Comparison of intraoperative vs postoperative optical coherence tomography measurement of implantable collamer lens vaulting.
To compare intraoperative vs postoperative optical coherence tomography (OCT) measurements of implantable collamer lens (ICL) vaulting. American University of Beirut Medical Center, Beirut, Lebanon. Prospective observational cohort study. Patients with myopia or myopic astigmatism undergoing ICL insertion in which intraoperative OCT measurements were obtained were included. Exclusion criteria included coexisting ocular problems and previous ocular surgery. The outcome measures were ICL vaulting as determined by OCT intraoperatively and postoperatively at 1 day, 1 week, 1 month, and 3 months. Forty-five eyes of 26 patients were included. Mean age was 27.23 ± 6.47 years (range 17 to 48 years), and mean manifest refraction spherical equivalent was -10.20 ± 3.92 diopters (D) (range -20.50 to -4.50 D). Mean ICL vaulting measured 731 ± 215 μm intraoperatively, 648 ± 219 μm at 1 day, 640 ± 204 μm at 1 week, 628 ± 212 μm at 1 month, and 632 ± 210 μm at 3 months postoperatively (P = .0009, with all postoperative vaulting measurements statistically similar to each other, but significantly different from the intraoperative measurement). However, intraoperative ICL vaulting had high predictability of postoperative vaulting at 3 months with r = 0.81 (P < .0001), and Bland-Altman analysis demonstrates a relatively constant difference between the 2 measurements as plotted against their mean with a bias of 98.27 μm and tight 95% limits of agreement range. Intraoperative ICL vaulting measured by OCT correlated highly with postoperative OCT vaulting and can be considered a reliable tool to predict the final ICL vault.


Nanopore stochastic detection of a liquid explosive component and sensitizers using boromycin and an ionic liquid supporting electrolyte.
We report a rapid and sensitive stochastic nanopore sensing method for the detection of monovalent cations and liquid explosive components and their sensitizers. The sensing element is a wild-type alpha-hemolysin protein pore with boromycin as a molecular adaptor, while a solution containing an ionic liquid was used as the background electrolyte. The analyte-boromycin complexes showed significantly different signatures. Specifically, their event mean dwell times and amplitudes were sufficiently distinct to permit the convenient differentiation and even simultaneous detection of liquid explosive components in aqueous environments. In addition, the results also demonstrate that the usage of specific ionic liquid salt solutions instead of NaCl or KCl solution as supporting electrolyte provides a useful means to greatly enhance the sensitivity of the nanopore for some analytes in stochastic sensing.


A nationwide multicentre study in Turkey for establishing reference intervals of haematological parameters with novel use of a panel of whole blood.
A nationwide multicentre study was conducted to establish well-defined reference intervals (RIs) of haematological parameters for the Turkish population in consideration of sources of variation in reference values (RVs). K2-EDTA whole blood samples (total of 3363) were collected from 12 laboratories. Sera were also collected for measurements of iron, UIBC, TIBC, and ferritin for use in the latent abnormal values exclusion (LAVE) method. The blood samples were analysed within 2 hours in each laboratory using Cell Dyn and Ruby (Abbott), LH780 (Beckman Coulter), or XT-2000i (Sysmex). A panel of freshly prepared blood from 40 healthy volunteers was measured in common to assess any analyser-dependent bias in the measurements. The SD ratio (SDR) based on ANOVA was used to judge the need for partitioning RVs. RIs were computed by the parametric method with/without applying the LAVE method. Analyser-dependent bias was found for basophils (Bas), MCHC, RDW and MPV from the panel test results and thus those RIs were derived for each manufacturer. RIs were determined from all volunteers' results for WBC, neutrophils, lymphocytes, monocytes, eosinophils, MCV, MCH and platelets. Gender-specific RIs were required for RBC, haemoglobin, haematocrit, iron, UIBC and ferritin. Region-specific RIs were required for RBC, haemoglobin, haematocrit, UIBC, and TIBC. With the novel use of a freshly prepared blood panel, manufacturer-specific RIs' were derived for Bas, Bas%, MCHC, RDW and MPV. Regional differences in RIs were observed among the 7 regions of Turkey, which may be attributed to nutritional or environmental factors, including altitude.


PCV3 in Thailand: Molecular epidemiology and relationship with PCV2.
Porcine circovirus type 3 has been circulating throughout the world and since their first report, various clinical signs and disease developments have been documented. The virus is similar to the closely related PCV2 and is associated with several clinical signs called porcine circovirus-associated diseases (PCVAD). PCV2 or PCV3 is occasionally reported with clinical signs such as PDNS, respiratory signs and reproductive failure. Retrospective research conducted in Thailand revealed that both PCV2 and PCV3 have been circulation for decades. However, awareness about PCV3 infection has just arisen in recent years because of the similarities observed in disease circulation and clinical signs that have led to concerns. This study was conducted to find the relationship between the quantity of PCV2 and PCV3 in Thai pigs displaying the clinical signs related to PCVAD. A total of 479 serum samples with different production phases and clinical signs were sent to Kamphaeng Saen Veterinary Diagnostic Center (KVDC) for qPCR to detect the presence of PCV2 or PCV3. There was no relationship between the PCV3 and PCVAD-related clinical signs. Also, the relationship between PCV2 and PCV3 with no clinical signs suggested that both viruses might come from the same reservoir or have been circulating in Thailand for a long time, leading to common incidents in finding. The viral load of PCV2 was significantly different among the pig groups with and without clinical signs. The capsid sequence analysis of PCV3 revealed that 22 capsid sequences obtained from this study were found as clusters within PCV3a with a minor variation. Additional control measures are further needed to reduce the findings of the viruses. A future study with a control experiment may be needed to clarify the pathogenesis of PCV3.


Surgical Treatment of Solitary Enchondromas of the Hand.
The present retrospective study evaluated the clinical and radiologic results of patients who underwent complete curettage and autologous bone grafting for hand-located isolated enchondromas with a minimum follow-up period of one year. Thirty-two patients with a follow-up period of at least 12 months who underwent operation between August 2010 and October 2018 due to the presence of solitary enchondroma of the hand were included in the study. All patients underwent complete curettage and filling of the defect via autologous bone grafting. Autologous bone graft was harvested from the iliac crest and distal radius in 24 and eight patients, respectively. The patients underwent radiography on the first postoperative visit and at six weeks, 12 weeks, and annually. The range of movement of the finger joint was evaluated by comparing it with the healthy contralateral side. Functional outcomes and radiologic outcomes were evaluated. The frequency of complications and recurrences were established. Twelve patients were male and 20 were female. The average age was 34 (range: 16-56) years. The most common digit involved was the little finger (nine cases, 28.125%); the proximal phalanx was the most common location (17 cases, 53.125%). Control radiography in the sixth week revealed graft consolidation in all patients. No case of nonunion or recurrence was detected clinically or radiologically, with a mean follow-up period of 54 (range: 12-96) months. Functional outcomes were classified as excellent in 28 patients and as good in four patients. The final radiographic appearances included Tordai's group 1 in 28 bones and group 2 in four bones. Conclusion: Curettage and autologous bone grafting are safe, costless, and effective treatment options for hand enchondroma, with satisfactory functional and radiographic outcomes. Harvesting bone graft from the distal radius provides a shorter length of hospital stay and lower complication rates compared to obtaining the graft from the iliac crest.


Seasonal and annual variations of metal uptake, bioaccumulation, and toxicity in Trifolium repens and Lolium perenne growing in a heavy metal-contaminated field.
The reclamation of nonferrous metal-polluted soil by phytoremediation requires an overall and permanent plant cover. To select the most suitable plant species, it is necessary to study metal effects on plants over the time, thereby checking that metals remain stored in root systems and not transferred to aerial parts. In this purpose, the seasonal and annual variations of metal bioaccumulation, transfer, and phytotoxicity in Trifolium repens and Lolium perenne grown in a Cd-, Pb-, and Zn-contaminated soil were also studied. The experimental site was located near a closed smelter. In spring 2004, two areas were sown with T. repens and L. perenne, respectively. Thereafter, the samplings of plant roots and shoots and surrounding soils were realized in autumn 2004 and spring and autumn 2005. The soil agronomic characteristics, the Cd, Pb, and Zn concentrations in the surrounded soils and plant organs, as well as the oxidative alterations (superoxide dismutase [SOD], malondialdehyde [MDA], and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) in plant organs were carried out. Whatever the sampling period, metal concentrations in soils and plants were higher than background values. Contrary to the soils, the fluctuations of metal concentrations were observed in plant organs over the time. Bioaccumulation and transfer factors confirmed that metals were preferentially accumulated in the roots as follows: Cd>Zn>Pb, and their transfer to shoots was limited. Foliar metal deposition was also observed. The results showed that there were seasonal and annual variations of metal accumulation in the two studied plant species. These variations differed according to the organs and followed nearly the same pattern for the two species. Oxidative alterations were observed in plant organs with regard to SOD antioxidant activities, MDA, and 8-OHdG concentrations. These alterations vary according to the temporal variations of metal concentrations. Metal concentrations in surrounded soils and plant organs showed the effective contamination by industrial dust emissions. Metals absorbed by plants were mainly stored in the roots. With regard to this storage, the plants seemed to limit the metal transfer to their aerial parts over the time, thereby indicating their availability for metal phytostabilization. Aerial deposition was another source of plant exposure to nonferrous metals. Despite the occurrence of metal-induced oxidative alterations in plant organs, both plant species seemed to tolerate a high metal concentration in soils. Taken together, these results indicated that T. repens and L. perenne were able to form a plant cover on highly Cd-, Pb-, and Zn-polluted soils, to limit the metal transfer to their aerial parts and were relatively metal-tolerant. All these characteristics made them suitable for phytostabilization on metal-contaminated soils. These findings also highlighted the necessity to take into account seasonal and annual variations for a future phytomanagement. In this work, the behavior of plant species grown in metal-polluted soil has been studied during 2 years. Obviously, this time is too short to ensure that metals remain accumulated in the root system and few are transferred in aerial parts over the time. It is why regular monitoring should be achieved during more than a decade after the settlement of the plant cover. This work will be completed by the study of the T. repens and L. perenne effects on mobility of metals in order to evaluate the quantities of pollutants which could be absorbed by the biota and transferred to groundwater. Bioaccessibility tests could be also realized on polluted soils in order to evaluate the phytostabilization impacts on the exposition risks for humans.


