Defining stem and progenitor cells within adipose tissue.
Adipose tissue-derived stem cells (ADSC) are routinely isolated from the stromal vascular fraction (SVF) of homogenized adipose tissue. Freshly isolated ADSC display surface markers that differ from those of cultured ADSC, but both cell preparations are capable of multipotential differentiation. Recent studies have inferred that these progenitors may reside in a perivascular location where they appeared to coexpress CD34 and smooth muscle actin (alpha-SMA) but not CD31. However, these studies provided only limited histological evidence to support such assertions. In the present study, we employed immunohistochemistry and immunofluorescence to define more precisely the location of ADSC within human adipose tissue. Our results show that alpha-SMA and CD31 localized within smooth muscle and endothelial cells, respectively, in all blood vessels examined. CD34 localized to both the intima (endothelium) and adventitia neither of which expressed alpha-SMA. The niche marker Wnt5a was confined exclusively to the vascular wall within mural smooth muscle cells. Surprisingly, the widely accepted mesenchymal stem cell marker STRO-1 was expressed exclusively in the endothelium of capillaries and arterioles but not in the endothelium of arteries. The embryonic stem cell marker SSEA1 localized to a pericytic location in capillaries and in certain smooth muscle cells of arterioles. Cells expressing the embryonic stem cell markers telomerase and OCT4 were rare and observed only in capillaries. Based on these findings and evidence gathered from the existing literature, we propose that ADSC are vascular precursor (stem) cells at various stages of differentiation. In their native tissue, ADSC at early stages of differentiation can differentiate into tissue-specific cells such as adipocytes. Isolated, ADSC can be induced to differentiate into additional cell types such as osteoblasts and chondrocytes.


The association between depression and the cortisol awakening response is moderated by loneliness in men from a non-clinical sample.
Previous studies investigating cortisol levels in people with depression or depressive symptoms have provided mixed findings. It has been suggested that the difficulty to generalize findings across studies in this field might be related to interindividual variability in experiencing depressive symptoms in terms of clinical and social contexts. Therefore, in the present study we aimed to test the association of morning cortisol levels and depressive symptoms in a non-clinical sample of young men taking into consideration the level of perceived loneliness. We hypothesized that the level of loneliness might moderate the association between morning cortisol levels and depressive symptoms. A total of 102 participants (aged 29.9 ± 5.0 years) completed questionnaires measuring the levels of depressive and anxiety symptoms, perceived stress, and loneliness. Cortisol levels were determined in four morning samples of saliva. There were significant positive correlations of the cortisol awakening response (CAR) and the mean increase in cortisol levels during the measurement period (MnInc) with the levels of depressive symptoms and loneliness. Moreover, a significant association of the depressive symptoms by loneliness interaction with the CAR and the MnInc was found. Specifically, the correlation of depressive symptoms with the CAR and the MnInc appeared to be significant and negative at high levels of loneliness. No significant association between depressive symptoms and the CAR was observed in men with low levels of loneliness. There were no significant associations of depressive symptoms, loneliness and the depressive symptoms by loneliness interaction with cortisol levels at awakening. In conclusion, findings from the present study indicate the importance of social contexts in understanding the association between altered activity of the hypothalamic-pituitary-adrenal axis and depressive symptoms in men.


Helminth parasites of fish and shellfish from the Santa Gilla Lagoon in southern Sardinia, Italy.
An extensive survey of helminth parasites in fish and shellfish species from Santa Gilla, a brackish water lagoon in southern Sardinia (western Mediterranean), resulted in the identification of 69 helminth parasite taxa and/or species from 13 fish species (n= 515) and seven bivalve species (n= 2322) examined between September 2001 and July 2011. The list summarizes information on the helminth parasites harboured by fish and molluscs contained in the available literature. Digenea species (37), both adults and larvae, dominated the parasite fauna, whereas Cestoda were the least represented class (three species). Monogenea, Nematoda and Acanthocephala were present with 17, 6 and 6 species, respectively, which were mainly adults. The most widespread parasite species was the generalist Contracaecum rudolphii A (Nematoda). Other species, such as the Haploporidae and Ascocotyle (Phagicola) spp. 1 and 2 (Digenea), showed a high family specificity in Mugilidae. Importantly, the study recorded the occurrence of potential zoonotic agents, such as Heterophyes heterophyes, Ascocotyle (Phagicola) spp. and C. rudolphii A, the latter two reaching the highest indices of infection in the highly marketed fish grey mullet and sea bass, respectively. The highest parasite richness was detected in Dicentrarchus labrax, which harboured 17 helminth species, whereas the lowest value was observed in Atherina boyeri, infected by only three species. The list includes the first geographical record in Italian coastal waters of Robinia aurata and Stictodora sawakinensis, and 30 reports of new host-parasite complexes, including the larval stages of Ascocotyle (Ascocotyle) sp. and Southwellina hispida in D. labrax.


CRISPR/Cas-mediated targeted mutagenesis in Daphnia magna.
The water flea Daphnia magna has been used as an animal model in ecology, evolution, and environmental sciences. Thanks to the recent progress in Daphnia genomics, genetic information such as the draft genome sequence and expressed sequence tags (ESTs) is now available. To investigate the relationship between phenotypes and the available genetic information about Daphnia, some gene manipulation methods have been developed. However, a technique to induce targeted mutagenesis into Daphnia genome remains elusive. To overcome this problem, we focused on an emerging genome editing technique mediated by the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system to introduce genomic mutations. In this study, we targeted a functionally conserved regulator of eye development, the eyeless gene in D. magna. When we injected Cas9 mRNAs and eyeless-targeting guide RNAs into eggs, 18-47% of the survived juveniles exhibited abnormal eye morphology. After maturation, up to 8.2% of the adults produced progenies with deformed eyes, which carried mutations in the eyeless loci. These results showed that CRISPR/Cas system could introduce heritable mutations into the endogenous eyeless gene in D. magna. This is the first report of a targeted gene knockout technique in Daphnia and will be useful in uncovering Daphnia gene functions.


Evidence for the direct involvement of transmembrane region 6 of the lutropin/choriogonadotropin receptor in activating Gs.
The luteinizing hormone/chorionic gonadotropin receptor (LHR) is a heptahelical receptor that interacts primarily with Gs. Previous studies by others have shown that some forms of familial male precocious puberty are associated with mutations of the human LHR in the sixth transmembrane region that result in constitutive activation of the receptor. This study demonstrates that a peptide corresponding to the lower portion of the sixth transmembrane region of the LHR can significantly activate adenylyl cyclase activity. Experiments with membranes derived from wild-type versus cyc- S49 cells demonstrate that the stimulation of cyclase by this peptide is due to an activation of Gs. As such, our data demonstrate a direct role for transmembrane region 6 of the rat LHR in activating Gs and therefore raise the possibility that mutations in transmembrane region 6 of the LHR may directly affect the coupling of the receptor to Gs. Significantly, these data are the first to demonstrate the ability of a transmembrane portion of a G protein-coupled receptor, in the absence of any contributions from an intracellular loop region, to activate a G protein.


Frequent silencing of popeye domain-containing genes, BVES and POPDC3, is associated with promoter hypermethylation in gastric cancer.
The Popeye domain-containing (POPDC) genes BVES, POPDC2 and POPDC3 encode proteins that regulate cell-cell adhesion and cell migration during development. Herein, we report the frequent downregulation of BVES and POPDC3 by promoter hypermethylation in gastric cancer. POPDC expression in 11 gastric cancer cell lines and 96 paired gastric tumor and normal adjacent tissues was analyzed with quantitative reverse transcription-polymerase chain reaction. The methylation status of BVES and POPDC3 was analyzed with methylated DNA immunoprecipitation sequencing, bisulfite sequencing and pyrosequencing. Expression of BVES and POPDC3 was downregulated in 73% of the gastric cancer cell lines and in 69% (BVES) and 87% (POPDC3) of the gastric cancer tissues. The BVES and POPDC3 promoter regions were hypermethylated in the gastric cancer cell lines in which they were silenced. Combined treatment with a DNA methylation inhibitor and a histone deacetylase inhibitor strongly induced BVES and POPDC3 expression. BVES and POPDC3 were hypermethylated in 69% (BVES) and 64% (POPDC3) of the gastric cancer tissues. We knocked down POPDC3 expression with short hairpin RNAs and examined the consequences on cell migration and invasion. Knockdown of POPDC3 in SNU-216 cells caused increased cell migration and invasion. Thus, epigenetic inactivation of BVES and POPDC3 occurs frequently in gastric tumors and may promote gastric cancer cell migration and invasion.


Electrocardiographic findings of acute organophosphate poisoning.
In this study, we evaluated 85 patients who presented to our Emergency Department with organophosphate (OP) poisoning and discuss their associated electrocardiographic (ECG) abnormalities. Over a period of 3 years, 85 patients with OP poisoning were included in this retrospective study. ECG analysis included the rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals. The mean age was 32.2 +/- 14.9 years. Sixty percent of the patients were female. The mean corrected QT interval (QTc interval) was 0.435 +/- 0.052 s. Prolongation of the QTc interval (55.5%) was the most common ECG abnormality, followed by sinus tachycardia (31.8%). Elevation of the ST segment and low amplitude T waves were seen in 15 cases (17.6%). Patients with OP poisoning might reveal ECG abnormalities such as QTc interval prolongation or non-specific ST-T changes. QTc interval prolongation cannot be used as a unique predictive factor in determining short-term prognosis in OP poisoning. We found no clear relation between OP poisoning-related malignant ventricular dysrhythmia and QTc interval.


