Random regression models for genetic evaluation of clinical mastitis in dairy cattle.
A genetic analysis of longitudinal binary clinical mastitis (CM) data recorded on about 90 000 first-lactation Swedish Holstein cows was carried out using linear random regression models (RRM). This method for genetic evaluation of CM has theoretical advantages compared to the method of linear cross-sectional models (CSM), which is currently being used. The aim of this study was to investigate the feasibility and suitability of estimating genetic parameters and predicting breeding values for CM with a linear sire RRM. For validation purposes, the estimates and predictions from the RRM were compared to those from linear sire longitudinal multivariate models (LMVM) and CSM. For each cow, the period from 10 days before to 241 days after calving was divided into four 1-week intervals followed by eight 4-week intervals. Within each interval, presence or absence of CM was scored as '1' or '0'. The linear RRM used to explain the trajectory of CM over time included a set of explanatory variables plus a third-order Legendre polynomial function of time for the sire effect. The time-dependent heritabilities and genetic correlations from the chosen RRM corresponded fairly well with estimates obtained from the linear LMVM for the separate intervals. Some discrepancy between the two methods was observed, with the more unstable results being obtained from the linear LMVM. Both methods indicated clearly that CM was not genetically the same trait throughout lactation. The correlations between predicted sire breeding values from the RRM, summarized over different time periods, and from linear CSM were rather high. They were, however, less than unity (0.74 to 0.96), which indicated some re-ranking of sires. Sire curves based on the time-specific breeding values from the RRM illustrated differences in intercept and slope among the best and the worst sires. To conclude, a linear sire RRM seemed to work well for genetic evaluation purposes, but was sensitive for estimation of genetic parameters.


How do enzymes work?
The principle of transition-state stabilization asserts that the occurrence of enzymic catalysis is equivalent to saying that an enzyme binds the transition state much more strongly than it binds the ground-state reactants. An outline of the origin and gradual acceptance of this idea is presented, and elementary transition-state theory is reviewed. It is pointed out that a misconception about the theory has led to oversimplification of the accepted expression relating catalysis and binding, and an amended expression is given. Some implications of the transition-state binding principle are then explored. The amended expression suggests that internal molecular dynamics may also play a role in enzymic catalysis. Although such effects probably do not make a major contribution, their magnitude is completely unknown. Two examples of recent advances due to application of the transition-state binding principle are reviewed, one pertaining to the zinc protease mechanism and the other to the generation of catalytic antibodies.


The Association of Pre-stroke Psychosis and Post-stroke Levels of Health, Resource Utilization, and Care Process: A Register-Based Study.
Background: While approximately one percent of the global population is formally diagnosed with psychosis or schizophrenia, the actual number is expected to be significantly higher. These patients often consume more healthcare resources and have poorer somatic health. In this study, we analyze potential differences in health, resources, and care process between stroke patients with and without a previous diagnosis of psychosis or schizophrenia. Methods: Ischemic stroke patients from seven regions in Sweden were identified via ICD-10 codes (I63.0-9) in regional administrative systems and the Swedish Stroke Register, and approximately 70% of all ischemic stroke cases in Sweden during 2008-2011 were included (n = 46,350). Relevant patient-level data from national registries were linked to enable multivariate regression analysis, including data on socioeconomics, mortality, municipality services, and filled prescriptions. History of psychosis or schizophrenia was defined via ICD-10 codes F20-29 (n = 389). Results: Patient-reported functional outcomes at 3 months and 1 year were significantly lower in the psychosis subgroup, and stroke recurrence was higher. Patients with pre-stroke psychosis did not receive the same levels of reperfusion treatment as the non-psychosis group. Time at the stroke unit was the same, as were first-year levels of somatic care, but dispensation of antihypertensives was less common. Conclusion: Our findings emphasize the importance of taking mental comorbidity into account during stroke treatment as well as when evaluating indicators for health, resources, and the care process, since mental comorbidity such as psychosis or schizophrenia may have a significant impact the year preceding and the year succeeding the stroke event.


Identification of the botanical origin of pine nuts found in food products by gas-liquid chromatography analysis of fatty acid profile.
Pine nuts are traditionally used in various part of the world for the preparation of desserts or sauces or in salads. Local production is not sufficient to cope with the high demand of pine nuts around the world, and countries such as China or Pakistan are exporting much of their production to Western countries. Almost all the nuts that are traditionally consumed belong to the Pinus genus, but over the past years, the number of consumer complaints following consumption of commercial pine nuts increased. Some consumers experienced taste disturbance lasting for up to two weeks after consumption. Food safety agencies raised some concerns regarding pine nuts imported from Asia and their association with taste disturbance. However, even though a formal association has not been found to date, the Pinus genus comprises species that are not classified as edible and could be eventually used to adulterate edible species. Pinus spp. seed lipids are known to contain very specific polyunsaturated fatty acids know as Delta5-olefinic acids. Seed fatty acid profile of conifers had been used in the past as a taxonomic marker, and in the present study to identify the botanical origin of pine nut in nine commercial products. Fast gas-liquid chromatography (GLC) was used to resolve the complete fatty acid profile of Pinus spp. samples in less than 5 min. A diagnostic index based on the relative levels of the main fatty acids including distinctive Delta5-olefinic acids was used to identify botanical origins. Results revealed the occurrence of the following Pinus spp. in commercial products: P. pinea, P. koraiensis, P. gerardiana, P. armandii and P. massoniana. The later two species, known as Chinese white pine and Chinese red pine, are only cultivated in China and are not listed as common source of edible pine nuts by the Food and Agriculture Organization (FAO). The present study shows that the botanical origin of pine nuts can be identified in products based on the fatty acid profile.


Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide.
Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear.


Limited effects from professional identity formation-oriented intervention on self-regulated learning in a preclinical setting: a randomized-controlled study in Japan.
Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning. We designed a professional identity formation-oriented reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical year curriculum. A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire. Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.


Trophic resource partitioning drives fine-scale coexistence in cryptic bat species.
Understanding the processes that enable species coexistence has important implications for assessing how ecological systems will respond to global change. Morphology and functional similarity increase the potential for competition, and therefore, co-occurring morphologically similar but genetically unique species are a good model system for testing coexistence mechanisms. We used DNA metabarcoding and high-throughput sequencing to characterize for the first time the trophic ecology of two recently described cryptic bat species with parapatric ranges, Myotis escalerai and Myotis crypticus. We collected fecal samples from allopatric and sympatric regions and from syntopic and allotopic locations within the sympatric region to describe the diets both taxonomically and functionally and compare prey consumption with prey availability. The two bat species had highly similar diets characterized by high arthropod diversity, particularly Lepidoptera, Diptera and Araneae, and a high proportion of prey that is not volant at night, which points to extensive use of gleaning. Diet overlap at the prey item level was lower in syntopic populations, supporting trophic shift under fine-scale co-occurrence. Furthermore, the diet of M. escalerai had a marginally lower proportion of not nocturnally volant prey in syntopic populations, suggesting that the shift in diet may be driven by a change in foraging mode. Our findings suggest that fine-scale coexistence mechanisms can have implications for maintaining broad-scale diversity patterns. This study highlights the importance of including both allopatric and sympatric populations and choosing meaningful spatial scales for detecting ecological patterns. We conclude that a combination of high taxonomic resolution with a functional approach helps identify patterns of niche shift.


Differences in osteon banding between human and nonhuman bone.
The objective of this paper is to compare patterns of osteon organization in human and nonhuman bone. A linear organization of Haversian systems in nonhuman bone, where osteons line up in rows, has been reported but has not been quantified. The present research provides a quantitative examination of this observation through a comparative analysis of the femoral midshaft from human and nonhuman bone. Femoral midshaft thin sections from 60 humans were compared to femoral midshaft sections from nine sheep and six miniature swine. The presence or absence of osteon banding was recorded and, if present, described. Results indicate that 2 out of 60 human sections and 5 out of 15 nonhuman sections exhibit osteon banding (chi2 = 9.46; p < 0.01). Further, the type of banding present in the human and nonhuman samples is easily distinguished, indicating that human and nonhuman bone can be distinguished where handing is present in this study.


Surface structures of the heart cell and their role in contractile control.
Studies which focus on calcium (Ca) at the cellular surface indicate: Ca in the vascular and interstitial spaces is in rapid equilibrium with that bound within the sarcolemmal-glycocalyx complex of the cell. At [Ca]o of 1.0-1.5 mM 80-85% of this Ca is bound to phospholipid of the sarcolemmal bilayer and amounts to 500-700 mumoles/kg wet wt. tissue. Phospholipids of net anionic charge (phosphatidylserine, phosphatidylinositol) or zwitterionic structure (phosphatidylethanolamine) are likely to play a predominant role in the binding. Augmentation of net anionic charge (formation of phosphatidate by phospholipase D, addition of dodecylsulfate) of the sarcolemma augments Ca binding and is positively inotropic. Conversely, insertion of a cationic amphiphile (Polymyxin B, dodecyltrimethylamine) displaces Ca and is negatively inotropic. Augmentation of anionic Ca binding sites induces a significant increase of Na-Ca exchange in sarcolemmal vesicles which may contribute to the associated positive inotropy found in the intact myocardium.