Neuroendocrine mechanisms in insulin resistance.
Dysregulated hormonal, metabolic and neural signalling within and between organs can contribute to development of metabolic diseases including type 2 diabetes. Insulin-antagonistic effects of hormones, cytokines and excess metabolic substrates such as glucose and fatty acids may be exerted via common mechanisms involving for example reactive oxygen species (ROS) accumulation and associated inflammatory responses. Visceral adiposity is a central component of the metabolic syndrome and it is also strongly associated with insulin resistance. Both visceral obesity and insulin resistance are important risk factors for the development of type 2 diabetes. In the development of insulin resistance, it is likely that intra-abdominal adipose tissue plays a critical role in a complex endocrine and neural network involving several tissues. This review paper focuses on neuroendocrine 'stress' factors that target insulin-responsive tissues, in particular adipose tissue. We propose that there are common pathways by which dysregulation in different endocrine systems may contribute to the development of type 2 diabetes.


Different tolerances to chemical contaminants between unicellular and colonial morph of Microcystis aeruginosa: excluding the differences among different strains.
In order to ascertain the different tolerances to chemical contaminants in one strain of Microcystis with different morphology, unicellular and colonial Microcystis in one strain was obtained from different conditions of light intensity and temperature. The samples were divided into 8 groups including control (no chemical addition), CuSO4, chloromycetin, and linear alkylbenzene sulfonatelas (LAS) treatments. The cell density, cell viability, superoxide dismutase (SOD), and malonaldehyde of Microcystis were analyzed. It was observed that cell density of both unicellular and colonial Microcystis increased from the beginning to day-5 in the control and the CuSO4 treatments. However, the growth of Microcystis was significantly inhibited in the culture with chloromycetin and LAS treatments. Notably, the inhibition rate was significantly high in unicellular Microcystis relative to the colonial Microcystis. The esterase activity in all the treatments decreased dramatically relating to the control. In addition, the esterase activity in colonial Microcystis was significantly higher than that of the unicellular Microcystis in all the treatments. Although there were no significant differences in activities of SOD between the two morphologies in the control treatments, in all the other treatments, significant differences were observed. The results proved that colony formation of Microcystis could be considered as a strategy in response to chemical stress.


ELECTRON MICROSCOPE OBSERVATIONS ON THE SURFACE ADENOSINE TRIPHOSPHATASE-LIKE ENZYMES OF HELA CELLS INFECTED WITH HERPES VIRUS.
HeLa cells infected with herpes simplex virus have been examined in thin sections by electron microscopy after cytochemical staining for the presence of surface enzymes splitting adenosine triphosphate. As with uninfected HeLa cultures (18), the opaque enzyme reaction product was localized at the plasma membranes of about half the cells, tending to be present where there were microvilli and absent on smooth surfaces. Where mature extracellular herpes particles were found in association with cell membranes showing the enzyme activity, they were invariably likewise stained, and conversely, those mature particles which lay close against cells without reaction product at the surface were themselves free of it. Particles found budding into cytoplasmic vacuoles were also always without opaque deposit since this was never seen at vacuolar membranes, even in cells having the activity at the surface. The enzyme reaction product thus provided a marker indicating the manner in which the particles escape from cells and mature by budding out through cellular membranes, carrying, in the process, a portion of the latter on to themselves to form the outer viral limiting membrane. In some instances, virus particles were observed with more opaque material covering them than was present at the cell membrane with which they were associated. This finding has been taken as evidence for a physiological waxing and waning of surface enzyme activity of adenosine triphosphatase type. The fine structure of the mature extracellular virus as prepared here, using glutaraldehyde fixation, is also recorded. The observations and interpretations are discussed in full.


Socioeconomic, demographic and geographic determinants of food consumption in Mexico.
What people eat affects public health and human wellbeing, agricultural production, and environmental sustainability. This paper explores the heterogeneity of food consumption patterns in an ecologically and culturally diverse country. Using a latent class approach (which creates clusters of individuals with homogeneous characteristics), we analyse a food questionnaire (from the National Health and Nutrition Survey) applied across Mexico. We identify four clusters of food consumption (staple, prudent, high meat and low fruit) and find that belonging to these clusters is determined by socioeconomic, demographic (age, sex) and geographic (region, urban/rural) characteristics. Maize and pulses tend to constitute a larger proportion of the diet of poor, rural populations living in the south, while urban populations eat more varied foods, including ingredients whose production systems tend to exert more pressure on natural resources (for instance, meat). Despite the importance given in the literature to the Mexican gastronomy and its diverse traditional regional diets, we find that only 6% of the population adopts a food consumption pattern resembling the traditional Mexican diet. Instead, most of the Mexican population has a food consumption pattern resembling a western diet, which is problematic in terms of public health and environmental sustainability.


Gut Microbiota Composition in Long-Remission Ulcerative Colitis is Close to a Healthy Gut Microbiota.
Microbiome studies report low gut microbial richness and diversity in ulcerative colitis (UC) patients. We explored whether UC patients who reach long-term clinical, endoscopic, and histological remission show a gut microbial ecosystem that is similar to healthy individuals. We collected 184 stool samples from 111 individuals (UC patients in long remission, short remission, flare, and healthy control subjects). Microbiota was analyzed by amplicon sequencing (16S ribosomal RNA) and quantitative polymerase chain reaction for specific taxa. All UC remission patients were followed-up for 2 years. A drop in species diversity and richness, underrepresentation of butyrate producers, and gain of potentially harmful bacteria were significantly detected in samples from disease-flare and short-remission patients. In contrast, Chao1 and Shannon indexes of diversity did not differ among patients in long remission and healthy control subjects. Long-remission patients also presented fecal bacterial composition closer to that in healthy control subjects. There was a positive correlation between Akkermansia muciniphila abundance and time in remission (rs = 0.53, P < .001). Logistic regression analysis showed that a high Shannon index (odds ratio, 4.83; 95% confidence interval, 1.5-20.6) or presence of A. muciniphila (odds ratio, 4.9; 95% confidence interval, 1.12-29.08) in fecal samples at entry was independently associated with clinical remission over a follow-up period of 24 months. UC patients who achieve long-term remission show evidence of substantial recovery of the gut microbial ecosystem in terms of diversity and composition. Recovery may just reflect adequate control of inflammatory activity, but higher bacterial diversity or the presence of A. muciniphila in fecal samples predicts flare-free outcomes.


Dependence of increased linear bone growth on age at oMT1a-oGH transgene expression in mice.
We have previously shown that growth hormone (GH) accelerates the rate and extends the duration of linear bone growth in a GH-transgenic mouse model. To determine if this GH effect was temporally regulated, bone lengths and growth plate widths were determined in transgenic mice carrying an ovine metallothionein 1a-ovine growth hormone (oMT1a-oGH) transgene. Transgene expression was initiated in oMT1a-oGH hemizygous transgenic mice by addition of 25 mM ZnSO4 to the water at 21 d of age; littermate control mice were also ZnSO4 supplemented. These mice were maintained on ZnSO4 until 70 d of age at which time the mice were killed and the ulna, humerus, and tibia were collected. Additional transgenic and control mice were stimulated at 21 d and the ZnSO4 stimulus withdrawn after 21 d of treatment and killed at 70 d or stimulated at 28 d with the stimulus withdrawn after 28 d and killed at 70 d. Continuously stimulated transgenic mice had longer bones than those of comparable control mice. The increased bone length in the transgenics was correlated with wider growth plates. Transgene expression initiated at 21 d of age increased bone length to the same or greater extent than that observed for mice with transgene expression initiated at 28 d but maintained for a longer interval thereby indicating that the age of GH initiation is more critical in bone elongation than the duration of GH exposure. The elevated GH effects were independent of circulating thyroid hormones and attainment of puberty. Elevated GH also increased the widths of all growth plate zones to the same extent by increasing cell numbers, rather than enhancing matrix production or individual cellular area.


Long-term risk of arrhythmias in patients with inflammatory bowel disease: A population-based, sibling-controlled cohort study.
Although previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD. Through a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias. In this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals.


Shortening Fermentation Period and Quality Improvement of Fermented Fish, Chouguiyu, by Co-inoculation of Lactococcus lactis M10 and Weissella cibaria M3.
Chouguiyu, a Chinese traditional fermented fish, is famous for its uniquely strong odor and desirable taste. However, traditional spontaneous fermentation often resulted in contamination and unstable quality of products. In this study, individual or conjunctive inoculation of two indigenous lactic acid bacteria (LAB), Lactococcus lactis M10 and Weissella cibaria M3, was tested for their effect on improving Chouguiyu's quality. It was shown that inoculation would not affect the system's pH, while increased the total bacteria count and lactic acid bacteria amounts. Matrix-assisted laser desorption/ionization time-of-flight mass (MALDI-TOF) analysis results revealed that Lactoc. lactis M10 and W. cibaria M3 could quickly occupy a dominant position in the ecosystem, and Lactoc. lactis M10 played an important role in the control of spoilage bacteria. Volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), and biogenic amines results also showed that Lactoc. lactis M10 had a positive effect on improving the product's quality. Co-inoculation of Lactoc. lactis M10 and W. cibaria M3 could promote the formation of flavor according to the E-nose and gas chromatography-mass spectrometer (GC-MS) analyses, especially for the aroma-active and key volatile compounds. PCA plots of E-nose and hierarchical clustering analysis of GC-MS profiles revealed that the co-inoculation sample at the fifth day (LW5) was the most similar to the natural fermentation sample at the seventh day (C7). The overall acceptance of LW5 was also the closest to that of C7 in sensory evaluation. In conclusion, mixed starter culture was shown to have a good effect on improving product quality and enhancing flavor with fermentation time shortened by 29%.