[Vaccination status of medical and dental students].
Infectious diseases are still a worldwide health problem, and hence physicians are responsible for providing the population with sufficient vaccinations. Until now, however, comprehensive studies on vaccination behaviour in German medical/dental students, the future physicians/dentists, are lacking. The study analysed vaccinations of medical/dental students against tetanus, diphtheria, poliomyelitis, hepatitis A + B and tried to find possible influences on the vaccination behaviour. 126 medical and 99 dental students participated by working on an anonymous questionnaire related to sociodemographic data, smoking/drinking habits, drug abuse and vaccinations. The response rate was between 76 and 85%. Altogether, the investigated students were not sufficiently vaccinated. Nevertheless, they were better vaccinated than a normal reference sample. Except for a significantly better immunisation against hepatitis B in dental students, no differences between medical and dental students were found. In comparison to male students, female students presented better immunisation. On the other hand, students from the former West Germany, smoking students and students who are taking illegal drugs, were more insufficiently immunised than the other students. To optimise vaccinations in future physicians and dentists, medical/dental education should focus more on infectious diseases and knowledge about vaccinations. This would help to protect future physicians and dentists against preventable infectious diseases. Additionally, they are better skilled to prevent infectious diseases by providing the population with information and vaccinations.


Genetic markers of osteoarthritis.
Osteoarthritis (OA) is a chronic arthropathy, in which cartilage loss, osteophyte formation, and subchondral bone sclerosis lead to pain, disability, and a reduction in quality of life. OA is a multifactorial disease and OA cases are affected by both genetics and environment to varying degrees. Strong familial aggregation and heritabilities have been reported for OA at the hip, knee, hand and spine. Candidate gene studies and genome-wide linkage studies have identified genes in the bone morphogenetic pathway (e.g. GDF5), the thyroid regulation pathway (DIO2), apoptotic pathways as involved in genetic risk of large joint OA. Genome wide association studies have reported structural genes (COL6A4/DVWA), inflammation related genes (PTGS2/PLA2G4A) and a locus on chr 7q22 associated with knee OA and a gene involved transcriptional regulation (A2BP1) to be associated with hand OA. During the coming years, as additional genetic and functional studies further define the genetic architecture of OA and the underlying molecular mechanisms, additional targets for novel therapies and improved diagnostic and prognostic tests will be identified.


Methodological aspects of design, analysis and reporting of studies with work participation as an outcome domain in patients with inflammatory arthritis: results of two systematic literature reviews informing EULAR points to consider.
To summarise the methodological aspects in studies with work participation (WP) as outcome domain in inflammatory arthritis (IA) and other chronic diseases. Two systematic literature reviews (SLRs) were conducted in key electronic databases (2014-2019): search 1 focused on longitudinal prospective studies in IA and search 2 on SLRs in other chronic diseases. Two reviewers independently identified eligible studies and extracted data covering pre-defined methodological areas. In total, 58 studies in IA (22 randomised controlled trials, 36 longitudinal observational studies) and 24 SLRs in other chronic diseases were included. WP was the primary outcome in 26/58 (45%) studies. The methodological aspects least accounted for in IA studies were as follows (proportions of studies positively adhering to the topic are shown): aligning the studied population (16/58 (28%)) and sample size calculation (8/58 (14%)) with the work-related study objective; attribution of WP to overall health (28/58 (48%)); accounting for skewness of presenteeism/sick leave (10/52 (19%)); accounting for work-related contextual factors (25/58 (43%)); reporting attrition and its reasons (1/58 (2%)); reporting both aggregated results and proportions of individuals reaching predefined meaningful change or state (11/58 (16%)). SLRs in other chronic diseases confirmed heterogeneity and methodological flaws identified in IA studies without identifying new issues. High methodological heterogeneity was observed in studies with WP as outcome domain. Consensus around various methodological aspects specific to WP studies is needed to improve quality of future studies. This review informs the EULAR Points to Consider for conducting and reporting studies with WP as an outcome in IA.


The Amsterdam Growth and Health Longitudinal Study. The past (1976-1996) and future (1997-?).
This article presents an overview of the Amsterdam Growth and Health Longitudinal Study (AGAHLS). This study was started in the 1970s, following a whole sample of 500 healthy 13-year-old boys and girls from two secondary schools. During the school period (12-17 years) annual measurements were performed with respect to anthropometrics, physiological and psychological parameters, lifestyle characteristics (activity, diet, smoking) and health parameters. A multiple longitudinal design was applied with overlapping birth cohorts and a cross-sectional measured control group to monitor for confounding factors such as time of measurement, cohort, dropout and testing effects. Emphasis is also placed on measures that enhance adherence of the subjects. The follow-up was extended with repeated measurements at age 21, 26 and 28. This enabled us to analyze the data with respect to tracking characteristics of biological and lifestyle variables over a period of 15 years between adolescence and adulthood and also to investigate quasi-causal relationships between the effects of a healthy lifestyle and indicators for cardiovascular diseases (CVD). Also new methods such as measurement of atherosclerosis and osteoporosis will be added and related to longitudinal measurements of the same subjects in the past. The main results that were obtained in the past are summarized and research questions for the near future are explained.


Effect of abdominal binders on breathing in tetraplegic patients.
We studied the effect on breathing of a conventional and a newly designed abdominal binder in seven patients with complete tetraplegia. The indices of respiratory ability used were the transdiaphragmatic pressure on maximal sniff (sniff Pdi), the maximum static inspiratory mouth pressure (PImax), and the vital capacity (VC). These were measured in patients with and without binders, in the supine position, raised up to 70 degrees on a tilt table, and seated upright. When patients were raised from the supine to the 70 degrees tilt and to the seated posture, sniff Pdi and VC decreased. Both binders improved VC in the seated position and at 70 degrees tilt, and sniff Pdi at 70 degrees tilt. The new binder was as effective as but no better than the conventional binder. PImax was too variable to be a valuable index of inspiratory power. These findings support the view that abdominal binders assist breathing in tetraplegic patients who are seated or raised to near vertical positions.


How to use tests for disorders of copper metabolism.
In paediatrics, one of our main aims in the diagnostic process is to identify any treatable conditions. The copper metabolism disorder Wilson's disease (WD) is one such condition that is caused by mutations in the ATP7B gene. Delay in treatment could result in irreversible disability or even death. Although liver disease is the most common presenting feature in children, some children may initially present with a subtle neurological presentation only. In patients presenting with dystonia, tremor, dysarthria or with a deterioration in school performance, there should be a high index of suspicion for WD. However, the differential of these clinical presentations is wide and exclusion of WD is difficult. No single diagnostic test can exclude WD and each of the biochemical tests has limitations. In this article, we discuss copper metabolism disorders including WD and Menke's disease. We then discuss the available diagnostic tests and how to investigate children for these rare disorders.


Endogenous μ-opioid-Neuropeptide Y Y1 receptor synergy silences chronic postoperative pain in mice.
Tissue injury creates a delicate balance between latent pain sensitization (LS) and compensatory endogenous analgesia. Inhibitory G-protein-coupled receptor (GPCR) interactions that oppose LS, including μ-opioid receptor (MOR) or neuropeptide Y Y1 receptor (Y1R) activity, persist in the spinal cord dorsal horn (DH) for months, even after the resolution of normal pain thresholds. Here, we demonstrate that following recovery from surgical incision, a potent endogenous analgesic synergy between MOR and Y1R activity persists within DH interneurons to reduce the intensity and duration of latent postoperative hypersensitivity and ongoing pain. Failure of such endogenous GPCR signaling to maintain LS in remission may underlie the transition from acute to chronic pain states.


Phantom energy: dark energy with w <--1 causes a cosmic doomsday.
We explore the consequences that follow if the dark energy is phantom energy, in which the sum of the pressure and energy density is negative. The positive phantom-energy density becomes infinite in finite time, overcoming all other forms of matter, such that the gravitational repulsion rapidly brings our brief epoch of cosmic structure to a close. The phantom energy rips apart the Milky Way, solar system, Earth, and ultimately the molecules, atoms, nuclei, and nucleons of which we are composed, before the death of the Universe in a "big rip."


Radical intermediates involved in the bleaching of the carotenoid crocin. Hydroxyl radicals, superoxide anions and hydrated electrons.
The participation of the primary radicals in the bleaching of aqueous solutions of the carotenoid crocin by ionizing radiation was investigated, employing both X-radiolysis and pulse radiolysis. The pulse-radiolytic data demonstrated a very rapid diffusion-controlled attack by both hydroxyl radicals (.OH) and hydrated electrons (eaq-), while superoxide anions (O2-) did not react at all. The site of the initial reaction of these radicals was not limited to the polyene chromophore. Slower secondary reactions involving crocin alkyl or peroxy radicals contribute mainly to the overall bleaching, in particular during steady-state irradiation.


Development and evaluation of an enzyme-linked immunosorbent assay (ELISA), using chlamydial group antigen, to detect antibodies, to Chlamydia trachomatis.
Chlamydial group antigen was extracted from Chlamydia trachomatis strain SA2(f) and used as the antigen for an ELISA. The assay was reproducible since chlamydial antibody titres differed by no more than twofold when sera were tested on up to eight occasions. In tests on sera from 75 patients attending venereal disease or rheumatology clinics, the results of the ELISA and of a microimmunofluorescence (MIF) technique were similar for 61 of the sera, that is an 81% agreement. However, the ELISA was a little more sensitive than the MIF technique and at least tenfold more sensitive than the complement fixation procedure. Chlamydial IgG antibody at a titre of 1/greater than or equal to 16 was detected by the ELISA in 6% of children's sera, in 20% of sera from adult patients attending hospital with non-venereal diseases and in 85% of sera from persons attending venereal disease or rheumatology clinics. IgM and IgG antibodies were detected also by the ELISA in the sera of chimpanzees and marmosets which had been infected genitally with C trachomatis and, in general, the titres were greater than those recorded by the MIF test. The value of the ELISA in comparison with the MIF test is discussed.


