Development of an indirect competitive enzyme-linked immunosorbent assay based on the multiepitope peptide for the synchronous detection of staphylococcal enterotoxin A and G proteins in milk.
Staphylococcal food poisoning (SFP), one of the most common foodborne diseases, results from ingestion of staphylococcal enterotoxins (SEs) in foods. In our previous studies, we found that SEA and SEG were two predominant SE proteins produced by milkacquired S. aureus isolates. Here, a tandemly arranged multiepitope peptide (named SEAGepis) was designed with six linear B-cell epitopes derived from SEA or SEG and was heterologously expressed. The SEAGepis-specific antibody was prepared by immunizing rabbit with rSEAGepis. Then, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on rSEAGepis and the corresponding antibody was developed to simultaneously detect SEA and SEG. Under the optimized conditions, the ic-ELISA standard curve for rSEAGepis was constructed in the concentration range of 0.5 to 512 ng/ml, and the average coefficients of variation of intra- and interassay were 4.28 and 5.61% during six standard concentrations. The average half-maximal inhibitory concentration was 5.07 ng/ml, and the limit of detection at a signal-to-noise ratio of 3 was 0.52 ng/ml. The anti-rSEAGepis antibody displayed over 90% cross-reactivity with SEA and SEG but less than 0.5% cross-reactivity with other enterotoxins. Artificially contaminated milk with different concentrations of rSEAGepis, SEA, and SEG was detected by the established ic-ELISA; the recoveries of rSEAGepis, SEA, and SEG were 91.1 to 157.5%, 90.3 to 134.5%, and 89.1 to 117.5%, respectively, with a coefficient of variation below 12%. These results demonstrated that the newly established ic-ELISA possessed high sensitivity, specificity, stability, and accuracy and could potentially be a useful analytical method for synchronous detection of SEA and SEG in milk.


Modulation of physical properties of polyvinylsiloxane impression materials by filler type combination.
Polyvinylsiloxanes (PVS), used as dental impression materials, were formulated with the variation of loading combination of six types of fillers including nano-sized fumed silica. The fillers were blended with three types of silicone polymers together with cross-linker and inhibitor in base paste and with plasticizer and platinum catalyst in catalyst paste. By replacing parts of crystalline quartz with other fillers, the setting time became much faster. The test group in which quarter of quartz was replaced with fumed silica showed the most ideal working and setting time for clinical use. There was a negative correlation between pH and setting time (p < 0.05). Combining the fumed silica was effective in increasing the viscosity, tensile strength and maximum% strain. Combining the diatomaceous earth reduced the setting time and maximum% strain, and dramatically increased the viscosity and tensile strength. The best modulation of physical properties of PVS material was possible by combining fillers during the formulation.


Patients' compliance with follow-up after treatment of gonococcal urethritis.
By means of telephone tracing 96% follow-up was achieved in men treated for gonococcal urethritis. A large proportion (34.8%) of patients required one or more calls before follow-up could be obtained. Frequency of sexual re-exposure, proportion with persistent gonorrhea or reinfection, and interval between initial therapy and follow-up were greater in those who required telephone contact for follow-up than in the group who returned for follow-up. Failure to reappear for follow-up does not imply either bacteriologic cure or disappearance of symptoms. Control of gonococcal infection still depends largely upon aggressive methods of case finding, appropriate therapy and careful follow-up.


Snakebites in French Guiana: Conclusions of an international symposium.
A workshop on epidemiology and management of snakebites in French Guiana was performed at Cayenne, French Guiana from September 15 to September 16, 2017, under the auspices of the French Regional Health Agency (ARS) and the Pan American Health Organization (PAHO). The activity was attended by experts from France (Angers, Martinique, French Guiana, Guadeloupe, and Paris), Costa Rica, Brazil, Saint Lucia, and Surinam. The epidemiology, clinical manifestations, clinical grading and the management of snakebite in French Guiana were discussed. The conclusions of this symposium illustrated the urgent need to ensure accessibility of effective and safe polyvalent viperid antivenom in French Guiana. Finally, the results of this symposium have forged ties based on mutual goals and objectives.


Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model.
Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF/Ei x B6.129S7-Ldlr(tm1Her)) x C57BL/6J-Ldlr(tm1Her) backcross mice, homozygous for the Ldlr null allele, were fed a Western-type diet for 3 months and then killed for quantification of aortic lesions. A genome scan was carried out by using DNA pools and microsatellite markers spaced at approximately 18-centimorgan intervals. Quantitative trait locus analysis of individual backcross mice confirmed linkages to chromosomes 4 (Athsq1, logarithm of odds = 6.2) and 6 (Athsq2, logarithm of odds = 6.7). Athsq1 affected lesions in females only whereas Athsq2 affected both sexes. Among females, the loci accounted for approximately 50% of the total variance of lesion area. The susceptible allele at Athsq1 was derived from the MOLF/Ei genome whereas the susceptible allele at Athsq2 was derived from C57BL/6J. Inheritance of susceptible alleles at both loci conferred a 2-fold difference in lesion area, suggesting an additive effect of Athsq1 and Athsq2. No associations were observed between the quantitative trait loci and levels of plasma total cholesterol, high density lipoprotein cholesterol, non-high density lipoprotein cholesterol, insulin, or body weight. We provide strong evidence for complex inheritance of atherosclerosis in mice with elevated plasma low density lipoprotein cholesterol and show a major influence of nonlipoprotein-related factors on disease susceptibility. Athsq1 and Athsq2 represent candidate susceptibility loci for human atherosclerosis, most likely residing on chromosomes 1p36--32 and 12p13--12, respectively.


Exploring training dental implant placement using computer-guided implant navigation system for predoctoral students: A pilot study.
Recent computer-guided dynamic navigation systems promise a novel training approach for implant surgery. This study aimed to examine learning progress in placement of dental implants among dental students using dynamic navigation on a simulation model. Senior students with no implant placement experience were randomly assigned five implant placement attempts involving either three maxillary or four mandibular implants distributed in the anterior/posterior, and left/right segments. Implant placement was planned using a Navident Dynamic Guidance system. Surgical time was recorded. Horizontal, vertical and angulation discrepancies between the planned and placed implant positions were measured using superimposed CBCT scans. Data were analysed with repeated measures regression with Tukey's adjusted pairwise comparisons (α = 0.05). Fourteen students participated, with a mean age of 26.1 years and equal males and females. Mean time for implant placement was associated with attempt number (P < 0.001), implant site (P = 0.010) and marginally related to gender (P = 0.061). Students had a significant reduction in time from their first attempt to their second (10.6 vs 7.6 minutes; adjusted P < 0.001) then plateaued. Overall 3D angulation (P < 0.001) and 2D vertical apex deviation (P = 0.014) improved with each attempt, but changes in lateral 2D (P = 0.513) and overall 3D apex deviations (P = 0.784) were not statistically significant. Implant sites were associated with lateral 2D, 2D vertical and overall 3D apex deviation (P < 0.001). Males were marginally faster than females, had slightly lower overall 3D angulation, and reported higher proficiency with video games. Novice operators improved significantly in speed and angulation deviation within the first three attempts of placing implants using dynamic navigation. Computer-aided dynamic implant navigation systems can improve implant surgical training in novice population.


Early intervention model of inpatient diabetes care improves glycemia following hospitalization.
Admission to hospital provides an opportunity to optimize long-term diabetes management, but clinical inertia is common. We previously reported the randomized study of a proactive inpatient diabetes service (RAPIDS), investigating an early intervention model of care and demonstrated improved in-hospital glycemia and clinical outcomes. This follow-up study assessed whether proactive care in hospital improved postdischarge HbA1c. In a subgroup of 298 RAPIDS trial participants with type 2 diabetes, age <80 years, and admission HbA1c ≥ 7.0%, diabetes treatment intensification occurred more often in early intervention versus usual care groups (37% vs. 19% [p = .001]), adjusted odds ratio 3.2 (95% confidence interval [CI]: 1.7-6.0). There was a greater change in HbA1c in the early intervention group (mean -0.9% [95% CI -1.3 to -0.4]) versus the usual care group (-0.3% [-0.6 to -0.1]), p = .029. The value of acute care by dedicated inpatient diabetes teams can extend beyond improving inpatient clinical outcomes and can lead to sustained improvement in glycemia.


Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells.
Clonogenic multipotent mouse hematopoietic stem cells (HSCs) and progenitor cells are contained within the c-kit(+) (K) lineage(-/lo) (L) Sca-1(+) (S) population of hematopoietic cells; long-term (LT) and short-term (ST) HSCs are Thy-1.1(lo). c-kit is a member of the receptor tyrosine kinase family, a class of receptors that are important in the proliferation and differentiation of hematopoietic cells. To establish whether the Flk-2/Flt3 receptor tyrosine kinase was expressed on the most primitive LT-HSCs, we sorted highly purified multipotent stem and progenitor cells on the basis of Flk-2 surface expression and used them in competitive reconstitution assays. Low numbers of Flk-2(-) HSCs gave rise to long-term multilineage reconstitution in the majority of recipients, whereas the transfer of Flk-2(+) multipotent cells resulted in mostly short-term multilineage reconstitution. The KLS subset of adult mouse bone marrow was analyzed for Flk-2 and Thy-1.1 expression. Three phenotypically and functionally distinct populations were isolated: Thy(lo) Flk-2(-) (LT-HSCs), Thy(lo) Flk-2(+) (ST-HSCs), and Thy(-) Flk-2(+) multipotent progenitors. The loss of Thy-1.1 and gain of Flk-2 expression marks the loss of self-renewal in HSC maturation. The addition of Flk-2 antibody to the lineage mix allows direct isolation of LT-HSC from adult bone marrow as c-kit(+) lin(-) Sca-1(+) Flk-2(-) from many strains of mice. Fetal liver HSCs are contained within Flk-2(-) and Flk-2(+) KTLS cells.