Reticulocyte Maturation and Variant Red Blood Cells.
The bone marrow produces billions of reticulocytes daily. These reticulocytes mature into red blood cells by reducing their plasma membrane by 20% and ejecting or degrading residual internal organelles, membranes and proteins not required by the mature cell. This process occurs by autophagy, protein degradation and vesiculation but is not well understood. We previously reported that Southeast Asian Ovalocytic RBCs demonstrate incomplete reticulocyte maturation and we have now extended this study to a number of other variant RBCs. By comparing the profile of a pure reticulocyte preparation of cultured red cells with these variant cells, we show that the largest of these cells, the overhydrated hereditary stomatocytosis cells, are the least mature, they barely reduced their plasma membrane and contain large amounts of proteins that should have been reduced or removed. Intermediate sized variant RBCs appear to be more mature but retain some endoplasmic reticulum and residual membrane proteins. We propose that the size and composition of these variant cell types correlate with the different stages of reticulocyte maturation and provide insight into the reticulocyte maturation process.


[Preoperative factors for postoperative resolution of metamorphopsia in idiopathic macular hole surgery].
To elucidate factors for resolution of metamorphopsia after successful surgery for idiopathic macular hole. A series of 15 cases of 15 patients with successful surgery for idiopathic macular hole were evaluated for signs of metamorphopsia before and one year after surgery. Preoperative and postoperative assessments included testing of metamorphopsia using M-CHART and optical coherence tomography. The postoperative state of the metamorphopsia was judged to have resolved when the test score was 0.2 or less and to be residual when it was more than 0.2. Classification of preoperative factors in two groups of patients included evaluation of metamorphopsia score, visual acuity, optical coherence tomography findings, and clinical stage of macular hole. Six of 15 eyes (40%) showed postoperative resolution of metamorphopsia. There was no significant correlation of postoperative metamorphopsia score with preoperative score or preoperative visual acuity. Eyes with postoperative resolution of metamorphopsia had a macular hole with a significantly smaller diameter and a significantly thinner retina surrounding the hole. Two eyes with clinical stage 4 macular hole had residual metamorphopsia after surgery. The diameter of a macular hole and the thickness of the retina surrounding a macular hole are significant preoperative factors for postoperative resolution of metamorphopsia after idiopathic macular hole surgery.


Taurine distribution in rat tissues during development.
1. Taurine levels have been determined in eight rat organs. 2. During postnatal growth the taurine content in retina, heart, small intestine, spleen and lung increases with advancing age, although adult values are not reached at the same time. 3. In contrast the taurine content decreases with age in brain cortex, liver and kidney. 4. The taurine in subcellular fractions of adult, 20-day-old and 5-day-old rat tissues exists predominantly in the cytosol of the cell. Taurine content in particulate fractions shows marked variations during development in the different organs. 5. Taurine distribution in the subcellular fractions suggests that some of the cellular taurine in the tissues is not freely mobile in cytosol.


Therapeutic Use of Regional Limb Perfusion in a Chicken.
A 2-year-old, 3.8-kg male Rhode Island red rooster was examined for lameness and progressive swelling of the right foot of several month's duration. Radiographs of the right foot demonstrated soft tissue swelling and a smoothly marginated periosteal reaction evident of inflammation affecting the bones. Results of a complete blood count showed a moderate leukocytosis and an elevated total protein concentration. Systemic antibiotic and anti-inflammatory therapy was started, but the bird had not improved at recheck examination. After intravenous catheterization of the medial metatarsal vein and placing a tourniquet at the femoral-tibiotarsal joint of the right leg, regional limb perfusion with amikacin and flunixin meglumine was performed. Dimensions of both feet were measured with digital calipers, and surface temperatures of the feet were measured with an infrared thermometer. The rooster had improved activity level with decrease in lameness and measurable decrease in swelling of the right foot. Regional limb perfusion with intravenous antibiotics and nonsteroidal anti-inflammatory drugs is a viable treatment modality in avian species for suspected distal limb infection and cellulitis. This technique has potential valuable implications for a variety of avian species. Fluid support should be provided if using nephrotoxic drugs.


HLAMatchmaker algorithm is not a suitable tool to predict the alloreactive cytotoxic T-lymphocyte response in vitro.
Both donor-specific anti-human leukocyte antigen (HLA) antibodies and cytotoxic T lymphocytes are important mediators of graft rejection. HLAMatchmaker determines the amino acid triplets on antibody-accessible sites of the HLA molecule that are not shared between patient and donor. A previous study showed a strong positive correlation between the number of triplet mismatches and the percentage of individuals producing HLA antibodies. In the present study, we tested whether the number of triplet mismatches is predictive for the cytotoxic T-lymphocyte precursor (CTLp) frequency in vitro. The analysis was performed on 108 HLA-DRB1 and DQB1 identical patient-donor combinations registered by the Europdonor foundation, with a single HLA class I mismatch and in healthy responder-stimulator combinations mismatched for at least one HLA class I antigen. The results show that there is no strong correlation between the number of triplet mismatches and the CTLp frequency. Even in the case of zero triplet mismatches, a high CTLp frequency can be found. This lack of correlation is probably caused by the fact that HLAMatchmaker considers only triplets on antibody-accessible positions, whereas CTLs also recognize other epitopes on the HLA molecule, including the bound peptides.


Multiexponential, multicompartmental, and noncompartmental modeling. II. Data analysis and statistical considerations.
Sums-of-exponentials models are widely used in biomedical research, chiefly as models of data, despite a sizable folklore criticizing their usefulness. Problems in multiexponential model fitting are addressed here, along with an exposition of how to quantify them and critically assess their quality with available statistical methods and computer programs. This class of models also is reconciled with two classes of models of systems: multicompartmental and noncompartmental models. Key issues include the importance of choosing a correct data error model, the necessity for computing model precision estimates, and the distinction between problems due to experiment design or overparameterization and purported difficulties with multiexponential models. Methods for obtaining statistical estimates of model precision, for checking goodness of fit of competing models, and for improving sampling designs are presented. Also the classic Lanczos problem is revisited, and some difficulties are resolved with a more efficient experiment design.


Reaction Mechanisms on Multiwell Potential Energy Surfaces in Combustion (and Atmospheric) Chemistry.
Chemical reactions occurring on a potential energy surface with multiple wells are ubiquitous in low-temperature combustion and in the oxidation of volatile organic compounds in Earth's atmosphere. The rich variety of structural isomerizations that compete with collisional stabilization makes characterizing such complex-forming reactions challenging. This review describes recent experimental and theoretical advances that deliver increasingly complete views of their reaction mechanisms. New methods for creating reactive intermediates coupled with multiplexed measurements provide many experimental observables simultaneously. Automated methods to explore potential energy surfaces can uncover hidden reactive pathways, and master equation methods enable a holistic treatment of both sequential and well-skipping pathways. Our ability to probe and understand nonequilibrium effects and reaction sequences is increasing. These advances provide the fundamental science base for predictive models of combustion and the atmosphere that are crucial to address global challenges.


Myosin MgADP release rate decreases at longer sarcomere length to prolong myosin attachment time in skinned rat myocardium.
Cardiac contractility increases as sarcomere length increases, suggesting that intrinsic molecular mechanisms underlie the Frank-Starling relationship to confer increased cardiac output with greater ventricular filling. The capacity of myosin to bind with actin and generate force in a muscle cell is Ca(2+) regulated by thin-filament proteins and spatially regulated by sarcomere length as thick-to-thin filament overlap varies. One mechanism underlying greater cardiac contractility as sarcomere length increases could involve longer myosin attachment time (ton) due to slowed myosin kinetics at longer sarcomere length. To test this idea, we used stochastic length-perturbation analysis in skinned rat papillary muscle strips to measure ton as [MgATP] varied (0.05-5 mM) at 1.9 and 2.2 μm sarcomere lengths. From this ton-MgATP relationship, we calculated cross-bridge MgADP release rate and MgATP binding rates. As MgATP increased, ton decreased for both sarcomere lengths, but ton was roughly 70% longer for 2.2 vs. 1.9 μm sarcomere length at maximally activated conditions. These ton differences were driven by a slower MgADP release rate at 2.2 μm sarcomere length (41 ± 3 vs. 74 ± 7 s(-1)), since MgATP binding rate was not different between the two sarcomere lengths. At submaximal activation levels near the pCa50 value of the tension-pCa relationship for each sarcomere length, length-dependent increases in ton were roughly 15% longer for 2.2 vs. 1.9 μm sarcomere length. These changes in cross-bridge kinetics could amplify cooperative cross-bridge contributions to force production and thin-filament activation at longer sarcomere length and suggest that length-dependent changes in myosin MgADP release rate may contribute to the Frank-Starling relationship in the heart.


Effect of tetracycline on puromycin-induced polysome degradation: influence of magnesium and polyamines.
Puromycin-induced polysome degradation has been shown to require G factor, guanosine 5'-triphosphate, and the presence of a ribosome release factor (Hirashima and Kaji, 1972, 1973). Tetracycline, which does not inhibit formation of peptidyl-puromycin (Gottesman, 1967; Sarkar and Thach, 1968) nor the guanosine 5'-triphosphate hydrolysis mediated by elongation factor Tu (Ono et al., 1969), inhibits polysome degradation. The tetracycline inhibition requires Mg(2+) at concentrations above 8 mM, which are inhibitory to protein synthesis in vitro. At concentrations of Mg(2+) below 8 mM, polysome degradation is insensitive to tetracycline, but not to fusidic acid. Addition of spermidine, but not of other polyamines, enables the tetracycline inhibition to occur at concentrations of Mg(2+) as low as 2 mM. The inhibition by tetracycline and by fusidic acid suggests that ribosome movement may be essential for the function of ribosome release factor, or that these antibiotics may directly affect its action.