High-throughput middle-down analysis using an orbitrap.
This report demonstrates the application of a capillary LC-LTQ-orbitrap system to provide automated middle-down analysis of proteolytic peptides in the mass range 3000 to 10,000 Da. The novel workflow combines an underutilized method in the orbitrap-high resolution, mass-accurate product ion measurements-with software tailored to search such data (ProSightPC 2.0) and an Asp-selective chemical cleavage approach that generates peptides across an extended mass range. The strategy using high resolution mass measurements on both precursor and product ions is analogous to that widely used on FT-ICR analyzers. The approach is demonstrated in an analysis of the highly basic ribosomal proteome isolated from human MCF7 cancer cells.


Building an artificial solid electrolyte interphase on spinel lithium manganate for high performance aqueous lithium-ion batteries.
Spinel lithium manganate (LiMn2O4) is a promising cathode for aqueous lithium-ion batteries (ALIBs). However, due to Mn dissolution and the Jahn-Teller effect it suffers from fast capacity fading, insufficient rate capability, and low overcharge resistance. Herein, a ∼2-3 nm artificial solid electrolyte interphase (SEI) layer (lithium polyacrylate, LiPAA) is constructed on the commercial LiMn2O4 (LiPAA@LiMn2O4). It is realized by an in situ polymerization hydrothermal reaction using an acrylic monomer. This artificial SEI layer can separate the electrode and aqueous electrolyte, thus suppressing Mn dissolution and the Jahn-Teller effect of LiMn2O4. Electrochemical analyses also suggest it may work as the Li+ conductor/reservoir to improve the Li+ diffusion coefficient of the electrode. Consequently, as the cathode of ALIBs, LiPAA@LiMn2O4 harvests a high capacity of 119 mA h g-1 at 0.6C, high rate capability (70 mA h g-1 at 12C), better durability (85.5%@100 cycles) and superior overcharge resistance.


Antiarthritic and immunoregulatory activity of spirogermanium.
Spirogermanium is a novel metal containing azaspirane compound with reported antitumor activity. The results of the present investigation demonstrate that spirogermanium also exhibits antiarthritic and immunoregulatory activities after p.o. administration to rats. Spirogermanium decreased hindleg inflammatory lesions of adjuvant arthritic rats when administered p.o. before or after the development of the arthritic lesions. After termination of spirogermanium administration, the adjuvant-injected hindleg lesions remained significantly suppressed for at least 2 weeks postdrug treatment; whereas, the uninjected, immune-mediated hindleg inflammation tended to increase postdrug treatment. In multiparameter ex vivo studies, untreated arthritic rats exhibited enhanced cyanine dye fluorescence in peripheral blood monocytes, enhanced interleukin (IL)-1 production by adherent spleen cells and depressed IL-2 and IL-3 production by splenic lymphocytes. Spirogermanium normalized these changes to various degrees, with the exception of the depressed IL-2 and IL-3 production. Spirogermanium administered to normal nonarthritic rats decreased mitogenic responses of spleen cells to Concanavalin A which was found to be caused, at least in part, by enhanced suppressor cell activity. The antiarthritic and immunoregulatory profile of spirogermanium appeared to be different from the profiles of the antiarthritic agents, auranofin and indomethacin.


The diagnostic accuracy, image quality and radiation dose of 64-slice dual-source CT in daily practice: a single institution's experience.
We wanted to evaluate the image quality, diagnostic accuracy and radiation exposure of 64-slice dual-source CT (DSCT) coronary angiography according to the heart rate in symptomatic patients during daily clinical practice. We performed a retrospective search for the DSCT coronary angiography reports of 729 consecutive symptomatic patients. For the 131 patients who underwent invasive coronary angiography, the image quality, the diagnostic performance (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV] for detecting significant stenosis ≥ 50% diameter) and the radiation exposure were evaluated. These values were compared between the groups with differing heart rates (HR): mean HR < 65 or ≥ 65 and HR variability (HRV) < 15 or ≥ 15. Among the 729 patients, the CT reports showed no stenosis or insignificant coronary artery stenosis in 72%, significant stenosis in 26% and non-diagnostic in 2%. For the 131 patients who underwent invasive coronary angiography, 95% of the patients and 97% of the segments were evaluable, and the overall per-patient/per-segment sensitivity, the perpatient/per-segment specificity, the per-patient/per-segment PPV and the per-patient/per-segment NPV were 100%/90%, 71%/98%, 95%/88% and 100%/97%, respectively. The image quality was better in the HR < 65 group than in the HR ≥ 65 group (p = 0.001), but there was no difference in diagnostic performance between the two groups. The mean effective radiation doses were lower in the HR < 65 or HRV < 15 group (p < 0.0001): 5.5 versus 6.7 mSv for the mean HR groups and 5.3 versus 9.3 mSv for the HRV groups. Dual-source CT coronary angiography is a highly accurate modality in the clinical setting. Better image quality and a significant radiation reduction are being rendered in the lower HR group.


Quantification of the aortic regurgitant volume with magnetic resonance phase velocity mapping: a clinical investigation of the importance of imaging slice location.
Current techniques for assessment of aortic regurgitation (AR) are mainly qualitative. Magnetic resonance phase velocity mapping (PVM) provides accurate measurements of arterial blood blow. In AR, the aortic regurgitant volume (ARV) can be quantified with a single imaging slice measurement in the ascending aorta. The aim was to use PVM to: (i) quantify the regurgitant volume in patients with AR using an in vitro validated technique; and (ii) confirm in vivo our previous in vitro findings of the importance of measurement location. Four healthy volunteers and 19 patients with AR, varying from mild to severe, were examined in a 1.5 Tesla MRI scanner. In 13 patients, the slice was placed: (i) between the aortic valve and the coronary ostia; (ii) at the sinotubular junction (SJ); and (iii) 2 cm above the SJ. In six patients, one measurement was taken as close as technically possible to the aortic valve. PVM measurements of the ARV were compared with angiographic/echocardiographic AR grading. No ARV was measured in healthy subjects. In patients, PVM results correlated well with angiographic/echocardiographic data. Repeatability of the PVM results was excellent and interobserver variability very small. The measured ARV decreased as the slice distance from the aortic valve increased, due to aortic compliance, in agreement to previous in vitro results. Close to the valve, acceleration did not affect the accuracy of velocity measurements. PVM has great potential to measure AR in a purely quantitative manner. Measurement location is important and results suggest that the closer the measurement to the valve the more accurate the ARV quantification.


Occult pregnancy. A pilot study.
As used herin, the term "occult pregnancy" is defined as a pregnancy which aborts so early that no clincial suspicion of its existence arises except perhaps that there has been a few days' delay in the onset of an otherwise normal menstrual period. Sixteen Clomid-induced ovulatory cycles as evidenced by biphasic temperature charts with hyperthermic phases of 12 days or more were studied. Of these, 10 had serum luteinizing hormone values in the late luteal phase normal for that part of the cycle (6-16 mIU/ml) and six, or 37.5% showed values sufficiently elevated (more than three standard deviations) to indicate a cross reaction with human chorionic gonadotropin and hence the presence of an otherwise unsuspected pregnancy. All had clinically normal menstrual periods 12 hours to 6 days later. The clinical significance of this finding is discussed.


Clinical Issues-March 2020.
Laundering microfiber cleaning supplies Key words: cloth, mop, microfiber, laundering, microorganisms. Significance of contact time during cleaning Key words: disinfectant, contact time, cleaning, bactericidal efficacy. Mask use during cystoscopy and tonsillectomy procedures Key words: surgical mask, splash, exposure, barrier level, blood-contaminated aerosols. Use of radiopaque towels Key words: radiopaque towels, radiopaque markers, soft goods, towel retention. Personal fragrances in the perioperative setting Key words: fragrances, fragrance sensitivity, asthma, disability.


Cytotoxic and antimicrobial mycophenolic acid derivatives from an endophytic fungus Penicillium sp. MNP-HS-2 associated with Macrozamia communis.
Macrozamia communis and its associated endophytic fungi are untapped sources of bioactive metabolites with great potential for medicinal exploitation. Chemical investigation of the mycelial extract derived from an endophytic fungus Penicillium sp. MNP-HS-2 associated with M. communis fruit afforded four mycophenolic acid derivatives recognized as previously undescribed natural products (1-4), together with nine known metabolites (5-13). Chemical structures of isolated compounds were determined based on extensive spectroscopic analyses, including 1D/2D NMR and HRESIMS. The absolute stereochemistry of alternatain E (1) was unambiguously established by comparing its experimental and calculated time-dependent density functional theory electronic circular dichroism spectra (TDDFT-ECD). All isolated compounds were assessed for their antimicrobial and cytotoxic activities, where mycophenolic acid methyl ester (7), displayed significant cytotoxic activity against seven different cell lines with IC50 values in the low micromolar to nanomolar range. Mycophenolene A (3) exhibited significant antibacterial activity against Staphylococcus aureus (MIC = 2.1 μg/mL).