Bone mineral density loss after combat-related lower extremity amputation.
Determine the incidence, severity, and associated risk factors for the development of low bone mineral density (BMD) after combat-related lower extremity amputation. Retrospective case-control comparison. Tertiary care military treatment facility. One hundred fifty-six lower extremity amputees, representing 182 amputations (121 unilateral, 35 bilateral). All patients underwent dual energy x-ray absorptiometry scanning during the treatment period. The Z score was the main outcome measure. We identified all patients with low BMD (Z < -1.0) and conducted multivariate analysis to identify significant risk factors for low BMD development. The observed rate of low BMD was 42%. The average Z score was -0.6 ± 1.1 among unilateral amputations and -1.2 ± 1.0 among bilateral amputations (P = 0.005). Risk factors for the development of low BMD were prolonged time to first ambulation [odds ratio (OR) = 1.39; 95% confidence interval (CI): 1.003-1.93; P = 0.048], prolonged time to dual energy x-ray absorptiometry (OR = 1.10; 95% CI: 1.02-1.18; P = 0.009), and more proximal amputation level (OR = 7.27; 95% CI: 3.21-16.49; P < 0.001). Among unilateral amputees, we detected a significant difference in the BMD of the intact and amputated limbs (-1.0; 95% CI: -1.1 to -0.8; P < 0.001). Proximal amputation level and delayed ambulation demonstrated a significant relationship with low BMD after traumatic and trauma-related amputation. We conclude that transfemoral amputees are at greater risk of BMD loss and that disuse atrophy is a primary factor in the development of low BMD. Prevention should focus on early and aggressive weight bearing rehabilitation and assessing levels and appropriately supplementing calcium and vitamin D.


[A clinical study of radiotherapy with HCFU for advanced and recurrent breast cancers. Radiation and HCFU Study Group for breast cancer].
We have investigated the usefulness of combination therapy with radiation and HCFU for advanced and recurrent breast cancer according to a clinical controlled multicenter trial from 1982 to 1984. One hundred cases were registered and 82 of them were available. Treatment sites were the lymph nodes, skin, bone and lung, and the overall response rate was 58% in CR and 19% in PR, while the duration of remission was 18 weeks in CR. Side effects were found in 10% of the patients. Combination therapy with radiation and HCFU may be useful in multimodal treatment for advanced recurrent breast cancer.


Effect of vibration emissions during shipping of artificial insemination doses on boar semen quality.
The shipping of semen doses to sow farms can impair boar semen quality. Unfortunately, there is currently no practice-oriented information available regarding general shipping conditions of boar semen. For this reason, a special mobile sensing app (TransportLog 1.0), utilizing the built-in sensors of smartphones, has been programmed to capture vibration emissions during shipping of semen doses (QuickTip Flexitubes®, Minitüb). Data were analyzed, transformed and used as standards for simulating vibration emissions from an orbital shaker IKA MTS 4 (Laborgeräte München) in a spermatological reference laboratory. Twenty ejaculates were collected randomly and diluted using a one-step isothermal process in a split-sample procedure in Beltsville Thawing Solution (BTS, Minitüb). The sperm concentration was adjusted to 24 × 106 sperm/mL. The dose filling volume was 85 ± 1 mL. Samples were stored for seven days at 17 °C. The results showed that circular horizontal vibration emissions with frequencies of 300 rpm for a duration of 6 h led to a significant alkalization of the BTS-extended semen. Semen motility, mitochondrial activity, acrosome and plasma membrane integrity as well as thermo-resistance all demonstrated a frequency-dependent negative response to vibration emissions during long-term storage. This study leads to new insights and recommendations for the shipping of boar semen in the artificial insemination industry. Furthermore, a new monitoring tool for boar semen shipping was established using mobile sensing.


BACE1 and BACE2 in pathologic and normal human muscle.
BACE1 and BACE2 are recently discovered enzymes participating in processing of amyloid beta precursor protein (AbetaPP). Their discovery is contributing importantly to understanding the mechanism of amyloid-beta generation, and hence the pathogenesis of Alzheimer's disease (AD). Sporadic inclusion-body myositis (s-IBM) and hereditary inclusion-body myopathy (h-IBM) are progressive muscle diseases in which overproduction of AbetaPP and accumulation of its presumably toxic proteolytic product amyloid-beta (Abeta) in abnormal muscle fibers appear to play an important upstream role in the pathogenic cascade. In normal human muscle AbetaPP was also shown to be present and presumably playing a role (a) at neuromuscular junctions and (b) during muscle development. To investigate whether BACE1 and BACE2 play a role in normal and diseased human muscle, we have now studied them by immunocytochemistry and immunoblotting in 35 human muscle biopsies, including: 5 s-IBM; 5 chromosome-9p1-linked quadriceps-sparing h-IBM; and 25 control muscle biopsies. In addition, expression of BACE1 and BACE2 was studied in normal cultured human muscle. Our studies demonstrate that BACE1 and BACE2 (a) are expressed in normal adult muscle at the postsynaptic domain of neuromuscular junctions, and in cultured human muscle; (b) are accumulated in the form of plaque-like inclusions in both s-IBM and h-IBM vacuolated muscle fibers; and (c) are immunoreactive in necrotizing muscle fibers. Accordingly, BACE1 and BACE2 participate in normal and abnormal processes of human muscle, suggesting that their functions are broader than previously thought.


The Melting Curve of Iron to 250 Gigapascals: A Constraint on the Temperature at Earth's Center.
The melting curve of iron, the primary constituent of Earth's core, has been measured to pressures of 250 gigapascals with a combination of static and dynamic techniques. The melting temperature of iron at the pressure of the core-mantle boundary (136 gigapascals) is 4800 +/- 200 K. whereas at the inner core-outer core boundary (330 gigapascals), it is 7600 +/- 500 K. Corrected for melting point depression resulting from the presence of impurities, a melting temperature for iron-rich alloy of 6600 K at the inner core-outer core boundary and a maximum temperature of 6900 K at Earth's center are inferred. This latter value is the first experimental upper bound on the temperature at Earth's center, and these results imply that the temperature of the lower mantle is significantly less than that of the outer core.


Social phobia and depression: prevalence and comorbidity.
Social phobia may seriously impair the functioning of affected individuals. It is frequently associated with other mental disorders. To estimate the co-occurrence of social phobia with major depressive disorder (MDD) and to analyze their interaction. Subjects were 18,980 individuals, aged 15 years or older, representative of the general population of the United Kingdom, Germany, Italy, Spain and Portugal, who were interviewed by telephone. DSM-IV diagnoses were made with the Sleep-EVAL system. The point prevalence for social phobia was 4.4% (95% confidence interval: 4.1-4.7%) of the sample. It was higher in women (odds ratio: 1.6) and decreased with age. MDDs were found in 19.5% of participants with social phobia. Co-occurrence of another anxiety disorder was high and increased when a MDD was present (65.2%). The odds of developing a major depressive episode 2 years after the appearance of the social phobia was of 5.74. Social phobia is highly prevalent in the general population. It increases the risk of developing a MDD and has a high comorbidity with other mental disorders. Social phobia is often present in the course of depression, more obviously during remission period of MDD. Physicians must explore and treat more systematically this frequent pathology.


Performance evaluation of existing de novo sequencing algorithms.
Two methods have been developed for protein identification from tandem mass spectra: database searching and de novo sequencing. De novo sequencing identifies peptide directly from tandem mass spectra. Among many proposed algorithms, we evaluated the performance of the five de novo sequencing algorithms, AUDENS, Lutefisk, NovoHMM, PepNovo, and PEAKS. Our evaluation methods are based on calculation of relative sequence distance (RSD), algorithm sensitivity, and spectrum quality. We found that de novo sequencing algorithms have different performance in analyzing QSTAR and LCQ mass spectrometer data, but in general, perform better in analyzing QSTAR data than LCQ data. For the QSTAR data, the performance order of the five algorithms is PEAKS > Lutefisk, PepNovo > AUDENS, NovoHMM. The performance of PEAKS, Lutefisk, and PepNovo strongly depends on the spectrum quality and increases with an increase of spectrum quality. However, AUDENS and NovoHMM are not sensitive to the spectrum quality. Compared with other four algorithms, PEAKS has the best sensitivity and also has the best performance in the entire range of spectrum quality. For the LCQ data, the performance order is NovoHMM > PepNovo, PEAKS > Lutefisk > AUDENS. NovoHMM has the best sensitivity, and its performance is the best in the entire range of spectrum quality. But the overall performance of NovoHMM is not significantly different from the performance of PEAKS and PepNovo. AUDENS does not give a good performance in analyzing either QSTAR and LCQ data.


Differentiation in light energy dissipation between hemiepiphytic and non-hemiepiphytic Ficus species with contrasting xylem hydraulic conductivity.
Hemiepiphytic Ficus species (Hs) possess traits of more conservative water use compared with non-hemiepiphytic Ficus species (NHs) even during their terrestrial growth phase, which may result in significant differences in photosynthetic light use between these two growth forms. Stem hydraulic conductivity, leaf gas exchange and chlorophyll fluorescence were compared in adult trees of five Hs and five NHs grown in a common garden. Hs had significantly lower stem hydraulic conductivity, lower stomatal conductance and higher water use efficiency than NHs. Photorespiration played an important role in avoiding photoinhibition at high irradiance in both Hs and NHs. Under saturating irradiance levels, Hs tended to dissipate a higher proportion of excessive light energy through thermal processes than NHs, while NHs dissipated a larger proportion of electron flow than Hs through the alternative electron sinks. No significant difference in maximum net CO2 assimilation rate was found between Hs and NHs. Stem xylem hydraulic conductivity was positively correlated with maximum electron transport rate and negatively correlated with the quantum yield of non-photochemical quenching across the 10 studied Ficus species. These findings indicate that a canopy growth habit during early life stages in Hs of Ficus resulted in substantial adaptive differences from congeneric NHs not only in water relations but also in photosynthetic light use and carbon economy. The evolution of epiphytic growth habit, even for only part of their life cycle, involved profound changes in a suite of inter-correlated ecophysiological traits that persist to a large extent even during the later terrestrial growth phase.