Post-heading heat stress and yield impact in winter wheat of China.
Wheat is sensitive to high temperatures, but the spatial and temporal variability of high temperature and its impact on yield are often not known. An analysis of historical climate and yield data was undertaken to characterize the spatial and temporal variability of heat stress between heading and maturity and its impact on wheat grain yield in China. Several heat stress indices were developed to quantify heat intensity, frequency, and duration between heading and maturity based on measured maximum temperature records of the last 50 years from 166 stations in the main wheat-growing region of China. Surprisingly, heat stress between heading and maturity was more severe in the generally cooler northern wheat-growing regions than the generally warmer southern regions of China, because of the delayed time of heading with low temperatures during the earlier growing season and the exposure of the post-heading phase into the warmer part of the year. Heat stress between heading and maturity has increased in the last decades in most of the main winter wheat production areas of China, but the rate was higher in the south than in the north. The correlation between measured grain yields and post-heading heat stress and average temperature were statistically significant in the entire wheat-producing region, and explained about 29% of the observed spatial and temporal yield variability. A heat stress index considering the duration and intensity of heat between heading and maturity was required to describe the correlation of heat stress and yield variability. Because heat stress is a major cause of yield loss and the number of heat events is projected to increase in the future, quantifying the future impact of heat stress on wheat production and developing appropriate adaptation and mitigation strategies are critical for developing food security policies in China and elsewhere.


Fetal cloacal anomalies: prenatal sonographic findings and differential diagnosis.
Serial sonographic findings are presented in three cases of cloacal anomalies. The following sonographic signs were noted: transient fetal ascites, bicystic intra-abdominal structure arising from the fetal pelvis, and oligohydramnios and impaired interval growth. This sequence of sonographic findings may help clarify the natural history of the developing cloacal anomaly: In the early state of its formation, urine enters the abdominal cavity via the fallopian tubes, causing ascites; later, chronic urinary and meconium irritation of tubal mucosa may cause tubal obstruction, which in turn may lead to the formation of genitourinary tract distention, hydronephrosis, and oligohydramnios. Timely diagnosis of cloacal anomalies improves the outcome of pregnancies (delivery in the tertiary care center, early operative correction).


A genetic interpretation of heightened risk of BSE in offspring of affected dams.
An analysis is presented of the results of a cohort study designed to test whether or not the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle can be transmitted maternally (vertically) from dam offspring. Various genetic models are fitted to the data under the assumption that the results could be explained entirely by genetic predisposition to disease (as opposed to maternal transmission) given exposure of offspring of diseased and unaffected dams to contaminated cattle feed. The analyses suggest that the results could be explained by the hypothesis of genetic predisposition, provided a large difference exists in the susceptibility of resistant and susceptible hosts, and explore the range of genotypic parameters and frequencies consistent with the limited currently available data. The results presented are broadly robust, even under the scenario that a portion of the observed maternally enhanced risk of BSE is due to a low level of maternal transmission in late incubation stage dams.


Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine.
The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.


[Antibiotic resistance caused by membrane impermeability and multidrug efflux systems].
Multiple antibiotic resistance(MDR) in bacteria was at first thought to be caused exclusively by the combination of several resistance mechanisms including membrane impermeability, the outer membrane barrier in gram-negative bacteria. More recently, it became clear that MDR are often achieved by interplay between impermeability and multidrug efflux pumps. Streptococcus pneumoniae MefA, Staphylococcus aureus NorA and Pseudomonas aeruginosa Mex of these pumps are significant, because those bacteria are more frequently isolated in clinical. In this review, we described on characteristics and clinical significance of P. aeruginosa Mex systems, MexA-MexB-OprM, MexC-MexD-OprJ, MexE-MexF-OprN and MexX-MexY-OprM, and furthermore, on interplay between the efflux systems, the outer membrane barrier, hydrolyzing enzyme and mutated target.


Sleep-related problems in common medical conditions.
Common medical problems are often associated with abnormalities of sleep. Patients with chronic medical disorders often have fewer hours of sleep and less restorative sleep compared to healthy individuals, and this poor sleep may worsen the subjective symptoms of the disorder. Individuals with lung disease often have disturbed sleep related to oxygen desaturations, coughing, or dyspnea. Both obstructive lung disease and restrictive lung diseases are associated with poor quality sleep. Awakenings from sleep are common in untreated or undertreated asthma, and cause sleep disruption. Gastroesophageal reflux is a major cause of disrupted sleep due to awakenings from heartburn, dyspepsia, acid brash, coughing, or choking. Patients with chronic renal disease commonly have sleep complaints often due to insomnia, insufficient sleep, sleep apnea, or restless legs syndrome. Complaints related to sleep are very common in patients with fibromyalgia and other causes of chronic pain. Sleep disruption increases the sensation of pain and decreases quality of life. Patients with infectious diseases, including acute viral illnesses, HIV-related disease, and Lyme disease, may have significant problems with insomnia and hypersomnolence. Women with menopause have from insomnia, sleep-disordered breathing, restless legs syndrome, or fibromyalgia. Patients with cancer or receiving cancer therapy are often bothered by insomnia or other sleep disturbances that affect quality of life and daytime energy. The objective of this article is to review frequently encountered medical conditions and examine their impact on sleep, and to review frequent sleep-related problems associated with these common medical conditions.


Non-cardiac surgery in patients with continuous-flow left ventricular assist devices: a single institutional experience.
With improvements in life expectancy for patients with continuous-flow left ventricular assist devices (LVADs), non-cardiac surgeons will increasingly encounter surgical problems in this population. 209 patients underwent LVAD placement between 10/1/2007 and 6/1/2015 at a single institution. Survival was compared between patients who had non-cardiac surgery (NCS) during the initial LVAD implantation hospitalization (n=36) and those who had NCS only in subsequent hospitalizations (n=33). Postoperative complication rates were examined. Index admission NCS was associated with lower 5-year survival compared with subsequent admission NCS (27.1% vs 39.4%, p=0.017). In subsequent admissions, the risks of bleeding and infectious complications were the same for elective or urgent NCS, but the risk of death was higher in the urgent surgery group. We conclude that elective NCS can be performed with low risk of death or LVAD dysfunction after sufficient recovery of patients from LVAD implantation.


The thyroid function and size in healthy man during 3 weeks treatment with beta-adrenoceptor-antagonists.
The influence of beta-adrenoceptor antagonists on serum TSH level (supersensitive method) and thyroid volume has not previously been studied. Thirty-two young non-smoking males were treated for 3 weeks with either atenolol 50 mg (b.i.d.), metoprolol 100 mg (b.i.d.) or propranolol 80 mg (b.i.d.) in a placebo controlled study. After 1 week, median serum TSH level increased in the atenolol (from 1.76 (range: 0.96-4.04) to 2.25 (range: 1.11-4.22) mU/l, P less than 0.05) and propranolol (from 1.91 (range: 0.90-3.83) to 2.44 (range: 0.75-6.30) mU/l, P less than 0.05) treated groups. After 3 weeks, median serum TSH reached pretreatment level in the atenolol treated, whereas median serum TSH decreased compared to pretreatment values in the propranolol treated (1.68 (range: 0.68-3.62) mU/l, P less than 0.05). Except for a slight increase in the atenolol treated group, no changes in median thyroid volume was seen after 3 weeks. The changes in serum TSH or thyroid volume were not related to changes in the concentrations of thyroid hormones, or of a magnitude likely to interfere with the clinical evaluation of thyroid function.


Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism.
Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria-derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40's effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation.


Engineering RNA Virus Interference via the CRISPR/Cas13 Machinery in Arabidopsis.
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are key immune mechanisms helping prokaryotic species fend off RNA and DNA viruses. CRISPR/Cas9 has broad applications in basic research and biotechnology and has been widely used across eukaryotic species for genome engineering and functional analysis of genes. The recently developed CRISPR/Cas13 systems target RNA rather than DNA and thus offer new potential for transcriptome engineering and combatting RNA viruses. Here, we used CRISPR/LshCas13a to stably engineer Arabidopsis thaliana for interference against the RNA genome of Turnip mosaic virus (TuMV). Our data demonstrate that CRISPR RNAs (crRNAs) guiding Cas13a to the sequences encoding helper component proteinase silencing suppressor (HC-Pro) or GFP target 2 (GFP-T2) provide better interference compared to crRNAs targeting other regions of the TuMV RNA genome. This work demonstrates the exciting potential of CRISPR/Cas13 to be used as an antiviral strategy to obstruct RNA viruses, and encourages the search for more robust and effective Cas13 variants or CRISPR systems that can target RNA.


Use of recombinant plasmids to investigate the structure of the human cytomegalovirus genome.
Human cytomegalovirus (HCMV) DNA was digested with restriction endonucleases and the fragments characterized with respect to molecular weight and relative mole proportions. The terminal fragments were identified by digesting HCMV DNA with exonucleases before restriction endonuclease treatment and subsequent gel analysis. The HindIII fragments of HCMV DNA were cloned in Escherichia coli and recombinant plasmids were characterized by digestion with restriction endonucleases and by molecular hybridization with HindIII, Bg/II and XbaI fragments of the virus genome. Data from these experiments were used to construct physical maps of HCMV DNA for the HindIII, Bg/II and XbaI restriction endonucleases. The terminal regions of the genome and the region containing fragment HindIII M were shown to be heterogeneous.