Stimulation by glucose of cyclic AMP accumulation in mouse pancreatic islets is mediated by protein kinase C.
The mechanism of glucose-stimulated cyclic AMP accumulation in mouse pancreatic islets was studied. In the presence of 3-isobutyl-1-methylxanthine, both glucose and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, enhanced cyclic AMP formation 2.5-fold during 60 min of incubation. Both TPA-stimulated and glucose-stimulated cyclic AMP accumulations were abolished by the omission of extracellular Ca2+. The Ca2+ ionophore A23187 did not affect cyclic AMP accumulation itself, but affected the time course of TPA-induced cyclic AMP accumulation, the effect of A23187 + TPA mimicking the time course for glucose-induced cyclic AMP accumulation. A 24 h exposure to TPA, which depletes islets of protein kinase C, abolished the effects of both TPA and glucose on cyclic AMP production. Both TPA-induced and glucose-induced cyclic AMP productions were inhibited by anti-glucagon antibody, and after pretreatment with this antibody glucose stimulation was dependent on addition of glucagon. Pretreatment of islets with TPA for 10 min potentiated glucagon stimulation and impaired somatostatin inhibition of adenylate cyclase activity in a particulate fraction of islets. Carbamoylcholine, which is supposed to activate protein kinase C in islets, likewise stimulated cyclic AMP accumulation in islets. These observations suggest that glucose stimulates islet adenylate cyclase by activation of protein kinase C, and thereby potentiates the effect of endogenous glucagon on adenylate cyclase.


[Cultivation of chorionic cells in studying the fetal karyotype in the 1st trimester of pregnancy].
Primary culture of chorion cells obtained during the first trimester of pregnancy (7-9 weeks) through artificial abortion or by transcervical biopsy of the chorion tissue is an object for cytogenetic examination of fetus cells. The application of this cell culture for prenatal diagnosis of human hereditary diseases has a considerable advantage in time as compared with a routine method of using amniotic fluid cell culture during the second trimester of pregnancy.


Evaluation of Atlas-Based White Matter Segmentation with Eve.
Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.


Effects of humic acid and competing cations on metal uptake by Lolium perenne.
Within the biotic ligand model, which describes relationships between chemical speciation and metal binding at an organism's surface, multicomponent (long-term) metal uptake by plants has seldom been studied. In the present work, we exposed perennial ryegrass to nutrient solutions with two levels of Cd, Cu, Ni, Pb, and Zn (1 and 0.1 microM) and with or without 30 mg/L of humic acid. Iron and Mn concentrations were constant over all treatments. The hypothesis tested was that humic acid lowers the free and labile metal concentration and, therefore, reduces the metal uptake and, finally, the metal content of the plant. The free metal ion concentrations in the nutrient solutions were measured by the Donnan membrane technique and labile metal concentrations by diffusive gradients in thin-films. The metal content of the shoots depends on the metal content of the roots. The metal content of the roots is a function of the adsorption of metals on the root surface. In a multicomponent system at metal concentrations of 1 microM, humic acid decreased Cu, Pb, and Fe adsorption at the root surface, but it increased Cd, Zn, and Mn adsorption at the root surface. Complexation of cations such as Cu, Pb, and Fe with high affinity for (dissolved) organic matter may lead to increased uptake of cations with low affinity for organic matter (Ni, Zn, and Cd) because of competition between cations at the root surface. The results suggest that competition between metal ions can play a major role in multicomponent metal uptake, which has to be taken into account during risk assessments of metal-polluted soils.


Attentional Modulation in Early Visual Cortex: A Focused Reanalysis of Steady-state Visual Evoked Potential Studies.
Steady-state visual evoked potentials (SSVEPs) are a powerful tool for investigating selective attention. Here, we conducted a combined reanalysis of multiple studies employing this technique in a variety of attentional experiments to, first, establish benchmark effect sizes of attention on amplitude and phase of SSVEPs and, second, harness the power of a large data set to test more specific hypotheses. Data of eight published SSVEP studies were combined, in which human participants (n = 135 in total) attended to flickering random dot stimuli based on their defining features (e.g., location, color, luminance, or orientation) or feature conjunctions. The reanalysis established that, in all the studies, attention reliably enhanced amplitudes, with color-based attention providing the strongest effect. In addition, the latency of SSVEPs elicited by attended stimuli was reduced by ∼4 msec. Next, we investigated the modulation of SSVEP amplitudes in a subset of studies where two different features were attended concurrently. Although most models assume that attentional effects of multiple features are combined additively, our results suggest that neuronal enhancement provided by concurrent attention is better described by multiplicative integration. Finally, we used the combined data set to demonstrate that the increase in trial-averaged SSVEP amplitudes with attention cannot be explained by increased synchronization of single-trial phases. Contrary to the prediction of the phase-locking account, the variance across trials of complex Fourier coefficients increases with attention, which is more consistent with boosting of a largely phase-locked signal embedded in non-phase-locked noise.


CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection.
Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates that CpG ODN treatment of rhesus macaques significantly reduces the severity of the lesions caused by a challenge with Leishmania: Leishmania superinfection is common in immunocompromised hosts, particularly those infected with HIV. This study shows that PBMCs from HIV-infected subjects respond to stimulation with CpG ODNs. To determine whether CpG ODNs can protect retrovirus-infected primates, SIV-infected macaques were treated with CpG ODNs and then challenged with Leishmania: Both lesion size and parasite load were significantly reduced in the CpG-treated animals. These findings support the clinical development of CpG ODNs as immunoprotective agents in normal and HIV-infected patients.


The biomechanical effects of variation in the maximum forces exerted by trunk muscles on the joint forces and moments in the lumbar spine: a finite element analysis.
The weakening of trunk muscles is known to be related to a reduction of the stabilization function provided by the muscles to the lumbar spine; therefore, strengthening deep muscles might reduce the possibility of injury and pain in the lumbar spine. In this study, the effect of variation in maximum forces of trunk muscles on the joint forces and moments in the lumbar spine was investigated. Accordingly, a three-dimensional finite element model of the lumbar spine that included the trunk muscles was used in this study. The variation in maximum forces of specific muscle groups was then modelled, and joint compressive and shear forces, as well as resultant joint moments, which were presumed to be related to spinal stabilization from a mechanical viewpoint, were analysed. The increase in resultant joint moments occurred owing to decrease in maximum forces of the multifidus, interspinales, intertransversarii, rotatores, iliocostalis, longissimus, psoas, and quadratus lumborum. In addition, joint shear forces and resultant joint moments were reduced as the maximum forces of deep muscles were increased. These results from finite element analysis indicate that the variation in maximum forces exerted by trunk muscles could affect the joint forces and joint moments in the lumbar spine.


Traumatic injuries of the immature hip and pelvis.
The pelvis and hip account for 0.3--4% of fractures of the immature skeleton, and generally result from high energy trauma. These fractures range in severity from apophyseal avulsions to complete disruptions of the pelvic ring. The purpose of this article is to review the presentation, diagnosis, treatment and complications of these injuries in order to inform clinicians involved in their management. There is a lack of evidence-based management protocols for fractures of the immature pelvis largely due to their rarity and lack of robust scientific literature on the topic. Computed tomography/MRI is essential as up to 30% of pelvis and 70% of acetabular fractures are not identified on initial radiographs. A sub-optimal outcome is common in unstable fractures treated conservatively and adequate reduction and surgical stabilization is often required to avoid long-term morbidity. A coordinated approach involves resuscitation and temporary stabilization with planned definitive fixation. It is generally accepted that these injures should be managed in paediatric trauma centres. Whilst injuries vary in pattern and severity, we present an overview that considers the evaluation and treatment of the paediatric patient with pelvic and hip fractures to ensure that these injuries are identified promptly and treated by surgeons familiar with contemporary management algorithms.


Blood lactate diagnostics in exercise testing and training.
A link between lactate and muscular exercise was seen already more than 200 years ago. The blood lactate concentration (BLC) is sensitive to changes in exercise intensity and duration. Multiple BLC threshold concepts define different points on the BLC power curve during various tests with increasing power (INCP). The INCP test results are affected by the increase in power over time. The maximal lactate steady state (MLSS) is measured during a series of prolonged constant power (CP) tests. It detects the highest aerobic power without metabolic energy from continuing net lactate production, which is usually sustainable for 30 to 60 min. BLC threshold and MLSS power are highly correlated with the maximum aerobic power and athletic endurance performance. The idea that training at threshold intensity is particularly effective has no evidence. Three BLC-orientated intensity domains have been established: (1) training up to an intensity at which the BLC clearly exceeds resting BLC, light- and moderate-intensity training focusing on active regeneration or high-volume endurance training (Intensity < Threshold); (2) heavy endurance training at work rates up to MLSS intensity (Threshold ≤ Intensity ≤ MLSS); and (3) severe exercise intensity training between MLSS and maximum oxygen uptake intensity mostly organized as interval and tempo work (Intensity > MLSS). High-performance endurance athletes combining very high training volume with high aerobic power dedicate 70 to 90% of their training to intensity domain 1 (Intensity < Threshold) in order to keep glycogen homeostasis within sustainable limits.


Brain abscess due to Aggregatibacter aphrophilus and Bacteroides uniformis.
The aim of this report was to describe the occurrence of a bacterial brain abscess in a healthy individual, without any predisposing condition. A thirteen-year old boy was admitted to the Department of Neurosurgery after the onset of vomiting, headache and dizziness. A neurological deficit was detected during the physical examination so urgent magnetic resonance imaging of the brain was performed, revealing an intrahemispheric, right positioned solitary expansive mass with ring enhancement. Purulent material was obtained during osteoplastic craniotomy with total extirpation of the brain abscess. Aggregatibacter aphrophilus and Bacteroides uniformis were isolated. The patient's general condition improved and the neurological deficit subsided as a result of the prompt recognition and treatment of this life threatening condition. To achieve a favourable clinical outcome, prompt recognition and surgical treatment of a brain abscess are of primary importance,followed by administration of appropriate antimicrobial therapy. To our best knowledge, this is the first report of this combination of microorganisms as the cause of a brain abscess.


