Gene expression profiles and neural activities of Kenyon cell subtypes in the honeybee brain: identification of novel 'middle-type' Kenyon cells.
In the honeybee (Apis mellifera L.), it has long been thought that the mushroom bodies, a higher-order center in the insect brain, comprise three distinct subtypes of intrinsic neurons called Kenyon cells. In class-I large-type Kenyon cells and class-I small-type Kenyon cells, the somata are localized at the edges and in the inner core of the mushroom body calyces, respectively. In class-II Kenyon cells, the somata are localized at the outer surface of the mushroom body calyces. The gene expression profiles of the large- and small-type Kenyon cells are distinct, suggesting that each exhibits distinct cellular characteristics. We recently identified a novel gene, mKast (middle-type Kenyon cell-preferential arrestin-related gene-1), which has a distinctive expression pattern in the Kenyon cells. Detailed expression analyses of mKast led to the discovery of novel 'middle-type' Kenyon cells characterized by their preferential mKast-expression in the mushroom bodies. The somata of the middle-type Kenyon cells are localized between the large- and small-type Kenyon cells, and the size of the middle-type Kenyon cell somata is intermediate between that of large- and small-type Kenyon cells. Middle-type Kenyon cells appear to differentiate from the large- and/or small-type Kenyon cell lineage(s). Neural activity mapping using an immediate early gene, kakusei, suggests that the small-type and some middle-type Kenyon cells are prominently active in the forager brain, suggesting a potential role in processing information during foraging flight. Our findings indicate that honeybee mushroom bodies in fact comprise four types of Kenyon cells with different molecular and cellular characteristics: the previously known class-I large- and small-type Kenyon cells, class-II Kenyon cells, and the newly identified middle-type Kenyon cells described in this review. As the cellular characteristics of the middle-type Kenyon cells are distinct from those of the large- and small-type Kenyon cells, their careful discrimination will be required in future studies of honeybee Kenyon cell subtypes. In this review, we summarize recent progress in analyzing the gene expression profiles and neural activities of the honeybee Kenyon cell subtypes, and discuss possible roles of each Kenyon cell subtype in the honeybee brain.


Testing mechanisms of coexistence among two species of frugivorous primates.
1. We examined mechanisms of coexistence between two congeneric species of frugivorous primates, the blue monkey (Cercopithecus mitis) and the red-tailed monkey (C. ascanius). 2. We used giving-up densities (the amount of food which animals leave in a patch) in fruit trees to measure foraging efficiency and to evaluate possible mechanisms of coexistence. Animals with higher giving-up densities are less likely to persist in the company of those with lower giving-up densities because the former are not able to exploit food patches used previously by the latter. We climbed trees to estimate giving-up densities by counting the fruit which primates left behind. 3. We tested five possible mechanisms of coexistence. Three mechanisms proposed that each frugivorous species has a lower giving-up density than the other in at least one of the following: (1) different tree species, (2) within-tree foraging zones or (3) seasons. The fourth mechanism predicted that the socially dominant species exploits resources first and that the subordinate species has lower giving-up densities. The final mechanism predicted that one species would find resources more quickly than the other, which would in turn have a lower giving-up density. 4. Four of the five mechanisms received no support from our data. Only a trade-off between interspecific dominance and giving-up densities was supported. 5. We discuss the generality of our results and possible interactions with other factors.


Neighbourhood sociodemographic factors and COVID-19 vaccine uptake in the Netherlands: an ecological analysis.
While overall COVID-19 vaccine uptake is high in the Netherlands, it lags behind in certain subpopulations. We aimed to explore the characteristics of groups with lower COVID-19 vaccine uptake at neighbourhood level to inform the strategy to improve uptake and guide research into barriers for vaccination. We performed an ecological study using national vaccination register and socio-demographic data at neighbourhood level. Using univariate and multivariable generalized additive models we examined the (potentially non-linear) effect of each determinant on uptake. We focused on those aged 50 years and older, since they are at highest risk of severe disease. In those over 50 years of age, a higher proportion of individuals with a non-Western migration background and higher voting proportions for right-wing Christian and conservative political parties were at neighbourhood level univariately associated with lower COVID-19 vaccine uptake. In contrast, higher socioeconomic status and higher voting proportions for right-wing liberal, progressive liberal and Christian middle political parties were associated with higher uptake. Multivariable results differed from univariate results in that a higher voting proportion for progressive left-wing political parties was also associated with higher uptake. In addition, with regard to migration background only a Turkish background remained significant. We identified determinants associated with COVID-19 vaccine uptake at neighbourhood level and observed heterogeneity in uptake between different subpopulations. Since the goal of vaccination is not only to reduce suffering and death by improving the average uptake, but also to reduce health inequity, it is important to focus on subpopulations with lower uptake.


[Interaction of the angular and linear components of the horizontal vestibulo-ocular reflex in the pigeon].
Pigeons were exposed to centric and eccentric horizontal rotations in darkness by velocity trapezoid. Different in sign the duration alterations of the opposite directed horizontal eye nystagmus occurred during otolith membrane shifts in sagittal as well as frontal planes. A direct dependence was found between the duration alterations of the primary nystagmus phase and the peak value alterations of its slow phase velocity under increased (but not decreased) centrifugal force. In the both cases, if duration of the primary nystagmus phase was enlarged, duration of its secondary phase was diminished and vice versa. It suggests the otolith component does not decay up to zero by constant velocity and at once after rotation; by deceleration it is biphasic. In affirms the own hypothesis that the linear component is asymmetric central neuronal activity that modifies the canal component even if this activity by itself is not enough for eye movement initiation.


Establishment of patient-like SCID mouse model by orthotopically implanting primary cultured cells from surgically-resected lung cancer tissues.
In our previous studies, we established a lymphogenous metastatic SCID mouse model using orthotopic implantation of human lung cancer cell lines. However, the lymphogenous metastatic potential of each cell line in our models does not reflect that of a primary tumor. In this study, we made orthotopic implanted models using primary cultured cells from surgically-resected lung cancer tissues. Tissues of 5 patients with non-small cell lung cancer (NSCLC) were applied to a primary culture method using a collagen gel coated flask. Suspensions of 2.0x10(4) cancer cells were injected into the left lung of SCID mice. We could maintain primary culture cells from 2 (FM205 and FT821 cells) of 5 lung cancers, and made orthotopically implanted SCID mouse models. The size of both tumors in implanted sites of the lung increased with time. The FM205 cells microscopically were metastasized to the mediastinum by 4 weeks after implantation and macroscopically metastasized by 16 weeks. The FT821 cells were microscopically metastasized to the mediastinum by 4 weeks after implantation and macroscopically metastasized by 6 weeks. The lymphogenous metastatic potential of these primary culture cells was similar to that of clinical tumors. As the lymphogenous metastatic potential of this model reflects that of the clinical tumor, it is useful for elucidating the mechanism of lymphogenous metastasis and selecting anticancer drugs suitable for an individual patients.


Activation of PI3K is associated with reduced survival in renal cell carcinoma.
The epidermal growth factor receptor- (EGFR) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway is associated with tumorigenesis and progression. The aims of the present study were to determine the expression patterns of Akt pathway parameters PI3K, phosphatase and tensin homolog (PTEN), phosphor-Akt (p-Akt) and their combination, for their possible prognostic value in renal cell carcinoma (RCC). PTEN dephosphorylates the liquid product of PI3K. Tumor samples from 176 RCC patients were investigated for PTEN, p-Akt and PI3K expression by immunohistochemistry. Expression levels were correlated to clinical variables and postoperative outcome by uni- and multivariate statistical analysis. The various expression levels within the tumor samples were independent of histological grade and tumor stage, due to different levels of activation of the PI3K/p-Akt pathway. The activation of PI3K protein was found to be significantly associated with reduced survival times (p = 0.0304, multivariate analysis). Analysis of combined biomarker expressions showed that decreased long-term survival was correlated with PTEN low/p-Akt high expression (p < 0.05). Activation of the PI3K pathway is significantly associated with adverse clinical outcome in RCC. Analysis of biomarker combinations might identify high-risk patients and a subsequent need to adapt treatment modalities. Molecular pathways regulating PI3K activation appear to be promising targets for drug development in the clinical management of RCC patients.


Interprofessional education for physiotherapy, medical and dietetics students: a pilot programme.
Interprofessional education (IPE) has been shown to enhance interprofessional practice among health professionals. Until recently there has been limited opportunity to undertake such initiatives within existing pre-registration degree courses in New Zealand. This study aimed to test the feasibility of delivering an interprofessional component within existing health professional courses for medicine, physiotherapy and dietetics at the University of Otago, Wellington, New Zealand. An interprofessional case-based course component (on chronic condition management) was developed by academic clinical teachers from schools of medicine, physiotherapy and dietetics at the same location. Evaluation was undertaken using a previously validated pre- and post-survey tool, to ascertain changes in attitude among students towards interprofessional practice, IPE and the effectiveness of health care teams. Focus groups were conducted with students and teachers. Survey results indicated pre-existing positive attitudes to interprofessional practice and education among students. There was a statistically significant increase in positive attitude towards such practice and education, and increased confidence in the effectiveness of heath care teams. Focus group findings were consistent with the survey results for students, and highlighted challenges experienced by the teachers. Students and teachers alike enjoyed the interprofessional interaction and benefited from a collaborative approach to chronic condition management. The timing and nature of learning activities and assessment methods created logistical challenges. Such course components have potential to improve collaborative practice and the quality and safety of health care among graduates. Interprofessional course components need to be equitable across disciplines and embedded in the unidisciplinary courses.