Mn(II) oxidation by an ascomycete fungus is linked to superoxide production during asexual reproduction.
Manganese (Mn) oxides are among the most reactive minerals within the environment, where they control the bioavailability of carbon, nutrients, and numerous metals. Although the ability of microorganisms to oxidize Mn(II) to Mn(III/IV) oxides is scattered throughout the bacterial and fungal domains of life, the mechanism and physiological basis for Mn(II) oxidation remains an enigma. Here, we use a combination of compound-specific chemical assays, microspectroscopy, and electron microscopy to show that a common Ascomycete filamentous fungus, Stilbella aciculosa, oxidizes Mn(II) to Mn oxides by producing extracellular superoxide during cell differentiation. The reactive Mn oxide phase birnessite and the reactive oxygen species superoxide and hydrogen peroxide are colocalized at the base of asexual reproductive structures. Mn oxide formation is not observed in the presence of superoxide scavengers (e.g., Cu) and inhibitors of NADPH oxidases (e.g., diphenylene iodonium chloride), enzymes responsible for superoxide production and cell differentiation in fungi. Considering the recent identification of Mn(II) oxidation by NADH oxidase-based superoxide production by a common marine bacterium (Roseobacter sp.), these results introduce a surprising homology between some prokaryotic and eukaryotic organisms in the mechanisms responsible for Mn(II) oxidation, where oxidation appears to be a side reaction of extracellular superoxide production. Given the versatility of superoxide as a redox reactant and the widespread ability of fungi to produce superoxide, this microbial extracellular superoxide production may play a central role in the cycling and bioavailability of metals (e.g., Hg, Fe, Mn) and carbon in natural systems.


Indoor firing ranges and elevated blood lead levels - United States, 2002-2013.
Indoor firing ranges are a source of lead exposure and elevated blood lead levels (BLLs) among employees, their families, and customers, despite public health outreach efforts and comprehensive guidelines for controlling occupational lead exposure. There are approximately 16,000-18,000 indoor firing ranges in the United States, with tens of thousands of employees. Approximately 1 million law enforcement officers train on indoor ranges. To estimate how many adults had elevated BLLs (≥10 µg/dL) as a result of exposure to lead from shooting firearms, data on elevated BLLs from the Adult Blood Lead Epidemiology and Surveillance (ABLES) program managed by CDC's National Institute for Occupational Safety and Health (NIOSH) were examined by source of lead exposure. During 2002-2012, a total of 2,056 persons employed in the categories "police protection" and "other amusement and recreation industries (including firing ranges)" had elevated BLLs reported to ABLES; an additional 2,673 persons had non-work-related BLLs likely attributable to target shooting. To identify deficiencies at two indoor firing ranges linked to elevated BLLs, the Washington State Division of Occupational Safety and Health (WaDOSH) and NIOSH conducted investigations in 2012 and 2013, respectively. The WaDOSH investigation found a failure to conduct personal exposure and biologic monitoring for lead and also found dry sweeping of lead-containing dust. The NIOSH investigation found serious deficiencies in ventilation, housekeeping, and medical surveillance. Public health officials and clinicians should ask about occupations and hobbies that might involve lead when evaluating findings of elevated BLLs. Interventions for reducing lead exposure in firing ranges include using lead-free bullets, improving ventilation, and using wet mopping or high-efficiency particulate air (HEPA) vacuuming to clean.


Grading nuclear, cortical and posterior subcapsular cataracts using an objective scatter index measured with a double-pass system.
To evaluate objectively intraocular scattering in eyes with nuclear, cortical and posterior subcapsular cataracts by means of an objective scatter index (OSI) obtained from double-pass images. To compare the results with those obtained using clinical conventional procedures. In this prospective, observational, cross-sectional, non-consecutive case series study, 188 eyes with cataracts of 136 patients were analysed (123 eyes had nuclear, 41 eyes had cortical and 24 eyes had posterior subcapsular cataracts). The control group consisted of 117 eyes of 68 healthy patients. Patient examination included subjective refraction, best spectacle-corrected visual acuity (BSCVA), cataract grade using the lens opacities classification system III (LOCS III) and OSI. We found a decrease in the BSCVA and an increase in the OSI with increasing cataract grade. Statistically significant differences were observed when the OSI of eyes without cataracts and those with different LOCS III were compared. The comparison between the OSI and LOCS III reported good percentages of agreement regarding the number of eyes classified in equivalent levels: 72.4% (nuclear cataracts), 86.6% (cortical cataracts) and 84.3% (posterior subcapsular cataracts). A non-linear regression model was applied between OSI and BSCVA, which resulted in the following multiple correlation coefficients: r=0.878 (nuclear), r=0.843 (cortical) and r=0.844 (posterior subcapsular). The results of the study showed that OSI is a useful parameter for evaluating large amounts of intraocular scattering that can be used, in combination with other conventional procedures, as a valuable tool in clinical practice to grade cataracts objectively.


Psychiatric comorbidities in new onset epilepsy: Should they be always investigated?
The new definition of epilepsy establishes that epilepsy is not only a disorder presenting with epileptic seizures but it can be often associated with cognitive and psychiatric comorbidities. In fact, the prevalence of psychiatric comorbidities is relatively high in patients with epilepsy (PWE), as one in three patients will have experienced a psychiatric disorder in the course of their life, with mood and anxiety disorders being the most frequent. Psychiatric comorbidities often precede the onset of the seizure disorder, and affect the life of these patients and the course of the seizure disorder at several levels, including a worse tolerance of pharmacotherapy with antiepileptic drugs (AEDs), in particular the development of iatrogenic psychiatric symptoms from pharmacologic and surgical treatments, an increased mortality risk, a worse quality of life and higher economic burdens of the patient, family and society as a hole. Accordingly, psychiatric comorbidities should be recognized at the time of the initial evaluation of every PWE and their treatment needs to be incorporated within the overall therapeutic plan. This question is addressed in this article.


Motility and tumoricidal activity of interleukin-2-stimulated lymphocytes.
The motility of murine splenic lymphocytes stimulated nonspecifically by recombinant interleukin 2 (RIL-2) was studied in a three-dimensional collagen-gel system. Nonadherent BALB/c splenic lymphocytes were cultured in medium containing Cetus RIL-2 (700 to 1000 units/ml) or excipient control. They were then allowed to locomote randomly for 16 to 18 h into slabs of type I rat tail collagen gel. The gels were digested with collagenase, and total lymphocyte populations and motile subpopulations were collected and compared with respect to their lymphokine-activated killer activity (measured as 4-h cytotoxicity against the natural killer-resistant mammary adenocarcinoma line 410.4), their natural killer activity (measured as 4-h cytotoxicity versus lymphoma YAC-1), and their subset distribution (defined by immunofluorescence). Some of the slabs were not digested but fixed for measurement of leading-front distance. RIL-2-stimulated lymphocyte populations displayed greater motility than unstimulated populations; the mean leading front distance was 2.4 times greater, and the percentage of cells exhibiting motility was approximately doubled. The most motile RIL-2-stimulated cells, however, were not the most tumoricidal. Motile subpopulations displayed approximately 25 to 60% lower lymphokine-activated killer activity than did the total populations from which they were derived. Natural killer activity followed a similar pattern. Motile subpopulations contained a lower proportion of asialo-GM1+ and T-null cells than did total populations and a higher proportion of L3T4+ cells. Chemokinetic stimulation with alpha-interferon increased overall motility, but the lymphokine-activated killer activity of the motile subpopulation was still lower than that of the total population. Lymphocyte motility is important in the infiltration of tumors and other inflammatory lesions. The results indicate that the most tumoricidal lymphocytes in RIL-2-stimulated populations may not be the best tumor infiltrators, and that the tumoricidal activity of circulating lymphocytes may be a misleading indicator of the effectiveness of immunotherapy.


Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement.
The innate immune response in vertebrates and invertebrates requires the presence of pattern recognition receptors or proteins that recognize microbial cell components including lipopolysaccharide, bacterial peptidoglycan (PGN), and fungal 1,3-beta-D-glucan. We reported previously that PGN and 1,3-beta-D-glucan recognition proteins from insect hemolymph were able to induce the activation of the prophenoloxidase-activating system, one of the major invertebrate innate immune reactions. The goal of this study was to characterize the biochemical properties and effects of the human counterparts of these molecules. Soluble pattern recognition proteins were purified from human serum and identified as human mannose-binding lectin (MBL) and L-ficolin. The use of specific microbial cell component-coupled columns demonstrated that MBL and L-ficolin bind to PGN and 1,3-beta-D-glucan, respectively. Purified MBL and L-ficolin were associated with MBL-associated serine proteases-1 and -2 (MASPs) and small MBL-associated protein as determined by Western blot analysis. Finally, the binding of purified MBL/MASP and L-ficolin/MASP complexes to PGN and 1,3-beta-D-glucan, respectively, resulted in the activation of the lectin-complement pathway. These results indicate that human PGN and 1,3-beta-D-glucan recognition proteins function as complement-activating lectins.