The Interplay of Sexual Arousal and Power-Related Emotions in Men's Alcohol-Involved Sexual Aggression Intentions.
Research has identified power/dominance and sexual arousal as key motivators of men's sexual aggression; however, little research has examined the interplay of these two factors in alcohol-involved sexual aggression. Two alcohol administration experiments investigated the roles of power-related sex motives and power- and sexual arousal-related emotions on men's sexual aggression intentions. In Study 1, participants (N = 96) read a sexual aggression scenario after random assignment to consume either an alcoholic (target peak BrAC = .10%) or nonalcoholic beverage. Results indicated that power-related sex motives indirectly predicted stronger sexual aggression intentions through greater in-the-moment power-related emotions but not through sexual arousal-related emotions. Intoxicated men with more severe perpetration histories reported stronger sexual aggression intentions. In Study 2, participants (N = 203) completed similar measures after random assignment to receive either a brief emotion regulation-focused intervention (cognitive restructuring or mindfulness) or a control, followed by either alcohol (target peak BrAC = .08%) or nonalcoholic beverage consumption. Results demonstrated that greater power-related sex motives indirectly predicted stronger sexual aggression intentions through greater feelings of power and sexual arousal. Additionally, findings suggest that cognitive restructuring approaches may mitigate these relationships in sober men, while mindfulness approaches may exacerbate these relationships in intoxicated men.


Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer.
Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.


Prevalence and Factors Associated with Inconsistent Condom Use among Men who Have Sex with Men (MSM) who use Mobile Geo-Social Networking Applications in Greater Tokyo.
This study examined the prevalence and factors associated with inconsistent condom use among men who have sex with men (MSM) who use gay mobile geo-social networking applications (gay mobile apps) in Greater Tokyo. Among a sample of 1657 MSM recruited through advertisements on gay mobile apps, inconsistent condom use was reported by over one-third (37%) of participants with regular male partners, 18% with casual male partners, and 20% with female partners. In multiple regression analysis, inconsistent condom use with both regular and casual male partners was more commonly reported among participants without a university education, and among participants reporting lower self-efficacy for safer sex. Inconsistent condom use with casual male partners was more commonly reported among participants living in the central 23 wards of Tokyo. Inconsistent condom use with regular male partners was more commonly reported among participants who identified as a member of the gay community, and who only had male partners. These results indicate that a substantial proportion of Greater Tokyo gay mobile app users use condoms inconsistently, particularly with regular partners, and may be at risk for HIV. This paper provides useful information to help design tailored strategies to reduce inconsistent condom use.


Severe Pneumonia Caused by Influenza A (H1N1) Virus Successfully Managed with Extracorporeal Life Support in a Comorbid Former Preterm Infant.
Influenza A (H1N1) virus infection is a global health burden, leading to significant pediatric morbidity and mortality. Prematurity, young age and comorbidities are important risk factors for unfavorable outcomes. Preventive strategies, such as healthcare workers and household contacts vaccination as well as the implementation of infection control practices during the epidemic season, are crucial to protect the most vulnerable populations. Early diagnosis, timely administration of antiviral drugs and supportive therapy are crucial to lead to a complete recovery. When conventional treatment fails, extracorporeal life support (ECLS) may be employed. In neonates and young infants, this high-tech support is burdened by specific technical complexity. Despite the potential risks related to this aggressive approach, ECLS is a life-saving procedure in 65% of pediatric viral pneumonia and in 73% of sepsis cases. Here, we report the successful outcome of a 51-day formerly preterm infant, suffering from a surgical necrotizing enterocolitis (NEC), complicated with hospital-acquired pneumonia due to influenza A (H1N1) virus. She developed a severe respiratory failure, unresponsive to conventional therapy, and successfully treated with ECLS. To our knowledge, this is the first report on the use of ECLS in a formerly preterm infant, suffering from NEC complicated by influenza A (H1N1) virus infection.


[Neuronal Intranuclear Inclusion Disease].
Neuronal intranuclear inclusion disease (NIID) is a gradually progressing neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and in certain visceral organs. The number of reported cases of NIID has recently increased after the introduction of skin biopsy for the diagnosis of NIID. Patients with sporadic NIID usually present with dementia, elevation of overall protein levels in the cerebrospinal fluid, leukoencephalopathy on head magnetic resonance imaging (MRI), and high signal intensity in the corticomedurally junction on a diffusion-weighted (DW) imaging. Among patients with familial NIID with age at onset <40 years, muscle weakness is observed most frequently; these cases are classified in the "limb weakness group." Among patients with familial NIID with age at onset >40 years, dementia is the most prominent symptom; these cases are classified in the "dementia dominant group." We proposed a flowchart for diagnosis adult-onset NIID. The prevalence rate of adult-onset NIID may be higher than previously thought, and NIID may be underdiagnosed in the population. NIID must be considered during the differential diagnosis of leukoencephalopathy and neuropathy, for which this flowchart for adult-onset NIID diagnosis may prove beneficial.


Afferent influences on cell death and birth during development of a cortical nucleus necessary for learned vocal behavior in zebra finches.
Forebrain nuclei that control learned vocal behavior in zebra finches are anatomically distinct and interconnected by a simple pattern of axonal pathways. In the present study, we examined afferent regulation of neuronal survival during development of the robust nucleus of the archistriatum (RA). RA projection neurons form the descending motor pathway of cortical vocal-control regions and are believed to be directly involved in vocal production.RA receives afferent inputs from two other cortical regions, the lateral magnocellular nucleus of the anterior neostriatum (lMAN) and the higher vocal center (HVC).However, because the ingrowth of HVC afferent input is delayed, lMAN projection neurons provide the majority of afferent input to RA during early vocal learning. lMAN afferent input to RA is of particular interest because lMAN is necessary for vocal learning only during a restricted period of development. By making lesions of lMAN in male zebra finches at various stages of vocal development (20-60 days of age) and in adults (>90-days old), we asked whether the survival of RA neurons depends on lMAN afferent input, and if so whether such dependence changes over the course of vocal learning. The results showed that removal of lMAN afferent input induced the loss of over 40% of RA neurons among birds in early stages of vocal development(20 days of age). However, lMAN lesions lost the ability to induce RA neuron death among birds in later stages of vocal development (40 days of age and older). These findings indicate that many RA neurons require lMAN afferent input for their survival during early vocal learning, whereas the inability of lMAN lesions to induce RA neuron death in older birds may indicate a reduced requirement for afferent input or perhaps the delayed ingrowth of HVC afferent input (at approx. 35 days of age)provides an alternate source of afferent support. Removal of lMAN afferent input also dramatically increased the incidence of mitotic figures in RA, but only among 20-day-old birds at 2 days post-lesion. The early, acute nature of the mitotic events raises the possibility that cell division in RA may be regulated by lMAN afferent input.


[A comparison of selected parameters of potatoes health quality from ecologically oriented and conventional farms].
The aim of work was to compare nutritional quality and wholesomeness of the potatoes from ecological (ECO) and conventional (CONV) farms. Other aim was to check if the west-european data telling about better nutritional quality of ECO potatoes can be confirmed in Polish agricultural conditions. Nine ECO farms located in Toruń and Sieradz provinces, having EKOLAND's certification were selected to study. A neighbour CONV farm with similar production conditions was selected to each ECO farm. ECO farmers manured potatoes with composted cow manure or compost giving on average 30 t/ha. CONV farmers used mineral fertilizers NPK in 1:1:1,5 ratio giving 100 kg N/ha. In the autumn several compounds were determined in potatoes: the contents of dry matter according to PN-88/R-04013, the contents of nitrates and nitrites according to Draft International Standard ISO, the contents of Pb and Cd by means of ASA method and the contents of vitamin C as L-ascorbic acid according to PN-90/A-75101/11. The ECO potatoes contained in both years significantly less nitrates than CONV potatoes. In 1992 the nitrates contents was much higher in both kinds of potatoes than in 1993. The nitrites contents was in both years higher in CONV potatoes but the difference was statistically significant only in 1993. The lead contents was low in both kinds of potatoes and didn't exceed permissible level. The cadmium contents was in 1992 significantly higher in CONV tubers than in ECO tubers and exceeded permissible level. In 1991 and 1993 both kinds of tubers contained similar cadmium levels. The contents of dry matter and vitamin C was similar in both kinds of tubers. The study has shown that ECO potatoes were more wholesome than CONV potatoes. The results obtained in Polish agricultural conditions confirmed west-european data.


Melatonin enhances the in vitro maturation and developmental potential of bovine oocytes denuded of the cumulus oophorus.
This study was designed to determine the effect of melatonin on the in vitro maturation (IVM) and developmental potential of bovine oocytes denuded of the cumulus oophorus (DOs). DOs were cultured alone (DOs) or with 10-9 M melatonin (DOs + MT), cumulus-oocyte complexes (COCs) were cultured without melatonin as the control. After IVM, meiosis II (MII) rates of DOs, and reactive oxygen species (ROS) levels, apoptotic rates and parthenogenetic blastocyst rates of MII oocytes were determined. The relative expression of ATP synthase F0 Subunit 6 and 8 (ATP6 and ATP8), bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) mRNA in MII oocytes and IFN-tau (IFN-τ), Na+/K+-ATPase, catenin-beta like 1 (CTNNBL1) and AQP3 mRNA in parthenogenetic blastocysts were quantified using real-time polymerase chain reaction (PCR). The results showed that: (1) melatonin significantly increased the MII rate of DOs (65.67 ± 3.59 % vs. 82.29 ± 3.92%; P < 0.05), decreased the ROS level (4.83 ± 0.42 counts per second (c.p.s) vs. 3.78 ± 0.29 c.p.s; P < 0.05) and apoptotic rate (36.99 ± 3.62 % vs. 21.88 ± 2.08 %; P < 0.05) and moderated the reduction of relative mRNA levels of ATP6, ATP8, BMP-15 and GDF-9 caused by oocyte denudation; (2) melatonin significantly increased the developmental rate (24.17 ± 3.54 % vs. 35.26 ± 4.87%; P < 0.05), and expression levels of IFN-τ, Na+/K+-ATPase, CTNNBL1 and AQP3 mRNA of blastocyst. These results indicated that melatonin significantly improved the IVM quality of DOs, leading to an increased parthenogenetic blastocyst formation rate and quality.


