Hyperglycemia attenuates myocardial preconditioning of remifentanil.
Hyperglycemia attenuates cardioprotection by remifentanil-preconditioning in ischemia-reperfusion in vivo in diabetic rats. However, the effects of hyperglycemia in cultured ventricular myocytes remains unknown. Therefore, we examined the in vitro effects of hyperglycemia on hypoxia-reoxygenation (H/R) and cardioprotection from remifentanil-preconditioning in isolated neonatal rat ventricular myocytes (NRVMs), including effects on apoptotic signaling pathways and Ca(2+) homeostasis. NRVMs were cultured in medium with 5.5 mM (normoglycemia) or 25.5 mM glucose for one day. Then, NRVMs in H/R groups were exposed to 1 h of hypoxia and 5 h of reoxygenation with or without remifentanil-preconditioning at 1 μM. Cell viability, apoptosis, and Ca(2+) homeostasis were assessed by MTT assay, caspase-3 assay, confocal microscopy and immunoblots. In normoglycemia, remifentanil-preconditioning improved the viability of cardiomyocytes (P < 0.01) and prevented the increase of caspase-3 activity and Ca(2+) overload after H/R injury (P < 0.05). In addition, decrease in Akt, ERK1/2, and Bcl-2, and the increase in Bax by H/R was attenuated by remifentanil-preconditioning (P < 0.05). However, in hyperglycemia, the viability was partially impaired after H/R but not improved by remifentanil-preconditioning. Apoptotic activity, Ca(2+) concentration, and apoptotic kinases except Akt were not affected by either H/R or remifentanil-preconditioning under hyperglycemia. Akt phosphorylation was decreased by H/R but not restored by remifentanil preconditioning. Remifentanil preconditioning under normoglycemia renders NRVMs resistant to H/R injury by reducing apoptosis and intracellular Ca(2+) concentrations. The mechanism appears to be modulation of apoptotic signaling. However, hyperglycemia mitigates H/R injury in NRVMs, and may reduce the protective effect of remifentanil-preconditioning that may be associated with the Akt pathways.


The effect of chlorine on spores of Clostridium bifermentans, Bacillus subtilis and Bacillus cereus.
The effect of chlorine on the germination, outgrowth, colony formation and structure of spores of Clostridium bifermentans, Bacillus subtilis var. niger and Bacillus cereus was examined. Chlorine decreased heat resistance and slowed or prevented germination and swelling, but spores that did swell were usualy able to elongate to form vegetative cells. Chlorine removed protein from spores, apparently from the coat, and allowed lysozyme to initiate germination. Treatment with other agents that remove spore-coat protein increased the lethal effect of chlorine by as much as 4000-fold, suggesting that coat protein protects spores against chlorine.


Changing prognosis for very low birth weight infants.
Obstetric decisions regarding extremely premature infants are based in part on their long-term prognosis. This review pools data from perinatal center reports to update mortality and morbidity trends for each subgroup of very low birth weight infants. Throughout the last 10 years, there has been steady and statistically significant improvement in neonatal mortality rates among inborn very low weight infants (1500 g or less). The most substantial improvement of the 1980s over the late 1970s is in the 750-1000-g birth weight group, in which today's infants have about a 70% chance of surviving if they have access to neonatal intensive care. Mortality in infants born weighing less than 750 g is still very high; overall about two-thirds die, but results are highly variable across centers, with several centers reporting 50-70% survival. The rate of serious long-term disability increases with decreasing birth weight, but within each birth weight group, the proportion of survivors who have serious handicaps has not changed significantly since the introduction of neonatal intensive care. For infants born between 1975-1985, 26% of surviving infants with birth weights below 800 g, 17% of survivors with birth weights between 750-1000 g, and 11% of survivors with birth weights between 1000-1500 g have major handicaps at 1 or 2 years of age. Because many very sick newborns who previously would have died are now surviving, an increasing rate of handicap might have been expected.


Goal attainment in a randomized controlled trial of rehabilitation after myocardial infarction.
Goal setting is an established strategy in health behavior change programs although its usefulness remains uncertain. The authors investigate the validity of attainment of a patient-identified goal as an outcome measure in cardiac rehabilitation after myocardial infarction. On entry into a randomized controlled trial of cardiac rehabilitation after an acute myocardial infarction, patients identified one activity that, if and when attained, would reflect their perception of a successful recovery. Patients reported whether they had attained their goal and the time of goal attainment. This was then related to trial outcomes that included generic and specific health-related quality of life and percent predicted exercise tolerance. Goals identified by 180 of the 201 (89.6%) patients, were attained by 51.5% at 8 weeks and by 86.5% at 12 months. At the end of the 8-week intervention, there was a substantial trend for fewer rehabilitation than usual care patients to have attained their identified goal (P < 0.06), although rehabilitation patients demonstrated greater improvement in specific health-related quality of life and exercise tolerance than usual care patients (P < 0.05). Among patients who identified a recreational physical activity goal (26.7%), significantly fewer (P < 0.007) rehabilitation than usual care patients had attained their goal at the end of the intervention with no differences in improvement in outcomes. Although improvement in outcomes was greater in rehabilitation patients than usual care patients at 8 weeks, goal attainment, particularly for the recreational physical activity goal, was greater among usual care patients. The validity of self-identified activity goal attainment as a measure of the efficacy of cardiac rehabilitation is unclear and might give misleading results.