Characteristics of people with pressure ulcers using one year's routinely collected data in a defined diverse community.
To determine if meaningful patient characteristics pertaining to pressure ulcers (PU) can be derived from routinely collected community health data. A retrospective cohort analysis of records was carried out. To provide a detailed dataset on PU for the community of interest, demographic, general medical and PU data were extracted from mandatory incident reports and audit of electronic and paper medical records. This study is reported in accordance with the RECORD Guidelines from the Equator Network. Adult patients were enrolled from a district nursing service in the target region (n=1085) during 2015. The target region was based on a geographical region bounded by a single postcode district (target region) consisting of 62,000 people of whom approximately 50,000 were adults, 3000 of whom were aged >75 years. The total number of recorded PUs was n=137 in 103 individuals. Data from mandatory incident reports was obtainable for nearly all variables. Electronic and paper medical records were less reliable due to missing data. Detailed characteristics of community-dwelling PU patients can be derived from routinely collected data, and provides various forms and levels of information which could feed into different projects. The use of mandatory reporting fields increases the level of reporting and reduces missing data. Data enriched with information from electronic and paper records could inform the addition of variables to mandatory forms to improve characterisation of community dwellers with PUs.


Molecular epidemiology of Clostridium difficile infection in a major chinese hospital: an underrecognized problem in Asia?
Clostridium difficile infection is almost unrecognized in mainland China. We have undertaken a study in a large Chinese teaching hospital in Changsha, Hunan, China, to identify cases of C. difficile, record patient characteristics, and define the molecular epidemiology with respect to ribotype distribution and cross-infection. Between April 2009 and February 2010, we examined fecal samples from 70 hospitalized patients with diarrhea who were receiving or had received antibiotics within the previous 6 weeks. Clinical information was collected and the samples were cultured for C. difficile retrospectively. Isolates were ribotyped, and multiple-locus variable-number tandem-repeat assay (MLVA) subtyping was performed on clusters of the same ribotype. The mean age of patients from whom C. difficile was cultured was 58 years, with only 4/21 patients aged >65 years. All patients, with a single exception, had received a third-generation cephalosporin and/or a quinolone antibiotic. Twenty-one isolates of C. difficile were recovered, and seven different ribotypes were identified, the dominant types being 017 (48%), 046 (14%), and 012 (14%). We identified two clusters of cross-infection with indistinguishable isolates of ribotype 017, with evidence of spread both within and between wards. We have identified C. difficile as a possibly significant problem, with cross-infection and a distinct ribotype distribution, in a large Chinese hospital. C. difficile may be underrecognized in China, and further epidemiological studies across the country together with the introduction of routine diagnostic testing are needed to ascertain the size of this potentially significant problem.


The Formation of Social Conventions in Real-Time Environments.
Why are some behaviors governed by strong social conventions while others are not? We experimentally investigate two factors contributing to the formation of conventions in a game of impure coordination: the continuity of interaction within each round of play (simultaneous vs. real-time) and the stakes of the interaction (high vs. low differences between payoffs). To maximize efficiency and fairness in this game, players must coordinate on one of two equally advantageous equilibria. In agreement with other studies manipulating continuity of interaction, we find that players who were allowed to interact continuously within rounds achieved outcomes with greater efficiency and fairness than players who were forced to make simultaneous decisions. However, the stability of equilibria in the real-time condition varied systematically and dramatically with stakes: players converged on more stable patterns of behavior when stakes are high. To account for this result, we present a novel analysis of the dynamics of continuous interaction and signaling within rounds. We discuss this previously unconsidered interaction between within-trial and across-trial dynamics as a form of social canalization. When stakes are low in a real-time environment, players can satisfactorily coordinate 'on the fly', but when stakes are high there is increased pressure to establish and adhere to shared expectations that persist across rounds.


Regional disparities and their contribution to the coverage of the tetanus toxoid vaccine among women aged 15-49 years in Indonesia.
Background: The prevention of Clostridium tetani bacterial infection through the administration of the tetanus toxoid (TT) vaccine in women is important. The purpose of this study was to determine the regional disparities and factors associated with TT vaccine coverage in women aged 15-49 years in Indonesia. Methods: The Indonesian Demographic Health Survey (IDHS) 2017 data was used in this study. A total of 36,028 women, aged 15-49 years were recruited using the two-stage stratified cluster sampling technique. The questionnaire used was based on the DHS Questionnaire Phase 7. Chi-squared and binary logistic regression were used in this study as part of the analysis. Results: We found that the TT vaccine coverage was 75.32% and that the majority were spread across several provinces. The provinces of Bali and Nusa Tenggara, the richer respondents, living in a rural area, visiting the health facility, having health insurance, and those currently working were factors making it more likely that the women would receive the TT vaccine. The respondents aged 15-24 years with a primary education level and the respondents who were divorced were less likely to receive the TT vaccine. Conclusion: The coverage of the TT vaccine among women can be increased by considering the regional disparities in Indonesia and the socio-economic demographic details of the respondents. Strengthening the policies from the central government in the local governments can improve the screening process and vaccine delivery outcomes. In addition, the importance of giving the TT vaccine to women needs to be relayed through health education in collaboration between health workers and the public.


Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.
To present the results (to January 1996, the end of blinded treatment) of the Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 micro g daily) designed to test the hypothesis that selenium supplementation (SS) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA. Original secondary analyses of the NPC to 1993 showed striking inverse associations between SS and prostate cancer incidence. A subsequent report revealed that this effect was accentuated among men with the lowest baseline plasma selenium concentrations. The effects of treatment overall and within subgroups of baseline prostate-specific antigen (PSA) and plasma selenium concentrations were examined using incidence rate ratios and Cox proportional hazards models. SS continued to significantly reduce the overall incidence (relative risk and 95% confidence interval) of prostate cancer (0.51, 0.29-0.87). The protective effect of SS appeared to be confined to those with a baseline PSA level of <or= 4 ng/mL (0.35, 0.13-0.87), although the interaction of baseline PSA and treatment was not statistically significant. Participants with baseline plasma selenium concentrations only in the lowest two tertiles (< 123.2 ng/mL) had significant reductions in prostate cancer incidence. A significant interaction between baseline plasma selenium and treatment was detected. To the end of the blinded treatment the NPC trial continued to show a significant protective effect of SS on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline PSA and plasma selenium concentrations.


[Eye developmental defects in Patau's syndrome (trisomy 13)].
The paper analyses results of pathomorphologic studies of eyes of 28 fetuses and newborns died from multiple malformations due to the Patau (trisomy 13) syndrome. Ocular malformations were recorded in 25 observations (89%). The most frequent and typical ocular malformations in this syndrome were microphthalmia, typical colobomas of the uveal tract, dysplasia of the retina, persistence and hyperplasia of the primary vitreous body, cataract and luxation of the lens.


Perioperative Implementation of Low-Dose Pregabalin in an Enhanced Recovery After Cardiac Surgery Protocol: A Pre-Post Observational Study.
Determine the effect of low-dose pregabalin in the perioperative enhanced recovery after cardiac surgery protocol. Pre-post observational study. Tertiary care hospital. Patients undergoing off-pump coronary artery bypass graft procedures. Pregabalin 75 mg BID for 48 hours postoperatively versus no pregabalin in a perioperative setting. Perioperative opioid use, pain scores, length of stay, time to extubation, and mortality were all measured. Descriptive data were presented as mean (SD), median (IQR), or N (%). Ordinal and continuous data used the t-test or Kruskal-Wallis test. Categorical data were compared between groups using the chi-square test or Fisher's exact test, as appropriate. Low-dose pregabalin administration (75 mg twice daily for 48 hours after surgery) was associated with a clinically significant reduction in opioid consumption on postoperative day 0 by 30.6%, with a median requirement of 318 (233, 397) morphine milligram equivalents (MME) in the pregabalin group compared with 458 (375, 526) MME in the control group (p < 0.001). There was no significant difference in pain scores between the groups with the exception at 0-to-12 hours, during which the pregabalin group had greater pain scores (median 3.32 [1.65, 4.36] v 2.0 [0, 3.25], p = 0.013) (Table 3). Moreover, there was no significant difference in pain scores on postoperative day 1 (p = 0.492), day 2 (p = 0.442), day 3 (p = 0.237), and day 4 (p = 0.649). The difference in average Richmond Agitation Sedation Score scores was also not statistically significant between groups at 12 hours (p = 0.954) and at 24 hours (p = 0.301). The pregabalin group had no increased incidence of adverse events or any significant differences in intensive care unit length of stay, time to extubation, or mortality. In this evaluation of perioperative pregabalin administration for patients requiring cardiac surgery, pregabalin reduced postoperative opioid use, with significant reductions on postoperative day 0, and without any significant increase in adverse reactions. However, no differences in intensive care unit length of stay, time to extubation, or mortality were noted. The implementation of low-dose perioperative pregabalin within an Enhanced Recovery After Cardiac Surgery protocol may be effective at reducing postoperative opioid use in the immediate postoperative period, and may be safe with regard to adverse events. Ideal dosing strategies have not been determined; thus, further randomized control trials with an emphasis on limiting confounding factors need to be conducted.


Endocrine system: part 2.
This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.