Oligomerization oscillations of L-lactic acid in solution.
We employ high-performance liquid chromatography with diode array, evaporative light scattering, and mass spectrometric detection to monitor the oligomerization of L-lactic acid in pure acetonitrile and in 70% aqueous ethanol. The production of higher oligomers appears to proceed in an oscillatory fashion. A model is presented that involves the formation of aggregates (micelles), which catalyze the oligomerization.


Multihormonal control of pre-pro-somatostatin mRNA levels in the periventricular nucleus of the male and female rat hypothalamus.
The influence of sex steroids as well as the possible involvement of dopaminergic pathways in the modulation of pre-pro-somatostatin (SS) mRNA levels was investigated by quantitative in situ hybridization in the hypothalamic periventricular nucleus (PeN) in adult male and female rats. In situ hybridization was performed using a [35S]-labeled cDNA probe encoding pre-proSS mRNA. Gonadectomy performed 14 days earlier decreased the mean number of silver grains/neuron corresponding to the relative pre-proSS mRNA levels by 22% in male and by 18-28% in female rats. A 14-day treatment with the nonaromatizable androgen dihydrotestosterone (DHT) increased the mean number of silver grains/neuron by 34-40% in gonadectomized animals of both sexes. Moreover, administration of 17 beta-estradiol (E2, 0.25 microgram twice daily) increased pre-proSS mRNA levels by 40% in ovariectomized (OVX) animals. Such treatment with E2 or DHT changed the frequency distribution profile of the hybridization signal intensity, thus increasing the percentage of highly labeled neurons (greater than or equal to 61 grains/neuron) by 10 to 12-fold. A 14-day treatment with the D2 dopamine receptor agonist bromocriptine (BRO) increased pre-proSS mRNA levels by 15 and 28% in intact female and OVX animals, respectively, while the dopaminergic antagonist haloperidol (HAL) decreased the value of this parameter by 20 and 30%. Furthermore, BRO increased pre-proSS mRNA levels by 10 and 20% in intact and castrated male rats, respectively, whereas HAL decreased pre-proSS mRNA levels by 25 and 14% in the same groups of animals. Administration of E2 in combination with HAL in OVX animals increased pre-proSS mRNA levels by 70% compared to those measured in OVX animals treated with HAL alone. In HAL-treated castrated male rats, administration of DHT increased the relative pre-proSS mRNA levels by 35% compared to those measured in castrated animals treated with HAL alone. The present data clearly demonstrate that androgens and estrogens as well as dopamine-mediated mechanisms could play a regulatory role in pre-proSS mRNA levels in somatostatinergic neurons in the hypothalamic PeN in both male and female rats.


Delocalization and heat transport in multidimensional trapped ion systems.
We study the connection between heat transport properties of systems coupled to different thermal baths in two separate regions and their underlying nonequilibrium dynamics. We consider classical systems of interacting particles that may exhibit a certain degree of delocalization and whose effective dimensionality can be modified through the controlled variation of a global trapping potential. We focus on Coulomb crystals of trapped ions, which offer a versatile playground to shed light on the role that spatial constraints play on heat transport. We use a three-dimensional model to simulate the trapped ion system and show in a numerically rigorous manner to what extent heat transport properties could be feasibly tuned across the structural phase transitions among the linear, planar zigzag, and helical configurations. By solving the classical Langevin equations of motion, we analyze the steady state spatial distributions of the particles, the temperature profiles, and total heat flux through the various structural phase transitions that the system may experience. The results evidence a clear correlation between the degree of delocalization of the internal ions and the emergence of a nonzero gradient in the temperature profiles. The signatures of the phase transitions in the total heat flux as well as the optimal spatial configuration for heat transport are shown.


Auditory problems in elderly patients with stroke.
Twenty-five CAT-scan-confirmed stroke patients and 25 matched controls were studied. All the stroke patients were stable 2-3 months after unilateral hemispheric stroke. Those with ear disease, other central neurological disorder, severe dysphasia and acute or chronic confusion were excluded. There were no significant differences between the groups for average pure tone hearing threshold (APTT) or ability to discriminate pre-recorded speech presented to one ear at 35 decibels (dB) above APTT. The stroke subjects had significantly impaired performance on dichotic competing sentence testing (DCST). Seventeen stroke patients but only one control subject failed DCST. Failure rate was similar for left and right stroke and for temporal and non-temporal lobe involvement. Two-thirds of patients failing DCST did so in the ear opposite the side of the cortical lesion. We conclude that (i) DCST is useful in detecting central auditory dysfunction in stroke patients; and (ii) stroke can affect central auditory perception in older patients.


Flow distribution in a single bifurcation during high-frequency oscillation.
The distribution of flow in a single bifurcation was studied to examine what factors played a critical role. Flow was preferentially directed down the straightest pathway when higher frequencies and/or larger tidal volumes were used, but otherwise followed the pattern dictated by the distal impedance regardless of bifurcation geometry. In a symmetrical model, the observed flow distribution was in good agreement with a mathematical prediction based on linear impedance theory, though this was not the case when tidal volumes were increased. The difference in mean pressure between the two terminal units was also a strong function of branching angle and the Reynolds number. These findings suggest that the geometrical factors and local flow conditions contribute to both the flow and mean pressure distribution in an inertia-induced nonlinear manner. Consequently, linear impedance theory can be applied only to the limited situation of low tidal volume and symmetric configuration.


Viability and isolation of marine bacteria by dilution culture: theory, procedures, and initial results.
Dilution culture, a method for growing the typical small bacteria from natural aquatic assemblages, has been developed. Each of 11 experimental trials of the technique was successful. Populations are measured, diluted to a small and known number of cells, inoculated into unamended sterilized seawater, and examined three times for the presence of 10 or more cells per ml over a 9-week interval. Mean viability for assemblage members is obtained from the frequency of growth, and many of the cultures produced are pure. Statistical formulations for determining viability and the frequency of pure culture production are derived. Formulations for associated errors are derived as well. Computer simulations of experiments agreed with computed values within the expected error, which verified the formulations. These led to strategies for optimizing viability determinations and pure culture production. Viabilities were usually between 2 and 60% and decreased with >5 mg of amino acids per liter as carbon. In view of difficulties in growing marine oligobacteria, these high values are noteworthy. Significant differences in population characteristics during growth, observed by high-resolution flow cytometry, suggested substantial population diversity. Growth of total populations as well as of cytometry-resolved subpopulations sometimes were truncated at levels of near 10 cells per ml, showing that viable cells could escape detection. Viability is therefore defined as the ability to grow to that population; true viabilities could be even higher. Doubling times, based on whole populations as well as individual subpopulations, were in the 1-day to 1-week range. Data were examined for changes in viability with dilution suggesting cell-cell interactions, but none could be confirmed. The frequency of pure culture production can be adjusted by inoculum size if the viability is known. These apparently pure cultures produced retained the size and apparent DNA-content characteristic of the bulk of the organisms in the parent seawater. Three cultures are now available, two of which have been carried for 3 years. The method is thus seen as a useful step for improving our understanding of typical aquatic organisms.


Real-time PCR detection of Helicobacter pylori clarithromycin resistance in Thrace, Greece.
Growing resistance to clarithromycin is a major concern regarding treating Helicobacter pylori (H. pylori) infection. Resistance rates have a great variation even in different geographic areas within the same country and are associated with point mutations of the microbial 23S rRNA (A2142C, A2142G, and A2143G). Given the absence of available data in Thrace, the objective of this study was to estimate the resistance of H. pylori to clarithromycin and identify specific mutations that contribute to clarithromycin resistance. In this prospective study, we enrolled consecutive patients referred for dyspeptic complaints who underwent upper gastrointestinal endoscopy over two years. Gastric biopsies from corpus and antrum were initially tested for the presence of urease by a rapid urease test. Urease positive samples were followed by real-time PCR to confirm the presence of H. pylori and to detect point mutations. A total of one hundred and thirty patients were included in the study (72 women and 58 men). Resistance to clarithromycin was detected at 23.2 %. Neither gender nor age was independently correlated with resistance rate in our patient group. The most common mutations were A2142G and A2143G. A high rate of H. pylori resistance to clarithromycin was observed in our region, implicating that it should be addressed in accordance with the recommendations provided by national and international guidelines. Molecular testing should be considered an integral tool for effective monitoring in case of suspected antibiotic resistance. HIPPOKRATIA 2021, 25 (2):51-55.


Swallowing function in advanced age.
To present current literature regarding swallowing function in advanced age, including healthy ageing, dysphagia and trends in multidisciplinary team service delivery. Normative studies support swallowing efficiency but greater variability in healthy advanced age, through to 100 years old. Deviations from normative data and symptoms of dysphagia leading to aspiration or nutritional risk, imply swallowing disorder, rather than simply the ageing process. Quantitative and qualitative studies are emerging that promote management of swallow dysfunction for an ageing society, including innovative assessment, home treatment, swallowing exercise and optimized mealtimes. Current literature on swallowing function in advanced age provides multidisciplinary perspectives and initiatives, with clear commitment to improving quality of life for older adults. The diversity of the older population and serious consequences of swallowing difficulties calls for routine screening tools for swallowing impairment and malnutrition risk. Representation of 'oldest old' in future normative studies is essential to guide swallowing management in adults over 85 years old.