Synergistic Antimicrobial Activity by Light or Thermal Treatment and Lauric Arginate: Membrane Damage and Oxidative Stress.
The need for more effective antimicrobials is critical for the food industry to improve food safety and reduce spoilage of minimally processed foods. The present study was initiated to develop an efficient and novel antimicrobial approach which combines physical treatments (UV-A or mild heat) and generally recognized as safe lauroyl arginate ethyl (LAE) to inactivate surrogate strains, including Escherichia coli and Listeria innocua Synergistic inactivation of bacteria resulted in an ∼6-log reduction of target bacteria, while individual treatments resulted in <1.5-log inactivation under the same set of conditions. In addition, the synergistic mechanism between LAE and UV-A/mild heat was evaluated by supplementing with a variety of antioxidants for suppressing oxidative stress and measurement of cell membrane damage by nucleic acid release. These results demonstrate that the synergistic antimicrobial activity of LAE and mild physical stresses was suppressed by supplementation with antioxidants. The research also compared LAE with another membrane-targeting lipopeptide antimicrobial agent, polymyxin B, to understand the uniqueness of LAE-induced synergy. Briefly, differences in modes of action between LAE and polymyxin B were characterized by comparing the MIC, damage to liposomes, and oxidative stress generation. These differences in the mode of action between LAE and polymyxin B suggested that both compounds target cell membrane but significantly differ in mechanisms, including membrane disruption and oxidative stress generation. Overall, this study illustrates synergistic antimicrobial activity of LAE with light or mild heat and indicates a novel oxidative stress pathway that enhances the activity of LAE beyond membrane damage.IMPORTANCE This study highlights an effective antimicrobial processing approach using a novel combination of lauroyl arginate ethyl (LAE) and two different physical treatments, light (UV-A) and mild heat. Both combinations demonstrated synergistic inactivation against a model Gram-negative bacterium or a Gram-positive bacterium or both by a >5-log reduction. Further mechanistic study revealed that oxidative stress is responsible for synergistic inactivation between LAE and UV-A, while both membrane damage and oxidative stress are responsible for the synergistic combination between LAE and mild heat. The mode of action of LAE was further compared to that of polymyxin B and analyzed using artificial membrane model systems and the addition of antioxidants. The proposed combination of LAE and common physical treatments may improve food preservation, food safety, and current sanitation processes for the food industry and the inactivation of pathogenic strains in biomedical environments.


Themes in Health Sciences Librarianship Literature, 2016-2020: A Keyword and Subject Analysis.
Previous investigations into trends in Library and Information Science literature have revealed changes in the topics librarians publish on over time, with older studies highlighting classification and indexing, and information retrieval and more recent studies highlighting keywords such as Internet, information technology, digital libraries, and again, information retrieval. No similar investigation has been conducted on current publication trends by health sciences librarians. This study analyzes the top themes on which health sciences librarians published from 2016 to 2020 by examining the frequency of keywords. Keywords and subject headings were analyzed from The Journal of the Medical Library Association, Medical References Services Quarterly, The Journal of Hospital Librarianship, and The Journal of Electronic Resources in Medical Libraries. A total of 8,806 keywords were downloaded for analysis and organized into 292 categories during taxonomy creation. The ten most frequent themes were: libraries, information, education, humans, demography, librarian, geographical locations, research, electronic resources, and technology. The study also found that data, psychiatry and psychology, informatics, and publishing were other key themes, indicating that health sciences librarians are publishing on a wide range of topics. Some keywords that appeared only once, such as telecommuting and flexible staffing, suggest emerging areas of research for librarians.


A review on the fruit components affecting uric acid level and their underlying mechanisms.
Uric acid (UA) is produced in the liver and excreted through the kidneys and intestines. If UA is overproduced or its excretion reduces, the concentration of UA increases, leading to hyperuricemia and gout. The high concentration of UA is also related to cardiovascular disease, hypertension, obesity, and other diseases. Fruits are healthy foods. However, fruits contain fructose and small amounts of purine, and the product of their metabolism is UA. Therefore, theoretically, eating fruits will increase the concentration of serum UA. Fruit components are numerous, and their effects on serum UA are complex. According to the current research, fructose, purine, polyphenols, vitamin C, dietary fiber, and minerals present in fruits influence serum UA concentrations. In addition to the UA synthesized by fructose and purine metabolism, the mechanisms by which other components affect the concentration of serum UA can be summarized as follows: (a) inhibiting xanthine oxidase; (b) reducing reabsorption of UA; and (c) improving the excretion of UA. In this review, we comprehensively discussed the fruit components that affect serum UA concentrations, and explained their mechanisms for the first time, which references for patients with hyperuricemia to take fruits. PRACTICAL APPLICATIONS: With the rising prevalence, hyperuricemia and gout have become public health problems that endanger our daily life. The key to the treatment of hyperuricemia is to control the level of serum UA within the normal range. Fruits are healthy foods. However, fruit components are numerous, and their effects on serum UA are complex. According to the current research, fructose, purine, polyphenols, vitamin C, dietary fiber, and minerals present in fruits influence serum UA concentrations. In this review, we comprehensively discussed the fruit components that affect serum UA concentrations. We also explained their mechanisms, which references for patients with hyperuricemia to take fruits.


Mitochondrial malate dehydrogenase: a new genetic polymorphism in man.
Starch-gel electrophoresis patterns of malate dehydrogenase from human tissue indicate a new genetic polymorphism for the mitochondrial form of the enzyme. Studies of families showed simple Mendelian segregation rather than maternal inheritance, suggesting that not all mitochondrial proteins are coded by mitochondrial DNA.


Gastrointestinal uptake of macromolecules.
Although the majority of dietary proteins undergo extensive digestion, small, nutritionally insignificant amounts of food proteins appear to cross the gastrointestinal mucosa intact. Experiments in a variety of allergic models has demonstrated that exposure of the gastrointestinal mucosa to the intact allergen leads to an anaphylactoid reaction. To examine the uptake of immunologically intact protein across the gastrointestinal epithelium, the mucosal to serosal movement of bovine serum albumin was measured in stripped gastric and intestinal mucosa mounted in modified Ussing-type chambers. Studies demonstrated that both gastric and intestinal mucosa are capable of actively transporting intact dietary proteins. In the intestine, the transport of intact molecules across the epithelium is a saturable, energy dependent process which utilizes the microtubular network and is regulated by the enteric nervous system. Transport across gastric mucosa is also dependent upon the microtubular network and is energy dependent.


Lower Urinary Tract Symptoms in Myasthenia Gravis.
It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS questionnaire devised for detecting neurogenic pelvic organ dysfunction (not validated) in an MG group and a healthy control group and compared the results. The MG group comprised 21 patients: 15 women and 6 men, with age range 22-73 (mean 47) years, illness duration range 0.2-8 (mean 3.5) years, median Myasthenia Gravis Foundation of America (MGFA) grade 2, all walking independently. Therapies included thymectomy in 17, predonisolone 5-20 mg/day in 10, and pyridostigmine bromide 60-180 mg/day in 9 patients. The control group, who were undergoing an annual health survey, comprised 235 consecutive subjects: 120 women and 115 men, with age range 30-69 (mean 48) years. The questionnaire had 9 questions. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). Statistical analysis was made using Student's t test. Compared with the control subjects, the frequency of LUTSs in the MG patients was significantly higher for daytime frequency (43%; p < 0.01), nocturia (24%; p < 0.01), and urinary incontinence (43%; p < 0.05). The LUTS-related QOL index for the MG patients was significantly higher for MG patients as a whole than that for all control patients (29%) (p < 0.05). In conclusion, our study results showed that MG patients had significantly more LUTSs (overactive bladder) than healthy control subjects and had worse LUTS-related QOL; therefore, amelioration of LUTS in MG is important.


Malignant giant cell tumor of the soft tissue: angiographic manifestations.
Two cases of malignant giant cell tumor originating within the soft tissues of the thigh are reported. In both instances, angiography demonstrated hypervascular masses with arterial and venous abnormalities indicative of an aggressive malignancy. The histopathologic appearance of the lesions was similar to that of osseous giant cell tumors. The clinical and radiographic features of this rare entity are briefly reviewed.


Change of calbindin D-28k protein expression in the mice hippocampus after lipopolysaccharide treatment.
A previous study showed that 1 mg/kg lipopolysaccharide (LPS) treatment did not lead to the any neuronal death/degeneration in the mouse hippocampus. In the present study, we examined the time-dependent changes of calbindin D-28k (CB) protein expression in the mouse hippocampus after a systemic administration of 1 mg/kg LPS. CB immunoreactivity was markedly increased in pyramidal cells of the hippocampal CA1/2 regions and in granule cells of the dentate gyrus from 3 hr to 48 hr after LPS treatment. At this point in time, CB protein level was also significantly increased in the mouse hippocampus. Thereafter, CB protein expression was decreased at 96 hr after LPS treatment. These results indicate that changes of CB protein expression may be associated with no neuronal death in the model of neuroinflammation with systemic administration of 1 mg/kg LPS.


Evaluation of effectiveness of cryotherapy on the treatment of cutaneous Kaposi's sarcoma.
Kaposi's sarcoma (KS) is a vascular tumor that affects the skin and other organs. Several therapeutic options are available, but the optimal therapy is unclear. The aim of this study was to determine the effectiveness and safety of cryotherapy in the treatment of KS. Thirty patients were evaluated. Cryotherapy was applied using liquid nitrogen. Each treatment consisted of two freeze-thaw cycles, with freezing times ranging from 15 to 40 seconds per cycle. One hundred twenty-five lesions were treated in an average of 3.2 sessions. Complete response was observed in 19 (63%) of the 30 patients after cryotherapy treatment with no recurrence. The subjects tolerated cryotherapy well. Blistering occurred frequently, but local pain was limited. There were no secondary infections. Liquid nitrogen cryotherapy is safe and cost-efficient and can be readily adopted as an effective primary therapy for cutaneous KS lesions that respond slowly or show incomplete cosmetic improvement after systemic therapies.