Polydopamine nanomaterials and their potential applications in the treatment of autoimmune diseases.
The conventional treatment methods used for the management of autoimmune diseases (ADs) have limited efficacy and also exhibit significant side effects. Thus, identification of novel strategies to improve the efficacy and safety of ADs treatment is urgently required. Overactivated immune response and oxidative stress are common characteristics associated with ADs. Polydopamine (PDA), as a polymer material with good antioxidant and photothermal conversion properties, has displayed useful application potential against ADs. In addition, PDA possesses good biosafety, simple preparation, and easy functionalization, which is conducive for the pharmacological development of PDA nanomaterials with clinical transformation prospects. Here, we have first reviewed the preparation of PDA, the different functional integration strategies of PDA-based biomaterials, and their potential applications in ADs. Next, the mechanism of action of PDA in ADs has been elaborated in detail. Finally, the application opportunities and challenges linked with PDA nanomaterials for ADs treatment are discussed. This review is contributed to design reasonable and effective PDA nanomaterials for the diagnosis and treatment of ADs.


Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression.
Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; and if variations in pro- and anti- inflammatory cytokine genes were associated with latent class membership. Self-report measures of pain, fatigue, sleep disturbance, and depression were completed by 168 oncology outpatients and 85 family caregivers (FCs). Using latent class profile analysis (LCPA), three relatively distinct classes were identified: those who reported low depression and low pain (83%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with younger age, being White, being a patient (versus a FC), having a lower functional status score, and having a higher number of comorbid conditions. Findings suggest that LPCA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of distinct phenotypes provides new evidence for the role of IL4 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.


Fatal co-infection--melioidosis and leptospirosis.
Co-infection of melioidosis and leptospirosis is uncommon. We report here four such cases, confirmed by blood culture for melioidosis and blood polymerase-chain reaction for leptospirosis, which occurred among rescuers involved in a search and rescue operation for a young man who was suspected to have drowned in Lubuk Yu, a recreational forest in Pahang, Malaysia. Despite treatment, three of the patients died from the co-infection.


Beam Effects on Atomic Dynamics in Metallic Glasses Studied With Electron Correlation Microscopy.
Electron correlation microscopy (ECM) is used to investigate atomic dynamics in metallic glasses (MG) close to metastable equilibrium. It temporally correlates diffracted intensities of a time series of dark-field images to deduce a metric for structural decays. The measurement parameters, such as time and temperature, must be chosen according to the material of interest. In this work, ECM was extended to measurements at room temperature. To ensure, or select, a time window with quasi-thermodynamic equilibrium/steady-state measurement conditions, two-time correlation functions of diffracted intensities were calculated. The dynamics at room temperature are partly driven by the electron beam, thus affecting the material and the results. A systematic analysis of the influence of the electron beam is presented, revealing an inverse relation between electron dose rate and intensity correlation decay times at 300 kV acceleration voltage. However, the underlying dynamical mechanisms, described by a stretching exponent, are found to be independent of the applied electron dose rate for a Pd40Ni40P20 MG. An extrapolation of the results to infinite long measurement times and zero dose rate agrees with X-ray photon correlation spectroscopy data and justifies the application of beam-driven ECM at room temperature to study the dynamics of disordered systems.


A microendoscopic test card for ophthalmic endoscopes.
Ophthalmic endoscopes allow examination of intraocular structures when traditional surgical microscopic visualization is limited or impossible. Periodic evaluation of the optical precision of these instruments is essential to ensure optimal intraoperative performance. A test card has been developed to aid in the calibration of ophthalmic endoscopes. Its 5 test targets assess white balance and fiberoptic bundle integrity, focus and resolution, orientation, color fidelity, and angle of view.


A multicenter analysis of the ophthalmic knowledge assessment program and American Board of Ophthalmology written qualifying examination performance.
To compare the performance on the American Board of Ophthalmology Written Qualifying Examination (WQE) with the performance on step 1 of the United States Medical Licensing Examination (USMLE) and the Ophthalmic Knowledge Assessment Program (OKAP) examination for residents in multiple residency programs. Comparative case series. Fifteen residency programs with 339 total residents participated in this study. The data were extracted from the 5-year American Board of Ophthalmology report to each participating program in 2009 and included residency graduating classes from 2003 through 2007. Residents were included if data were available for the USMLE, OKAP examination in ophthalmology years 1 through 3, and the WQE score. Residents were excluded if one or more of the test scores were not available. Two-sample t tests, logistic regression analysis, and receiver operating characteristic (ROC) curves were used to examine the association of the various tests (USMLE, OKAP examination year 1, OKAP examination year 2, OKAP examination year 3, and maximum OKAP examination score) as a predictor for a passing or failing grade on the WQE. The primary outcome measure of this study was first time pass rate for the WQE. Using ROC analysis, the OKAP examination taken at the third year of ophthalmology residency best predicted performance on the WQE. For the OKAP examination taken during the third year of residency, the probability of passing the WQE was at least 80% for a score of 35 or higher and at least 95% for a score of 72 or higher. The OKAP examination, especially in the third year of residency, can be useful to residents to predict the likelihood of success on the high-stakes WQE examination.


Distribution characteristics of insect diversity in long-term fixed monitoring plots in Northeast China.
The spatial patterns of field arthropod communities are an essential part of ecology and can provide fundamental data regarding field ecological processes and reveal the mechanism of ecosystem biodiversity maintenance. This study investigated the spatial distribution pattern of field insect communities to detect the spatial relationships between insect communities in farmland. The study site was located at the Dehui Agro-ecological Experimental Station of Black Soil, Jilin, China. Insect communities and environmental factors were sampled at 121 uniformly distributed points in a 400 × 400 m plot in August, September, and October 2015. The analysis revealed that insect communities from June to October demonstrated significant spatial correlation, and 6085 samples of 47 species and 47 families in 11 orders were collected from the insect community in the farmland. The farmland insect community structure changes and dynamic changes of nutritional function groups occur with time. According to the 400 x 400 m plot, the diversity of farmland insect communities and functional groups is maintained at a relatively high and stable level. In this study, a total of 6085 samples of corn farmland insects were obtained using the fluke method and direct observation method, including 11 orders, 26 families and 47 species, 4 absolute dominant populations, 6 main dominant populations, and 37 other populations. These studies can provide help for pest control in the spring corn area of Northeast China.


HUMTRN and EFFECTS: age and sex specific dosimetric and physiological human population dynamics models for dose assessment.
A human simulation model called HUMTRN and a population risk assessment model called EFFECTS were developed at Los Alamos National Laboratory as a major component of the BIOTRAN environmental risk assessment model. HUMTRN simulates growth using dietary and physiological characteristics and kinetics of radionuclides to predict radiation doses to selected organs of both sexes in different age groups. The model called EFFECTS was interfaced with output from HUMTRN to predict cancer risks in a dynamic human population. EFFECTS is based on the National Research Council Committee on the Biological Effects of Ionizing Radiation (BEIR)-III radiation cancer mortality estimates from the U.S. population mortality and natality estimates for both sexes between the ages of 1 and 70. These models track radiation intake from air, water, and food, calculate uptake in major growing organs, and estimate cancer mortality risks. This report documents the use of an IBM Personal Computer AT to run HUMTRN and EFFECTS. Air, water, and food contaminant concentrations are provided as input to HUMTRN, which then provides input for EFFECTS. The limitations of this approach are also discussed.


Cost-effectiveness of oral anticancer drugs and associated individualised dosing approaches in patients with cancer: protocol for a systematic review.
Oral anticancer drugs (OADs) have rapidly expanded with more than 70 OADs targeting several molecular targets. Many of the OADs exert an exposure-response relationship but still, a 'one-size fits-all' dose is used, ignoring interindividual variability. Several of these OADs share similar mechanisms of actions and thus target the same cancer and has resulted in a substantial research focus on comparing the health benefit of each. However, significantly less is known about the cost-benefit associated with OADs. This paper will provide a protocol to systematically review studies that have evaluated the cost-effectiveness of OADs and their associated individualised dosing interventions. Systematic review methodology will be applied to identify, select and extract data from published economic evaluation (costs and outcomes/benefits) studies of OADs and their associated individualised dosing interventions. Bibliographic databases (eg, Ovid EMBASE, Ovid MEDLINE) will be used to perform the systematic literature search (between 1 January 2000 and October 2020). Only full economic evaluations will be included, but no restrictions on study outcomes will be applied. The quality of included primary studies will be assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist for reporting economic evaluations. Studies with low-quality evidence will be excluded. A narrative synthesis of the results from the included studies will be undertaken, with a subgroup analysis where appropriate. This systematic review will not require ethics approval as there will not be any collection of primary data. Findings of this review will be disseminated through publications in peer-reviewed journals, presentations at workshops or conferences and sharing through a media release. Findings from this review will provide evidence to direct and inform policy-makers where cost-neutral strategies may be effective or where dose individualising strategies may be economically beneficial. Additionally, gaps will be identified in the current literature to inform future-related research. CRD42020218170. The online version of this article contains supplemental material, which is available to authorised users.