Receptor-like protein kinases RPK1 and BAK1 sequentially form complexes with the cytoplasmic kinase OST1 to regulate ABA-induced stomatal closure.
Regulation of plant water status occurs via abscisic acid (ABA)-induced stomatal closure. Open Stomata 1 (OST1) is a critical ABA signaling component regulating this process in guard cells. We previously reported that BRI1-associated receptor kinase 1 (BAK1) positively regulates ABA-induced stomatal closure by interacting with and phosphorylating OST1. Here, using Arabidopsis, we show that the receptor-like protein kinase 1 (RPK1), previously known to be induced by ABA, is a positive ABA-signaling component in guard cell movement, and interacts with OST1. ABA-inducible expression patterns were observed in RPK1 and OST1, but not in BAK1. We investigated the underlying mechanisms by which the RPK1-OST1 and BAK1-OST1 complexes interact in stomatal guard cells by monitoring the complex formation continuously using fluorescence resonance energy transfer analyses. We found that the BAK1-OST1 complex was formed earlier than the RPK1-OST1 complex in response to ABA. In vitro and semi-in vivo kinase assays revealed that a transphosphorylation event occurred in the RPK1-OST1 complex, which differs from that in the BAK1-OST1 complex, wherein only OST1 phosphorylation occurred via BAK1. ABA-insensitive 1 (ABI1) only dephosphorylated OST1 in the BAK1-OST1 complex, but dephosphorylated both RPK1 and OST1 proteins in the RPK1-OST1 complex. Our results suggest that there are multiple coordinated ABA signaling systems to regulate stomatal movement.


[Microbiological diagnosis of malaria and amoebiasis].
All stages of malaria and amebiasis may be sensitively and specifically diagnosed by means of microbiological methods. Microscopical parasitology holds a key position when supplemented by immunodiagnostic assays. Molecular biology techniques are currently still inferior to the above procedure. Tests for the differentiation between pathogenic and nonpathogenic Entamoeba histolytica (Entamoeba dispar) require further simplification before generally applicable.


Real-time transmembrane translocation of penetratin driven by light-generated proton pumping.
Cell penetrating peptides (CPPs) are small peptides that are able to penetrate the plasma membrane of mammalian cells. Because these peptides can also carry large hydrophilic cargos such as proteins, they could potentially be used to transport biologically active drugs across cell membranes to modulate in vivo biology. One characteristic feature of the CPPs is that they typically have a net positive charge. Therefore, a key issue associated with the transport mechanism is the role of the transmembrane electrochemical potential in driving the peptides across the membrane. In this study, we have reconstituted bacteriorhodopsin (bR) in large unilamellar vesicles (LUVs) with fluorescein-labeled CPP penetratin enclosed within the LUVs under conditions when the fluorescence is quenched. Illumination of the bacteriorhodopsin-containing LUVs resulted in creation of a transmembrane proton electrochemical gradient (positive on the inside). Upon generation of this gradient, an increase in fluorescence was observed, which shows that the proton gradient drives the translocation of penetratin. The mechanism most likely can be generalized to other CPPs.


Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals.
Individual human health is determined by a complex interplay between genes, environment, diet, lifestyle, and symbiotic gut microbial activity. Here, we demonstrate a new "nutrimetabonomic" approach in which spectroscopically generated metabolic phenotypes are correlated with behavioral/psychological dietary preference, namely, "chocolate desiring" or "chocolate indifferent". Urinary and plasma metabolic phenotypes are characterized by differential metabolic biomarkers, measured using 1H NMR spectroscopy, including the postprandial lipoprotein profile and gut microbial co-metabolism. These data suggest that specific dietary preferences can influence basal metabolic state and gut microbiome activity that in turn may have long-term health consequences to the host. Nutrimetabonomics appears as a promising approach for the classification of dietary responses in populations and personalized nutritional management.


The shielding function of task sets and its relaxation during task switching.
The goal of the presented experiments was to investigate the dynamic interplay of task shielding and its relaxation during task switching. Task shielding refers to the finding that single task sets in terms of 2-choice categorization rules help shielding against distraction from irrelevant stimulus attributes. During task switching, this shielding should temporarily be relaxed to prevent the perseveration of the previous task, on the downside making the system more vulnerable toward the intrusion of irrelevant information. Participants had to switch between a digit and a letter categorization task. An irrelevant stimulus feature (Experiment 1: color, Experiment 2: font) varied randomly, orthogonal to the task. The presence or absence of an interaction of the irrelevant feature (switch vs. repetition) and the response (switch vs. repetition) was taken as evidence for the absence or presence of task shielding, respectively. Replicating previous results, irrelevant feature and response did not interact on task repetitions, indicating successful shielding. On task switches, however, the irrelevant feature interacted with the response, supporting the assumption that task shielding is temporarily relaxed during task switching.


Noninvasive evaluation of liver fibrosis using real-time tissue elastography and transient elastography (FibroScan).
The purpose of this study was to assess liver fibrosis with real-time tissue elastography and to compare the results with those of transient elastographic (FibroScan; Echosens, Paris, France) measurements by using liver biopsy as the reference standard. Real-time tissue elastography and percutaneous liver biopsy were performed in 166 patients with chronic hepatitis B (estimation group). The relationship between the parameters obtained via real-time tissue elastography and the hepatic fibrosis stage was evaluated by a stepwise multiple linear regression, and the regression equation was used to calculate the liver fibrosis index. The diagnostic performance of the liver fibrosis index was validated and compared with FibroScan in 121 other patients with chronic hepatitis B (validation group). The liver fibrosis index was calculated as follows: liver fibrosis index = 0.043 low-strain area ratio + 4.520 skewness + 0.033 mean - 1.002 kurtosis. The liver fibrosis index and liver stiffness measured by FibroScan were both significantly associated with the fibrosis stage in the validation group (r= 0.667 and 0.664, respectively; both P< .001). The areas under the receiver operating characteristic curves for the liver fibrosis index and liver stiffness were 0.880 and 0.909 for predicting substantial fibrosis (scores ≥F2), 0.868 and 0.874 for predicting severe fibrosis (≥F3), and 0.752 and 0.815 for predicting cirrhosis (F4), respectively. Real-time tissue elastography is an effective method for assessing liver fibrosis, with diagnostic performance similar to that of transient elastography.


Providing primary care to the HIV-at-risk and infected child.
Pediatric HIV disease is a growing epidemic in the United States. As the incidence of pediatric HIV disease increases, so will the need for primary care providers knowledgeable in pediatric HIV disease. Primary care providers must have the knowledge and expertise to identify those infants at risk for HIV and be able to implement essential interventions to ensure the most optimal outcomes for these at-risk infants. It is no longer feasible for all at-risk children to be cared for by tertiary care facilities. Community based, primary care centers will need to fill an increasingly large role in this area of care.


[Digital stereotactic breast microbiopsy with the mammotome: study of 122 cases].
To evaluate the diagnostic value of vacuum-assisted biopsy (VB) with digital stereotactic Mammotome on dubious mammary lesions clinically and sonographically negative as an alternative to surgical biopsy diagnosis. From November 1999 to November 2000, 122 biopsies were performed using a vacuum suction aspiration device with digital stereotactic-guided Mammotome (Fischer prone table) on 116 patients between the age of 34 and 74 years (median 51 yrs). Sampling was performed with an 11 gauge probe. All patients were previously subjected to mammography in which dubious lesions were evidenced without clinical and sonogram confirmation. All lesions that were obviously benign or malignant were excluded. Mammography demonstrated isolated microcalcifications, small opacities and parenchymal distortions. Microcalcifications were then subdivided into lobular, rad-shaped, granular, mixed and pulverulent, according to Tabar's classification. The median diameter of lesions was 13 mm (range 3-50). The median number of Mammotome biopsy samples was 10.8 (range 3-19). All samples were radiographed and magnified. In 76 patients, the Mammotome biopies were incisional (only a part of the lesion was removed) and in 46 the biopsy was excisional (the entire lesion was removed). The biopsy site was marked with a non-magnetic metallic clip in 83 patients. Slight bleeding was noted during the procedure in two cases. Ultrasound visualization evidenced a hematoma at the biopsy site in one patient which was successfully resolved in one month with local therapy. No noticeable pain or patient intolerance to the procedure was observed. Histological probe sample examination was negative in 91 patients (74.6%) and positive in 31 patients (25.4%). The benign histologies included adenosis and epitheliosis (47 pts), sclerosing adenosis (7 pts), fibroadenoma (7 pts), fibrosis and fibrocystic mastopathy (30 pts). Of the 31 positive patients, 14 were infiltrating carcinomas (45%) and 17 ductal carcinomas in situ (DCIS) (55%). All positive cases underwent surgery. The post-surgical histological examination confirmed all diagnoses of infiltrating carcinoma while the diagnosis of DCIS was confirmed in 15 cases; infiltrating microfoci associated with DCIS were evidenced in two cases. VB with digital stereotactic Mammotome was shown to be a valid method for dubious mamographic lesions in which cytology often supplies an inadequate or false-negative responses. This method distinguishes between benign and malignant lesions rapidly without discomfort to the patient, thus reducing the number of diagnostic surgical biopsies. Moreover, in positive cases, it offers the advantage of avoiding extemporaneous intraoperative procedures and the possibility to perform biological tests on the tumor before surgery (estrogen and progesterone receptors, HER-2 neu, grading, Ki 67, p53 ), thus providing patient benefits and a distinct reduction of costs. However, this method is purely diagnostic and is not sufficient for therapeutical purposes.