Transformation of Mature Osteoblasts into Bone Lining Cells and RNA Sequencing-Based Transcriptome Profiling of Mouse Bone during Mechanical Unloading.
We investigated RNA sequencing-based transcriptome profiling and the transformation of mature osteoblasts into bone lining cells (BLCs) through a lineage tracing study to better understand the effect of mechanical unloading on bone loss. Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen three times a week starting at postnatal week 7, and subjected to a combination of botulinum toxin injection with left hindlimb tenotomy starting at postnatal week 8 to 10. The animals were euthanized at postnatal weeks 8, 9, 10, and 12. We quantified the number and thickness of X-gal(+) cells on the periosteum of the right and left femoral bones at each time point. Two weeks after unloading, a significant decrease in the number and a subtle change in the thickness of X-gal(+) cells were observed in the left hindlimbs compared with the right hindlimbs. At 4 weeks after unloading, the decrease in the thickness was accelerated in the left hindlimbs, although the number of labeled cells was comparable. RNA sequencing analysis showed downregulation of 315 genes in the left hindlimbs at 2 and 4 weeks after unloading. Of these, Xirp2, AMPD1, Mettl11b, NEXN, CYP2E1, Bche, Ppp1r3c, Tceal7, and Gadl1 were upregulated during osteoblastogenic/osteocytic and myogenic differentiation in vitro. These findings demonstrate that mechanical unloading can accelerate the transformation of mature osteoblasts into BLCs in the early stages of bone loss in vivo. Furthermore, some of the genes involved in this process may have a pleiotropic effect on both bone and muscle.


Measurement of an exceptionally weak electron-phonon coupling on the surface of the topological insulator Bi2Se3 using angle-resolved photoemission spectroscopy.
Gapless surface states on topological insulators are protected from elastic scattering on nonmagnetic impurities which makes them promising candidates for low-power electronic applications. However, for widespread applications, these states should have to remain coherent at ambient temperatures. Here, we studied temperature dependence of the electronic structure and the scattering rates on the surface of a model topological insulator, Bi2Se3, by high-resolution angle-resolved photoemission spectroscopy. We found an extremely weak broadening of the topological surface state with temperature and no anomalies in the state's dispersion, indicating exceptionally weak electron-phonon coupling. Our results demonstrate that the topological surface state is protected not only from elastic scattering on impurities, but also from scattering on low-energy phonons, suggesting that topological insulators could serve as a basis for room-temperature electronic devices.


Biologic treatment for rheumatic disease: real-world big data analysis from the Greek country-wide prescription database.
To directly assess the prevalence of inflammatory rheumatic disease under treatment with biologic disease modifying anti-rheumatic drugs (b-DMARDs) and compare treatment patterns between rheumatoid arthritis (RA) and spondyloarthropathy (SpA), including psoriatic arthritis. The obligatory country-wide prescription electronic database covering 10.223.000 Greek citizens (95.1% of the population, 99.5% Caucasian), all of whom with fully reinbursed access to b-DMARDs, was used to retrospectively capture all patients under b-DMARDs for RA/SpA between June 2014-May 2015. Age, gender and medications for RA/SpA and co-morbid classical cardiovascular risk factors (hypertension, dyslipidaemia, diabetes) were retrieved and analysed. A total of 9.824 RA (61.2±14.0 years, 79% women) and 9.279 SpA patients (51.4±13.1 years, 41% women) using pharmacy-dispensed prescriptions for b-DMARDs were identified (overall prevalence 0.19%). Tumour necrosis factor inhibitors were used in 73% and 99% of RA and SpA patients, respectively. B-DMARD monotherapy (RA: 18.71%, SpA: 52.11%), b-DMARD switching during 12 months (RA: 7.73%, SpA: 6.26%), and use of methotrexate (RA: 50.25%, SpA: 27.35%) and corticosteroids (RA: 55.8%, SpA: 23.63%) differed between the two patient subgroups. In both subgroups, women received more often than men methotrexate, leflunomide, hydroxychloroquine and corticosteroids, and less often b-DMARD monotherapy. After adjustments for age, gender and concomitant drugs, the probability for anti-hypertensive and lipid-lowering drug prescription was higher in SpA than RA [OR=1.41 (95%CI: 1.29-1.54) and 1.24 (1.14-1.36), respectively, p<0.001], whereas for anti-diabetics it was similar. In the first country-wide study that examines the characteristics of rheumatic disease patients under b-DMARD we show that their exact prevalence is 0.19%, with RA patients being older by 10 years, only slightly more numerous, and less likely to receive treatment for hypertension and dyslipidaemia than their demographically matched SpA counterparts. Longitudinal studies should assess the implications of these novel findings on the differential financial burden of rheumatic diseases, as well as on cardiovascular morbidity and mortality of these patients.


Arterial stiffness and wave reflections in relation to plasma advanced glycation end products in a Chinese population.
Accumulation of advanced glycation end products (AGEs) in the human body might engender arterial stiffening. We investigated the relationship of plasma AGE concentration with arterial stiffness and wave reflections in a Chinese population. The study subjects were recruited from a newly established residential area in the suburb of Shanghai in 2009. Using the SphygmoCor system, we measured carotid-femoral pulse wave velocity (cfPWV) and central augmentation indices (cAI) and peripheral augmentation indices (pAI). Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. The 1,051 study participants (mean age = 55.1±13.1 years) included 663 (63.1%) women, 390 (37.1%) hypertensive patients, and 90 (8.6%) diabetic or prediabetic subjects. Plasma AGE concentration was higher in men than women (5.62 vs. 5.07 μg/ml; P = 0.02) and with older age (r = 0.13 in both sexes; P ≤ 0.01) and higher serum total/high-density lipoprotein cholesterol ratio (r = 0.20 in men and r = 0.15 in women; P < 0.0001). In multiple regression analyses, plasma AGE concentration was significantly associated with cAI and pAI (1.9% and 4.0% increase per 10-time increase in plasma AGE concentration, respectively; P ≤ 0.02) but not with cfPWV (P = 0.62). However, there was significant (P = 0.001) interaction between plasma AGE concentration and age in relation to cfPWV. Only in subjects aged ≥70 years, cfPWV increased with higher levels of plasma AGE concentration (bottom vs. top quintile distributions = 8.10 vs. 8.90 m/s; P = 0.02). AGEs accumulate with aging and high cholesterol and are associated with arterial wave reflections and, in an age-dependent manner, with arterial stiffness.


Effects of green tea application time on bond strength after enamel bleaching.
This study evaluated the effect of green tea application time on the bond strength of enamel after enamel bleaching. Enamel samples were obtained from 80 third molars and randomly divided into 7 experimental groups (G1-G7) and 1 group without treatment (G8): G1, bleached with 10% carbamide peroxide (CP); G2, CP + 10% sodium ascorbate gel (SA) for 15 min; G3, CP + SA for 30 min; G4, CP + SA for 60 min; G5, CP + 10% green tea gel (GT) for 15 min; G6, CP + GT for 30 min; G7, CP + GT for 60 min. The CP was applied onto the enamel surface for 8 h for 14 days. The SA was applied in groups 2, 3 and 4, and the GT was applied in groups 5-8 according to the above described application times. Immediately after treatment, the specimens were bonded with Adper Single Bond 2 and Filtek Z350XT. The specimens were prepared to microtensile bond strength analysis. Fracture mode analysis was performed using a stereoscopic loupe. The data were statistically analyzed by two-way analysis of variance, the Tukey's and Dunnett's tests (=5%). The means (standard deviation) were: G1, 23.3 (3.2); G2, 25.2 (3.9); G3, 26.4 (5.4); G4, 30.2 (4.5); G5, 26.6 (3.4); G6, 22.0 (5.4); G7, 31.4 (3.3); G8, 31.4 (3.2). All groups had a high percentage of adhesive failures. In conclusion, the bond strength values were higher than the value in the bleached group only when the antioxidants were applied for 60 min.


Effects of sodium ipodate and propylthiouracil in athyreotic human subjects, role of triiodothyronine and pituitary thyroxine monodeiodination in thyrotrophin regulation.
To investigate the respective role of triiodothyronine (T3) and thyroxine (T4) in the regulation of TSH secretion, we studied the action of sodium ipodate and propylthiouracil (PTU) in 11 athyreotic patients. The LT4 replacement dose was adjusted to obtain, in each patient, a normal basal TSH level and a normal TSH response to TRH. In the 5 ipodate-treated patients (single 6 g oral dose), the mean serum T3 level fell by 64% below the baseline value and serum rT3 rose 180% above the baseline. The free T4 index (FT4I) did not change whereas the mean serum TSH concentration increased 280% above baseline values. In the 6 PTU-treated patients (250 mg orally every 6 h for 10 days), serum T3 levels fell 33%, serum rT3 increased up to 82% and the FT4I did not change. The mean serum TSH concentration increased 68% above the baseline value. Thus, the mean percentage increase in serum TSH was less in PTU- than in ipodate-treated patients (68% vs 280%). Statistical analysis of the correlation between the serum T3 decrease (delta T3) and the serum TSH (delta TSH) increase demonstrated that for the same T3 diminution, the ipodate-treated group displayed higher increase of TSH than the PTU-treated patients. In the rat, PTU interferes with the 5'-deiodination of T4 in the liver and kidney but not in the pituitary, while ipodate appears to have the same effect in all tissues. If this holds true for human subjects, our data strongly suggest that circulating T4 (through its intrapituitary conversion to T3) shares with serum T3 the capacity to regulate TSH secretion in man.


Hypoglycemia in Prospective Multicenter Study of Pregnancies with Pre-Existing Type 1 Diabetes on Sensor-Augmented Pump Therapy: The LOIS-P Study.
Background: Pregnancies in type 1 diabetes are high risk, and data in the United States are limited regarding continuous glucose monitoring (CGM)-based hypoglycemia throughout pregnancy while on sensor-augmented insulin pump therapy. Materials and Methods: Pregnant women with type 1 diabetes in the LOIS-P Study (Longitudinal Observation of Insulin use and glucose Sensor metrics in Pregnant women with type 1 diabetes using continuous glucose monitors and insulin pumps) were enrolled before 17 weeks gestation at three U.S. centers and we used their personal insulin pump and a study Dexcom G6 CGM. We analyzed data of 25 pregnant women for CGM hypoglycemia based on international consensus guidelines for percentage time <63 and 54 mg/dL, hypoglycemic events and prolonged hypoglycemia events for 24-h, daytime, and overnight periods, and severe hypoglycemia (SH) episodes. Results: For a 24-h period, biweekly median percentage of time <63 mg/dL ranged from 0.8% at biweek 4-5 to 3.7% at biweek 14-15 with high variability throughout pregnancy. Median percentage of time <63 and 54 mg/dL was higher overnight than daytime (P < 0.01). Hypoglycemic events occurred throughout the pregnancy, ranged 1-4 events per 2 weeks, significantly decreased after the 20th week, and occurred predominantly during daytime (P < 0.01). For overnight period, hypoglycemia and events were more concentrated from 12 to 3 am. Seven prolonged hypoglycemia events without any associated SH occurred in four participants (16%), primarily overnight. Three participants experienced a single episode of SH. Conclusions: Our results suggest a higher overall risk of hypoglycemia throughout pregnancy during the overnight period with continued daytime risk of hypoglycemic events in pregnancies complicated by type 1 diabetes.