In vivo recording of renal pelvic pacemaker potential.
Attempts have been successful to obtain electromyographic (EMG) recording of discharges of action potentials at the proximal end of canine renal pelvis in vivo by application of the Gil-Vernet procedure of extended pyelolithotomy. The discharges recorded in vivo from the proximal end of the renal pelvis in adult mongrel dogs showed EMG patterns characterized by a slow-rising positive waveform with virtually constant discharge intervals, irrespective of micturitional condition: normosthenuric or diuretic. The EMG pattern had striking resemblance to that obtained for the pacemaker of pyeloureteral peristalsis at the pelvicalyceal border in vitro. Potentials recorded at the lower pelvis, pyeloureteral junction and ureter in vivo showed increased frequencies of discharge during diuresis, compared to normal condition, the discharge intervals being always integral multiples of the interval of potentials at the proximal end of the renal pelvis.


Investigation on the Electrocatalytic Determination and Photocatalytic Degradation of Neurotoxicity Drug Clioquinol by Sn(MoO4)2 Nanoplates.
Transition-metal molybdates have concerned enormous curiosity as supercapacitors, photocatalysts, and electrocatalysts. These materials are the best alternatives to noble-metal-based catalysts, which are generally show a limited photocatalytic and electrocatalytic activity. In addition, the antiprotozoal drug can usually pollute the environment through improper disposable and incomplete metabolism, and it is very dangerous to humans as well as aquatic animals. Therefore, here, we have studied the electrochemical determination and photodegradation of neurotoxicity clioquinol (CQL) by nanoplate-like tin molybdate (Sn(MoO4)2, denoted as SnM), which is used as both an electro- and a photocatalyst. The as-prepared catalyst delivered a highly efficient activity toward the detection and degradation of CQL. The proposed nanoplate-like SnM was prepared through a simple wet-chemical route, and its physicochemical properties were characterized by various spectroscopic and analytical techniques. As an electrochemical sensor, the SnM electrocatalyst exhibited tremendous activity for the detection of CQL in terms of lower potential and enhanced anodic peak current. In addition, it showed high selectivity, a wide linear concentration range, a lower detection limit, and good sensitivity. From the UV-vis spectroscopy study, the SnM photocatalyst delivered an excellent photocatalytic activity toward the degradation of CQL in terms of increasing contact time and reducing CQL concentration, resulting in the increasing of the degradation efficiency about 98% within 70 min under visible light irradiation and showing an appreciable stability by observation of the reusability of the catalyst.


Global structure analysis of acid-unfolded myoglobin with consideration to effects of intermolecular coulomb repulsion on solution X-ray scattering.
To obtain information on the global structure of protein in the acid-unfolded (AU) state, the structure of apomyoglobin (apoMb) was analyzed by using the solution X-ray scattering (SXS) method. SXS profiles were obtained over a wide range of protein concentrations, 1-18 mg mL-1, under strongly acidic conditions. From analysis of the SXS profile extrapolated to a zero protein concentration, the mean square radius, Rsq, of AU-apoMb at 20 mM HCl was estimated to be 4.81 +/- 0.31 nm. This estimate is more than 1.3 nm larger than those of 3.0-3.5 nm reported thus far. The difference originates from the fact that effects of Coulomb repulsive forces acting between AU-apoMb molecules have not been correctly taken into account in the conventional analysis. In fact, even at a low protein concentration of 1 mg mL-1 close to the limit of measurement in the present SXS method, the solution condition applicable to estimating accurately structural parameters of AU-apoMb is very limited. At HCl concentrations lower than 10 mM, the scattering intensity at a small scattering vector decreases remarkably through the effect of intermolecular repulsive forces and the forward scattering intensity is significantly lower than the estimate from the partial specific volume of protein. On the other hand, at HCl concentrations higher than 50 mM, some compact molten-globule-like structures emerge. As a result, the intermediate concentration of 20 mM HCl is the best choice of the solution condition for determining Rsq of AU-apoMb. The effect of intermolecular Coulomb repulsion on the SXS profile of AU-apoMb is at its maximum for forward scattering and decreases monotonously with an increase in the scattering angle to be virtually negligible at K approximately 0.63 nm(-1). Whereas urea-denatured apoMb shows a SXS profile typical of Gaussian chains, the intrinsic SXS profile of AU-apoMb differs significantly from those of Gaussian chains.


Emergence of Caenorhabditis elegans as a Model Organism for Dissecting the Gut-Brain Axis.
Accumulating evidence links the gut microbiome to neuronal functions in the brain. Given the increasing prevalence of brain disorders, there is a critical need to understand how gut microbes impact neuronal functions so that targeted therapeutic interventions can be developed. In this commentary, we discuss what makes the nematode Caenorhabditis elegans a valuable model for dissecting the molecular basis of gut microbiome-brain interactions. With a fully mapped neuronal circuitry, C. elegans is an effective model for studying signaling of the nervous system in a context that bears translational relevance to human disease. We highlight C. elegans as a potent but underexploited tool to interrogate the influence of the bacterial variable on the complex equation of the nervous system. We envision that routine use of gnotobiotic C. elegans to examine the gut-brain axis will be an enabling technology for the development of novel therapeutic interventions for brain diseases.


In Vivo Mapping of FACT-Histone Interactions Identifies a Role of Pob3 C-terminus in H2A-H2B Binding.
Histone chaperones assist nucleosomal rearrangements to facilitate the passage of DNA and RNA polymerases through chromatin. The FACT (facilitates chromatin transcription) complex is a conserved histone chaperone involved in transcription, replication, and repair. The complex consists of two major subunits, Spt16 and SSRP1/Pob3 in mammals and yeast, which engage histones and DNA by multiple contacts. However, the precise mechanism of FACT function is largely unclear. Here, we used the genetically installed UV-activatable cross-linker amino acid p-benzoylphenylalanine (pBPA) to map the interaction network of FACT in living yeast. Unexpectedly, we found the acidic C-terminus of Pob3 forming cross-links to histone H2A and H2B most efficiently. This observation was independent of the performed cross-linking chemistry since similar histone cross-links were obtained using p-azidophenylalanine (pAzF). Further analyses identified a C-terminal nuclear localization sequence in Pob3. Its interaction with Importin-α interfered with H2A-H2B binding, which suggests a possible regulatory role in FACT recruitment to chromatin. Deletion of acidic residues from the Pob3 C-terminus creates a hydroxyurea-sensitive phenotype in budding yeast, suggesting a potential role for this domain in DNA replication.


Protein-decorated reduced oxide graphene composite and its application to SERS.
A globular protein, β-lactoglobulin (BLG), was used to decorate reduced graphene oxide sheets (RGO) and the obtained BLG-RGO composite can be dispersed in aqueous solution with pH-sensitive solubility. The morphology of the BLG-RGO composite was studied by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The results indicate that BLG-RGO is effectively exfoliated with an average thickness of 2.5 nm. UV-vis spectra were performed to examine the reduction degree and determine the optimum concentration of β-lactoglobulin and appropriate pH value. Furthermore, Raman spectra demonstrate that β-Lactoglobulin promotes the chemical reduction process of graphene oxide and benefits to repair the crystal defects. Due to the adsorption of β-Lactoglobulin on the surface of graphene sheets, the BLG-RGO composite was further used as template for Au nanoparticles assembly. These Au nanoparticles assembled on the BLG-RGO composite were shown to yield a large SERS enhancement for Rhodamine 6G.


[Effect of hypotonic liquid containing colloid on hemorrhagic dogs with celiac seawater immersion wound].
To determine hypotonic liquid containing colloid on hemorrhagic dogs with celiac seawater immersion wound. Thirty-five dogs were randomly divided into five groups: control group (group A), 0.9% NaCl therapy group (group B) and 0.45% NaCl therapy group (group C), 5% glucose therapy group(group D) and hypotonic liquid containing colloid therapy group (group E). Changes of mean artery pressure (MAP), cardiac output (CO), urine volume, plasma osmotic pressure and pathologic changes of lung and brain were observed. hypotonic liquid containing colloid could effectively ameliorate MAP and CO, improve urine volume, decrease plasma osmotic pressure and prevent occurrence of lung and brain edema. Hypotonic liquid containing colloid can exert satisfactory therapeutic effects on hemorrhagic dogs with celiac seawater immersion wound.


The influence of electrokinetic bioremediation on subsurface microbial communities at a perchloroethylene contaminated site.
There is an increased interest in finding remedies for contamination in low permeability and advection-limited aquifers. A technology applicable at these sites, electrokinetic-enhanced bioremediation (EK-BIO), combines traditional bioremediation and electrokinetic technologies by applying direct current to transport bioremediation amendments and microbes in situ. The effect of this technology on the native soil microbial community has only been previously investigated at the bench scale. This research explored the influence of EK-BIO on subsurface microbial communities at a field-scale demonstration site. The results showed that, similar to the findings in laboratory studies, alpha diversity decreased and beta diversity differed temporally, based on treatment phase. Enrichments in specific taxa were linked to the bioaugmentation culture and electron donor. Overall, findings from our study, one of the first field-scale investigations of the influence of electrokinetic bioremediation on subsurface microbial communities, are very similar to bench-scale studies on the topic, suggesting good correlation between laboratory and field experiments on EK-BIO and showing that lessons learned at the benchtop are important and relevant to field-scale implementation. KEY POINTS: • Microbial community analysis of field samples validates laboratory study results • Bioaugmentation cultures and electron donors have largest effect on microbial community.


Thyrotropin releasing hormone levels in human cerebrospinal fluid in various neurologic diseases.
Thyrotropin releasing hormone (TRH) in the human cerebrospinal fluid (CSF) of 102 patients with non-neurologic and neurologic diseases was measured by a specific TRH radioimmunoassay. TRH levels in CSF were 17.6 +/- 3.4 pg/ml (mean +/- SE) in non-neurologic diseases. TRH levels in CSF were significantly elevated in cases of spinal cord tumor and multiple sclerosis (acute phase). Elevated TRH levels in CSF were decreased in these diseases by operation or prednisolone treatment, respectively. From these data, it is suggested that TRH is present in the human CSF and that measurement of TRH levels in CSF may be a useful indicator of the activity of certain neurologic diseases.