B16-BL6 melanoma cells release inhibitory factor(s) of active pump activity in isolated lymph vessels.
We investigated whether supernatant cultured with melanoma cell lines B16-BL6 and K1735 or the Lewis lung carcinoma cell line (LLC) can regulate lymphatic pump activity with bioassay preparations isolated from murine iliac lymph vessels. B16-BL6 and LLC supernatants caused significant dilation of lymph microvessels with cessation of pump activity. B16-BL6 supernatant produced dose-related cessation of lymphatic pump activity. There was no significant tachyphylaxis in the supernatant-mediated inhibitory response of lymphatic pump activity. Pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) or 10(-7) M or 10(-6) M glibenclamide and 5 x 10(-4) M 5-hydroxydecanoic acid caused significant reduction of supernatant-mediated inhibitory responses. Simultaneous treatment with 10(-3) M L-arginine and 3 x 10(-5) M L-NAME significantly lessened L-NAME-induced inhibition of the supernatant-mediated response, suggesting that endogenous nitric oxide (NO) plays important roles in supernatant-mediated inhibitory responses. Chemical treatment dialyzed substances of <1,000 molecular weight (MW), producing complete reduction of the supernatant-mediated response. In contrast, pretreatment with heating or digestion with protease had no significant effect on supernatant-mediated response. These findings suggest that B16-BL6 cells may release nonpeptide substance(s) of <1,000 MW, resulting in significant cessation of lymphatic pump activity via production and release of endogenous NO and activation of mitochondrial ATP-sensitive K(+) channels.


The role of nonlinear dynamics in cardiac arrhythmia control.
The field of nonlinear dynamics has made important contributions toward a mechanistic understanding of cardiac arrhythmias. In recent years, many of these advancements have been in the area of arrhythmia control. This paper reviews the literature on analytical, modeling, and experimental nonlinear dynamical arrhythmia control with a focus on stimulation and pharmacologic techniques that have been developed, and in some cases used in experiments, to control reentrant rhythms (including spiral and scroll waves) and fibrillation. Although such approaches currently have practical limitations, they offer hope that nonlinear dynamical control techniques will be clinically useful in the coming years.


A perspective of preconception health activities in the United States.
Information regarding the type and scope of preconception care programs in the United States is scant. We evaluated State Title V measurement and indicator data and abstracts presented at the National Summit on Preconception Care (June 2005) in order to identify existing programs and innovative strategies for preconception health promotion. We used the web-based Title V Information System to identify state Performance Measures and Priority Needs pertaining to preconception health as reported for the 2005-2010 Needs Assessment Cycle. We also present a detailed summary of the abstracts presented at the National Summit on Preconception Care. A total of 23 states reported a Priority Need that focused on preconception health and health care. Forty-two states and jurisdictions identified a Performance Measure associated with preconception health or a related indicator (e.g., folic acid, birth spacing, family planning, unintended pregnancy, and healthy weight). Nearly 60 abstracts pertaining to preconception care were presented at the National Summit and included topics such as research, programs, patient or provider toolkits, clinical practice strategies, and public policy. Strategies for improving preconception health have been incorporated into numerous programs throughout the United States. Widespread recognition of the benefits of preconception health promotion is evidenced by the number of states identifying related indicators.


Dopaminergic regulation of septohippocampal cholinergic neurons.
The extent to which acetylcholine (ACh) release in the hippocampus is regulated by dopaminergic mechanisms was assessed using in vivo microdialysis in freely moving rats. Systemic administration of the dopamine (DA) receptor agonist apomorphine (1.0 mg/kg) or the specific D1 agonist CY 208-243 (1.0 mg/kg) increased microdialysate concentrations of ACh in the hippocampus. The D2 receptor agonist quinpirole (0.5 mg/kg) produced a small but statistically significant decrease in hippocampal ACh release. d-Amphetamine (2.0 mg/kg) increased ACh release, an effect that was blocked by the D1 receptor antagonist SCH 23390 (0.3 mg/kg) but not by the D2 antagonist raclopride (1.0 mg/kg). These findings suggest that endogenous DA stimulates septohippocampal cholinergic neurons primarily via actions at D1 receptors. In addition, these results are similar to previous findings regarding the dopaminergic regulation of cortical ACh release, and suggest that the anatomical continuum formed by basal forebrain cholinergic neurons that project to the cortex and hippocampus acts as a functional unit, at least with respect to its regulation by DA.


Hepcidin, a candidate modifier of the hemochromatosis phenotype in mice.
Hereditary hemochromatosis (HH) type I is a disorder of iron metabolism caused by a mutation in the HFE gene. Whereas the prevalence of the mutation is very high, its penetrance seems very low. The goal of our study was to determine whether hepcidin, a recently identified iron-regulatory peptide, could be a genetic modifier contributing to the HH phenotype. In mice, deficiency of either HFE (Hfe(-/-)) or hepcidin (Usf2(-/-)) is associated with the same pattern of iron overload observed in patients with HH. We intercrossed Hfe(-/-) and Usf2(+/-) mice and asked whether hepcidin deficiency increased the iron burden in Hfe(-/-) mice. Our results showed that, indeed, liver iron accumulation was greater in the Hfe(-/-)Usf2(+/-) mice than in mice lacking Hfe alone. This result, in agreement with recent findings in humans, provides a genetic explanation for some variability of the HH phenotype.


Bis(hydroxyamino)triazines: versatile and high-affinity tridentate hydroxylamine ligands for selective iron(III) chelation.
A new versatile family of chelating agents based on bis(hydroxyamino)-1,3,5-triazines, BHTs, is described. The properties of different BHT ligands are determined by electrochemistry, spectroscopy and titrimetry revealing high redox stability, transparency in the visible range, and diprotic acid-like behaviour in the 5-9 pH range. The iron(III) and iron(II)-BHT complexes were studied revealing high affinity of BHTs to iron(III). Electrochemical studies show exceptional preference of the BHT ligands to iron(III) over iron(II), this, in addition to their small size and their fast and reversible electrochemistry makes them potentially useful electrochemical redox couples for the low end of the aqueous potential window (<0.6 V, vs. NHE). The synthetic versatility of the new ligands allows easy tuning of the hydrophobicity, redox potential, and to some extent the stability constant of the complexes by alteration of the peripheral groups appended to the BHTs.


Effect of experimenter-delivered and self-administered cocaine on extracellular beta-endorphin levels in the nucleus accumbens.
Beta-endorphin is an endogenous opioid peptide that has been hypothesized to be involved in the behavioral effects of drugs of abuse including psychostimulants. Using microdialysis, we studied the effect of cocaine on extracellular levels of beta-endorphin in the nucleus accumbens, a brain region involved in the reinforcing effects of psychostimulant drugs. Experimenter-delivered cocaine (2 mg/kg, i.v.) increased extracellular beta-endorphin immunoreactive levels in the nucleus accumbens, an effect attenuated by 6-hydroxy-dopamine lesions or systemic administration of the D1-like receptor antagonist, SCH-23390 (0.25 mg/kg, i.p.). The effect of cocaine on beta-endorphin release in the nucleus accumbens was mimicked by a local perfusion of dopamine (5 microm) and was blocked by coadministration of SCH-23390 (10 microm). Self-administered cocaine (1 mg/kg/infusion, i.v.) also increased extracellular beta-endorphin levels in the nucleus accumbens. In addition, using functional magnetic resonance imaging, we found that cocaine (1 mg/kg, i.v.) increases regional brain activity in the nucleus accumbens and arcuate nucleus. We demonstrate an increase in beta-endorphin release in the nucleus accumbens following experimenter-delivered and self-administered cocaine mediated by the local dopaminergic system. These findings suggest that activation of the beta-endorphin neurons within the arcuate nucleus-nucleus accumbens pathway may be important in the neurobiological mechanisms underlying the behavioral effects of cocaine.


Iron Metabolism in Aging and Age-Related Diseases.
Iron is a trace metal element necessary to maintain life and is also involved in a variety of biological processes. Aging refers to the natural life process in which the physiological functions of the various systems, organs, and tissues decline, affected by genetic and environmental factors. Therefore, it is imperative to investigate the relationship between iron metabolism and aging-related diseases, including neurodegenerative diseases. During aging, the accumulation of nonheme iron destroys the stability of the intracellular environment. The destruction of iron homeostasis can induce cell damage by producing hydroxyl free radicals, leading to mitochondrial dysfunction, brain aging, and even organismal aging. In this review, we have briefly summarized the role of the metabolic process of iron in the body, then discussed recent developments of iron metabolism in aging and age-related neurodegenerative diseases, and finally, explored some iron chelators as treatment strategies for those disorders. Understanding the roles of iron metabolism in aging and neurodegenerative diseases will fill the knowledge gap in the field. This review could provide new insights into the research on iron metabolism and age-related neurodegenerative diseases.


Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies.
Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 are enzymes which post-translationally modify proteins through poly(ADP-ribosyl)ation (PARylation)-the transfer of ADP-ribose chains onto amino acid residues-with a resultant modulation of protein function. Many targets of PARP-1/2-dependent PARylation are involved in the DNA damage response and hence, the loss of these proteins disrupts a wide range of biological processes, from DNA repair and epigenetics to telomere and centromere regulation. The central role of these PARPs in DNA metabolism in cancer cells has led to the development of PARP inhibitors as new cancer therapeutics, both as adjuvant treatment potentiating chemo-, radio-, and immuno-therapies and as monotherapy exploiting cancer-specific defects in DNA repair. However, a cancer is not just made up of cancer cells and the tumor microenvironment also includes multiple other cell types, particularly stromal and immune cells. Interactions between these cells-cancerous and non-cancerous-are known to either favor or limit tumorigenesis. In recent years, an important role of PARP-1 and PARP-2 has been demonstrated in different aspects of the immune response, modulating both the innate and adaptive immune system. It is now emerging that PARP-1 and PARP-2 may not only impact cancer cell biology, but also modulate the anti-tumor immune response. Understanding the immunomodulatory roles of PARP-1 and PARP-2 may provide invaluable clues to the rational development of more selective PARP-centered therapies which target both the cancer and its microenvironment.