Population genetic analysis of bi-allelic structural variants from low-coverage sequence data with an expectation-maximization algorithm.
Population genetics and association studies usually rely on a set of known variable sites that are then genotyped in subsequent samples, because it is easier to genotype than to discover the variation. This is also true for structural variation detected from sequence data. However, the genotypes at known variable sites can only be inferred with uncertainty from low coverage data. Thus, statistical approaches that infer genotype likelihoods, test hypotheses, and estimate population parameters without requiring accurate genotypes are becoming popular. Unfortunately, the current implementations of these methods are intended to analyse only single nucleotide and short indel variation, and they usually assume that the two alleles in a heterozygous individual are sampled with equal probability. This is generally false for structural variants detected with paired ends or split reads. Therefore, the population genetics of structural variants cannot be studied, unless a painstaking and potentially biased genotyping is performed first. We present svgem, an expectation-maximization implementation to estimate allele and genotype frequencies, calculate genotype posterior probabilities, and test for Hardy-Weinberg equilibrium and for population differences, from the numbers of times the alleles are observed in each individual. Although applicable to single nucleotide variation, it aims at bi-allelic structural variation of any type, observed by either split reads or paired ends, with arbitrarily high allele sampling bias. We test svgem with simulated and real data from the 1000 Genomes Project. svgem makes it possible to use low-coverage sequencing data to study the population distribution of structural variants without having to know their genotypes. Furthermore, this advance allows the combined analysis of structural and nucleotide variation within the same genotype-free statistical framework, thus preventing biases introduced by genotype imputation.


LMTK3 deficiency causes pronounced locomotor hyperactivity and impairs endocytic trafficking.
LMTK3 belongs to the LMTK family of protein kinases that are predominantly expressed in the brain. Physiological functions of LMTK3 and other members of the LMTK family in the CNS remain unknown. In this study, we performed a battery of behavioral analyses using Lmtk3(-/-) mice and showed that these mice exhibit abnormal behaviors, including pronounced locomotor hyperactivity, reduced anxiety behavior, and decreased depression-like behavior. Concurrently, the dopamine metabolite levels and dopamine turnover rate are increased in the striata of Lmtk3(-/-) mice compared with wild-type controls. In addition, using cultured primary neurons from Lmtk3(-/-) mice, we found that LMTK3 is involved in the endocytic trafficking of N-methyl-d-aspartate receptors, a type of ionotropic glutamate receptor. Altered membrane traffic of the receptor in Lmtk3(-/-) neurons may underlie behavioral abnormalities in the mutant animals. Together, our data suggest that LMTK3 plays an important role in regulating locomotor behavior in mice.


Aqueous ionic liquids and their influence on peptide conformations: denaturation and dehydration mechanisms.
Low concentrated aqueous ionic liquids (ILs) and their influence on protein structures have attracted a lot of interest over the last few years. This can be mostly attributed to the fact that aqueous ILs, depending on the ion species involved, can be used as protein protectants or protein denaturants. Atomistic molecular dynamics (MD) simulations are performed in order to study the influence of different aprotic ILs on the properties of a short hairpin peptide. Our results reveal distinct binding and denaturation effects for 1-ethyl-3-methylimidazolium (EMIM) in combination with different anions, namely, chloride (CL), tetrafluoroborate (BF4) and acetate (ACE). The simulation outcomes demonstrate that the studied ILs with larger anions reveal a more pronounced accumulation behavior of the individual ion species around the peptide, which is accomplished by a stronger dehydration effect. We can relate these findings to the implications of the Kirkwood-Buff theory, which provides a thermodynamic explanation for the denaturation strength in terms of the IL accumulation behavior. The results for the spatial distribution functions, the binding energies and the local/bulk partition coefficients are in good agreement with metadynamics simulations in order to determine the energetically most stable peptide conformations. The free energy landscapes indicate a decrease of the denaturation strength in the order EMIM/ACE, EMIM/BF4 and EMIM/CL, which coincides with a decreasing size of the anion species. An analysis of the potential binding energies reveals that this effect is mainly of enthalpic nature.


Apoptosis-mediated in vivo toxicity of hydroxylated fullerene nanoparticles in soil nematode Caenorhabditis elegans.
Although a number of manufactured nanoparticles are applied for the medical and clinical purposes, the understanding of interaction between nanomaterials and biological systems are still insufficient. Using nematode Caenorhabditis elegans model organism, we here investigated the in vivo toxicity or safety of hydroxylated fullerene nanoparticles known to detoxify anti-cancer drug-induced oxidative damages in mammals. The survival ratio of C. elegans rapidly decreased by the uptake of nanoparticles from their L4 larval stage with resulting in shortened lifespan (20 d). Both reproduction rate and body size of C. elegans were also reduced after exposure to 100 μg mL(-1) of fullerol. We found ectopic cell corpses caused by apoptotic cell death in the adult worms grown with fullerol nanoparticles. By the mutation of core pro-apoptotic regulator genes, ced-3 and ced-4, these nanoparticle-induced cell death were significantly suppressed, and the viability of animals consequently increased despite of nanoparticle uptake. The apoptosis-mediated toxicity of nanoparticles particularly led to the disorder of digestion system in the animals containing a large number of undigested foods in their intestine. These results demonstrated that the water-soluble fullerol nanoparticles widely used in medicinal applications have a potential for inducing apoptotic cell death in multicellular organisms despite of their antioxidative detoxifying property.


Self-care Moderates the Relationship Between Symptoms and Health-Related Quality of Life in Heart Failure.
Physical symptoms and depression in heart failure (HF) are key drivers of health-related quality of life (HRQOL). Heart failure self-care behaviors are believed to influence how symptoms affect HRQOL. The goal of this study was to determine if HF self-care behaviors moderate the relationships between physical and depressive symptoms and HRQOL. In a cohort of adults with moderate to advanced HF, multivariate linear regression was used to evaluate the interaction between self-care behaviors (Self-care of HF index maintenance and management scales) and physical HF symptoms (HF Somatic Perception Scale) on emotional HRQOL (emotional dimension of Minnesota Living With HF Questionnaire). The interaction between self-care behaviors and depression (9-item Patient Health Questionnaire) was evaluated on physical HRQOL (physical dimension of Minnesota Living With HF Questionnaire). The mean age of the sample (N = 202) was 57 ± 13 years, 50% were women, and 61% had New York Heart Association class III or IV HF. Controlling for age, Seattle HF score, functional ability, and comorbidities, self-care maintenance and management moderated the relationship between physical HF symptoms and emotional HRQOL. Only self-care maintenance moderated the relationship between depression and physical HRQOL. In HF, HRQOL is dependent on both the severity of physical and depressive symptoms and the level of engagement in HF self-care behaviors. Future research should consider both self-care behaviors and symptoms when examining patient HRQOL.


Cannabidiol protects the liver from α-Amanitin-induced apoptosis and oxidative stress through the regulation of Nrf2.
α-Amanitin, the primary lethal toxin of Amanita, specifically targets the liver, causing oxidative stress, hepatocyte apoptosis, and irreversible liver damage. As little as 0.1 mg/kg of α-amanitin can be lethal for humans, and there is currently no effective antidote for α-amanitin poisoning. Cannabidiol is a non-psychoactive natural compound derived from Cannabis sativa that exhibits a wide range of anti-inflammatory, antioxidant, and anti-apoptotic effects. It may play a protective role in preventing liver damage induced by α-amanitin. To investigate the potential protective effects of cannabidiol on α-amanitin-induced hepatocyte apoptosis and oxidative stress, we established α-amanitin exposure models using C57BL/6J mice and L-02 cells in vitro. Our results showed that α-amanitin exposure led to oxidative stress, apoptosis, and DNA damage in both mouse hepatocytes and L-02 cells, resulting in the death of mice. We also found that cannabidiol upregulated the level of Nrf2 and antioxidant enzymes, alleviating apoptosis, and oxidative stress in mouse hepatocytes and L-02 cells and increasing the survival rate of mice. Our findings suggest that cannabidiol has hepatoprotective effects through the regulation of Nrf2 and antioxidant enzymes and may be a potential therapeutic drug for Amanita poisoning.


Tumors and tumor-like lesions of infrapatellar fat pad and surrounding tissues: A review of the literature.
The infrapatellar fat pad (IFP) is an intracapsular structure with critical importance both mechanically and endocrinologically. Its dysfunction must be considered while clinically investigating the symptoms arising from the knee joint. Infrapatellar fat pad may be subject to trauma, impingement, inflammation or tumoral formations. Although tumors arising within or adjacent to IFP are not extremely rare, the literature can only provide limited information about them. This article aims to briefly review the current literature on tumors and tumor-like lesions of the IFP and surrounding tissues; focusing on diagnosis and treatment management.


Extended SRC: undersampled face recognition via intraclass variant dictionary.
Sparse Representation-Based Classification (SRC) is a face recognition breakthrough in recent years which has successfully addressed the recognition problem with sufficient training images of each gallery subject. In this paper, we extend SRC to applications where there are very few, or even a single, training images per subject. Assuming that the intraclass variations of one subject can be approximated by a sparse linear combination of those of other subjects, Extended Sparse Representation-Based Classifier (ESRC) applies an auxiliary intraclass variant dictionary to represent the possible variation between the training and testing images. The dictionary atoms typically represent intraclass sample differences computed from either the gallery faces themselves or the generic faces that are outside the gallery. Experimental results on the AR and FERET databases show that ESRC has better generalization ability than SRC for undersampled face recognition under variable expressions, illuminations, disguises, and ages. The superior results of ESRC suggest that if the dictionary is properly constructed, SRC algorithms can generalize well to the large-scale face recognition problem, even with a single training image per class.