The impact of living-unrelated transplant on establishing deceased-donor liver program in Syria.
Liver transplant is the criterion standard for patients with end-stage liver disease. Yet there is no liver transplant in Syria. Traveling abroad for a liver transplant is a luxury few Syrians can afford. There is currently an on-going debate whether to start a liver transplant program using living or deceased donors. In 2003, a new law was enacted, authorizing the use of organs from volunteer strangers and deceased donors. Despite the positive aspects of this law (allowing unrelated donors to increase the number of transplants in the country); the negative aspects also were obvious. The poor used the law to sell their organs to the rich, and this model is in violation of the Istanbul Declaration. To better document transplant communities' perceptions on organ donation, an e-mail survey was sent to a nationally representative sample of physicians (n = 115) that showed that 58% of respondents did not support the start of liver transplant from live donors, as they fear a considerable risk for the donor and the recipient. Seventy-one percent of respondents believe that unrelated kidney donation has contributed to tarnishing the reputation of transplant, and 56% believe that a deceased-donor program can run in parallel with unrelated organ donations. The interest in deceased-donor program has been affected negatively by the systematic approach of using poor persons as the source of the organ. This lack of interest has affected starting a liver program that relies on deceased donors; especially the need for kidneys is more than livers. Health authorities in Syria were inclined to initiate a liver transplant program from live donors, despite the risks of serious morbidities and mortality. In conclusion then, paid kidney donation in actual effect is actually a hindrance to establishing a deceased-donor liver program.


Multi-omics of the esophageal microenvironment identifies signatures associated with progression of Barrett's esophagus.
The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host. Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest. Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment of Campylobacter species as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found between Campylobacter and napsin B aspartic peptidase. Targeted culture of Campylobacter species from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for these Campylobacter strain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to the Campylobacter isolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression. We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.


Rotational-echo double resonance characterization of vancomycin binding sites in Staphylococcus aureus.
Solid-state NMR experiments with stable isotope-labeled Staphylococcus aureus have provided insight into the structure of the peptidoglycan binding site of a potent fluorobiphenyl derivative of chloroeremomycin (Eli Lilly LY329332). Rotational-echo double resonance (REDOR) NMR provided internuclear distances from the 19F of this glycopeptide antibiotic to natural-abundance 31P and to specific 13C and 15N labels biosynthetically incorporated into the bacteria from labeled alanine, glycine, or lysine in the growth medium. Results from experiments with intact late log phase bacteria and cell walls indicated homogeneous drug-peptidoglycan binding. Drug dimers were not detected in situ, and the hydrophobic fluorobiphenyl group of LY329332 did not insert into the bilayer membrane. A model of the binding site consistent with the REDOR results positions the vancomycin cleft around an un-cross-linked D-Ala-D-Ala peptide stem with the fluorobiphenyl moiety of the antibiotic near the base of a second, proximate stem in a locally ordered peptidoglycan matrix.


What is post TBI fatigue?
Fatigue is among the most common sequelae of traumatic brain injury (TBI). To summarize the empirical and theoretical literature on Post TBI fatigue (PTBIF) and identify some of the challenges that continue to confront clinicians, researchers and individuals with TBI. Qualitative literature review. The epidemiology, characteristics, and correlates of PTBIF are described. Challenges in the operational definition and measurement of fatigue are discussed and the empirical literature on measurement of PTBIF and theoretical models of the potential etiology of PTBIF is summarized. Existing treatments of PTBIF and the research supporting them are reviewed. Future directions for clinical research are presented. Although PTBIF is a high incidence condition after TBI that is related to significant suffering and reduced quality of life, it remains inadequately measured and treated. Its etiology and precipitants are poorly understood and intervention research is inadequate. Further research is necessary to develop psychometrically-sound objective and subjective measures of PTBIF and examine the efficacy of treatments for fatigue. Interventions shown to improve fatigue in other populations should be considered in treating PTBIF.


Force decay evaluation of latex and non-latex orthodontic intraoral elastics: in vivo study.
This clinical study was conducted in order to evaluate force decay over time of latex and non-latex orthodontic intraoral elastics. Patients (n = 15) were evaluated using latex and non-latex elastics in the periods of : 0, 1, 3, 12 and 24 hours. The rubber bands were transferred to the testing machine (EMIC DL-500 MF), and force values were recorded after stretching the elastic to a length of 25mm. Paired t test was applied and analysis of variance (ANOVA) was used to evaluate the variation of force generated. LSD (Fisher's least significant difference) post-hoc test was thus employed. As regards the initial forces (zero time), the values of force for non-latex elastic were slightly higher than for the latex elastic. In the subsequent times, the forces generated by the latex elastic showed higher values. Regarding the material degradation, at the end of 24 hours the highest percentage was observed for non-latex elastic. The latex elastics had a more stable behavior during the studied period, compared with non-latex.


Open to Exploration? Association of Personality Factors With Complementary Therapy Use After Breast Cancer Treatment.
Many cancer survivors seek complementary therapies (CTs) to improve their quality of life. While it is well-known that women who are younger, more highly educated, and have higher incomes are more likely to use CTs, individual differences such as personality factors have been largely unexplored as predictors of CT use. In a secondary analysis of a larger study, 270 women with stage I to III breast cancer completed self-report measures of demographic and illness-related information, personality variables, and use of several different types of CTs. A series of logistic regression models were used to explore whether demographic, illness-related, and personality variables predicted different types of CT use. Prior relationships between education and CT use were replicated. There were no significant relationships between illness-related variables and different types of CT use. Of the 5 personality factors, only openness to experience was a significant predictor of multiple types of CT use. Openness to experience may represent an individual difference variable that predicts CT use among cancer survivors. CTs themselves may represent a form of intellectual curiosity and novelty seeking. Further studies are needed to replicate and examine the generalizability of the relationship between openness to experience and CT use in oncology populations.


Association between Mediterranean diet and periodontitis among US adults: The mediating roles of obesity indicators.
This study aimed to assess the association between the Mediterranean diet (MedDiet) and periodontitis in US adults and to further explore the mediating roles of obesity indicators in this association. The relationship between MedDiet and periodontitis is controversial. And it is unclear whether obesity indicators are potential mediators of this relationship. Using data derived from the National Health and Nutrition Examination Survey (2009-2014). Weighted binary logistic regression and restricted cubic spline were used to assess the association between MedDiet and periodontitis. Weighted ordinal logistic regression was performed to evaluate the relationship between MedDiet and periodontitis severity. The mediating roles of body mass index (BMI) and waist circumference in the relationship between the MedDiet and periodontitis were explored. Association analyses were further performed using mean clinical attachment loss (CAL) or mean periodontal probing depth (PPD) as dependent variables. The false discovery rate method was used to correct the p-values in the regression analyses. A total of 8290 eligible participants (4159 participants with periodontitis and 4131 without periodontitis) were included. A negative association between the MedDiet adherence score and periodontitis was observed in the binary logistic regression model (adjusted odds ratio = 0.94, 95% confidence interval: 0.90-0.97, p = .001). Restricted cubic spline regression revealed a dose-response relationship between the MedDiet adherence score and periodontitis. BMI and waist circumference significantly mediate this association, with mediation proportions of 9.7% (p = .032) and 9.3% (p = .012), respectively. Multivariable ordinal logistic regression showed that the MedDiet adherence score was negatively associated with the severity of periodontitis (all p < .05). Additionally, the MedDiet adherence score was negatively associated with mean PPD or mean CAL (all p < .05). This study suggests a significant negative association between adherence to the MedDiet and periodontitis and a possible mediating role of obesity indicators in this association. Furthermore, studies are still warranted to confirm our findings.


Single-stage hybrid repair of a ruptured Kommerell diverticulum associated with dextrorotation, bovine arch, and bicuspid aortic valve.
A strategy for the surgical repair of ruptured Kommerell diverticulum has not yet been established. The aim of this study is to demonstrate that this entity could be associated with a number of other cardiac anomalies and this lesion can be successfully treated by a hybrid approach. The patient, with a combination of ruptured Kommerell diverticulum, dextrorotation, bovine arch, and bicuspid aortic valve, underwent emergency surgery. A single stage hybrid surgical/endovascular repair including subclavian artery revascularization, aortic resection with open proximal anastomosis under circulatory arrest, endovascular stenting, and valve repair was performed. Histological studies indicated the presence of the aortic wall media degeneration. Postoperative course was uneventful and patient is free of symptoms during 2-year follow up. Less invasive hybrid technique is safe and effective treatment option. Accumulated knowledge of Kommerell diverticulum has lead to understanding the best clinical treatment for this complicated aortic anomaly.


[Listeria monocytogenes rhomboencephalitis. Report of three cases].
An unusual number of cases of rhomb encephalitis have occurred in Chile because of the increased frequency of infections caused by Listeria monocytogenes. We report three females aged 36, 40 and 55 years, with the disease. All presented with a prodrome characterized by headache, nausea, vomiting and fever, followed by ataxia and unilateral palsies of the third, seventh and twelfth cranial nerves. One patient presented also a hemi-hypoesthesia. Magnetic resonance showed lesions in the posterior aspect of the brain stem, specifically in relation to the floor of the fourth ventricle. Blood cultures were positive for Listeria monocytogenes.