Effect of protein-energy malnutrition on the growth of mandible and long bone in newborn male and female rats.
Several parameters were measured in the growth centers of mandible and long bone of rat pups suckled on dams fed 25% or 6% protein diets. No sex-related differences were found in any parameter either during normal growth or in response to malnutrition. While the total contents of protein, DNA, RNA and calcium were reduced in both tissues, mandible was less affected than long bone, although it appeared to be affected earlier. Moreover, malnutrition reduced the number of cells in the mandible without changing cell size or calcium content. In contrast, long bone appeared to be affected later than mandible, and to be modified differently. In this case, not only cell number, but also cell size and cellular content of calcium were reduced. The results can be interpreted to mean that the critical periods of growth for mandible and long bone are different. Moreover, some suggestion of differences in relative sensitivity to malnutrition of these two hard tissues was also observed.


Morphology and elemental analysis of free range and stabled Polish Konik horses hair using Energy-dispersive X-ray spectroscopy (EDS).
Hair is a more biologically stable material than other tissues and contains a relatively constant level of minerals, drugs or toxins. The content of essential elements in hair depends on dietary and non-dietary factors. The aim of this study was to assess and compare the effect of diet on the elemental composition and morphological properties of the hair of healthy Polish Konik horses. Mane hair was collected from 19 horses living in The National Park in Popielno in Poland. Six of these horses were free-ranged all year with permanent access to pasture, while 13 horses were kept in the stable and fed oats, hay and straw. The samples were analyzed using a Scanning Electron Microscope combined with Energy-dispersive X-ray spectroscopy (SEM-EDS). Each hair was analyzed for its microscopic appearance and elemental Mg, Si, S, Ca, Mn, Co, Zn and Se content. No significant changes in the morphological properties and elemental composition were observed. There was inter- individual variability in element content between horses in both groups, but this did not affect their health. The comparison of the present results with other studies shows that the level of elements in the hair of Polish Konik horses is significantly lower than in healthy horses of other breeds. The traditional feeding plan containing pasture, oats and hay does not contain a sufficient amount of main mineral elements. Further investigation is needed to explain the effect of diet and maintenance on the mineral balance of horses.


Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010: revised recommendations for the use of contraceptive methods during the postpartum period.
Initiation of contraception during the postpartum period is important to prevent unintended pregnancy and short birth intervals, which can lead to negative health outcomes for mother and infant. In 2010, CDC published U.S. Medical Eligibility Criteria for Contraceptive Use, 2010 (US MEC), providing evidence-based guidance for choosing a contraceptive method based on the relative safety of contraceptive methods for women with certain characteristics or medical conditions, including women who are postpartum. Recently, CDC assessed evidence regarding the safety of combined hormonal contraceptive use during the postpartum period. This report summarizes that assessment and the resulting updated guidance. These updated recommendations state that postpartum women should not use combined hormonal contraceptives during the first 21 days after delivery because of the high risk for venous thromboembolism (VTE) during this period. During 21-42 days postpartum, women without risk factors for VTE generally can initiate combined hormonal contraceptives, but women with risk factors for VTE (e.g., previous VTE or recent cesarean delivery) generally should not use these methods. After 42 days postpartum, no restrictions on the use of combined hormonal contraceptives based on postpartum status apply.


[Professor A.G. Kolesnik].
Anatoly Grigoryevich Kolesnik made a significant contribution to the development of CRIIS, in the walls of which he worked for 46 years. His professional life was devoted to actual problems of experimental and practical dentistry.


Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I.
The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.


Quality improvement projects: finding a pathway through policies.
It is increasingly common for mental health nurses to develop and implement quality improvement and/or research projects. The requirement that these activities be conducted in accordance with local, state and national policy; organizational accreditation frameworks; and within ethical frameworks is daunting. This paper aims to define relevant terms, relate some of the competing demands to each other and outline a pathway for developing nurse-based quality-related projects. When a specific exemplar is required, protocols from Central Sydney Area Mental Health Service will be drawn upon as it is likely that policy developed in this health area will not be significantly different to that of other health areas in New South Wales and other Australian States.


Inhibition of mitogen-activated protein kinase signalling by Bacillus anthracis lethal toxin causes destabilization of interleukin-8 mRNA.
Bacillus anthracis must overcome host innate immune defences to establish a systemic anthrax infection. This is facilitated in part by lethal toxin (LT), a secreted virulence factor that consists of a cell-binding moiety, protective antigen (PA), and an enzymatic moiety, lethal factor (LF). PA binds cells through protein receptors and mediates the delivery of LF to the cytosol. LF is a protease that cleaves amino-terminal fragments from mitogen-activated protein kinase kinases (MAPKKs), preventing phosphorylation of their downstream targets. Here we report that LT reduces the amount of interleukin (IL)-8 produced and secreted by human endothelial cells. The reduction of IL-8 levels by LT was not attributable to reduced expression from the IL-8 promoter, but resulted from destabilization of IL-8 mRNA. Destabilization by LT was mediated through the 3' untranslated region of the IL-8 transcript and could be mimicked by pharmacological inhibitors of MAPK pathways. LT diminished the induction of IL-8 mRNA and protein by lipopolysaccharide, indicating that the toxin can impair the ability of these cells to initiate an immune response. Destabilization of a cytokine transcript represents a new interference strategy used by either a bacterial or viral pathogen to reduce cytokine expression and may help B. anthracis to evade host immune defences.


Effects of gonadotrophin releasing hormone administration on the pituitary-ovarian axis in anoestrous vs ovariectomized bitches.
The aim of this study was to determine the effects of gonadotrophin releasing hormone (GnRH) administration on the plasma concentrations of reproductive hormones in intact and ovariectomized (OVX) bitches. Therefore, blood samples were collected at multiple times before and after the administration of 10 microg/kg GnRH (Fertagyl)) for the determination of the plasma concentrations of luteinizing hormone (LH), oestradiol, progesterone and testosterone in six anoestrus and in six OVX bitches. The mean plasma LH concentrations before and 60 min after GnRH administration were significantly lower in the anoestrous bitches than in the OVX bitches. In both groups GnRH administration resulted in a significant increase in the plasma LH concentration. The highest plasma LH concentrations were found at 10 min after GnRH administration and these values did not differ significantly between the two groups. Only in the anoestrous bitches a significant increase in plasma oestradiol concentrations was found after GnRH administration and these values were significantly higher than those in the OVX bitches. The plasma concentrations of progesterone and testosterone were low (close to or below the limit of quantitation) both before and after GnRH administration and the differences between anoestrous and OVX bitches were not significant. It can be concluded that (i) basal plasma LH concentration is significantly higher in OVX bitches than in anoestrous bitches, (ii) plasma LH concentration increases after GnRH administration in both anoestrous and OVX bitches, (iii) GnRH administration causes a significant rise in plasma oestradiol concentration only if ovarian tissue is present and (iv) measurement of plasma progesterone and testosterone concentrations before and after GnRH administration does not aid in distinguishing between anoestrous and OVX bitches. The results of this study may provide a basis for the diagnosis of remnant ovarian tissue and verification of neuter status in the bitch.


Homocysteine and thrombosis: from basic science to clinical evidence.
Homocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.


In vitro bactericidal activity of 4- and 5-chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA.
A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f), N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log10 CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log10 CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.


Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions.
The recent discovery of hydropersulfides (RSSH) in mammalian systems suggests their potential roles in cell signaling. However, the exploration of RSSH biological significance is challenging due to their instability under physiological conditions. Herein, we report the preparation, RSSH-releasing properties, and cytoprotective nature of alkylamine-substituted perthiocarbamates. Triggered by a base-sensitive, self-immolative moiety, these precursors show efficient RSSH release and also demonstrate the ability to generate carbonyl sulfide (COS) in the presence of thiols. Using this dually reactive alkylamine-substituted perthiocarbamate platform, the generation of both RSSH and COS is tunable with respect to half-life, pH, and availability of thiols. Importantly, these precursors exhibit cytoprotective effects against hydrogen peroxide-mediated toxicity in H9c2 cells and cardioprotective effects against myocardial ischemic/reperfusion injury, indicating their potential application as new RSSH- and/or COS-releasing therapeutics.


Drug release kinetics and front movement in matrix tablets containing diltiazem or metoprolol/λ-carrageenan complexes.
In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.


Hydrophobically-Modified PEG Hydrogels with Controllable Hydrophilic/Hydrophobic Balance.
This work reports on a novel method to synthesize hydrophobically-modified hydrogels by curing epoxy monomers with amines. The resulting networks contain hydrophilic poly(ethylene glycol) (PEG) segments, poly(propylene glycol) (PPG) segments, and C18 alkyl segments. By varying the content of C18 segments, networks with different hydrophilic-lipophilic balance (HLB) are obtained. All networks show an amphiphilic behavior, swelling considerably both in organic solvents and in aqueous media. In the latter they display a thermosensitive behavior, which is highly affected by the network HLB and the pH of the solution. A decrease in HLB results in an increment of the polymer weight content (wp) due to hydrophobic association. Furthermore, a reduction in HLB induces a remarkable increase in initial modulus, elongation at break and tensile strength, especially when wp becomes greater than about 10%. Low field nuclear magnetic resonance (LF-NMR) experiments evidence that, when HLB decreases, a sudden and considerable increase in hydrogel heterogeneity takes place due to occurrence of extensive physical crosslinking. Available data suggest that in systems with wp ≳ 10% a continuous physical network superimposes to the pre-existing chemical network and leads to a sort of double network capable of considerably improving hydrogel toughness.


Metabolic and cyclic nucleotide enzyme activities in muscle and nonmuscle cells of rat heart during perinatal development.
Enzyme activities related to aerobic metabolism and cyclic nucleotides were evaluated in muscle and nonmuscle cells of rat heart. The perinatal period from weaning to adult was studied. Malate dehydrogenase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities of nonmuscle cells equal or exceed muscle cell activities in the weanling heart. Aerobic enzymes remain unchanged in nonmuscle cells during growth; however, muscle cell activities are enhanced. Adenylate cyclase and guanylate cyclase activities are higher in heart homogenates of weanling than adult rats. Despite elevated adenylate cyclase activity, cyclic AMP levels are identical in weanling and adult rats. Cyclic GMP levels are twofold higher in weanling than in adult rats. Muscle cell metabolism and cyclic nucleotide levels are associated with growth-related changes in heart function and cellularity, respectively.