Chemical fluorescence-based dye staining for 3-dimensional histopathology analysis.
Tissue clearing for 3-dimensional (3D) imaging is increasingly utilized in many biomedical applications, including the pathological examination of human biopsy specimens. Although many protocols offer rapid and efficient tissue clearing (>1 d), immunofluorescence labeling of thick specimens is a highly time-consuming process. The use of low molecular weight chemical dyes has potential benefits in terms of speed and quality of 3D labeling. Accordingly, we tested several chemical dyes to assess their potential applications in 3D imaging. The combination of SYTO 16 and eosin (S&E) was found to be a potential fluorescent version of the hematoxylin-eosin (H&E) stain. Furthermore, picrosirius red (for collagen), Congo red (for senile plaques), and fluorescent Nissl (for neurons in the normal brain or blood vessels in the injured brain) stains can be used alone or in combination with antibody labeling. As chemical labeling requires a relatively short incubation time (<1 d), fluorescent chemical dyes could expedite the 3D imaging process.


[Effect of cleft palate syndrome on quality of life of elderly patients].
The study is devoted to the problem of congenital disorder--cleft palate in elderly population. This theme is almost not investigated in the Russian Federation, whereas such studies are periodically made abroad and foreign investigations describe tasks of rehabilitation of this group of patients including their age features. Main characteristics of cleft palate syndrome and its influence on quality of life are described in the article.


Asthma, wheezy bronchitis, and atopy across two generations.
Although the prevalence of asthma has risen significantly during the last 30 yr, it is not clear whether this has occurred primarily in persons with a strong genetic predisposition to asthma and atopy or in other sections of the population. We have investigated outcomes in children of nuclear families selected through probands previously characterized by studies in 1964 and 1989 as having histories of persistent childhood onset atopic asthma, transient childhood wheezy bronchitis, and no respiratory symptoms or atopy. Children of wheezy bronchitic probands had a significantly better symptomatic outcome in adolescence, irrespective of the atopic status of the parent proband, than do children of either asthmatic or asymptomatic probands, suggesting that this may be a syndrome that shows familial aggregation and is distinct from asthma. Total serum IgE levels were significantly lower in children of nonatopic asymptomatic probands, including those with wheezing symptoms. In contrast children of nonatopic asymptomatic probands had an unexpectedly high prevalence of wheezing (33%), positive skin prick tests (56%), and positive specific serum IgE to common allergens (48%) that was similar to that found in children of atopic asthmatic probands. Our findings support the concept that wheezy bronchitis is a separate syndrome from atopic asthma. High total serum IgE levels within our population appear to be an important marker of genetic predisposition to atopy. Our data also suggest that much of the increase in asthma prevalence is associated with specific IgE sensitization and is occurring in persons previously considered to be at low risk of developing asthma or atopy.


Development and Properties of New Mullite Based Refractory Grog.
The presented study is focused on optimization and characterization of a high-alumina refractory aggregate based on natural raw materials-kaolins, claystone, and mullite dust by-product (used to increase the alumina and mullite contents, respectively). In total, four individual formulas with the Al2O3 contents between 45 and 50 wt.% were designed; the samples were subsequently fired, both in a laboratory oven and an industrial tunnel furnace. The effects of repeated firing were examined during industrial pilot tests. Mineral and chemical compositions and microstructures, of both the raw materials and designed aggregates, were thoroughly investigated by the means of X-ray fluorescence spectroscopy, powder X-ray diffraction, and optical and scanning electron microscopies. Porosity, mineral composition, and mullite crystal-size development during the firing process were also studied. Based on the acquired results, the formula with the perspective to be used as a new mullite grog, featuring similar properties as the available commercial products, however, with reduced production expenses, was selected. The quality of grog determines to a large extent the properties of the final product. Hence, optimization of aggregates for specific refractories is of a great importance. The production of engineered aggregates provides the opportunity to utilize industrial by-products.


A unified model for simulating liquid and gas phase, intermolecular energy transfer: N₂ + C₆F₆ collisions.
Molecular dynamics simulations were used to study relaxation of a vibrationally excited C6F6* molecule in a N2 bath. Ab initio calculations were performed to develop N2-N2 and N2-C6F6 intermolecular potentials for the simulations. Energy transfer from "hot" C6F6 is studied versus the bath density (pressure) and number of bath molecules. For the large bath limit, there is no heating of the bath. As C6F6* is relaxed, the average energy of C6F6* is determined versus time, i.e., ⟨E(t)⟩, and for each bath density ⟨E(t)⟩ is energy dependent and cannot be fit by a single exponential. In the long-time limit C6F6 is fully equilibrated with the bath. For a large bath and low pressures, the simulations are in the fixed temperature, independent collision regime and the simulation results may be compared with gas phase experiments of collisional energy transfer. The derivative d[⟨E(t)⟩]/dt divided by the collision frequency ω of the N2 bath gives the average energy transferred from C6F6* per collision ⟨ΔE(c)⟩, which is in excellent agreement with experiment. For the ~100-300 ps simulations reported here, energy transfer from C6F6* is to N2 rotation and translation in accord with the equipartition model, with no energy transfer to N2 vibration. The energy transfer dynamics from C6F6* is not statistically sensitive to fine details of the N2-C6F6 intermolecular potential. Tests, with simulation ensembles of different sizes, show that a relatively modest ensemble of only 24 trajectories gives statistically meaningful results.


Progress in the treatment of severe mitral regurgitation.
Organic mitral regurgitation (MR) is prevalent in the general population. Disease progression, involving potentially irreversible left ventricular dysfunction, implies a poor prognosis for patients who do not receive appropriate treatment. Immediate rescue surgery is indicated in those with severe MR in whom subclinical left ventricular dysfunction is suggested by echocardiographic measurements or the presence of symptoms, however minor. Patients whose symptomatology is unclear should be evaluated by exercise testing. Not all forms of severe organic MR are the same: the presence of risk factors in patients with severe asymptomatic MR and preserved ventricular function indicates a suboptimal prognosis over the medium-to-long term and should prompt early mitral repair if there is a low surgical risk and the probability of a successful repair is >90-95%. The patient should be referred to a specialized surgical center if necessary. Appropriate training of surgeons in mitral repair is essential. Ischemic MR carries a worse prognosis and the risk of surgery is higher. Consequently, treatment decisions must be patient-specific and take into account the possibility of repair, the risk of surgery, and the need for concomitant surgical revascularization. New percutaneous approaches to mitral repair are being developed for selected patient groups.


Identification of motifs that are conserved in 12 Drosophila species and regulate midline glia vs. neuron expression.
Functional complexity of the central nervous system (CNS) is reflected by the large number and diversity of genes expressed in its many different cell types. Understanding the control of gene expression within cells of the CNS will help reveal how various neurons and glia develop and function. Midline cells of Drosophila differentiate into glial cells and several types of neurons and also serve as a signaling center for surrounding tissues. Here, we examine regulation of the midline gene, wrapper, required for both neuron-glia interactions and viability of midline glia. We identify a region upstream of wrapper required for midline expression that is highly conserved (87%) between 12 Drosophila species. Site-directed mutagenesis identifies four motifs necessary for midline glial expression: (1) a Single-minded/Tango binding site, (2) a motif resembling a pointed binding site, (3) a motif resembling a Sox binding site, and (4) a novel motif. An additional highly conserved 27 bp are required to restrict expression to midline glia and exclude it from midline neurons. These results suggest short, highly conserved genomic sequences flanking Drosophila midline genes are indicative of functional regulatory regions and that small changes within these sequences can alter the expression pattern of a gene.


MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary.
The midbrain-hindbrain boundary (MHB) is a long-lasting organizing center in the vertebrate neural tube that is both necessary and sufficient for the ordered development of midbrain and anterior hindbrain (midbrain-hindbrain domain, MH). The MHB also coincides with a pool of progenitor cells that contributes neurons to the entire MH. Here we show that the organizing activity and progenitor state of the MHB are co-regulated by a single microRNA, miR-9, during late embryonic development in zebrafish. Endogenous miR-9 expression, initiated at late stages, selectively spares the MHB. Gain- and loss-of-function studies, in silico predictions and sensor assays in vivo demonstrate that miR-9 targets several components of the Fgf signaling pathway, thereby delimiting the organizing activity of the MHB. In addition, miR-9 promotes progression of neurogenesis in the MH, defining the MHB progenitor pool. Together, these findings highlight a previously unknown mechanism by which a single microRNA fine-tunes late MHB coherence via its co-regulation of patterning activities and neurogenesis.