Pyrene Molecular Orbital Shuffle-Controlling Excited State and Redox Properties by Changing the Nature of the Frontier Orbitals.
We show that by judicious choice of substituents at the 2- and 7-positions of pyrene, the frontier orbital order of pyrene can be modified, giving enhanced control over the nature and properties of the photoexcited states and the redox potentials. Specifically, we introduced a julolidine-like moiety and Bmes2 (mes=2,4,6-Me3 C6 H2 ) as very strong donor (D) and acceptor (A), respectively, giving 2,7-D-π-D- and unsymmetric 2,7-D-π-A-pyrene derivatives, in which the donor destabilizes the HOMO-1 and the acceptor stabilizes the LUMO+1 of the pyrene core. Consequently, for 2,7-substituted pyrene derivatives, unusual properties are obtained. For example, very large bathochromic shifts were observed for all of our compounds, and unprecedented green light emission occurs for the D/D system. In addition, very high radiative rate constants in solution and in the solid state were recorded for the D-π-D- and D-π-A-substituted compounds. All compounds show reversible one-electron oxidations, and Jul2 Pyr exhibits a second oxidation, with the largest potential splitting (ΔE=440 mV) thus far reported for 2,7-substituted pyrenes. Spectroelectrochemical measurements confirm an unexpectedly strong coupling between the 2,7-substituents in our pyrene derivatives.


Homology Modeling of Leishmania donovani Enolase and its Molecular Interaction with Novel Inhibitors.
The treatment of Indian tropical disease such as kala-azar is likely to be troublesome to the clinicians as AmpB- and miltefosine-resistant Leishmania donovani has been reported. The rationale behind designed a novel inhibitors of model of L. donovani enolase and performing a binding study with its inhibitors to gain details of the interaction between protein residues and ligand molecules. The L. donovani enolase model consists of two typical domains. The N-terminal one contains three-stranded antiparallel β-sheets, followed by six α-helices. The C-terminal domain composes of eleven-stranded mixed α/β-barrel with connectivity. The first α-helix within the C-terminal domain, H7, and the second β-strand, S7, of the barrel domain was arranged in an antiparallel fashion compared to all other α-helices and β-strands. The root-mean-square deviation between predicted model and template is 0.4 Å. The overall conformation of L. donovani enolase model is similar to those of Trypanosoma cruzi enolase and Streptococcus pneumoniae enolase crystal structures. The key amino acid residues within the docking complex model involved in the interaction between model enolase structure and ligand molecule are Lys70, Asn165, Ala168, Asp17, and Asn213. Our theoretical prediction may lead to the establishment of prophylactic and therapeutic approaches for the treatment of kala-azar. This biomedical informatics analysis will help us to combat future kala-azar.


Reassessing the Etiology of Aspergillus Vine Canker and Summer Bunch Rot of Table Grapes in California.
Fungal taxonomy is in constant flux and the advent of reliable DNA barcodes has enabled the enhancement of plant pathogen identification accuracy. In California, Aspergillus Vine Canker (AVC) and Summer Bunch Rot (SBR) are economically important diseases that affect the wood and fruit of grapevines, respectively, and their causal agents are primarily species of black aspergilli (Aspergillus section Nigri). During the last decade, the taxonomy of this fungal group has been rearranged several times using morphological, physiological and genetic analyses, resulting in the incorporation of multiple cryptic species that are difficult to distinguish. Therefore, in this study, we aimed to reassess the etiology of AVC and SBR using a combination of morphological observations with phylogenetic reconstructions based on nucleotide sequences of the calmodulin (CaM) gene. Results revealed that the isolates causing AVC from recent isolations corresponded to A. tubingensis, whereas the isolates obtained from initial surveys when the disease was discovered were confirmed as A. niger and A. carbonarius. Similarly, the isolates obtained from table grapes with SBR symptoms and from spore traps placed in those vineyards were identified primarily as A. tubingensis, followed by A. niger and A. carbonarius. Notably, the A. niger isolates formed a subclade with strains previously known as A. welwitschiae, a species that was recently synonymized with A. niger. Overall, the most prevalent species was A. tubingensis, associated with both AVC and SBR, and representative isolates recovered from AVC-symptomatic wood, berries with SBR symptoms, and spore traps were equally pathogenic in healthy wood and berries of 'Red Globe' grapevines. This study also constitutes the first report of A. tubingensis causing Aspergillus Vine Canker and Summer Bunch Rot of grapes in California and in the United States.


Adaptation and Validation of the Basque Version of the Emotional Creativity Inventory in Higher Education.
Emotional creativity is defined as the ability to feel and express emotions in a new, effective and authentic way. There are currently no Basque-language self-report instruments to provide valid and reliable measures of this construct. Thus, this paper describes the process of adapting and validating the Emotional Creativity Inventory (ECI) for the Basque-speaking population. The sample was comprised of 594 higher education students (388 women and 206 men) aged between 18 and 32 years old (Mage = 20.47; SD = 2.48). The Basque version of the ECI was administered along with the TMMS-23, NEO PI-R, and PANAS. The results of exploratory and confirmatory factor analyses on the Basque ECI corroborated the original scale's three-factor structure (preparedness, novelty, and effectiveness/authenticity). Those dimensions showed acceptable indexes of internal consistency (α = .80, .83, and .83) and temporal stability (r = .70, .69, and .74). The study also provided some evidence of external validity (p < .05) based on the relationships found between emotional creativity and emotional intelligence, personality, affect, and sex. The Basque ECI can be regarded as a useful tool to evaluate perceived emotional creativity during the preparation and verification phases of the creative process.


Transient contribution of mast cells to pulmonary eosinophilia but not to hyper-responsiveness.
We have recently demonstrated that the transfer of interleukin (IL)-5-producing CD4+ T cell clones into unprimed mice is sufficient for the development ofeosinophilic inflammation in the bronchial mucosa upon antigen inhalation. The aim of this study was to elucidate the possible contribution of mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR), and to discriminate between the roles of CD4+ T cells and mast cells. Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1-+/+) were immunized with ovalbumin and challenged by inhalation with the relevant antigen. Airway eosinophilia was induced with equivalent intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In contrast, 48 h after antigen challenge, eosinophilic infiltration into the bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice. Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were administered next, demonstrating that the airway eosinophilia of W/Wv mice induced 48 h after antigen challenge was almost completely inhibited by each of these three treatments, but that of +/+ mice was significantly less susceptible. Bronchial responsiveness to acetylcholine was increased 48 h after antigen challenge and was not significantly different between +/+ and W/Wv mice. Administration of anti-IL-5 mAb completely inhibited the development of BHR in both +/+ and W/Wv mice. These results indicate that, in mice, mast cells do have a supplemental role in the development of pulmonary eosinophilia but not BHR. CD4+ T cells totally regulate these responses by producing IL-5.


Effects of epigallocatechin gallate on the cell-wall structure of Mycobacterial smegmatis mc²155.
Epigallocatechin gallate (EGCG) is the main component of green tea extracts that inhibits the growth of Mycobacterial smegmatis mc(2)155, and the mechanism is not clear. This study showed the effects of EGCG on the growth of mc(2)155. The content and the structure of EGCG in LB medium with mc(2)155 were identified by HPLC and LC/MS. Transmission electron microscopy was utilised to identify the cell envelope structure. As a result, the optional inhibition concentration was determined to be 20 μg mL(-1). Most of EGCG was transferred into its isomeride in LB medium, but the inhibition effects against mc(2)155 had yet been maintained. The changes of cell envelope structure were showed after EGCG treatment for 18 h. The cell wall appeared to have a less electron-translucent zone, turn rougher and thicker. The results show that EGCG impacts the integrity of mycobacterial cell wall and is likely be a better prophylactic agent against tuberculosis.


Alpha-synuclein activates the classical complement pathway and mediates complement-dependent cell toxicity.
Synucleinopathies are characterized by neurodegeneration and deposition of the presynaptic protein α-synuclein in pathological protein inclusions. Growing evidence suggests the complement system not only has physiological functions in the central nervous system, but also is involved in mediating the pathological loss of synapses in Alzheimer's disease. However, it is not established whether the complement system has a similar role in the diseases Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy (MSA) that are associated with α-synuclein aggregate pathology. To investigate if the complement system has a pathological role in synucleinopathies, we assessed the effect of the complement system on the viability of an α-synuclein expressing cell model and examined direct activation of the complement system by α-synuclein in a plate-based activation assay. Finally, we investigated the levels of the initiator of the classical pathway, C1q, in postmortem brain samples from MSA patients. We demonstrate that α-synuclein activates the classical complement pathway and mediates complement-dependent toxicity in α-synuclein expressing SH-SY5Y cells. The α-synuclein-dependent cellular toxicity was rescued by the complement inhibitors RaCI (inhibiting C5) and Cp20 (inhibiting C3). Furthermore, we observed a trend for higher levels of C1q in the putamen of MSA subjects than that of controls. α-Synuclein can activate the classical complement pathway, and the complement system is involved in α-synuclein-dependent cellular cytotoxicity suggesting the system could play a prodegenerative role in synucleinopathies.