Comparison of gene regulatory networks of benign and malignant breast cancer samples with normal samples.
The aim of this study was to explain the pathogenesis and deterioration process of breast cancer. Breast cancer expression profile data GSE27567 was downloaded from the Gene Expression Omnibus (GEO) database, and breast cancer-related genes were extracted from databases, including Cancer-Resource and Online Mendelian Inheritance In Man (OMIM). Next, h17 transcription factor data were obtained from the University of California, Santa Cruz. Database for Annotation, Visualization, and Integrated Discovery (DAVID)-enrichment analysis was applied and gene-regulatory networks were constructed by double-two-way t-tests in 3 states, including normal, benign, and malignant. Furthermore, network topological properties were compared between 2 states, and breast cancer-related bub genes were ranked according to their different degrees between each of the two states. A total of 2380 breast cancer-related genes and 215 transcription factors were screened by exploring databases; the genes were mainly enriched in their functions, such as cell apoptosis and proliferation, and pathways, such as p53 signaling and apoptosis, which were related with carcinogenesis. In addition, gene-regulatory networks in the 3 conditions were constructed. By comparing their network topological properties, we found that there is a larger transition of differences between malignant and benign breast cancer. Moreover, 8 hub genes (YBX1, ZFP36, YY1, XRCC5, XRCC4, ZFHX3, ZMAT3, and XPC) were identified in the top 10 genes ranked by different degrees. Through comparative analysis of gene-regulation networks, we identified the link between related genes and the pathogenesis of breast cancer. However, further experiments are needed to confirm our results.


Exploring relationships between inspiratory muscle strength and functional capacity in childhood cancer survivors: a pilot study.
Childhood cancer survivors (CCS) experience short- and long-term side effects from cancer treatment that often impair functional capacity. Inspiratory muscle weakness is a potential mechanism for reduced functional capacity. The objective of this pilot study was to examine the relationship between inspiratory muscle strength and functional capacity in 10 CCS. Inspiratory muscle strength was measured by maximal inspiratory pressure (MIP) while functional capacity was measured by the two-minute walk test (2MWT), the physiological cost index and hemodynamic response to exercise according to changes in heart rate, blood pressure and rate-pressure product (RPP). Overall, MIP and 2MWT distance were below predicted values. Hemodynamic responses to the 2MWT were consistent with little variation, except for elevated diastolic blood pressure (DBP) response. MIP had significant relationships with resting DBP (Spearman's rank correlation coefficient [rs] = -0.70; p = 0.03) and DBP response (rs = 0.72; p = 0.02). Time since completion of cancer treatment had a significant positive relationship with RPP response (rs = 0.67; p = 0.03). Inspiratory muscle weakness in childhood cancer could be an indicator of skeletal muscle dysfunction and should be considered when symptoms of dyspnea or poor functional capacity arise. Inspiratory muscle strength was found to be related to changes in blood pressure in CCS. Future studies should further investigate these relationships and the impact of inspiratory muscle training on hemodynamics and functional capacity in CCS.


Maximum entropy principle in recurrence plot analysis on stochastic and chaotic systems.
The recurrence analysis of dynamic systems has been studied since Poincaré's seminal work. Since then, several approaches have been developed to study recurrence properties in nonlinear dynamical systems. In this work, we study the recently developed entropy of recurrence microstates. We propose a new quantifier, the maximum entropy (Smax). The new concept uses the diversity of microstates of the recurrence plot and is able to set automatically the optimum recurrence neighborhood (ϵ-vicinity), turning the analysis free of the vicinity parameter. In addition, ϵ turns out to be a novel quantifier of dynamical properties itself. We apply Smax and the optimum ϵ to deterministic and stochastic systems. The Smax quantifier has a higher correlation with the Lyapunov exponent and, since it is a parameter-free measure, a more useful recurrence quantifier of time series.


Thoracic sarcoma case series in Hospital Kuala Lumpur, Malaysia.
Thoracic sarcomas (TS) are rare neoplasms that may present with non-specific pulmonary symptoms. Chest radiographs and computed tomography of the thorax are the investigations of choice, while pre-operative minimally invasive biopsies may not be entirely helpful with the diagnosis. The commonly identified variants of thoracic sarcomas include liposarcomas, leiomyosarcomas and synovial sarcomas. Complete excision of the tumour with clear margins remain the sole definite form of management and there is limited role with adjuvant chemotherapy and radiotherapy. In the present case series, we explore our experience with three patients who presented with TS and the management decisions that was made.


The role of impulsivity in relapse vulnerability.
Drug dependence in humans is often accompanied by behavioral disturbances such as maladaptive levels of impulsivity. In turn, there is accumulating evidence from preclinical laboratory animal and clinical studies indicating that impulsive behavior might be causally linked to several distinct processes in drug addiction, including the onset, maintenance and relapsing nature of drug use. This leads to the question as to whether pharmacological or behavioral approaches aimed at ameliorating impulsivity might prove effective therapeutic interventions in human drug dependence. This paper reviews evidence for an important role of impulsivity as a determinant of drug dependence with a particular focus on relapse vulnerability and addresses the implications of these findings for the clinical management of relapse prevention.


Overview of Current and Future First-Line Systemic Therapy for Metastatic Clear Cell Renal Cell Carcinoma.
Treatment of metastatic clear cell renal cancer (mccRCC) has seen substantial progress over the last 20 years, with many regulatory approvals since 2006 culminating in a substantial increase to overall survival (OS). Six therapies are currently available for first-line use, with additional treatments currently being tested in this setting, some of which are expected to be approved soon based on new data from the CABOSUN and CheckMate-214 trials. Based on the available evidence, we strongly believe that vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) therapy over mechanistic target or rapamycin (mTOR; formerly known as mammalian target of rapamycin) inhibitor therapy is the most effective first-line option regardless of risk category assignment. High-dose interleukin-2 (HDIL-2) therapy remains a reasonable treatment option in patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and have minimal comorbid conditions. In the near future, these agents are likely to be surpassed by cabozantinib and by combination immune checkpoint inhibitor therapy with nivolumab and ipilimumab. Independent review has recently confirmed superiority of first-line cabozantinib over sunitinib in a phase 2 trial of 157 patients with intermediate or poor risk mccRCC (progression-free survival [PFS] 8.6 vs 5.3 months, hazard ratio [HR] 0.48, p = 0.0008). In a separate study of 1096 patients treated with either upfront sunitinib or the combination of nivolumab and ipilimumab, those with intermediate and poor risk had significant improvement in both PFS (11.6 vs 8.4 months, HR 0.82, p = 0.0331) and OS (not reached vs 26 months, p < 0.0001). Responses were greater in patients with positive programmed death receptor ligand-1 (PD-L1) tumor staining, and pending regulatory approval may become standard of care in untreated patients with intermediate to poor risk disease with positive PD-L1 status. This likely represents the beginning of additional novel immunotherapy combinations for the first-line treatment of mccRCC.


Synthesis of novel antimicrobial aryl himachalene derivatives from naturally occurring himachalenes.
Five new 2,9,9-trimethyl-6,7,8,9-tetrahydro-benzocyclohepten-5-ylidene-amine derivatives (16a-16e) were synthesized from α-dehydro-ar-himachalene (11) that was originally prepared from an isomeric mixture of α, β and γ himachalenes (10), the abundant sesquiterpenes of Cedrus deodara essential oil. In addition, different aryl himachalenes derivatives (9, 12, 14 and 15) were also formed from 11. The structures of the synthesized compounds were confirmed on the basis of their NMR, IR and mass spectral data. The prepared compounds were tested against a group of sixteen organisms including gram positive and gram negative bacterial and fungal strains. The introduction of a series of substituted imine groups into aryl himachalenes at 5(th) position (16a-16e) enhanced antimicrobial activity as compared to the aromatized derivatives (9, 12, 14 and 15) against gram-positive bacteria Bacillus subtilis, Micrococcus luteus and Staphylococcus aureus, and mycotoxigenic fungi Aspergillus parasiticus, A. ochraceous and A. sydowii. graphical Abstract, Figure 1(Fig. 1).


Pre- and peripartal management of a woman with McArdle disease: a case report.
McArdle disease or glycogen storage disease (GSD) type V is a rare autosomal recessive inherited disorder in skeletal muscle metabolism leading to exercise intolerance, muscle cramps and in some cases to rhabdomyolysis and acute renal failure due to elevated serum myoglobin levels. Albeit the uterine smooth muscle is not affected, pregnancy and delivery can be physically strenuous and may require specific anesthesiologic care. However, data on pregnancy progress and outcome and on special implications linked to anesthesia in women with McArdle's disease is scarce, thus posing a challenge to pre- and peripartal management. We report a case of a pregnant woman with Morbus McArdle who was monitored during her pregnancy and delivered a healthy male via cesarean section under spinal anesthesia. Pregnancy, delivery and recovery were uneventful. Our findings, combined with a literature review, lead to the conclusion that uncomplicated pregnancy and delivery can be expected.


The influence of temporally varying noise from seismic air guns on the detection of underwater sounds by seals.
Standard audiometric data are often applied to predict how noise influences hearing. With regard to auditory masking, critical ratios-obtained using tonal signals and flat-spectrum maskers-can be combined with noise spectral density levels derived from 1/3-octave band levels to predict signal amplitudes required for detection. However, the efficacy of this conventional model of masking may vary based on features of the signal and noise in question. The ability of resource managers to quantify masking from intermittent seismic noise is relevant due to widespread geophysical exploration. To address this, spotted and ringed seals with previously measured critical ratios were trained to detect low-frequency tonal signals within seismic pulses recorded 1 and 30 km from an operational air gun array. The conventional model of masking accurately predicted the extent of masking only in certain cases. When noise amplitude varied significantly in time, the results suggested that detection was driven by higher signal-to-noise ratios within time windows shorter than the full signal duration. This study evaluates when it is appropriate to use average noise levels and critical ratios to predict auditory masking experienced by marine mammals, and suggests how masking models can be improved by incorporating time-based analyses of signals and noise.


Dilazep prevents glomerulosclerosis in accelerated Masugi nephritis in the rat.
The effects of Dilazep on immunologically induced glomerular injuries were examined. Accelerated Masugi nephritis in rats produced glomerulosclerosis with proteinuria following administration of a single dose of nephrotoxic serum (NTS). When 5 mg/kg/day of Dilazep had been administered prior to the NTS injection, the proteinuria was resolved rapidly after reaching a maximum level. The glomeruli 3 months later showed significant suppression of glomerulosclerosis and lesser adhesive lesions as compared to those in control rats with Masugi nephritis. On the other hand, when Dilazep was administered from 2 weeks after the injection of NTS, the rats displayed persistent proteinuria and glomerulosclerosis at similar levels to those in the Masugi group. Dilazep appears to exert some protective effects in the early stages of glomerular injuries induced by immunological mechanisms.