Chromogranin A polymorphisms are associated with hypertensive renal disease.
Chromogranin A is released together with epinephrine and norepinephrine from catecholaminergic cells. Specific endopeptidases cleave chromogranin A into biologically active peptide fragments, including catestatin, which inhibits catecholamine release. Previous studies have suggested that a deficit in this sympathetic "braking" system might be an early event in the pathogenesis of human hypertension. Whether chromogranin A (CHGA) polymorphisms predict end-organ complications of hypertension, such as end-stage renal disease, is unknown. Among blacks, we studied common genetic variants spanning the CHGA locus in 2 independent case-control studies of hypertensive ESRD. Two haplotypes were significantly more frequent among subjects with hypertensive ESRD: 1) in the promoter (5') region, G-462A-->T-415C-->C-89A, haplotype ATC (adjusted odds ratio = 2.65; P = 0.037), and 2) at the 3'-end, C11825T (3'-UTR, C+87T)-->G12602C, haplotype TC (adjusted odds ratio = 2.73, P = 0.0196). Circulating levels of catestatin were lower among those with hypertensive ESRD than controls, an unexpected finding given that peptide levels are usually elevated in ESRD because of reduced renal elimination. We found that the 3'-UTR + 87T variant decreased reporter gene expression, providing a possible mechanistic explanation for diminished catestatin. In summary, common variants in chromogranin A associate with the risk of hypertensive ESRD in blacks.


The cytoprotective role of the Keap1-Nrf2 pathway.
An elaborate network of highly inducible proteins protects aerobic cells against the cumulative damaging effects of reactive oxygen intermediates and toxic electrophiles, which are the major causes of neoplastic and chronic degenerative diseases. These cytoprotective proteins share common transcriptional regulation, through the Keap1-Nrf2 pathway, which can be activated by various exogenous and endogenous small molecules (inducers). Inducers chemically react with critical cysteine residues of the sensor protein Keap1, leading to stabilisation and nuclear translocation of transcription factor Nrf2, and ultimately to coordinate enhanced expression of genes coding for cytoprotective proteins. In addition, inducers inhibit pro-inflammatory responses, and there is a linear correlation spanning more than six orders of magnitude of concentrations between inducer and anti-inflammatory activity. Genetic deletion of transcription factor Nrf2 renders cells and animals much more sensitive to the damaging effects of electrophiles, oxidants and inflammatory agents in comparison with their wild-type counterparts. Conversely, activation of the Keap1-Nrf2 pathway allows survival and adaptation under various conditions of stress and has protective effects in many animal models. Cross-talks with other signalling pathways broadens the role of the Keap1-Nrf2 pathway in determining the fate of the cell, impacting fundamental biological processes such as proliferation, apoptosis, angiogenesis and metastasis.


Reaction of soluble penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus with beta-lactams and acyclic substrates: kinetics in homogeneous solution.
The kinetics of reaction of solubilized penicillin-binding protein 2a (sPBP2a) of methicillin-resistant Staphylococcus aureus with a variety of beta-lactams and acyclic species was studied in homogeneous aqueous solution at 37 degreesC in 25 mM Hepes buffer, pH7.0, containing 1 M NaCl. Under these conditions, but not at lower salt concentrations, protein precipitation did not occur either during or after the reaction. The reactions of beta-lactams in general could be monitored by competition with a chromophoric beta-lactam, nitrocefin, or directly in certain cases by protein fluorescence. Rate constants for reaction of a wide variety of beta-lactams are reported. The interactions are characterized by a slow second-order acylation reaction followed by a slower deacylation. For example, the rate constants for benzylpenicillin were 12 M-1.s-1 and 3x10(-5) s-1 respectively. The acylation is slow in comparison with those of normal non-resistant high-molecular-mass penicillin-binding proteins. sPBP2a also seemed to catalyse the slow hydrolysis of a variety of acyclic depsipeptides but not that of a d-Ala-d-Ala peptide. The reactions with certain depsipeptides also led to protein precipitation. These reactions were, however, not affected by prior blockage of the beta-lactam-binding site by benzylpenicillin and thus might take place elsewhere on the enzyme. Two classes of potential transition- state analogue inhibitors, phosphonate monoesters and boronates, seemed to have little effect on the rate of reaction of sPBP2a with nitrocefin and therefore seem to have little affinity for the beta-lactam-binding/D,D-peptidase site.


Genetic diversity and potential vectors and reservoirs of Cucurbit aphid-borne yellows virus in southeastern Spain.
The genetic variability of a Cucurbit aphid-borne yellows virus (CABYV) (genus Polerovirus, family Luteoviridae) population was evaluated by determining the nucleotide sequences of two genomic regions of CABYV isolates collected in open-field melon and squash crops during three consecutive years in Murcia (southeastern Spain). A phylogenetic analysis showed the existence of two major clades. The sequences did not cluster according to host, year, or locality of collection, and nucleotide similarities among isolates were 97 to 100 and 94 to 97% within and between clades, respectively. The ratio of nonsynonymous to synonymous nucleotide substitutions reflected that all open reading frames have been under purifying selection. Estimates of the population's genetic diversity were of the same magnitude as those previously reported for other plant virus populations sampled at larger spatial and temporal scales, suggesting either the presence of CABYV in the surveyed area long before it was first described, multiple introductions, or a particularly rapid diversification. We also determined the full-length sequences of three isolates, identifying the occurrence and location of recombination events along the CABYV genome. Furthermore, our field surveys indicated that Aphis gossypii was the major vector species of CABYV and the most abundant aphid species colonizing melon fields in the Murcia (Spain) region. Our surveys also suggested the importance of the weed species Ecballium elaterium as an alternative host and potential virus reservoir.


Regional differences in early stage bladder cancer care and outcomes.
In part because of its protracted natural history, bladder cancer is among the most expensive malignancies from diagnosis to death. In light of the uncertainty surrounding the optimal care, we evaluated regional differences in initial treatment intensity and outcomes among patients with early stage (ie, superficial) bladder cancer. We identified 20,328 patients diagnosed with early stage bladder cancer between 1992 and 2002 using SEER-Medicare data. Patients were assigned to a hospital service area (HSA) according to their ZIP code and followed longitudinally through 2005. Next, HSAs were sorted into equally sized groups according to their average treatment intensity, as measured by all Medicare payments for bladder cancer in the first 2 years after diagnosis. We assessed relationships between regional treatment intensity and patient outcomes, including the use of major interventions and survival. Medicare payments were nearly $4000 USD per capita more in high vs. low treatment intensity regions ($5594 to $9554 USD). High-spending regions used more bladder cancer-related services and major interventions than low-spending regions (all P < .001). However, greater spending did not improve survival. In fact, patients in lower spending regions had superior cancer-specific survival (adjusted hazard ratio, low vs. high 0.83; 95% CI .71-.97). Among patients with early stage bladder cancer, those in high-intensity regions do not benefit in terms of survival or in the avoidance of major interventions. Although the cause is unclear, patients residing in low-spending regions are less likely to die of their disease, while avoiding potentially unnecessary and costly care.


Cryobanking of viable biomaterials: implementation of new strategies for conservation purposes.
Cryobanking, the freezing of biological specimens to maintain their integrity for a variety of anticipated and unanticipated uses, offers unique opportunities to advance the basic knowledge of biological systems and their evolution. Notably, cryobanking provides a crucial opportunity to support conservation efforts for endangered species. Historically, cryobanking has been developed mostly in response to human economic and medical needs - these needs must now be extended to biodiversity conservation. Reproduction technologies utilizing cryobanked gametes, embryos and somatic cells are already vital components of endangered species recovery efforts. Advances in modern biological research (e.g. stem cell research, genomics and proteomics) are already drawing heavily on cryobanked specimens, and future needs are anticipated to be immense. The challenges of developing and applying cryobanking for a broader diversity of species were addressed at an international conference held at Trier University (Germany) in June 2008. However, the magnitude of the potential benefits of cryobanking stood in stark contrast to the lack of substantial resources available for this area of strategic interest for biological science - and society at large. The meeting at Trier established a foundation for a strong global incentive to cryobank threatened species. The establishment of an Amphibian Ark cryobanking programme offers the first opportunity for global cooperation to achieve the cryobanking of the threatened species from an entire vertebrate class.


[The prognostic role of gamma-glutamyltransferase for cardiovascular events].
Serum gamma-glutamyltransferasis activity is a low-cost, highly sensitive laboratory test. Though it is currently considered as an index of hepato-biliary dysfunction and alcohol abuse, recent epidemiological and pathologic studies have proposed its independent role in the pathogenesis and clinical evolution of cardiovascular diseases brought by atherosclerosis, associated with a gamma-glutamyltransferase-linked prooxidant effect of glutathione catabolism within the plaque.


The alteration landscape of the cerebral cortex.
Growing evidence is challenging the assumption that brain disorders are diagnostically clear-cut categories. Transdiagnostic studies show that a set of cerebral areas is frequently altered in a variety of psychiatric as well as neurological syndromes. In order to provide a map of the altered areas in the pathological brain we devised a metric, called alteration entropy (A-entropy), capable of denoting the "structural alteration variety" of an altered region. Using the whole voxel-based morphometry database of BrainMap, we were able to differentiate the brain areas exhibiting a high degree of overlap between different neuropathologies (or high value of A-entropy) from those exhibiting a low degree of overlap (or low value of A-entropy). The former, which are parts of large-scale brain networks with attentional, emotional, salience, and premotor functions, are thought to be more vulnerable to a great range of brain diseases; while the latter, which include the sensorimotor, visual, inferior temporal, and supramarginal regions, are thought to be more informative about the specific impact of brain diseases. Since low A-entropy areas appear to be altered by a smaller number of brain disorders, they are more informative than the areas characterized by high values of A-entropy. It is also noteworthy that even the areas showing low values of A-entropy are substantially altered by a variety of brain disorders. In fact, no cerebral area appears to be only altered by a specific disorder. Our study shows that the overlap of areas with high A-entropy provides support for a transdiagnostic approach to brain disorders but, at the same time, suggests that fruitful differences can be traced among brain diseases, as some areas can exhibit an alteration profile more specific to certain disorders than to others.