The onset of testicular differentiation in the rat: An ultrastructural study.
The structure of developing rat testes was studied by light and electron microscopy. Ultrastructural differentiation of Sertoli and Leydig cells was followed from 14 days of gestation through birth. Specialized morphology in Sertoli cells was first seen at 16 days of gestation. In these cells the rough endoplasmic reticulum increased and became organized as numerous short cisternae loaded with a homogenous material. Typical Leydig cells were found among the stromal cells, around day 17 of gestation. There is good correlation between the time of appearance of ultrastructural specialization and published data on secretory capacity of the fetal testes, in respect to the inhibition and differentiation of the Müllerian and Wolffian ducts.


Microstereolithography and characterization of poly(propylene fumarate)-based drug-loaded microneedle arrays.
Drug-loaded microneedle arrays for transdermal delivery of a chemotherapeutic drug were fabricated using multi-material microstereolithography (μSL). These arrays consisted of twenty-five poly(propylene fumarate) (PPF) microneedles, which were precisely orientated on the same polymeric substrate. To control the viscosity and improve the mechanical properties of the PPF, diethyl fumarate (DEF) was mixed with the polymer. Dacarbazine, which is widely used for skin cancer, was uniformly blended into the PPF/DEF solution prior to crosslinking. Each microneedle has a cylindrical base with a height of 700 μm and a conical tip with a height of 300 μm. Compression test results and characterization of the elastic moduli of the PPF/DEF (50:50) and PPF/drug mixtures indicated that the failure force was much larger than the theoretical skin insertion force. The release kinetics showed that dacarbazine can be released at a controlled rate for five weeks. The results demonstrated that the PPF-based drug-loaded microneedles are a potential method to treat skin carcinomas. In addition, μSL is an attractive manufacturing technique for biomedical applications, especially for micron-scale manufacturing.


Diabetes provides an unfavorable environment for muscle mass and function after muscle injury in mice.
It is of common knowledge that diabetes decreases skeletal muscle contractility and induces atrophy. However, how hyperglycemia and insulin deficiency modify muscle mass and neuromuscular recovery after muscle injury is not well known. We have analyzed two models of diabetes: streptozotocin (STZ)-treated Swiss mice and Akita mice that spontaneously develop diabetes. A fast muscle, the tibialis anterior, was injured following injection of a myotoxic agent (cardiotoxin). Neuromuscular function was evaluated by examining in situ isometric contractile properties of regenerating muscles in response to nerve stimulation 14, 28 and 56 days after myotoxic injury. We found that STZ-induced diabetes reduces muscle weight and absolute maximal tetanic force in both regenerating and uninjured muscles (p = 0.0001). Moreover, it increases specific maximal tetanic force and tetanic fusion in regenerating and uninjured muscles (p = 0.04). In the Akita mice, diabetes decreases muscle weight and absolute maximal tetanic force, and increases tetanic fusion in both regenerating and uninjured muscles (p < or = 0.003). Interestingly, STZ-induced diabetes exerts more marked effects than diabetes of genetic origin, in particular on muscle weight. This reduction in muscle mass was not due to an increased expression of the atrogenes MuRF1 and atrogin-1 during STZ-induced diabetes. The present study in mice demonstrates that both models of diabetes impair regenerating muscles as well as uninjured muscles. Regenerating fast muscles are weaker, lighter and slower in diabetic compared with nondiabetic mice.


The Role of Stress in Brain Development: The Gestational Environment's Long-Term Effects on the Brain.
During gestation, the fetal brain develops dramatically as structures and connections form, providing the foundation for all future development. The fetal environment plays a critical role in these early neural processes, for better or for worse. Scientists now know that exposure to maternal stress can sometimes have deleterious effects on the fetus, depending on the cause, timing, duration, and intensity of stress. Fortunately, postnatal interventions, such as a secure parent-infant bond and an enriched environment, can buffer the potential negative consequences.


Fall incidence and fall prevention practices at acute care hospitals in Singapore: a retrospective audit.
To investigate the incidence of falls and explore fall prevention practices at acute care hospitals in Singapore. A retrospective audit to collect baseline data on (1) incidence of falls (patient fall rates and fall injury rates) and (2) fall prevention practices, was conducted in five acute care hospitals in Singapore from December 2004 to March 2005. Medical record data (n = 6000) of patients admitted into the medical, surgical and geriatric units in the five hospitals. Fall incidence was obtained from the hospital's fall databases and incident reports for the period of June 2003 to May 2004. In total, 6000 medical records from five hospitals were randomly selected, retrieved and reviewed to determine whether falls, fall assessments and interventions were being initiated and documented. The number of fallers for all hospitals was 825. Analysis showed that patient fall rates ranged from 0.68 to 1.44 per 1000 patient days, and the proportion of falls associated with injury ranged from 27.4% to 71.7%. The use of a fall risk assessment tool by nurses was recorded in 77% of all the nursing records. This study has laid the foundation for further research for fall prevention in Singapore by describing current fall rates, fall-associated injury rates and the status of fall prevention practices in acute care settings. The results will be used to inform the development of a tailored multifaceted strategy to facilitate the implementation of Fall Prevention Clinical Practice Guidelines to reduce the burden of falls and fall injuries in hospitals in Singapore.


Predictors of psychological distress in advanced cancer patients under palliative treatments.
This work aims to investigate the factors associated with psychological distress in advanced cancer patients under palliative treatment. We comprehensively assessed the demographic, psychosocial and health factors of 158 advanced cancer patients. Patients with high and low distress, according to the Hospital Anxiety and Depression Scale, were compared. A regression analysis was built to identify the best predictors of distress. Patients with high psychological distress (81%) were more likely to have lung cancer, suicidal ideation, hopelessness, low quality of life and poor body image than those without. In the multivariate model, only poor emotional functioning (OR = .89; 95% CI = .83-.95; p ≤ .001), hopelessness (OR = .86; 95% CI = .78-.94; p ≤ .001) and body image distortions (OR = .77; 95% CI = .68-.85; p = .005) were retained. High levels of hopelessness, impaired emotional functioning and body image distortions are the main factors associated with psychological distress in patients with advanced cancer. Potential interventions to modify these factors in palliative units are discussed.


Prospective surveillance of hypertension in firefighters.
The authors evaluated blood pressure and antihypertensive medication use in 334 firefighters in an occupational medical surveillance program. Firefighters received written summaries of their examination results, including blood pressures, and were encouraged to see their personal physicians for any abnormal results. The mean age of the participants was 39 years, and the vast majority were men (n=330). The prevalence of hypertension was 20% at baseline (1996), 23% in 1998, and 23% in 2000. Among firefighters with high blood pressure readings, only 17%, 25%, and 22% were taking antihypertensive medications at the baseline, 1998, and 2000 examinations, respectively. Medical surveillance was effective in detecting hypertension in firefighters; however, after 4 years of follow-up, only 42% of hypertensives were receiving treatment with medications, including only 22% of firefighters with hypertensive readings. Overall, 74% of hypertensives were not adequately controlled. Possible reasons for low treatment rates may be the inadequate recognition among primary care physicians that mild hypertension is a significant risk factor for cardiovascular disease.


Role of cytochrome P450 enzyme induction in the metabolic activation of benzo[c]phenanthrene in human cell lines and mouse epidermis.
The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cells and the low activation of B[c]Ph in mouse skin, cells of the MCF-7 and the human hepatoma HepG2 cell lines were treated with the potent Ah receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to exposure to B[c]Ph for 24 h. Mice were treated topically with 1 microg of TCDD or vehicle (control) for 73 h and then with 2 micromol of B[c]Ph for 24 h. In MCF-7 cells, TCDD exposure increased B[c]PhDE-DNA adduct levels more than 3-fold with a 10-fold increase in the (-)-B[c]PhDE-2-dA(t) adduct. Treatment of HepG2 cells with TCDD prior to B[c]Ph application did not increase B[c]PhDE-DNA binding. Total B[c]PhDE-DNA adducts increased 3-fold in TCDD-treated mouse epidermis: the majority of the increase resulted from (+)-B[c]PhDE-1-dA adducts. Analysis of P450 enzymes by Western blotting detected a large increase of P4501B1 but almost no increase in P4501A1 in MCF-7 cells exposed to 10 microM B[c]Ph for 24 or 48 h. In HepG2 cells, there were no detectable levels of P4501A1 or P4501B1 after treatment with 10 microM B[c]Ph for 24 h. In contrast, topical application of 2 micromol of B[c]Ph to mouse skin for 48 or 72 h increased P4501A1, but no P4501B1 was detected. As a measure of P450 activity, the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) was analyzed in microsomes prepared from MCF-7 and HepG2 cells exposed to 0.1% DMSO, 10 microM B[c]Ph, or 10 nM TCDD for 24 or 48 h and from mouse epidermis treated with 1 microg of TCDD, or vehicle control for 72 h, or 2 micromol of B[c]Ph for 48 h. The levels of DMBA metabolites were low or undetectable in microsomes from B[c]Ph-treated MCF-7 and HepG2 cells, but a metabolite pattern consistent with P4501A1 metabolism of DMBA was present in B[c]Ph-exposed mouse epidermal microsomes. TCDD-treated MCF-7 cells, HepG2 cells, and mouse epidermis had DMBA metabolism patterns characteristic of P4501A1 activity. Microsomes from TCDD-treated human cells formed a higher proportion of the proximate carcinogenic metabolite DMBA-3,4-dihydrodiol (16% of total identified metabolites) than TCDD-treated mouse epidermis (2%). In mouse epidermis, the weak ability of B[c]Ph to increase hydrocarbon-metabolizing activity and the increase in mainly P4501A1, leading to formation of the less carcinogenic stereoisomer B[c]PhDE-1, may explain the low carcinogenic activity of B[c]Ph. In a human mammary carcinoma cell line, treatment with B[c]Ph increases mainly P4501B1 and results in formation of a higher proportion of the more carcinogenic B[c]PhDE-2. This indicates that cells in which B[c]Ph treatment increases P4501B1 levels effectively activate B[c]Ph to potent carcinogenic metabolites.