The intergenerational transmission of childhood maltreatment: Nonspecificity of maltreatment type and associations with borderline personality pathology.
One generation's experience of childhood maltreatment is associated with that of the next. However, whether this intergenerational transmission is specific to distinct forms of maltreatment and what factors may contribute to its continuity remains unclear. Borderline personality pathology is predicted by childhood maltreatment and characterized by features (e.g., dysregulated emotion, relationship instability, impulsivity, and inconsistent appraisals of others) that may contribute to its propagation. Among 364 older adults and 573 of their adult children (total n = 937), self-reported exposure to distinct forms of childhood maltreatment (i.e., emotional, physical, and sexual abuse, and emotional and physical neglect as assessed by the Childhood Trauma Questionnaire) showed homotypic and heterotypic associations across generations with little evidence that latent factors unique to specific forms of maltreatment show generational continuity. General nonspecific indices of childhood maltreatment showed evidence of intergenerational transmission after accounting for demographic factors and parent socioeconomic status (b = 0.126, p = 9.21 × 10-4). This continuity was partially mediated by parental borderline personality pathology (assessed longitudinally through a variety of measures and sources, indirect effect: b = 0.031, 95% confidence interval [0.003, 0.060]). The intergenerational continuity of childhood maltreatment may largely represent general risk for nonspecific maltreatment that may, in part, be propagated by borderline personality pathology and/or shared risk factors.


Simvastatin and the Rho-kinase inhibitor Y-27632 prevent myofibroblast transformation in Peyronie's disease-derived fibroblasts via inhibition of YAP/TAZ nuclear translocation.
To uncover the anti-myofibroblast (MFB) properties of Rho-kinase inhibitor (compound Y-27632) and simvastatin in an in vitro model of Peyronie's disease (PD), a sexually debilitating disease caused by an irreversible fibrotic plaque in the penile tunica albuginea (TA). Primary human fibroblasts (FBs) were isolated from surgically obtained TA tissue from patients with PD. To induce MFB status, cells were stimulated with 3 ng/mL transforming growth factor-β1 (TGF-β1). Increasing doses of Y-27632 and simvastatin were added. Real-time quantitative PCR was used to assess mRNA expression of α-smooth muscle actin (α-SMA), collagen III, elastin and connective tissue growth factor (CTGF) after 72 h. Western blot analysis was used to quantify α-SMA protein contents, and immunofluorescence (IF) was used to visualize MFB differentiation by staining for α-SMA after 72 h. A resazurin-based assay was used to assess cell viability to ensure the anti-MFB effect of the drugs. A mechanistic study was performed using IF staining for YAP/TAZ nuclear translocation. After 72 h of stimulation with TGF-β1, a six- to 10-fold upregulation of α-SMA could be observed. When treated with Y-27632 or simvastatin, the α-SMA, collagen III, elastin and CTGF mRNA expression was impeded. Additionally, TGF-β1 stimulation showed a twofold increase in α-SMA protein expression, which was reversed to non-stimulated levels after treatment with Y-27632 and simvastatin. Using IF, stimulated cells were identified as MFB (α-SMA+, Vim+) as opposed to the non-stimulated, Y-27632- and simvastatin-treated cells (α-SMA-, Vim+). The resazurin-based assay confirmed that the cell viability was not compromised by the administered drugs. On stimulation with TGF-β1, nuclear translocation of YAP/TAZ could be observed, which was prevented by adding the aforementioned compounds. Transformation of FBs into the contractile and extracellular matrix-producing MFBs occurs after TGF-β1 stimulation. In our experiments, Rho-kinase inhibition and simvastatin treatment were shown to prevent this in TGF-β1-stimulated cells on an RNA and protein level through the inhibition of YAP/TAZ nuclear translocation. Y-27632 and simvastatin could become a novel treatment option in the early treatment of PD.


An integrated dataset of malaria notifications in the Legal Amazon.
Malaria is an infectious disease that annually presents around 200,000 cases in Brazil. The availability of data on malaria is crucial for enabling and supporting studies that can promote actions to prevent it. Therefore, the goal of this paper is to contribute to such studies by offering an integrated dataset containing data on reported and suspected cases of malaria in the Brazilian Legal Amazon comprising the period from the years 2009 to 2019. This paper presents a dataset with all medical records of patients who were tested for malaria in the Brazilian Legal Amazon from 2009 to 2019. The dataset has 40 attributes and 22,923,977 records of suspected cases of malaria. Around 12% of the data correspond to confirmed cases of malaria. The attributes include data regarding the notifications, examinations, as well as personal patient information, which are organized into health regions.


Posttransfusion crises in sickle cell anemia: role of delayed hemolytic reactions to transfusion.
We describe ten patients with sickle cell anemia who became acutely ill within a few days after a blood transfusion. Two patients died. In eight cases the posttransfusion detection of alloantibodies suggested that delayed hemolytic reactions to transfusion were involved in precipitating the acute illness. In some cases the illnesses mimicked vaso-occlusive crises, with bone marrow infarction, while in other cases transient biliary obstruction or transient renal insufficiency was documented. Profound anemia mimicked aplastic crises, but we observed a remarkable capacity of the bone marrow to restore the hemoglobin level without further transfusion. In view of the prevalence of delayed hemolytic transfusion reactions in these patients receiving frequent transfusions and whose red cell antigens differ from those of the white population, we suggest that efforts to more closely match recipient and donor red cell antigens would be clinically, technically, and financially advantageous. Moreover, criteria for transfusion in sickle cell anemia should be strictly scrutinized. Quantitation of transfused hemoglobin A has proved useful in confirming delayed hemolytic reactions in sickle cell disease.


A zero-dose synthetic baseline for the personalized analysis of [18F]FDG-PET: Application in Alzheimer's disease.
Brain 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG-PET) is widely used in the diagnostic workup of Alzheimer's disease (AD). Current tools for uptake analysis rely on non-personalized templates, which poses a challenge as decreased glucose uptake could reflect neuronal dysfunction, or heterogeneous brain morphology associated with normal aging. Overcoming this, we propose a deep learning method for synthesizing a personalized [18F]FDG-PET baseline from the patient's own MRI, and showcase its applicability in detecting AD pathology. We included [18F]FDG-PET/MRI data from 123 patients of a local cohort and 600 patients from ADNI. A supervised, adversarial model with two connected Generative Adversarial Networks (GANs) was trained on cognitive normal (CN) patients with transfer-learning to generate full synthetic baseline volumes (sbPET) (192 × 192 × 192) which reflect healthy uptake conditioned on brain anatomy. Synthetic accuracy was measured by absolute relative %-difference (Abs%), relative %-difference (RD%), and peak signal-to-noise ratio (PSNR). Lastly, we deployed the sbPET images in a fully personalized method for localizing metabolic abnormalities. The model achieved a spatially uniform Abs% of 9.4%, RD% of 0.5%, and a PSNR of 26.3 for CN subjects. The sbPET images conformed to the anatomical information dictated by the MRI and proved robust in presence of atrophy. The personalized abnormality method correctly mapped the pathology of AD subjects while showing little to no anomalies for CN subjects. This work demonstrated the feasibility of synthesizing fully personalized, healthy-appearing [18F]FDG-PET images. Using these, we showcased a promising application in diagnosing AD, and theorized the potential value of sbPET images in other neuroimaging routines.


Autocatalytic demetalation of a Zn(salphen) complex provoked by unprotected N-heterocycles.
The interaction of Zn(salphen) complex with biologically important structures such as (benz)imidazoles and purine has been studied and revealed in the case of unprotected purine and (benz)imidazole derivatives a demetalated product, whereas for structurally related 1-methyl-(benz)imidazole the formation of 1 : 1 coordination complexes was evidenced by NMR, MS and X-ray crystallography.


Circulating microRNA profile predicts disease progression in patients receiving second-line treatment of lapatinib and capecitabine for metastatic pancreatic cancer.
Patients exhibiting pancreatic cancer possess poor rates of survival. Therefore, the identification of a biomarker that can be measured non-invasively and be used to predict patient outcomes is required for the successful treatment of pancreatic cancer. The present study evaluated serum microRNA (miRNA/miR) profiles in patients exhibiting pancreatic cancer, who were treated with lapatinib and capecitabine in a phase II trial. Serum samples were collected for the measurement of a panel of miRNAs (miR-21, miR-210, miR-221 and miR-7) associated with the epidermal growth factor receptor (EGFR)1 and human epidermal growth factor receptor (HER)2 pathways. Preclinically, human pancreatic cancer PANC-1, MIA PaCa-2 and BXCP-3 cell lines were utilized for miRNA and drug resistance studies. In total, 6/17 patients treated experienced disease progression following 2 cycles of treatment [non-responders (NRS)], while another 6/17 patients exhibited a stable disease state and received >4 cycles of treatment [responders (RS); range, 4-22 cycles]. Five patients withdrew from the study due to severe toxicity or mortality. The mean overall survival time was 6.5 vs. 10.4 months for NRS and RS, respectively. Significant upregulation of serum miRNAs at earlier time points (3-6 weeks) was observed in NRS. miRNA levels increased with cancer progression, and lapatinib and 5-fluorouracil (5-FU; the active form of capecitabine) treatment increased the miRNA levels (specifically miR-210 and miR-221) in the treatment-resistant pancreatic cancer PANC-1 and MIA PaCa-2 cell lines. However, lapatinib and 5-FU treatment did not increase the miRNA levels in the treatment-sensitive BXPC-3 cell line. Inhibition of miR-221 increased the sensitivity of the PANC-1 cells to treatment. In conclusion, an increase in specific serum miRNAs was associated with resistance to lapatinib and capecitabine treatment. Additional investigation is required with regard to the application of the miRNA panel investigated in the present study as a potential predictor of patient responses to anti-EGFR/HER2 treatment.