Assessment of the graduate studies background of CLS faculty in university-based programs.
To identify the degrees held and the graduate majors or fields of study for faculty teaching full-time and part-time in university-based, baccalaureate-degree clinical laboratory science/medical technology (CLS/MT) programs. A survey and letter of project explanation was sent electronically to the 110 program directors of NAACLS-accredited university-based CLS/MT programs in the United States in May, 2003. Program directors were requested to provide for each full-time and part-time faculty member the following information: titles for all degrees held, major/field of study for each degree held, all specialist certifications held, all other formal degrees or certificates held, and all courses/areas taught in the CLS curriculum. Information was provided on 288 faculty in 52 CLS/MT programs, for a response rate of 47%. The majority of faculty (75%) described were full-time. A doctorate was held by 43% of the reported faculty, while 46% held a master's degree as their highest degree, and 11 % only a BS in CLS or in biology plus a certificate from a hospital-based CLS/MT program. Graduate degrees in a science major or field represented 52% of the degrees held by the reported faculty, while 48% of the graduate degrees were in education, public health, or administration. Only 13% of the reported faculty held master's degrees specifically in CLS. Detailed results are provided for degrees held, majors/fields of study, and specialist certifications by specific courses/areas of the curriculum taught. The results of this survey indicate that many faculty teaching in university-based CLS/MT programs are extending their preparation as scientists to the graduate level. This should prepare these faculty for their responsibilities in not only teaching but also research. A case cannot be made that a doctorate, as opposed to a master's degree, is viewed as the 'terminal degree' as less than half of the reported faculty in this study as well as others, held a doctorate. The results reported provide a national perspective on the graduate backgrounds of CLS faculty for comparison to an individual program's faculty during programmatic or institutional accreditation reviews.


The effects of olive oil consumption on cognitive performance: a systematic review.
The Mediterranean diet is marked by the regular intake of olive oil, which may play a role in preventing and protecting against cognitive deterioration and dementia. The strength of these effects have been examined by several recent randomized controlled trials (RCTs), but their findings have not been consistent. In light of this inconsistency, the present study performed a systematic review to examine the relationship between the consumption of olive oil and cognition. The Web of Science, Scopus, PubMed, and Google Scholar were systematically searched up to August 11, 2023. The review included RCTs, cross-sectional studies, cohort studies and case-control studies that explored the impact of olive oil consumption on cognitive performance among those older than 55 years old. Studies were excluded if they employed a design other than those mentioned above, involved participants under 55 years old, or did not specifically examine the cognitive effects of olive oil consumption. The quality of the included studies were measured using the Cochrane risk-of-bias tool and the Newcastle Ottawa Scale checklists. Eleven studies were identified, which were comprised of four cross-sectional studies, four prospective cohort studies and three RCTs. The cohort studies and RCTs consistently found that olive oil consumption had a favorable effect on cognitive performance across a number of cognitive domains over time. Similarly, all of the cross-sectional studies reported that the consumption of olive oil was positively associated with cognitive health. The consumption of olive oil was found to enhance cognitive functioning and to reduce cognitive decline. Further large-scale investigations are required to strengthen this conclusion.


Psychometrics in action, science as practice.
Practitioners in health sciences education and assessment regularly use a range of psychometric techniques to analyse data, evaluate models, and make crucial progression decisions regarding student learning. However, a recent editorial entitled "Is Psychometrics Science?" highlighted some core epistemological and practical problems in psychometrics, and brought its legitimacy into question. This paper attempts to address these issues by applying some key ideas from history and philosophy of science (HPS) discourse. I present some of the conceptual developments in HPS that have bearing on the psychometrics debate. Next, by shifting the focus onto what constitutes the practice of science, I discuss psychometrics in action. Some incorrectly conceptualize science as an assemblage of truths, rather than an assemblage of tools and goals. Psychometrics, however, seems to be an assemblage of methods and techniques. Psychometrics in action represents a range of practices using specific tools in specific contexts. This does not render the practice of psychometrics meaningless or futile. Engaging in debates about whether or not we should regard psychometrics as 'scientific' is, however, a fruitless enterprise. The key question and focus should be whether, on what grounds, and in what contexts, the existing methods and techniques used by psychometricians can be justified or criticized.


Transactions of an international conference. Worldwide concern: better dental care for more people. An international collaborative study. How the study was designed.
The study originated from the common need felt by the United States Public Health Service and the World Health Organization for objective information about various national dental care delivery systems and their effectiveness in the societies in which they were used. The relationships between consumers, providers and administrators within each system were emphasized rather than the comparison between systems since each operated within a specific biological and ecological environment. Six systems all of which had been in existence for at least twenty years were originally selected for study to encompass those dependent on a majority of government or private enterprise, use or non-use of auxiliaries, differeing systems of financing and of definition of target groups for receipt of services. The countries originally taking part were Australia, the Federal Republic of Germany, Japan, New Zealand, Norway and Bulgaria, though Bulgaria withdrew early in 1975.


Ionization of acids on the quasi-liquid layer of ice.
The ice quasi-liquid layer (QLL) forms on ice surfaces below the bulk ice melting temperature. It is abundant in the atmosphere, and its importance for atmospheric chemistry is recognized. In the present work, we have studied the microscopic mechanisms of acid ionization on the QLL using ab initio molecular dynamics. The model system QLL is established by nanosecond time scale simulations with empirical force fields, while the reactivity of the QLL is studied using ab initio molecular dynamics. Our ab initio simulations reveal that QLL is reactive, exhibiting stable crystalline point defects, which contribute to efficient acid solvation, ionization, and proton transfer. We study in detail deuterated hydrogen iodide (DI) and nitric acid (DNO3). Ionization in both cases benefits from the abundance of weakly bonded hydrogen-bond single-acceptor double-donor water molecular species available on the QLL in high relative concentration. Picosecond time scale ionization is demonstrated for both molecular species. Our results suggest efficient reactivity of acid ionization and proton transfer at temperature ranges appropriate for the upper troposphere and lower stratosphere.


Choosing MUSE: Validation of a Low-Cost, Portable EEG System for ERP Research.
In recent years there has been an increase in the number of portable low-cost electroencephalographic (EEG) systems available to researchers. However, to date the validation of the use of low-cost EEG systems has focused on continuous recording of EEG data and/or the replication of large system EEG setups reliant on event-markers to afford examination of event-related brain potentials (ERP). Here, we demonstrate that it is possible to conduct ERP research without being reliant on event markers using a portable MUSE EEG system and a single computer. Specifically, we report the results of two experiments using data collected with the MUSE EEG system-one using the well-known visual oddball paradigm and the other using a standard reward-learning task. Our results demonstrate that we could observe and quantify the N200 and P300 ERP components in the visual oddball task and the reward positivity (the mirror opposite component to the feedback-related negativity) in the reward-learning task. Specifically, single sample t-tests of component existence (all p's < 0.05), computation of Bayesian credible intervals, and 95% confidence intervals all statistically verified the existence of the N200, P300, and reward positivity in all analyses. We provide with this research paper an open source website with all the instructions, methods, and software to replicate our findings and to provide researchers with an easy way to use the MUSE EEG system for ERP research. Importantly, our work highlights that with a single computer and a portable EEG system such as the MUSE one can conduct ERP research with ease thus greatly extending the possible use of the ERP methodology to a variety of novel contexts.


Transcriptional and translational effects of intronic CAPN3 gene mutations.
Variants of unknown significance in the CAPN3 gene constitute a significant challenge for genetic counselling. Despite the frequency of intronic nucleotide changes in this gene (15-25% of all mutations), so far their pathogenicity has only been inferred by in-silico analysis, and occasionally, proven by RNA analysis. In this study, 5 different intronic variants (one novel) that bioinformatic tools predicted would affect RNA splicing, underwent comprehensive studies which were designed to prove they are disease-causing. Muscle mRNA from 15 calpainopathy patients was analyzed by RT-PCR and splicing-specific-PCR tests. We established the previously unrecognized pathogenicity of these mutations, which caused aberrant splicing, most frequently by the activation of cryptic splicing sites or, occasionally, by exon skipping. The absence or severe reduction of protein demonstrated their deleterious effect at translational level. We concluded that bioinformatic tools are valuable to suggest the potential effects of intronic variants; however, the experimental demonstration of the pathogenicity is not always easy to do even when using RNA analysis (low abundance, degradation mechanisms), and it might not be successful unless splicing-specific-PCR tests are used. A comprehensive approach is therefore recommended to identify and describe unclassified variants in order to offer essential data for basic and clinical geneticists.