Boundary force effects exerted on solitons in highly nonlinear media.
We study the effects caused by remote boundaries on soliton dynamics in nonlinear media with a large range of nonlocality, and demonstrate theoretically and experimentally how asymmetric boundary forces can lead to soliton steering and oscillation in predetermined trajectories.


Assessment of Lumbar Lordosis Distribution with a Novel Mathematical Approach and Its Adaptation for Lumbar Intervertebral Disc Degeneration.
Low back pain and disc degeneration could be linked to global spinal geometry. Our study aimed to develop a reliable new mathematical method to assess the local distribution of total lumbar lordosis with a single numeric parameter and compare it with lumbar intervertebral disc degeneration using routine MRI scans. An online, open access, easy-to-use platform for measurements was developed based on a novel mathematical approach using MRIs of 60 patients. Our Spinalyze Software can be used online with uploaded MRIs. Several new parameters were introduced and assessed to describe variation in segmental lordosis distribution with a single numerical value. The Pfirrmann grading system was used for the classification of lumbar intervertebral disc degeneration. Relationships were investigated between the grade categories of L1-S1 lumbar discs and the MRI morphological parameters with correlation analysis. Results confirm that the determination of measurement points and calculated parameters are reliable (ICCs and Pearson r values > 0.90), and these parameters were independent of gender. The digression percentage (K%), one of our new parameters, did not show a statistical relationship with the Cobb-angle. According to our results, the maximum deflection breaking-point of lumbar lordosis and its location can be different with the same Cobb-angle and the distribution of global lordosis is uneven because the shape of the lumbar lordosis is shifted downward and centered around the L4 lumbar vertebra. The interobserver reliability of the Pfirrmann grades reading was in the excellent agreement category (88.33% agreement percentage, 0.84 kappa), and digression percentage (K%) showed a significant negative correlation with all L1-S1 disc grades with increasing r correlation values. This means that the smaller the value of digression percentage (K%), the more the number of worn discs in the lower lumbar sections. Spinalyze Software based on a novel mathematical approach provides a free, easy-to-use, reliable, and online measurement tool using standard MRIs to approximate the curvature of lumbar lordosis. The new reliable K% (digression percentage) is one single quantitative parameter to assess the local distribution of total lumbar lordosis. The results indicate that digression percentage (K%) may possibly be associated with the development of lumbar intervertebral disc degeneration. Further evaluation is needed to assess its behavior and advantage.


No evidence of linkage between familial combined hyperlipidemia and genes encoding lipolytic enzymes in Finnish families.
Familial combined hyperlipidemia (FCHL) is characterized by different lipid phenotypes (IIa, IIb, IV) and elevated apolipoprotein B (apo B) levels in affected family members. Despite intensive research, the genes involved in the expression of this complex disorder have not been identified, probably because of problems associated with phenotype definition, unknown mode of inheritance, and most probably genetic heterogeneity. To explore the genetics of FCHL in the genetically homogeneous Finnish population, we collected 14 well-documented Finnish pedigrees with premature coronary heart disease and FCHL-like dyslipidemia. The lipolytic enzymes lipoprotein lipase (LPL), hepatic lipase (HL), and hormone-sensitive lipase (HSL) were selected as initial candidate genes because of their central roles in apo B and triglyceride metabolism. On the basis of the pedigree structures, a dominant mode of inheritance was adopted for linkage analyses, and serum total cholesterol and/or triglyceride levels exceeding the 90th percentile level were set as diagnostic criteria (criterion 1). In pairwise linkage analyses with intragenic markers, no evidence for linkage was found. Instead, the significantly negative LOD scores suggested exclusion of all three loci for single major gene effect. LOD scores were -14.63, -5.03, and -5.70 for the three LPL polymorphisms (theta=0.00); -9.40, -6.30, and -4.74 for the three HL polymorphisms (theta=0.00); and -15.29 for the HSL polymorphism (theta=0.00). The results were very similar when apo B levels over the 90th percentile were used as criteria for affected status (criterion 2). Also, when linkage calculations were carried out using an intermediate or recessive mode of inheritance, the results of pairwise linkage analysis remained negative. Furthermore, when haplotypes were constructed from multiple polymorphisms of the LPL and HL genes, no segregation with the FCHL phenotype could be observed in the 14 Finnish families. Data obtained by the affected sib-pair method supported these findings, suggesting that the LPL, HL, or HSL genes do not represent major loci influencing the expression of the FCHL phenotype.


[A case of primary hypoparathyroidism and hypothyroidism co-existing with chronic renal failure].
A case of 24-year old woman with chronic renal failure and primary hypoparathyroidism is presented. Primary hypothyroidism and bilateral hypoacousis were also found. Typically concomitant with chronic renal failure is development of secondary hyperparathyroidism and its co-morbidities, i.e. renal osteodystrophy that consists of osteomalacia, osteoporosis and pathological fractures. In case of some patients with very high concentration of parathormone (PTH) and with signs of renal osteodystrophy, which is the case of tertiary hyperparathyroidism, subtotal parathyroidectomy is the optimal treatment. Reduction of PTH concentration protects bones from further destruction and from accumulation of calcium phosphate in tissues. The accompanying primary parathyroid failure would probably protect from the further consequences of PTH over-production--renal osteodystrophy. The case is reported in view of a rare occurrence of such co-existence, lack of its description in Polish literature as well as diagnostic difficulties.


Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients.
Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder characterized by facial gestalt, neurodevelopmental delay, skeletal anomalies and growth retardation, which is caused by variation of KMT2A gene. To date, only 2 Chinese WDSTS patients have been reported. Here, we report the phenotypes and KMT2A gene variations in 14 unrelated Chinese WDSTS patients and investigate the phenotypic differences between the Chinese and French cohorts. Next generation sequencing was performed for each patient, and the variants in the KMT2A gene were validated by Sanger sequencing. The phenotypes of 16 Chinese WDSTS patients were summarized and compared to 33 French patients. Genetic sequencing identified 13 deleterious de novo KMT2A variants in 14 patients, including 10 truncating, 2 missenses and 1 splicing variants. Of the 13 variants, 11 are novel and two have been reported previously. One of the patients is mosaic in the KMT2A gene. The variation spectra and phenotypic profiles of the Chinese WDSTS patients showed no difference with patients of other ethnicities; however, differ in the frequencies of several clinical features. We demonstrated that variations in the KMT2A gene can lead to both advanced and delayed bone age. We identified 6 novel phenotypes, which include microcephaly, deep palmar crease, external ear deformity, carpal epiphyseal growth retardation, dyslipidemia, and glossoptosis. In addition, patients harbored missense variants in the CXXC zinc finger domain of KMT2A showed more severe neurophenotypes. Our study consists of the largest cohort of Chinese WDSTS patients that continues to expand the WDSTS phenotypic and variation spectrum. Our results support the notion that the CXXC zinc finger domain of KMT2A gene is a hotspot for missense variants associated with more severe neurophenotypes.


Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes.
Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages. To assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). We studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS-I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro. As compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS-I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS-I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages. Plasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli.


New imidazole alkaloids and zinc complexes from the micronesian sponge Leucetta cf. chagosensis.
Four new imidazole alkaloids, 2-5, along with the known isonaamidine B (1) were isolated from a Pacific sponge, Leucetta cf. chagosensis, collected from Yap, Federated States of Micronesia. Among these, 4 and 5 are zinc complexes derived from isonaamidine B and isonaamidine D. The structures of the new compounds were elucidated from spectral data. Isonaamidine D (3) showed weakly antifungal activity against Aspergillus niger with MIC = 100 micrograms/mL.


Enhanced analogue front-end for the measurement of the high state of wide-band voltage pulses with 87 dB common-mode rejection ratio and ±0.65 ppm 1-day offset stability.
An improved analogue front-end for measuring the high state of trapezoidal voltage pulses with transition duration of 3 μs is presented. A new measurement system, composed by a front-end and the state-of-the-art acquisition board NI PXI-5922, has been realized with improved Common Mode Rejection Ratio (CMRR) of more than 87 dB at DC and 3-sigma stability of ±0.65 ppm over 1 day. After highlighting the main design enhancements with respect to state-of-the-art solutions, the CMRR measurement is reported. The output drift due to temperature and humidity is assessed to be negligible. Finally, the worst-case repeatability is measured both with shorted-to-ground inputs and with an applied common-mode voltage of 10 V, which represents the nominal working condition.


AMP-activated protein kinase activation prevents denervation-induced decline in gastrocnemius GLUT-4.
This study was designed to determine whether the reductions in GLUT-4 seen in 3-day-denervated muscles can be prevented through chemical activation of 5'-AMP-activated protein kinase (AMPK). Muscle AMPK can be chemically activated in rats using subcutaneous injections with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). In this study, the tibial nerve was sectioned on one side; the other was sham operated but without nerve section. Acute injections of AICAR resulted in significantly increased AMPK activity in denervated gastrocnemius but not soleus muscles. Acetyl-CoA carboxylase activity, a reporter of AMPK activation, declined in both gastrocnemius and soleus in both denervated and contralateral muscles. Three days after denervation, GLUT-4 levels were significantly decreased by approximately 40% in gastrocnemius muscles and by approximately 30% in soleus muscles. When rats were injected with AICAR (1 mg/g body wt) for 3 days, the decline in GLUT-4 levels was prevented in denervated gastrocnemius muscles but not in denervated soleus muscles. The extent of denervation-induced muscle atrophy was similar in AICAR-treated vs. saline-treated rats. These studies provide evidence that some effects of denervation may be prevented by chemical activation of the appropriate signaling pathways.


RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse.
Transcriptional and post-transcriptional regulation of gene expression is of fundamental importance to numerous biological processes. Nowadays, an increasing amount of gene regulatory relationships have been documented in various databases and literature. However, to more efficiently exploit such knowledge for biomedical research and applications, it is necessary to construct a genome-wide regulatory network database to integrate the information on gene regulatory relationships that are widely scattered in many different places. Therefore, in this work, we build a knowledge-based database, named 'RegNetwork', of gene regulatory networks for human and mouse by collecting and integrating the documented regulatory interactions among transcription factors (TFs), microRNAs (miRNAs) and target genes from 25 selected databases. Moreover, we also inferred and incorporated potential regulatory relationships based on transcription factor binding site (TFBS) motifs into RegNetwork. As a result, RegNetwork contains a comprehensive set of experimentally observed or predicted transcriptional and post-transcriptional regulatory relationships, and the database framework is flexibly designed for potential extensions to include gene regulatory networks for other organisms in the future. Based on RegNetwork, we characterized the statistical and topological properties of genome-wide regulatory networks for human and mouse, we also extracted and interpreted simple yet important network motifs that involve the interplays between TF-miRNA and their targets. In summary, RegNetwork provides an integrated resource on the prior information for gene regulatory relationships, and it enables us to further investigate context-specific transcriptional and post-transcriptional regulatory interactions based on domain-specific experimental data. Database URL: http://www.regnetworkweb.org.


Supporting better adherence among patients engaged in intermittent self-catherisation.
Coloplast has conducted a qualitative study among health professionals working in the field of continence care. Interviews with health professionals working in urology and rehabilitation provided insights into the barriers to, and supporters of, adherent behaviour-suggesting ways in which health professionals can work with patients performing intermittent self-catheterisation (ISC) to support better adherence. This includes individualised training that addresses individual fears, ensures correct understanding of the body and the treatment, and eliminates misconceptions. They can also help patients set realistic ambitions, and give them practical advice that will help them adapt ISC to their daily life. Patients need to know how to handle urinary tract infections, how to cope with contradictory instructions from other sources, and how to identify support resources and accurate information. Specific challenges relating to support for urology patients and rehabilitation patients were also highlighted.


Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein.
This study reports the use of radiolabeled antibodies to alpha-fetoprotein for the detection and localization of hepatocellular and germ cell carcinomas. Twelve patients with histories of histologically-confirmed neoplasia received a total dose between 1.0 and 4.4 mCi of 131I-labeled goat IgG prepared against human alpha-fetoprotein. Total-body photoscans were taken with a gamma scintillation camera at various intervals after injection of the radioactive antibody. Computer subtraction of radioactive technetium background images from the antibody 131I scans permitted the visualization of all tumor sites known to be present in 4 patients with either primary hepatocellular cancer or metastatic germ cell carcinoma of the testis. In contrast to the results with the specific antibody, radioactive normal goat IgG given to one of these patients with metastatic embryonal carcinoma of the testis failed to show equivalent localization. Among 8 patients with diverse neoplasms not believed to contain alpha-fetoprotein, 5 of 19 tumor sites showed radioactive antibody accretion, although significantly less than in the patients with liver or testicular cancer. Circulating antigen levels of up to 15,000 ng per milliliter did not prevent successful tumor imaging after intravenous injection of the radioantibody. This investigation indicates that alpha-fetoprotein-containing tumors can be detected and localized in vivo by the method of radioimmunodetection.


Investigation of menopause-induced changes on hair by Raman spectroscopy and chemometrics.
The ending of estrogen production in the ovaries after menopause results in a series of important physiologic changes, including hair texture and growth. In this study we demonstrate that Raman spectroscopy can be used successfully as a tool to probe menopause-induced changes on hair, in particular when coupled with suitable chemometrics approaches. The detailed analysis of the average Raman spectra (in particular of the Amide I and νS-S stretching spectral regions) of the hair samples of women pre- and post-menopause allowed to estimate that absence of estrogen in post-menopause women leads to an average reduction of ∼12% in the thickness of the hair cuticle, compared to that of pre-menopause women, and revealed the strong prevalence of disulphide bonds in the most stable gauche-gauche-gauche conformation in the hair cuticle. From the analysis of the νS-S stretching spectral region it could also be concluded that the amount of α-helix keratin is slightly higher for post-menopause than for pre-menopause women. A series of statistical models were developed in order to classify the hair samples. Outperforming the traditional PCA-LDA (principal component analysis - linear discriminant analysis) approach, in the present study a GA-LDA (genetic algorithm - linear discriminant analysis) strategy was used for variable reduction/selection and samples' classification. This strategy allowed to develop of a statistical model (L16), which has exceptional prediction capability (total accuracy of 96.6%, with excellent sensitivity and selectivity) and can be used as an efficient instrument for the hair samples' classification. In addition, a new chemometrics approach is here presented, which allows to overcome the intrinsic limitations of the GA algorithm and that can be used to develop statistical models that use GA as the variable reduction/selection method, but superseding its stochastic nature. Three suitable models for classification of the hair samples according to the menopause status of the women were developed using this novel approach (LV17, BLV20 and PLS7 models), which are based on the Fisher's and Bayers' LDA approaches and the PLS-DA method. The followed new chemometrics approach uses the results of a large set of GA-LDA runs over the full data matrix for the selection of the reduced data matrices. The criterion for the selection of the variables is their statistical significance in terms of number of occurrences as solutions of the whole set of GA-LDA runs.


[Lectin histochemical study of epidermal nevi].
3 epidermal nevi were investigated by means of FITC-labeled lectins (LCA, RCA II, ConA, WGA). In comparison with normal skin, we observed selective modifications of the lectin-binding patterns. These findings suggest an increased presence of GlcNAc residues.


Association between morphological traits and yield components in the durra sorghums of Ethiopia.
The Ethio-Sudan region is recognized as the center of origin and diversity for cultivated sorghum. All major races of the crop are widely grown in Ethiopia with durras being dominant. The objective of the present study was to determine the extent of morphological variability among the Ethiopian durras and examine the pattern of relationships among these traits and their association with yield and yield components. Two hundred accessions collected from major sorghum-growing regions of the country were evaluated during the 2007 season at two locations representing hot and dry low land and mild mid-altitude environments. A randomized complete block design with three replications was used. Data were collected on phenology, plant height, a range of leaf traits and yield components. Significant variation was observed among all traits measured. Phenological traits and plant height were significantly correlated with each other and with all leaf traits. There was positive correlation among leaf traits, and between leaf traits and yield components except thousand kernel weight (TKW) and panicle length (PL). Grain fill duration was negatively correlated with all traits except days to maturity, TKW, and leaf length. Yield components except PL and TKW were positively correlated with each other. Selection that focuses on key yield components, larger leaf area, and on enhancing the grain filling rate by reducing excessive grain fill duration may contribute to yield improvement.


The structure, location, and function of perlecan, a prominent pericellular proteoglycan of fetal, postnatal, and mature hyaline cartilages.
The aim of this study was to immunolocalize perlecan in human fetal, postnatal, and mature hyaline cartilages and to determine information on the structure and function of chondrocyte perlecan. Perlecan is a prominent component of human fetal (12-14 week) finger, toe, knee, and elbow cartilages; it was localized diffusely in the interterritorial extracellular matrix, densely in the pericellular matrix around chondrocytes, and to small blood vessels in the joint capsules and perichondrium. Aggrecan had a more intense distribution in the marginal regions of the joint rudiments and in para-articular structures. Perlecan also had a strong pericellular localization pattern in postnatal (2-7 month) and mature (55-64 year) femoral cartilages, whereas aggrecan had a prominent extracellular matrix distribution in these tissues. Western blotting identified multiple perlecan core protein species in extracts of the postnatal and mature cartilages, some of which were substituted with heparan sulfate and/or chondroitin sulfate and some were devoid of glycosaminoglycan substitution. Some perlecan core proteins were smaller than intact perlecan, suggesting that proteolytic processing or alternative splicing had occurred. Surface plasmon resonance and quartz crystal microbalance with dissipation experiments demonstrated that chondrocyte perlecan bound fibroblast growth factor (FGF)-1 and -9 less efficiently than endothelial cell perlecan. The latter perlecan supported the proliferation of Baf-32 cells transfected with FGFR3c equally well with FGF-1 and -9, whereas chondrocyte perlecan only supported Baf-32 cell proliferation with FGF-9. The function of perlecan therefore may not be universal but may vary with its cellular origin and presumably its structure.


Pattern of semen analysis in male partners of infertile couples in Western Ethiopia: Retrospective cross-sectional study.
This study assesses the pattern of semen analysis results in male partners of infertile couples at Gimbie Adventist Hospital, Western Ethiopia, 2021. A retrospective cross-sectional study on 131 semen samples of male partners of infertile couples was conducted at Gimbie Adventist Hospital from 5 September 2021 to 5 October 2021. All semen samples were processed and analyzed according to methods and standards outlined by the World Health Organization laboratory manual for the examination and processing of human semen 2010. The data were coded and entered into EpiData version 3.1, and then cleaned and exported to Statistical Package for Social Sciences (SPSS for Windows version 25) for analysis. The results were presented in tables, figures, and charts. The age of study participants ranges from 20 to 65 years with a mean age of 30.2 ± 8.1 years. Sperm cell count, morphology, total motility, and vitality below the World Health Organization reference level were found in 48.9%, 27.5%, 43.5%, and 67.2% of the analyzed samples, respectively. Low power of hydrogen and high viscosity were observed in 31.3% and 16.8% of the semen samples, respectively. The majority, 84%, had one or more abnormal semen analysis parameters. Asthenozoospermia (43.5%), necrozoospermia (25.2%), oligozoospermia (24%), azoospermia (24%), and oligoasthenoteratozoospermia (25.2%) were the severe forms of abnormal semen analysis findings detected in this study. The decline in sperm cell morphology and motility were noticed after the age of 31-34 years. In this study, both sperm quantity and quality were more affected when compared to similar studies. Only 16% of analyzed samples had normal semen parameters. Given this finding, identifying risk factors and introducing advanced diagnostic modalities for the workup of male infertility in the study area are highly recommended.


Spit tobacco: not a safe alternative.
Contrary to popular belief spread by misleading advertisements, spit tobacco is not a safe alternative to cigarettes. An abundance of evidence indicates that these products are not only dangerous to health, but often lethal. In Michigan, a statewide educational campaign is now underway to alert the public to the facts about spit tobacco. The National Institute of Health recommends that dentists ask all patients, beginning at age 5, about their tobacco use. The use of nationally known celebrities seems a critically important ingredient in this anti-tobacco campaign, in order to offset the glamorous advertisements from the tobacco industry. Ultimately, however, it is steady, sure, ever-serious reminders by health professionals of the dangers of spit tobacco that will carry the most weight. Above all, it is the dentist who has this opportunity and this responsibility.