The morphogenesis of hindbrain crowding associated with lumbosacral myeloschisis.
The teratogenicity of ethylenethiourea (ETU) was investigated in Sprague-Dawley rats and Landrace pigs. Pregnant rats each received a single intragastric dose of ETU on a given day from day 8 to day 19 of gestation, and pregnant pigs were given a single dose of ETU from day 15 to day 19. Control animals received an ETU-free vehicle. The newborn pigs were all normal, whereas there were high incidences of specific types of congenital malformation of the central nervous and other systems in the rats. A high incidence of lumbosacral myeloschisis associated with hindbrain crowding was observed in rat fetuses exposed to ETU on day 11 of gestation. This abnormality is considered comparable to Chiari type II malformation associated with spinal dysraphism (Arnold-Chiari malformation) in humans. Morphogenetic fetuses were examined by light and scanning electron microscopy and interactive image analysis. At gestational days 12 and 13, the volume of the caudal end of the neural tube from the anterior border of the hindlimb bud to the most caudal portion of the fetus was significantly greater in ETU-exposed than in control rat embryos. Experimental rat embryos also exhibited disturbance in closure of the posterior neuropore, with extrusion of neural tissue through the opening. An apparently unrelated abnormality in ETU-exposed rat fetuses was underdevelopment of the cranium, leading to hindbrain crowding.(ABSTRACT TRUNCATED AT 250 WORDS)


MicroRNAs and cancer.
The general basis of cancer is the loss of cell identity and inappropriate proliferation of cells. Classically, a universal paradigm in oncogenesis is the accumulation of mutations in the open reading frames of protein-encoding oncogenes and tumor suppressors. The identification of new classes of noncoding RNAs (ncRNA) important for development and cell homeostasis will likely change this current paradigm. Recent data suggests that a special class of ncRNAs called microRNAs might be involved in human disease. This review proposes a role for microRNAs in oncogenesis.


CPT-symmetric coupler with intermodal dispersion.
A dual-core waveguide with balanced gain and loss in different arms and with intermodal coupling is considered. The system is not invariant under the conventional PT symmetry, but obeys CPT symmetry where an additional spatial inversion C corresponds to swapping the coupler arms. We show that second-order dispersion of coupling allows for unbroken CPT symmetry and supports propagation of stable vector solitons along the coupler. Small-amplitude solitons are found in explicit form. The combined effect of gain-and-loss and dispersive coupling results in several interesting features which include a separation between the components in different arms, nontrivial dependence of stability of a soliton on its velocity, and the existence of more complex stationary two-hump solutions. Unusual decay dynamics of unstable solitons are also discussed.


[Four-bone fusion of the wrist: review of 17 cases at an average 3.4 years follow-up].
We reviewed retrospectively outcome after intracarpal arthrodesis for advanced-stage osteoarthritis of the wrist. Among the 20 patients who underwent a four-bone fusion between 1989 and 1998 in our unit, 17 were available for analysis. Mean age of the study population was 41.5 years. These young patients had an occupational activity and 80% of them were manual laborers. Preoperatively, pain was the main complaint; 95% of the patients considered pain to be invalidating. Grip force was 48.5% compared to the healthy side. Joint amplitudes were limited in all patients: flexion-extension 85 degrees, radio-ulnar inclination 22.5 degrees with 12.5 degrees for the ulnar side. Mean loss of motion compared with the healthy side was 32.5% for flexion-extension, and 44% for radio-ulnar inclination. The preoperartive radiograph showed degenerated capito-lunate joints in 63% of the cases, degenerative scapho-capital joints in 58% and total loss of the radio-scaphoid joint space in 100%. Degeneration was considered to be global in 58% of the wrists. Mean follow-up for the 17 wrists studied was 3.4 years (range 1-10). At last follow-up, 41% of the wrists were pain free, 24% were painful occasionally, and 35% were bothersome for heavy work. The patients did not express any difficulties in daily activities. Grip force was only slightly improved with a 7.5% gain over the preoperative value. Joint motion at last follow-up was, on the average, 70 degrees flexion-extension (40 degrees flexion and 30 degrees extension) and 35 degrees radio-ulnar inclination (17.5 degrees ulnar). Eleven patients (65%) had resumed their occupational activities at the same level two months after surgery. Outcome was deemed satisfactory by 65% of the patients, fair by 17.5%, and poor by 17.5% (3 patients). Radiological fusion was achieved in 16 wrists at a mean 4.5 weeks. Mean carpal height was 0.42 compared with 0.52 for the healthy side and 0.47 preoperatively. There was no significant relationship between carpal height and poor outcome. Data in the literature are in agreement with the good results obtained for pain and activity level despite the inconstant effect on grip force and joint amplitude. Four-bone fusion is an effective treatment for patients with advanced-stage osteoarthritis of the wrist where the level of degeneration rules out resection. The consequences of total wrist arthroplasty are much more invalidating.


Dynamics of the negative thermal expansion in tellurium based liquid alloys.
Negative thermal expansion (NTE) in tellurium based liquid alloys (GeTe6 and GeTe12) is analyzed through the atomic vibrational properties. Using neutron inelastic scattering, we show that the structural evolution resulting in the NTE is due to a gain of vibrational entropy that cancels out the Peierls distortion. In the NTE temperature range, these competing effects give rise to noticeable changes in the vibrational density of states spectra. Additional first principles molecular dynamics simulations emphasize the role of the temperature dependance of the Ge atomic environment in this mechanism. For comparison, we extended our study to Ge2Sb2Te5 and Ge1Sb2Te4 phase-change materials.


Synthesis of anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-11-methylbenzo[a]pyrene and its reaction with DNA.
Substitution of a methyl group in the bay region can enhance the tumorigenicity of polycyclic aromatic hydrocarbons such as chrysene, benz[a]anthracene, and others. This phenomenon has been related to facile DNA adduct formation of bay region diol epoxides with a methyl group and epoxide ring in the same bay. While anti-7, 8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and its DNA adduct formation have been studied extensively, it is not known whether a methyl substituent in the bay region alters the reactivity of DNA in this system. This is of interest because 11-methylbenzo[a]pyrene, which has a bay region methyl group, is more tumorigenic than benzo[a]pyrene. To examine the question, we have devised and employed an efficient synthesis based on photochemical cyclization, and prepared anti-7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydro-11-methylbenzo[a]pyrene, the likely ultimate carcinogen of 11-methylbenzo[a]pyrene. We have then reacted anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-11-methylbenzo[a]pyrene with calf thymus DNA and found that it gives three major adducts. These were identified as having resulted from cis- and trans-ring opening of the (S,R,R, S)-enantiomer and from trans-ring opening of the (R,S,S, R)-enantiomer. The standard deoxyguanosine adduct markers were prepared, and their structures were tentatively assigned on the basis of their CD and 1H NMR spectra. The adduct distribution of anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-11-methylbenzo[a]pyrene is quite different from that observed in the reaction of DNA with the corresponding diol epoxides of benzo[a]pyrene or with 5-methylchrysene. The heterogeneity of adducts obtained with anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-11-methylbenzo[a]pyrene thus may be related to the enhanced tumorigenicity of 11-methylbenzo[a]pyrene.


Targeting SHP2 phosphatase in breast cancer overcomes RTK-mediated resistance to PI3K inhibitors.
PI3K signaling is frequently activated in breast cancer and is targeted by PI3K inhibitors. However, resistance of tumor cells to PI3K inhibition, often mediated by activated receptor tyrosine kinases, is commonly observed and reduces the potency of PI3K inhibitors. Therefore, new treatment strategies to overcome resistance to PI3K inhibitors are urgently needed to boost their efficacy. The phosphatase SHP2, which plays a crucial role in mediating signal transduction between receptor tyrosine kinases and both the PI3K and MAPK pathways, is a potential target for combination treatment. We tested combinations of PI3K and SHP2 inhibitors in several experimental breast cancer models that are resistant to PI3K inhibition. Using cell culturing, biochemical and genetic approaches, we evaluated tumor cell proliferation and signaling output in cells treated with PI3K and SHP2 inhibitors. Combination treatment with PI3K and SHP2 inhibitors counteracted both acquired and intrinsic breast cancer cell resistance to PI3K inhibition that is mediated by activated receptor tyrosine kinases. Dual PI3K and SHP2 inhibition blocked proliferation and led to sustained inactivation of PI3K and MAPK signaling, where resistant cells rapidly re-activated these pathways upon PI3K inhibitor monotreatment. In addition, we demonstrate that overexpression of SHP2 induced resistance to PI3K inhibition, and that SHP2 was frequently activated during the development of PI3K inhibitor resistance after prolonged treatment of sensitive cells. Our results highlight the importance of SHP2 as a player in resistance to PI3K inhibitors. Combination treatment with PI3K and SHP2 inhibitors could pave the way for significant improvements in therapies for breast cancer.


Pharmacological activity of 5-phenyl-1:3:4-thiadiazole (L 1538), 2-amino-5-phenyl-1:3:4-thiadiazole (L 1460) and 2-amino-5-(2'-thienyl)-1:3:4-thiadiazole (L 1458).
The pharmacological actions of 5-phenyl-1:3:4-thiadiazole (L 1538), 2-amino-5-phenyl-1:3:4-thiadiazole (L 1460) and 2-amino-5-(2'-thienyl)-1:3:4-thiadiazole (L 1458) have been studied and compared with those of other muscular relaxant drugs. The three compounds have paralysing effects in mice, rats, cats, and dogs. They block the tonic component of maximal electroshock seizures and protect against strychnine, though not against leptazol-induced convulsions in mice. Like other centrally acting paralysing drugs, they depress spinal polysynaptic transmission in doses which leave monosynaptic transmission relatively unaffected. The rigidity of the decerebrate cat is reduced but not always abolished. The compounds do not induce synchronization in epidural electroencephalogram recordings. In doses not greatly affecting muscular tone and spontaneous activity, they prolong the hypnotic effects of pentobarbitone and other barbiturates in mice. Autonomic functions are only slightly affected. The similar actions of substituted thiadiazoles and 2-amino-benzothiazoles confirm a previous hypothesis that pharmacological equivalence may result either from condensing heterocyclic nuclei with aromatic nuclei or from introducing aryl substituents into them.