Technical possibilities for coronary artery bypass surgery and the outlook for graft patency.
In an attempt to analyse the results of saphenous bypass grafting 213 patients were re-investigated by repeat coronary, graft and left ventricular angiography. In this series, the presence of diffuse arterial disease was not considered as a contra-indication to operation. Instead, additional endarterectomy was performed. The overall patency rate was 88% and was not significantly altered by the passage of time, although the patency rate during the first 6 months was 94%. The patency rate did not appear to be influenced by the age of the patient, the severity of the lesion pre-operatively, the artery grafted nor additional endarterectomy. The run-off was judged to be good in 82% of grafts investigated before 6 months, compared to 70% of those investigated later. Progress of the disease in the native vessels appeared to be slightly accelerated in the segment proximal to the graft.


Microsurgical technique as a method for prevention of recurrent laryngeal nerve injury in thyroid surgery. Review of seven consecutive cases.
Vocal cord paresis or paralysis due to iatrogenic injury of the recurrent laryngeal nerve is one of the main problems in thyroid surgery. Although many procedures have been introduced to prevent the nerves from lesion the incidence of recurrent laryngeal nerve palsy varies between 1.5-14%. The aim of the study was to evaluate the role of the microsurgical technique as a method, which can help the surgeon to identify the recurrent laryngeal nerve in the operative field. Fourteen nerves in 7 patients were identified with Zeiss multidiscipline universal surgical microscope with a 250-mm ocular lens. All were female patients with mean age of 35 years (Range 16-53) and diagnosis papillary cancer. They were admitted and operated in the Department of Ear, Nose, and Throat Diseases of the Higher Medical Institute in Plovdiv, Bulgaria. In all patients the recurrent laryngeal nerves were successfully identified along their whole length from the inferior thyroid artery to their entering the laryngeal muscles. None of the patients had temporary or permanent vocal cord palsy. Microsurgical technique could be a procedure of great value for prevention of the recurrent laryngeal nerves during thyroid surgery, especially in reoperations, thyroid cancer or retrosternal goitre.


Clinical applications of advances in the genetics of IBD.
Our rapidly expanding understanding of the genetics of inflammatory bowel disease (IBD) has led to important clinical applications. It is becoming apparent that genes help determine the clinical phenotype, intestinal and extraintestinal complications, response to treatment, and drug toxicities in these disorders. For example, NOD2/CARD15 mutations are associated with ileal Crohn's disease, possibly with a fibrosing/obstructing phenotype, but do not influence responses to infliximab treatment. Similarly, certain human leukocyte antigen (HLA) haplotypes are associated with aggressive, extensive ulcerative colitis and strongly influence extraintestinal manifestations of IBD, including uveitis and various forms of arthritis. Expression of the glucocorticoid receptor b determines the clinical response to corticosteroids, whereas genetically regulated levels of enzymes metabolizing 6-mercaptopurine/azathioprine may determine clinical responses and toxicities to these important immunosuppressive agents. Once we have a more sophisticated understanding of the mechanisms of genetic defects in IBD, it may be feasible to restore physiologic function to prevent the onset of disease in susceptible individuals. However, because we do not have the ability to prevent disease at the present time, it is premature to screen offspring and first-degree relatives of IBD patients for the NOD2/CARD15 genotype. One can anticipate that it will become feasible to prospectively determine a patient's genotype and to individualize a drug regimen, leading to highly effective, safe treatments for IBD patients on a rational, rather than empiric, basis.


Point-Of-Care Ultrasound as an Adjunct in the Diagnosis of Neonatal and Pediatric Superficial Soft Tissue Infection: A Report of Two Cases.
Considerable technological advances, good safety profile, and ease of use have converged to support the use of ultrasound (US) as an important adjunct in the evaluation of superficial soft tissue infections (SSTI) in general and the differential diagnosis of cellulitis and abscess in particular. However, its use in neonatal populations has not been described. Pediatric studies report clinical examination is not always a reliable method of distinguishing cellulitis from abscess. Two (2) case reports are presented to supplement the growing body of published data that describe US imaging of SSTIs. In both cases, the US exam included the affected area as well as contralateral or adjacent normal skin for comparison. Case 1 describes a preterm infant boy who required placement of a peripheral intravenous (PIV) line and subsequently developed warm, painful, erythematous, and indurated skin in the area of the insertion. Point-of-care US (POC-US) was used to diagnose cellulitis, which initiated treatment with intravenous antibiotics. Case 2 involves a 7-year-old boy with multiple comorbidities who developed a PIV extravasation-related injury that subsequently progressed to cellulitis, likely secondary to wound infection with methicillin-resistant Staphylococcus aureus. Both patients healed completely and without any complications. Because treatment of cellulitis is different from that of abscess, it is important to obtain real-time data supportive of an accurate diagnosis. In these cases, POC-US confirmed the clinical diagnosis of cellulitis and ruled out the presence of an abscess.


Postoperative MRI Visualization of the Cervical Spine Following Cervical Disc Arthroplasty: A Prospective Single-Center Comparison of a Titanium and Cobalt-Chromium Prosthesis.
Prospective non-randomized single-center cohort study. To analyze the quality of postoperative magnetic resonance imaging of 2 structurally different cervical disc arthroplasty devices at the index and adjacent levels. A non-randomized, comparative, prospective, single-center study included 40 patients (23 men and 17 women) aged 32 (26-40) years. Two study groups were utilized: in the first (n = 20), a titanium prosthesis was used; in the second (n = 20), a cobalt-chromium implant was used. Evaluation of MRI studies before and after surgery was performed using sagittal and axial T2 weighted images by 2 specialists who were blinded to the prosthesis that was used. To determine the quality of an MRI image, the classification of Jarvik 2000, the radiological and orthopedic scales for assessing artifacts were used. There was good-to-excellent inter-observer agreement for all of the MR parameters used for the titanium and satisfactory-to-good for the cobalt chromium group. The analysis of the quality of postoperative imaging using the Jarvik 2000 scale showed a statistically significant deterioration in MR images in the cobalt chromium group (P < 0.001), compared to the titanium (P = 0.091). Following a single-level total arthroplasty, the titanium group had better MRI images according to radiological and orthopedic scales (P < 0.001). Titanium cervical disc arthroplasty devices result in superior postoperative MR imaging, as compared to cobalt chromium prostheses, as the latter significantly reduces image quality due to the pronounced ferromagnetic effect.


Influence of lake characteristics on the biomagnification of persistent organic pollutants in lake trout food webs.
The biomagnification of polychlorinated biphenyls (PCBs) and major organochlorine pesticides (OCPs) was studied using lake trout (Salvelinus namaycush) and other food web organisms collected from 17 lakes in Canada and the northeastern United States between 1998 and 2001. Whole lake trout (n = 357) concentrations of the sum (Sigma) of 57 PCB congeners ranged between 1.67 and 2,890 ng/g wet weight (median 61.5 ng/g wet wt). Slimy sculpin had the highest mean concentrations of SigmaPCB of all forage fish (32-73 ng/g wet wt). Positive relationships between log (lipid wt) concentrations of PCB congener 153, PCB congener 52, p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene, cis-chlordane, trans-nonachlor, or dieldrin and trophic level (determined using stable nitrogen isotope ratios) were found for most of the 17 food webs, indicating biomagnification of these PCBs and OCPs. The p,p'-dichlorodiphenyldichloroethylene had the highest trophic magnification factors (TMFs) of the 14 individual compounds studied, averaging 4.0 +/- 1.8 across the 17 lakes, followed by trans-nonachlor (3.6 +/- 1.5) and PCB congener 153 (3.4 +/- 1.2). Average TMFs for 14 individual PCBs or OCPs were significantly correlated with log octanol-water partition coefficient, implying that the rate of accumulation along the food web is dependent on hydrophobicity and recalcitrance. Significant correlations (p < 0.05) were found between TMFs of SigmaPCBs, hexachlorobenzene, alpha-hexachlorocyclohexane, and lindane and lake area, latitude, and longitude, but not for 11 other PCBs or OCPs. Overall, the results of the present study show that biomagnification of PCBs and most OCPs, as measured by TMFs, is only weakly influenced by such factors as latitude and longitude. Exceptions are hexachlorocyclohexane isomers and hexachlorobenzene, which had generally greater TMFs in northern lakes, possibly due to lower rates of elimination and biotransformation in the food web.


Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats.
Hypertension-induced structural remodeling of the left atrium (LA) has been suggested to involve the renin-angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32-week-old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age- and sex-matched Wistar-Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin-43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy.


Maxillofacial Fractures Associated With Interpersonal Violence.
Interpersonal violence is a major cause of maxillofacial fractures. The aim of this study was to analyze the characteristics of these fractures associated in an effort to develop more effective management. The clinical records and radiographs of 272 patients with maxillofacial fractures associated with interpersonal violence collected during a 36-year period were retrospectively analyzed. Two hundred and nineteen patients were male (80.5%) and 53 (19.5%) were female. The patients ranged in age from 1 to 77 years. Two hundred and two patients (74.3%) were aged 10 to 29 years. The injury was the result of impact by a fist/hand/elbow in 224 patients (82.3%). The fracture site was the mandible in 191 patients (70.2%), the midface in 78 (28.7%), and both sites in 3 (1.1%). One hundred and eight (39.6%) of 273 mandibular fractures were in the angle, 75 (27.5%) were in the symphysis, and 90 (33.0%) were at other sites. Forty-three (53.1%) of 81 fractures in the midface were in the zygoma, 19 (23.5%) were in the maxilla, and 19 (23.5%) were at other sites. Fractures were more common on the left side. Nine patients (3.3%) also had injuries at other body sites. Ninety-five patients (34.9%) were treated by maxillomandibular fixation, 84 (30.9%) by open reduction and internal fixation, 59 (21.7%) by observation, 14 (5.1%) by intramaxillary splinting, 14 (5.1%) by transcutaneous reduction, and 6 (2.2%) by other procedures. Interpersonal violence-related maxillofacial fractures have characteristic features, especially with regard to site and laterality.