[Effects of phosphatidylserine in an experimental model of generalized epilepsy].
The possible antiepileptic activity of PS has been tested in a model of generalized epilepsy induced by penicillin in the cat. In acute experiments, topical application to the cortex of PS (from 20 mg/ml to 50 mg/ml) produced a reverse in the polarity of the spike and wave complex and, sometimes, a decrease in the voltage as well as a morphological deformation of s-w bursts. Chronic intraperitoneal administration of PS induced a decrease of the epileptic burst frequency. The effect was already apparent after 14 days and of greater extent after 21 days. Finally the antiepileptic effect of 0,2-0,5 mg/Kg diazepam, given in a single dose during the maximal epileptic activity resulted markedly reinforced in animals chronically treated with PS.


Temporal framing and persuasion to adopt preventive health behavior: moderating effects of individual differences in consideration of future consequences on sunscreen use.
Previous work on temporal framing of health communications has focused upon detection behaviors that possess an inherent immediate risk of negative consequences. The present studies evaluate the role of temporal frame for a preventive behavior, using sunscreen. Two experimental field studies manipulated the temporal frame in which positive and negative consequences of using sunscreen were presented. Cognitive responses, intention, and behavior (experiment 2). Consistent with hypotheses, Experiment 1 showed that individual differences in consideration of future consequences (CFC; A. Strathman, F. Gleicher, D. S. Boninger, & C. S. Edwards, 1994) moderated (a) the processing of long- versus short-term consequences and (b) the persuasive impact of the different temporal frames on behavioral intentions. In Experiment 2, the balance of positive versus negative thoughts generated by reading the persuasive communications was shown to mediate the effects of the Temporal Frame x CFC interaction on a behavioral measure. Findings extend previous work by demonstrating the importance of individual differences in CFC to the processing of health communication about a preventive health behavior and to a behavioral outcome.


[Patterns of cognitive impairment and apolipoprotein genotype in persons with Alzheimer's disease].
The aim of this study was to test the possible relationship between patterns of cognitive deficits--especially impairment of memory processes--and ApoE genotype in patients with AD. Fifty seven right-handed subjects (31 males and 26 females) were tested in this study. The age of subjects ranged from 50 to 79, the education lasted from 11 to 16 years. All subjects were diagnosed as probable AD patients on the basis of DSM IV and NINCDS-ADRDA criteria. Each subject was examined for: 1) ApoE genotype, 2) general level of activity (GDS and MMSE), 3) neuropsychological evaluation of cognitive processes, using full test battery. 37 patients had at least one of ApoE epsilon 4 allele (e2/4, 3 and 4/4) and 20 patients had none of ApoE 4 allele (e 2/3 and 3/3). The group of tested subjects were subdivided into 2 groups. The first group was comprised by 31 patients with 3-rd stage (according to GDS) of mental activity. Twenty six patients with 4-th stage were included into the second group. Those subgroups did not significantly differ if age, education, gender or ApoE allele were considered. Experimental data were normalized and then analyzed using a statistical package SPSS/PC+. The analysis of variance showed that the type of test, stage of disease and two-way interaction ApoE x type of test were highly significant (P < 0.0001). Some results were obvious and not surprising (e.g. that results of patients with 4-th stage were much worse than the results of patients with stage 3-rd). It turned out that the best results were obtained by our patients in naming tests, the worst--in learning test with distraction. Patients with ApoE epsilon 4 performed better than patients with none ApoE epsilon 4 in the Rey's test, in the similarity test and in the test which required repeating numbers starting from the last one. The differences between the subgroups of patients with different ApoE alleles were confirmed by different distributions of correlations. All statistical analyses were repeated for more homogenous group of patients (only with stage 3-rd). The pattern of results resembled the previous one (i.e. better performance in the same tests) with one exception: additionally, in delayed recall test patients with none ApoE epsilon 4 performed much better that ApoE epsilon 4. Our results showed that some cognitive processes depended on ApoE genotype. Patients with none ApoE epsilon 4 genotype had less severe deficits in delayed recall of new information. On the other hand, working memory appeared to be less affected in patients with ApoE epsilon 4 genotype. Independent of genotype, both group showed similar impairment of learning ability without deficits in remote memory.


Secondary vortex street in the wake of two tandem circular cylinders at low Reynolds number.
The experiments on two tandem circular cylinders were conducted in a horizontal soap film tunnel for the Reynolds number Re=60 , 80, and 100 and the nondimensional center-to-center spacing Gamma ranging in 1 approximately 12. The flow patterns were recorded by a high-speed camera and the vortex shedding frequency was obtained by a spatiotemporal evolution method. The secondary vortex formation (SVF) mode characterized by the formation of a secondary vortex street in the wake of the downstream cylinder was found at large gamma. Moreover, some typical modes predicted by previous investigations, including the single bluff-body, shear layer reattachment, and synchronization of vortex shedding modes, were also revisited in our experiments. Further, numerical simulations were carried out using a space-time finite-element method and the results confirmed the existence of the SVF mode. The mechanism of SVF mode was analyzed in terms of the numerical results. The dependence of the Strouhal number Sr on Gamma was given and the flow characteristics relevant to the critical spacing values and the hysteretic mode transitions were investigated.


Intellectual performance of 36 phenylketonuria patients and their nonaffected siblings.
Thirty-six patients with a confirmed diagnosis of phenylketonuria (PKU) were identified and placed on dietary therapy before reaching 121 days of age. These children are currently between 4 and 6 years old, and have been given the Stanford-Binet Intelligence Scale. Subsequently, their normal siblings of closet age were selected as matched-pair controls and were also tested with the Stanford-Binet. The mean age of the PKU sample when tested was 50.0 months, and 50.9 months for the normal controls. The 36 index patients scored a mean IQ of 94 and their nonaffected siblings obtained a mean IQ of 99. This five-point mean difference was significant at the .02 level, and suggests the presence of a minimal intellectual impairment associated with PKU, even when treatment begins early and is rigorously monitored.


Analysis of conjugated linoleic acids as 9-anthrylmethyl esters by reversed-phase high-performance liquid chromatography with fluorescence detection.
A simple and highly sensitive method for determining the fatty acid composition of food lipids containing conjugated linoleic acid (CLA) is described. The method is based on the separation of the 9-anthrylmethyl ester derivatives of saturated and unsaturated (conjugated and non-conjugated) fatty acids by reversed-phase high-performance liquid chromatography with fluorescence detection. Just like the other fatty acids, CLA reacts readily with 9-anthryldiazomethane at room temperature to produce 9-anthrylmethyl esters without isomerization and decomposition of the conjugated double bonds. Clear resolution of the individual fatty acids as their 9-anthrylmethyl esters is achieved on a highly efficient octadecylsilylated silica column (150- x 3-mm i.d., 3-microm particle size) using a stepwise gradient elution with methanol-water. The method is standardized with commercially available CLA isomers (cis-9, trans-11 and trans-10, cis-12-octadecadienoic acids, and their cis,cis and trans,trans isomers) and applied for determination of the fatty acid compositions of milk and sdairy products.


Endovascular treatment of hepatic artery stenosis after liver transplantation.
Hepatic artery stenosis (HAS) after orthotopic liver transplantation is a significant risk factor for subsequent hepatic artery thrombosis (HAT). HAT is associated with a 30%-50% risk of liver failure culminating in retransplantation or death. Traditional treatment of hepatic artery complications has been surgical, with hepatic artery revision or retransplantation. Endovascular therapy of HAS, described primarily in the interventional radiology literature, may provide a less-invasive treatment option. This was a retrospective review of all endovascular interventions performed for HAS after orthotopic liver transplantation over a 31-month period (August 2009 to January 2012). Patients with duplex ultrasound imaging evidence of severe main HAS (peak systolic velocity of >400 cm/s, resistive index of <.5) underwent endovascular treatment with either primary stent placement or percutaneous transluminal angioplasty (PTA) alone. Patients were followed with serial ultrasound imaging to assess for treatment success and late restenosis. Reintervention was performed if significant restenosis occurred. Thirty-five hepatic artery interventions were performed in 23 patients. Over the 31-month study period, 318 orthotopic liver transplantations were performed, yielding a 7.4% (23/318) rate of hepatic artery intervention. Primary technical success was achieved in 97% (34/35) of cases. Initial treatment was with PTA alone (n = 10) or primary stent placement (n = 13). The initial postintervention ultrasound images revealed improvements in hepatic artery peak systolic velocity (267 ± 118 [posttreatment] vs 489.9 ± 155 cm/s [pretreatment]; P < .0001) and main hepatic artery resistive index (0.61 ± 0.08 [posttreatment] vs 0.41 ± 0.07 [pretreatment]; P < .0001). At a mean follow-up of 8.2 ± 1.8 months (range, 0-29), there were 12 reinterventions in 10 patients for recurrent HAS. Thirty-one percent (n = 4/13) of patients undergoing initial stent placement required reintervention (at 236 ± 124 days of follow-up) compared with 60% (n = 6/10) of patients undergoing initial PTA (at 62.5 ± 44 days of follow-up). Primary patency rates (Kaplan-Meier) after primary stent placement were 92%, 85%, and 69% at 1, 3, and 6 months, respectively, compared with 70%, 60%, and 50% after PTA (P = .17). Primary-assisted patency for the entire cohort was 97% at 6 and 12 months. Major complications were one arterial rupture managed endovascularly and one artery dissection that precipitated HAT and required retransplantation. The overall rate of HAT in the entire cohort was 4.3% (1/23). Endovascular treatment of HAS can be performed with high technical success, excellent primary-assisted patency, and acceptable morbidity. Initial use of a stent may improve primary patency when compared with PTA. The need for reintervention is common, placing particular importance on aggressive surveillance. Longer follow-up and a larger cohort are needed to confirm these encouraging early results.