Three distal anterior cerebral artery aneurysms in the same branch associated with five additional intracranial aneurysms.
Multiple distal anterior cerebral artery (DACA) aneurysms appear as rare findings. Simultaneous treatment of such lesions can be particularly challenging. A report of three aneurysms on the same parent artery has not been reported before. We report a case of three DACA aneurysms treated within one microsurgical operation in a patient with eight aneurysms. A 62-year-old woman incidentally presented with multiple various size saccular aneurysms, including tree on the left DACA. One of the DACA aneurysm was located on the A3 segment, and the other two were on the A4 and A5 segments. Ligation of all three of these aneurysms was planned in one operation. A standard anterior interhemispheric approach was utilized. Three aneurysms were successfully clipped using four clips. Intraoperative angiography confirmed aneurysm occlusion with parent artery patency preservation. The patient showed no new postoperative neurological deficit. Clipping multiple DACA aneurysms within a single microneurosurgical operation is a feasible treatment option. Meticulous analysis of preoperative imaging features is crucial for selecting the best, patient-specific treatment strategy.


Multimodal FLAIR/MPRAGE segmentation of cerebral cortex and cortical myelin.
The MR signal from gray matter has been long known to present small differences in intensity that have been attributed to variations in cortical myelin content. Previous studies have shown that the T1-, T2-weighted signal and their ratio are sensitive to these variations. Here, we investigated different combinations of signal from MPRAGE and FLAIR images in multimodal segmentation with parametric models of signal intensity to identify a procedure for the identification of contrast in cortical gray matter and the segmentation of different cortical components at 3T. We show that a three-modal combination of these signals delivers a stable segmentation of the cortical mantle in which two distinct components are reliably identified. The resulting intensity maps correspond well to known regional myeloarchitectural differences between cortical regions. These results confirm that widely available MR sequences contain signal that may be used to reliably detect subtle differences in the composition of gray matter with a segmentation approach.


Bradhyrhizobium japonicum hydrogen-ubiquinone oxidoreductase activity: quinone specificity, inhibition by quinone analogs, and evidence for separate sites of electron acceptor reactivity.
The purified H2-uptake hydrogenase of Bradyrhizobium japonicum, containing no cytochrome b, catalyzed efficient H2-ubiquinone oxidoreductase activity. Hydrogen-oxidizing membranes also catalyzed H₂-ubiquinone oxidoreductase activity, and the site of ubiquinone reduction was localized to the He-quinone oxidoreductase complex based on comparative antimycin A and HQNO titrations of both H₂-ubiquinone-1 oxidoreductase and ubiquinol-1 oxidase activities. A variety of quinones could function as electron acceptors of both pure or membrane-bound hydrogenase, including ubiquinone-0 (Q₀), ubiquinone-1 (Q₁), duroquinone and menadione, indicating relatively loose substrate specificity with regard to the quinone head group. Both the redox potential and the quinone structure determined the efficiency of hydrogenase turnover. Among short-chain ubiquinones, the isoprenoid chain length had a profound affect on Kin, with each additional isoprenoid unit resulting in the K m of the membrane-bound enzyme to decrease more than an order of magnitude. For pure enzyme, the K m values for Q₀, Q₁ and Q₂ were 1.97 mM, 68.8 /xM and 3.1 /~M, respectively. Vma x was also influenced by the substrate isoprenoid chain length for the pure enzyme. The inhibition patterns of H₂-dependent Q₁ versus MB reduction by the quinone analogs (2-n-heptyl-4-hydroxyquinoline N-oxide and Antimycin A) were significantly different, and clear differences in pH optima for the two activities were observed. In addition, the two hydrogen-dependent electron acceptor activities (Q₁ and MB) exhibited different time-dependent inactivation patterns by the chemical modification reagent diazobenzene sulfonate. Ubiquinone and MB therefore react by different mechanisms (perhaps at different sites) within the hydrogenase complex in situ. The inhibition pattern of hydrogen-ubiquinone oxidoreductase activity by antimycin A was clearly different than antimycin A inhibition of ubiquinol oxidation at the bc₁ complex. This is, to our knowledge, the first report of antimycin A inhibition of a hydrogenase complex, and also of a quinone reducing site of a primary dehydrogenase. When pure hydrogenase is assayed in the absence of dithionite, a delay (lag phase) is observed prior to attainment of full activity. The length of this lag period (in minutes) was inversely dependent on ubiquinone concentration, and was greatly reduced (but not eliminated) at saturating ubiquinone levels. These effects were obtained with both Q₁ and MB as electron acceptor, and the lag phases with Q₁ were significantly longer than with MB. Electron acceptor binding to hydrogenase is thus required for reductive activation of hydrogenase during turnover.


[Microbial community structure analyzed by single-strand conformation polymorphism technique in sulfate-reducing reactor].
Analyses of microbial community structure and the relationships between Sulfate-Reducing Bacteria (SRBs) and Acidogenic Bacteria (ABs) in a completely stirred sulfate-reducing reactor were carried out by modified polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) targeted eubacterial 16S ribosomal RNA gene. A total of 13 bands were obtained and 6 of them (A1, A3, A4, A5, A9, A10) were sequenced. The sequences are similar to Leuconostoc mesenteroides (GenBank Access No. AY453065), some uncultured bacteria (AJ318147, AF227834, AJ576427), Ethanologenbacterium (AY434722), Clostridiaceae (AB084627), etc. In order to investigate the SRBs in the reactor,the active sludge was cultured on SRB-selected media and also did SSCP with the compound cultured bacteria. Two new bands appeared, one similar to Bacteroidetes (AB074606) and another similar to Desulfovibrio (Y12254, U42221). The experimental results indicate that the proportion of SRBs in the reactor is probably less than 1.5 percent. But the few SRBs play a very important role during the course of sulfate reduction via cooperation with acidogenic


The first documented case of Candida dubliniensis leptomeningeal disease in an immunocompetent host.
In June 2008, a 25-year-old man presented to the Royal Adelaide Hospital, Australia, with Candida dubliniensis leptomeningeal disease. On examination the patient had focal neurological deficits, both sensory and motor. He tested negative for HIV and had normal T cell subsets. The patient was treated with 6 weeks of intravenous liposomal amphotericin B and oral flucytosine, and had a full recovery.


A diamond nanoneedle array for potential high-throughput intracellular delivery.
A dense diamond nanoneedle array is capable of rapidly and conveniently delivering fluorescent probe and drug molecules to a large number of cells. This simple approach paves the way for potential high-throughput delivery of genes, drugs, and fluorescent probes into cells without endocytosis.


Effect of nickel on red blood cell parameters and on serum vitamin B12, folate and homocysteine concentrations during pregnancy with and without anemia.
Research to date suggests that nickel affects not only the metabolism of vitamin B12 but also folates and thus may affect hematopoiesis processes. The aim of the study was to examine the relationship of nickel (Ni) status to red blood cell (RBC) parameters and serum vitamin B12, folate and homocysteine concentrations in the course of normal pregnancy and in pregnant women with anemia. The study included fifty-three pregnant women recruited to the study from the Lower Silesia region of Poland, 17 % of whom developed anemia. Nickel concentration was determined in urine, whole blood and food samples by atomic absorption spectrometry. At the same time as the food and urine samples were taken, blood was also collected for the determination of RBC parameters and serum vitamin B12, homocysteine and folate concentrations. The median reported Ni intake, and the urinary and whole blood nickel contents for the studied pregnant women for the first trimester were respectively - 162.46 μg/day, 3.98 μg/L and 3.32 μg/L; for the second trimester - 110.48 μg/day, 6.86 μg/L and 1.04 μg/L; and for the third trimester - 132.20 μg/day, 3.41 μg/L and 0.70 μg/L. With regard to Ni concentration in whole blood (p = 0.0204) and in urine (p = 0.0003), the differences in the values for individual trimesters were statistically significant. The whole blood Ni level was significantly higher (9.28 vs 3.62 μg/L, p = 0.0114), while the concentration of homosysteine was significantly lower (4.09 vs 5.04 μmol/L, p = 0.0165) in pregnant women with anemia compared to those without anemia. The whole blood Ni concentration was negatively correlated with almost all RBC parameters in non-anemic pregnant women. Ni status changes with the development of normal pregnancy, and in the case of anemia, an increase in Ni concentration in whole blood is observed. The demonstrated correlations between the Ni status in pregnant women and RBC parameters as well as serum vitamin B12 and folate concentrations suggest that nickel is associated with the methionine-folate cycle, iron homeostasis and bacterial synthesis of vitamin B12 in humans.


The fittest versus the flattest: experimental confirmation of the quasispecies effect with subviral pathogens.
The "survival of the fittest" is the paradigm of Darwinian evolution in which the best-adapted replicators are favored by natural selection. However, at high mutation rates, the fittest organisms are not necessarily the fastest replicators but rather are those that show the greatest robustness against deleterious mutational effects, even at the cost of a low replication rate. This scenario, dubbed the "survival of the flattest", has so far only been shown to operate in digital organisms. We show that "survival of the flattest" can also occur in biological entities by analyzing the outcome of competition between two viroid species coinfecting the same plant. Under optimal growth conditions, a viroid species characterized by fast population growth and genetic homogeneity outcompeted a viroid species with slow population growth and a high degree of variation. In contrast, the slow-growth species was able to outcompete the fast species when the mutation rate was increased. These experimental results were supported by an in silico model of competing viroid quasispecies.