TnpR encoded by an ISPpu12 isoform regulates transposition of two different ISL3-like insertion sequences in Pseudomonas stutzeri after conjugative interaction.
Pseudomonas stutzeri AN10 has two ISL3-like insertion sequences (ISs). One of them has been recently described as ISPst9. In this study we show that the second IS, situated 4.5 kb upstream of ISPst9, is an isoform of ISPpu12 from Pseudomonas putida mt-2. Although both ISL3-like ISs are flanked by nearly identical (21/24 conserved residues) inverted repeats (IRs) and harbor similar transposases (93% amino acid identity), they differ in their accompanying genes. As described for ISPst9, the isoform of ISPpu12 also transposes by a conservative mechanism, forms circular double-stranded DNA (dsDNA) transposition intermediates, and is induced by interaction with the conjugative strain Escherichia coli S17-1lambda(pir) (conjugative interaction) but not with the nonconjugative E. coli DH5alpha. In fact, we demonstrate that ISPst9 transposition after conjugative interaction occurs only when ISPpu12 is present, indicating that ISPpu12 is upregulating transposition of both ISs under such conditions. We also demonstrate that this conjugative interaction-mediated induction of ISPpu12 is not exclusive to the P. stutzeri AN10 strain but is a more general phenomenon, at least in Pseudomonas. Mutation of TnpR, a MerR-like transcriptional regulator present in ISPpu12 but not in ISPst9, reduced the transcription of tnpA (ISPpu12 transposase-encoding gene) and decreased formation of circular dsDNA transposition intermediates after conjugative interaction. Complementation of the TnpR mutant restored the phenotype. In addition, the presence of TnpR in an ISPpu12-free genetic background did not induce ISPst9 after conjugative interaction. Thus, our results suggest that TnpR, after conjugative interaction, activates transcription of tnpA of ISPpu12. Then, TnpA of ISPpu12 would bind to IRs of both ISs, ISPpu12 and ISPst9, causing their transposition.


Three cases of genetic defects affecting sperm tail: a FISH study.
Submicroscopic alterations in the cytoskeletal structure of sperm flagellum are associated with severely reduced or completely absent motility in subfertile or infertile men. Sometimes these alterations can be related to well known genotypic defects when the same anomaly affects the whole sperm population. Transmission electron microscopy (TEM) is the only tool able to specifically characterize the morphological features of genetic sperm defects. In this study, the frequencies of aneuploid and diploid spermatozoa were identified in three patients showing specific flagellar anomalies, each of them affecting the whole sperm population: dysplasia of the fibrous sheath, primary ciliary dyskinesia and absence of fibrous sheath. All these defects were highlighted by TEM. Fluorescence in situ hybridization (FISH) analysis was performed on decondensed sperm nuclei for chromosomes 18, X and Y, highlighting higher diploidies and sex chromosome disomies in cases of dysplasia of the fibrous sheath and primary ciliary dyskinesia, in agreement with other reports. We have also described FISH results in spermatozoa with absence of fibrous sheath. In this case, the only one reported due to the rarity of this defect, the aneuploidies and diploidies were within normal range. These data contribute to the growing evidence that genetic sperm defects of sperm flagella are generally correlated with meiotic segregation derangement. For this reason, genetic counseling is advisable, although all the genes involved and the possible mechanisms of these mutations have not yet been fully characterized.


The stacking dependent electronic structure and optical properties of bilayer black phosphorus.
By employing density-functional theory, the G0W0 method and Bethe-Salpter equation, we explore quasi-particle energy bands, optical responses and excitons of bilayer black phosphorus (BBP) with four different stacking patterns. All the structures are direct band gap semiconductors and the band gap is highly dependent on the stacking pattern, with a maximum of 1.31 eV for AB-stacking and a minimum of 0.92 eV for AD-stacking. Such dependence can be well understood by the tight-binding model in terms of the interlayer hopping. More interestingly, stacking sensitive optical absorption and exciton binding energy are observed in BBPs. For x-polarized light, more red-shift of optical adsorption appears in AA-stacking and the strong exciton binding energy in the AA-stacking bilayer can be as large as 0.82 eV, that is ∼1.7 times larger than that of AD-stacking bilayer.


Identification of pestiviruses contaminating cell lines and fetal calf sera.
Three pestiviruses in fetal calf serum (FCS), a pestivirus in porcine ST cell line, and two pestiviruses in two of five bovine cell lines were detected by RT-PCR method employing panpestivirus primers selected from the 5'-non-coding region (5'-NCR). The 288 bp products were sequenced in both directions. To identify these pestiviruses, their nucleotide sequences and those of reference pestiviruses were used for construction of a dendrogram. Three viruses present in FCS and a virus present in the bovine RP-15 cell line were identified as bovine viral diarrhea virus I (BVDV-1). Bovine viral diarrhea virus 2 (BVDV-2) was identified in a batch of the bovine MDBK cell line. A pestivirus contaminating the porcine ST cell line was identified as a Border disease virus (BDV).


Vascular leiomyosarcoma originating from the right ovarian vein: a case report and literature review.
Primary leiomyosarcoma (LMS) of vascular origin is a rare lesion, and patients with LMS of vascular origin have poorer prognoses than patients with LMS of other origins. The inferior vena cava is the most commonly affected vessel and accounts for 60% of all vascular cases. However, LMS originating from the ovarian vein is extremely rare, and we are only aware of 15 reported cases. Therefore, we report our experience with a case of LMS originating from the right ovarian vein and review the related literature. A 71-year-old Japanese woman with no symptoms was admitted to our hospital because of abnormal findings in a routine abdominal ultrasonography check-up. Contrast-enhanced computed tomography of the abdomen revealed a well-defined, lobulated solid mass with a diameter of 5.5 cm in the right retroperitoneal space. The mass exhibited relatively low uptake during 18F-fluorodeoxyglucose positron emission tomography. Based on these findings, the differential diagnosis included a retroperitoneal tumor, such as a desmoid tumor, leiomyoma, LMS, and malignant mesothelioma. Operative findings confirmed that the mass had originated from the right ovarian vessels, and en bloc excision was performed for the mass and the right ovarian vessels. The final pathological diagnosis was LMS originating from the right ovarian vein, and the surgical resection margins were free from tumor cells. After histological findings confirmed the LMS diagnosis, the patient underwent adjuvant radiation therapy and has not exhibited signs of local recurrence or metastasis in the 6 months after surgery. We encountered a 71-year-old woman with LMS originating from her right ovarian vein. The prognosis of vascular LMS is generally poor. Therefore, careful follow-up will be required for our patient.


[Experimental study of hydroxycamptothecine and theprubicine in the treatment of adenoid cystic carcinoma lung metastases].
To investigate anticancer effect of hydroxycamptothecine and theprubicine in the treatment of established human adenoid cystic carcinoma (ACC) lung metastasis of nude mice and to determine the best therapy sequence of the two drugs. The model of ACC lung metastasis (60 animals) was established by injecting the ACC-M cells into the nude mice from their tail veins. Animals were divided into six groups: v acuity control group, HCPT group, THP group, HCPT and THP group 1, HCPT and THP group 2, HCPT and THP group 3 (No.1 - No.6). Different treatment sequence was performed on these groups. The lung samples were collected and observed after HE staining. The area of metastases and lung tissue were analyzed by the images analysis system. The size of the metastatic lesion in the treatment groups were smaller than that in the control group (P < 0.01). The treatment effects between the group with simultaneous administration of HCPT and THP and the group with single drug administration were not different (P > 0.05). No.5 and No.6 groups showed better effect of treatment than the other treatment groups (P < 0.05). There are two recommended sequences: (1) HCPT should be used after THP; (2) THP is used 48 hours, After HCPT is administered. Because using two drugs together will decrease the anticancer effect, HCPT and THP should not be used simultaneously.


Detection of calcitonin-encoding mRNA by radioactive and non-radioactive in situ hybridization: improved colorimetric detection and cellular localization of mRNA in thyroid sections.
The localization of mRNA encoding calcitonin was studied by in situ hybridization using 35S-labeled RNA probes and biotin-labeled DNA probes. Radiolabeled probes were detected by autoradiography and biotin-labeled probes by streptavidin-biotin-peroxidase. To intensify the colorimetric signal, the indirect avidin-biotin complex (ABC) method was performed. However, the results were often variable. To improve the sensitivity, the peroxidase reaction signal was enhanced with a gold-silver deposit intensification reaction. To shorten the incubation times and to enhance the colorimetric reaction, several reaction steps were performed in a microwave oven. The localization of calcitonin mRNA in thyroid tissue, as detected with in situ hybridization, was confirmed by immunohistochemical localization of the calcitonin polypeptide. The results of in situ hybridization using biotinylated probes were compared to in situ hybridization using radioactive probes. Our data show that the results of in situ hybridization applied on frozen and paraffin-embedded sections using biotinylated DNA probes, detected with an indirect streptavidin-biotin-peroxidase reaction and intensified by silver-gold enhancement, were comparable to those obtained with radioactive probes. The localization of calcitonin encoding mRNA was in agreement with the localization of the calcitonin polypeptide.


