILC or immune populations. ILCs are a tissue-resident population that is particularly enriched in the mucosa, where they promote homeostasis and rapidly respond to damage or infection. Organoid co-cultures with ILCs have already begun shedding light on new epithelial-immune signaling modules in the gut, revealing how different ILC subsets impact intestinal epithelial barrier integrity and regeneration. This protocol will enable further investigations into reciprocal interactions between epithelial and immune cells, which hold the potential to provide new insights into the mechanisms of mucosal homeostasis and inflammation.


[Organization of the primary polytene chromosome in the ovaries of 12 species of the "virilis" group of the genus Drosophila (Sophophora)].
Organization of chromosomes was analyzed in ovarian nurse cells in 12 species of the virilis group of Drosophila. A diffuse chromocenter containing a clearly detectable block of heterochromatin was shown to be characteristic of the phylogenetically ancestral species D. virilis and D. kanekoi. Similar organization of chromosomes was observed in two daughter species, D. lummei and D. falvomontana. The chromocenter disappeared either completely or partially in the phylads montana and virilis, respectively. These species exhibited separate chromosomes attached to a nuclear envelope and dispersed within the nucleus. Detected alterations in chromosome architecture confirm evolutionary trends previously revealed in species of the melanogaster subgroup.


Hyperbaric oxygenation therapy alleviates chronic constrictive injury-induced neuropathic pain and reduces tumor necrosis factor-alpha production.
The development of hyperalgesia and allodynia after chronic constrictive injury (CCI) is associated with significantly increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Theoretically, if the production of TNF-α and/or IL-1β could be reduced, neuropathic pain syndrome may be alleviated. Recently, a beneficial effect of hyperbaric oxygenation therapy (HBOT) in the treatment of pain disorders has been suggested. Our present study was designed to examine the hypotheses that (1) CCI-induced neuropathic pain may be associated with increased production of TNF-α and IL-1β, (2) HBOT may alleviate CCI-induced neuropathic pain, and (3) the alleviated neuropathic pain may be associated with reduced production of TNF-α and/or IL-1β. Male rats (weighing 250-300 g) were anesthetized with ketamine and xylazine. The common sciatic nerve was exposed through the biceps femoris. Proximal to the sciatic's trifurcation, 4 ligatures were loosely tied around the nerve. In the sham group, an identical dissection was performed without ligation of the sciatic nerve. Mechanical allodynia and cold allodynia were tested by von Frey filament stimulation and the spread of acetone, respectively. HBO rats (n =18) were exposed to pure oxygen for 1 hour at 2.4 atm once a day. Non-HBO (n =18) and sham rats (n =6) were placed in the HBOT chamber breathing air. TNF-α and IL-1β in the sciatic nerve were assayed with ELISA. The presence of TNF-α protein in homogenates was verified by Western blot analysis. CCI induced significant cold and mechanical allodynia as measured after CCI on days 4 and 7. The cold allodynia response frequency was significantly lower in HBO rats than in non-HBO rats. The values were 20% ± 1.6% vs 50% ± 4.5% on day 4 and 40% ± 4.6% vs 70% ± 4.5% on day 7 (F =87.42, confidence interval [for the difference between HBO and non-HBO]=29.612 ± 8.781, P < 0.05 for day 4 and day 7). The threshold of mechanical allodynia significantly increased in HBO rats compared with non-HBO rats. The values were 6.20 ± 0.9 vs 4.1 ± 1.0 g on day 4 and 3.8.2 ± 0.5 vs 2.3 ± 0.4 g on day 7 (F =18.8, confidence interval [for the difference between HBO and non-HBO]=1.806 ± 1.171, P < 0.05 for day 4 and day 7). TNF-α content was significantly higher in non-HBO rats than in sham rats on day 4 (17.89 ± 0.83 vs 10.66 ± 1.1 pg/mg protein, P < 0.05) and day 7 (18.97 ± 1.57 vs 9.09 ± 1.5 pg/mg protein, P < 0.05). HBOT significantly reduced TNF-α content to near the level in sham rats, which was 10.94 ± 2.78 and 11.32 ± 2.98 pg/mg protein on day 4 (P < 0.05 versus non-HBO) and 7 (P < 0.05 versus non-HBO), respectively. Western blot analysis confirmed the presence of proteins with molecular weights of 51 kDa in the rat sciatic nerve homogenates. IL-1β content was also significantly higher in non-HBO rats than in sham rats on day 4 (636 ± 74 vs 256 ± 31 pg/mg protein, P < 0.05) and on day 7 (687 ± 89 vs 288 ± 35 pg/mg protein, P < 0.05). HBOT had no effect on IL-1β content, which was 671 ± 85 pg/mg protein on day 4 and 672 ± 75 pg/mg protein on day 7 in HBO rats (P =not significant versus non-HBO rats). These data show that HBOT alleviates CCI-induced neuropathic pain and inhibits endoneuronal TNF-α production, but not IL-1β in CCI-induced neuropathic pain. Reduced TNF-α production may, at least in part, contribute to the beneficial effect of HBOT.


Sjögren's syndrome.
The diagnosis of Sjögren's syndrome, a multi-systemic disease, is often difficult. Sialography is useful; however, biopsy of labial salivary glands is a simple procedure that aids significantly in arriving at a positive diagnosis. Treatment of the disease is usually on the basis of symptoms.


Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer.
There is emerging evidence for the prognostic role of various microRNA (miRNA) molecules in colon cancer. The aim of this study was therefore to compare the miRNA profiles in the primary tumor of patients with recurrent and non-recurrent colon cancer. The study population included 110 patients, 51 (46%) with stage I and 59 (54%) with stage II disease, who underwent curative colectomies between 1995 and 2005 without adjuvant therapy and for whom reliable miRNA expression data were available. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples. Initial profiling, using microarrays, was done in order to identify potential biomarkers of recurrence. The miRNA expression was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 months of surgery (bad prognosis group, n=23, 21%) and those who did not (good prognosis group, n=87, 79%) in the entire group and within each stage. The results showed that in stage I, none of the 903 miRNAs tested showed differential expression between patients with good prognosis compared with those with poor prognosis. In contrast, in stage II, one miRNA, miR-29a, showed a clear differential expression between the groups (p=0.028). High expression of miR-29a was associated with a longer disease-free survival (DFS), on both univariate and multivariate analyses. Using miR-29a, the positive predictive value for non-recurrence was 94% (2 recurrences among 31 patients). The differential expression of miR-29a was verified by qRT-PCR, showing a similar impact of this miR on DFS. In conclusion, this study demonstrated a significant impact of miR-29a on the risk of recurrence in patients with stage II but not in patients with stage I colon cancer. Based on these results, a validation study is planned.


New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat.
Niemann-Pick disease type C (NP-C) is an autosomal recessive disorder characterized by progressive neurological deterioration leading to premature death. The disease is caused by mutations in one of two genes, NPC1 or NPC2, leading to impaired intracellular lipid transport and build-up of lipids in various tissues, particularly the brain. Miglustat (Zavesca(R)), a reversible inhibitor of glycosphingolipid synthesis, has recently been authorized in the European Union, Brazil and South Korea for the treatment of progressive neurological symptoms in adult and pediatric patients, and represents the first specific treatment for NP-C. Here we review current data on the pharmacology, efficacy, safety and tolerability of miglustat in patients with NP-C, based on findings from a prospective clinical trial, preclinical and retrospective studies, and case reports. Findings demonstrated clinically relevant beneficial effects of miglustat on neurological disease progression in adult, juvenile and pediatric patients with NP-C, particularly those diagnosed in late childhood (6-11 years) and in juveniles and adults (12 years and older), compared with those diagnosed in early childhood (younger than 6 years). Miglustat therapy was well-tolerated in all age groups. With the approval of miglustat, treatment of patients with NP-C can now be aimed toward stabilizing neurological disease, which is likely the best attainable therapeutic goal for this disorder.


Attentional avoidance of threatening stimuli.
Aversive conditioning has been shown to influence the control of attention, such that aversively conditioned stimuli receive elevated priority. Although aversively conditioned but task-irrelevant distractors are known to capture attention during speeded search in rapid orienting tasks, it is unclear whether this bias extends to situations where orienting can be more deliberate. We demonstrate that punishment, via electric shock, does not give rise to oculomotor capture by shock-associated stimuli during a foraging task; rather, such aversively conditioned stimuli are actively avoided when searching through a display. On the other hand, even during a foraging task, we found some evidence for a covert attentional bias to threat. Our findings indicate that the previously described effects of aversive conditioning on visual search may not generalize beyond the initial glance and can be suppressed when conditions allow for more deliberate search strategies. More generally, our findings reveal that sustained attentional avoidance of aversively conditioned stimuli is possible during active search.


Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone.
Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.


Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction.
The diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation worldwide and is directly associated with comorbidity, disability and mortality. Oxidative stress mechanisms have been implicated in the pathogenesis of these wounds. Intra-lesional infiltration of epidermal growth factor has emerged as a potential therapeutic alternative to allow for physiological benefit while avoiding the proteolytic environment at the centre of the wound. The aim of this study was to characterise the response of patients with DFUs to epidermal growth factor treatment in terms of redox status markers. Experimental groups included patients with DFUs before and 3-4 weeks after starting treatment with epidermal growth factor; compensated and non-compensated diabetic patients without ulcers; and age-matched non-diabetic subjects. Evaluations comprised serum levels of oxidative stress and antioxidant reserve markers. Patients with DFUs exhibited the most disheveled biochemical profile, with elevated oxidative stress and low antioxidant reserves, with respect to non-ulcerated diabetic patients and to non-diabetic subjects. Epidermal growth factor intra-lesional administration was associated with a significant recovery of oxidative stress and antioxidant reserve markers. Altogether, our results indicate that epidermal growth factor intra-ulcer therapy contributes to restore systemic redox balance in patients with DFUs.


TRANSPARENT TESTA1 interacts with R2R3-MYB factors and affects early and late steps of flavonoid biosynthesis in the endothelium of Arabidopsis thaliana seeds.
Wild type seed coats of Arabidopsis thaliana are brown due to the accumulation of proanthocyanidin pigments (PAs). The pigmentation requires activation of phenylpropanoid biosynthesis genes and mutations in some of these genes cause a yellow appearance of seeds, termed transparent testa (tt) phenotype. The TT1 gene encodes a WIP-type zinc finger protein and is expressed in the seed coat endothelium where most of the PAs accumulate in wild type plants. In this study we show that TT1 is not only required for correct expression of PA-specific genes in the seed coat, but also affects CHS, encoding the first enzyme of flavonoid biosynthesis. Many steps of this pathway are controlled by complexes of MYB and BHLH proteins with the WD40 factor TTG1. We demonstrate that TT1 can interact with the R2R3 MYB protein TT2 and that ectopic expression of TT2 can partially restore the lack in PA production in tt1. Reduced seed coat pigmentation was obtained using a TT1 variant lacking nuclear localisation signals. Based on our results we propose that the TT2/TT8/TTG1 regulon may also comprise early genes like CHS and discuss steps to further unravel the regulatory network controlling flavonoid accumulation in endothelium cells during A. thaliana seed development.