Physician advice on exercise and diet in a U.S. sample of obese Mexican-American adults.
To document the prevalence of obese Mexican-Americans never advised by health professionals regarding exercise and diet, and to determine risk factors for no advice. Data came from 1787 obese Mexican-American adults (body mass index ≥30; age ≥18 years) in the Medical Expenditure Panel Survey. The survey included self-reported receipt of health care provider advice on exercise and diet as well as sociodemographic, health-related, and provider-related factors. Multivariable logistic regression models were performed separately for advice regarding exercise and advice regarding diet. Overall, 45% of respondents reported that they had never received advice from a doctor or health care professional to exercise more, and 52% reported that they have received advice to eat fewer higher-fat/high-cholesterol foods. Men, nonmarried respondents, lower-educated respondents, those who preferred to speak Spanish at home, and those without comorbid chronic conditions were less likely to receive advice. Results suggest that obese Mexican-Americans are insufficiently advised by health care providers regarding exercise and diet. Given the seriousness of obesity-related health risks and the increasing prevalence of overweight status and obesity among Mexican-Americans, it is vital that providers are involved in finding ways to effectively educate and/or treat overweight patients.


Association between person-centredness and financially driven postponement of care in European primary care: a cross-sectional multicountry study.
Previous research has shown that person-centred care has beneficial effects on several health-related outcomes. We investigated the association between a general practitioner's person-centred attitude and financially driven postponement of care in European countries. In this cross-sectional study, data were collected within the Quality and Costs of Primary Care in Europe study, which included 69 201 patients and 7183 general practitioners from 31 European countries (all 27 European Union member states, 2 candidate states [former Yugoslav Republic of Macedonia and Turkey], Norway and Switzerland). Financially driven postponement of care was measured by asking patients whether they had postponed care for financial reasons in the previous 12 months. We constructed a variable for person-centredness using a previously published conceptual framework: 1) exploring both the disease and the illness experience, 2) understanding the whole person, 3) finding common ground and 4) enhancing the patient-physician relationship. We analyzed the data using multilevel logistic regression modelling, adjusting for the strength of a country's primary care system. Having a low income was associated with higher financially driven postponement of care. General practitioners with a person-centred attitude were associated with lower rates of financially driven postponement among their patients. An increase in general practitioners' person-centredness with 1 standard deviation was associated with a decreased likelihood of postponement of care for financial reasons (odds ratio 0.923, 95% confidence interval 0.869-0.981). Person-centred care by general practitioners in Europe was associated with lower financially driven postponement of care, irrespective of the strength of a country's primary care system.


Marfan syndrome. What you need to know.
Marfan syndrome is a heritable disorder of the connective tissue. The major abnormalities occur in the ocular, skeletal, and cardiovascular systems, with variable expression in different patients. Most common are dislocated lens, which may or may not affect visual acuity, arachnodactyly, and mitral valve prolapse and aortic root dilatation. Cardiovascular complications cause about 90% of the excess early mortality seen with the syndrome. With proper management, including annual examination, some of the problems associated with these abnormalities may be avoided. The biochemical explanation for the disorder is not clear. Some investigators maintain that a defect in collagen is responsible, while others point to elastin as the culprit. Further studies are needed to disclose the exact defect; both proteins may be found to play a role in this highly variable disorder.


Correction of liver dysfunction in DNA repair-deficient mice with an ERCC1 transgene.
The ERCC1 gene is essential for the repair of UV-induced DNA damage. Unlike most genes in the nucleotide excision repair (NER) pathway, ERCC1 is also involved in recombinational repair. Perhaps for this reason, ERCC1 knockout mice are not a model for the human NER deficiency disorder, xeroderma pigmentosum. Instead, ERCC1 null mice are severely runted and die before weaning from liver failure with accelerated hepatocyte polyploidy that is more reminiscent of a premature ageing disorder. To permit study of the role of ERCC1 in other tissues we have corrected the liver ERCC1 deficiency with a transgene under the control of a liver-specific promoter. The transgene alleviated runting and extended the lifespan. The elevated level of oxidative DNA damage and premature liver polyploidy were reversed and liver function was corrected. A widespread mitochondrial dysfunction was identified and an essential role for ERCC1 in the kidney was also revealed with transgene-containing ERCC1-deficient animals going on to die of renal failure. The nuclei of kidney proximal tubule cells became polyploid in a similar way to the premature liver polyploidy observed in younger ERCC1-deficient animals. We believe that this is a response to the accumulation of endogenous DNA damage in these particularly susceptible tissues which cannot be repaired in ERCC1-deficient animals.


Alzheimer Disease: "It's okay, Mama, if you want to go, it's okay".
About 4 million people in the United States have Alzheimer disease (AD) and the number of incident cases is expected to more than double from 377,000 in 1995 to 959,000 in 2050. Patients, their families, and health care professionals struggle with a relentless and irreversible neurological syndrome that can last from 2 to 20 years. Alzheimer disease causes both cognitive and functional impairments that predispose the patient to behavioral symptoms, destroy intellectual capacity and personality, erase the ability to communicate one's wishes for care, and lead to life-threatening consequences. At the close of life, family members and clinicians face decisions regarding degrees of intensive medical care to be provided for treatment of the late-stage consequences of AD, including withdrawal of invasive interventions, initiation of hospice, and treatment of a range of progressive medical conditions. Physicians can assist patients with AD and their loved ones through the terminal phases of the illness by preparing them for the relentless progression of the disease and by supporting them through the intellectual and emotional conflicts accompanying the end of life.


[Advances in research on pharmacodynamics and chemical conversion of catalpol].
Catalpol is a active component in Rehmannia Root, and its pharmacological effects are extensive. In this paper its effects and chemical changes were summarized. This will offer the reference for further research work catalpol.


Decentralized formation flying control in a multiple-team hierarchy.
In recent years, formation flying has been recognized as an enabling technology for a variety of mission concepts in both the scientific and defense arenas. Examples of developing missions at NASA include magnetospheric multiscale (MMS), solar imaging radio array (SIRA), and terrestrial planet finder (TPF). For each of these missions, a multiple satellite approach is required in order to accomplish the large-scale geometries imposed by the science objectives. In addition, the paradigm shift of using a multiple satellite cluster rather than a large, monolithic spacecraft has also been motivated by the expected benefits of increased robustness, greater flexibility, and reduced cost. However, the operational costs of monitoring and commanding a fleet of close-orbiting satellites is likely to be unreasonable unless the onboard software is sufficiently autonomous, robust, and scalable to large clusters. This paper presents the prototype of a system that addresses these objectives-a decentralized guidance and control system that is distributed across spacecraft using a multiple team framework. The objective is to divide large clusters into teams of "manageable" size, so that the communication and computation demands driven by N decentralized units are related to the number of satellites in a team rather than the entire cluster. The system is designed to provide a high level of autonomy, to support clusters with large numbers of satellites, to enable the number of spacecraft in the cluster to change post-launch, and to provide for on-orbit software modification. The distributed guidance and control system will be implemented in an object-oriented style using a messaging architecture for networking and threaded applications (MANTA). In this architecture, tasks may be remotely added, removed, or replaced post launch to increase mission flexibility and robustness. This built-in adaptability will allow software modifications to be made on-orbit in a robust manner. The prototype system, which is implemented in Matlab, emulates the object-oriented and message-passing features of the MANTA software. In this paper, the multiple team organization of the cluster is described, and the modular software architecture is presented. The relative dynamics in eccentric reference orbits is reviewed, and families of periodic, relative trajectories are identified, expressed as sets of static geometric parameters. The guidance law design is presented, and an example reconfiguration scenario is used to illustrate the distributed process of assigning geometric goals to the cluster. Next, a decentralized maneuver planning approach is presented that utilizes linear-programming methods to enact reconfiguration and coarse formation keeping maneuvers. Finally, a method for performing online collision avoidance is discussed, and an example is provided to gauge its performance.


Co-culture of adipose-derived stem cells and chondrocytes on three-dimensionally printed bioscaffolds for craniofacial cartilage engineering.
Reconstruction of craniofacial cartilagenous defects are among the most challenging surgical procedures in facial plastic surgery. Bioengineered craniofacial cartilage holds immense potential to surpass current reconstructive options, but limitations to clinical translation exist. We endeavored to determine the viability of utilizing adipose-derived stem cell-chondrocyte co-culture and three-dimensional (3D) printing to produce 3D bioscaffolds for cartilage tissue engineering. We describe a feasibility study revealing a novel approach for cartilage tissue engineering with in vitro and in vivo animal data. Porcine adipose-derived stem cells and chondrocytes were isolated and co-seeded at 1:1, 2:1, 5:1, 10:1, and 0:1 experimental ratios in a hyaluronic acid/collagen hydrogel in the pores of 3D-printed polycaprolactone scaffolds to form 3D bioscaffolds for cartilage tissue engineering. Bioscaffolds were cultured in vitro without growth factors for 4 weeks and then implanted into the subcutaneous tissue of athymic rats for an additional 4 weeks before sacrifice. Bioscaffolds were subjected to histologic, immunohistochemical, and biochemical analysis. Successful production of cartilage was achieved using a co-culture model of adipose-derived stem cells and chondrocytes without the use of exogenous growth factors. Histology demonstrated cartilage growth for all experimental ratios at the post-in vivo time point confirmed with type II collagen immunohistochemistry. There was no difference in sulfated-glycosaminoglycan production between experimental groups. Tissue-engineered cartilage was successfully produced on 3D-printed bioresorbable scaffolds using an adipose-derived stem cell and chondrocyte co-culture technique. This potentiates co-culture as a solution for several key barriers to a clinically translatable cartilage tissue engineering process. NA. Laryngoscope, 128:E251-E257, 2018.


Facial lesions on a college basketball player.
A 20-year-old male African-American college basketball player reported to the training room for evaluation of recurrent bumps on his face. He stated that these lesions began occurring after he started shaving. His healthcare provider had told him that they were "shaving bumps" and that there was nothing he could do for them. The patient had tried an over-the-counter product (Bump Stopper, Long Beach, California) with minimal success. He used a single-edged razor, and was concerned because some of the lesions were painful and leaving scars.