Monochorionic twin fetuses showing a reversal of donor-recipient phenotypes in severe twin-twin transfusion syndrome without oligo-polyhydramnios sequence.
Antenatal sonographic diagnosis of twin-twin transfusion syndrome (TTTS) is based on findings of a twin oligo-polyhydramnios sequence (TOPS) observed in monochorionic twin fetuses. However, TTTS can develop without a significant characteristic intertwin discordance in the amniotic fluid volumes. We report an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other. Based on sonographic findings, it is considered that the recipient twin became the donor later in gestation, and vice versa. It is concluded therefore that even in the absence of TOPS, the possibility of severe TTTS with a suspected reversal of donor-recipient phenotypes during pregnancy should not be excluded, and serial Doppler studies including the measurement of the middle cerebral artery peak systolic velocity should be routinely performed even in seemingly uncomplicated monochorionic twin fetuses without TOPS.


Pulmonary function and high-resolution CT findings five years after disease onset in patients with Wegener's granulomatosis.
Although pulmonary involvement is common in Wegener's granulomatosis (WG), little is known about the pulmonary outcome. We evaluated the relationship between clinical disease characteristics and pulmonary function and high-resolution computed tomography (HRCT) findings after disease duration of 5 years. A pulmonary function test (PFT) and pulmonary HRCT were performed in 41 patients from a population-based register of WG. Clinical predictors for abnormal PFT and HRCT were tested by logistic regression. Previous WG-related lung involvement (PLI) had occurred in 80% of patients, but only 24% of patients still reported pulmonary symptoms at the research visit. One-third of patients had abnormal PFT findings, with reduced alveolar diffusion by KCO (transfer coefficient) being most common (24%). The number of PLI episodes was associated with reduced KCO and reduced FEV1% (forced expiratory volume in 1 s as a percentage of forced vital capacity) (overall presence 10%). Reduced KCO was also associated with disease duration. Reduced total lung capacity (TLC) (overall presence 8%) was only related to prior WG-related lung nodules. Pulmonary HRCT was abnormal in 80%, but with more severe abnormalities in only 30%. Pleural thickening and parenchymal bands were associated with PLI. None of the treatment variables was associated with the PFT or HRCT findings. Five years after disease onset a quarter of the WG patients reported pulmonary symptoms, had severe abnormalities on HRCT, and abnormal PFT. The correlation between these abnormalities was poor, but the number of pulmonary involvements was a risk factor for reduced gas diffusion, obstructive lung disease, parenchymal bands, and pleural thickening. Treatment variables had no discernible negative pulmonary effects.


Relationship between the number and type of alcohol outlets and mortality due to liver cirrhosis and traffic accidents.
The aim of the study was to determine the effect on liver cirrhosis and driver and motorcyclist mortality of changing the alcohol outlet rates in New South Wales relative to the adjacent control State of Victoria. A longitudinal study design with a six year before period (1968-1973) and a nine year after period (1974-1982) was used. A 10.5% relative increase in the total outlet rate for New South Wales during the after period was associated with significant increases in liver cirrhosis mortality (males + 22.1%, females + 17.7%) and driver and motorcyclist mortality (males + 19.8%, females + 18.9%) in comparison to the control state. The analyses also indicated that the increases in the dependent variables were apparently due to the higher outlet rates for restaurants and stores rather than for hotels and taverns. Attention is drawn to a number of limitations of the study design.


Malignant melanoma: a clinicopathologic study of 22 cases.
To provide updated clinicopathologic information on malignant melanoma, we studied 22 cases of malignant melanoma registered at Tri-Service General Hospital, Taiwan from 1983 to 1988. About 60% (13/22) of the patients had a tumor thickness of more than 2.5 mm and 45% (10/22) of the patients of over 4 mm. No patient had a thin melanoma (tumor thickness less than 0.76mm) when first diagnosed. Forty-four percent of the patients, which was twice as many as those (22%) in a previous study done at the same hospital, were classified as stage III. Eleven patients (50%) had acral lentiginous melanoma, the most common type of malignant melanoma in Orientals as previously reported. The cumulative survival rate was 59% and 39% at 3 years and 5 years respectively. The age primary sites, clinical stage and tumor thickness were retrospectively evaluated. Due to the small sample size, the accuracy of the statistical analysis of survival is questionable. An extensive island-wide multicenter epidemiologic study is mandatory to clarify this issue.


Diagnostic Value and Prognostic Use of Presepsin Versus Procalcitonin in Sepsis.
Sepsis is a medical problem beyond belief despite the use of modern antibiotics and frequently updated guidelines on resuscitation therapies. It is at this crucial juncture where inflammatory biomarkers have been providing an incredible and easy way to detect sepsis. Various biomarkers have been used over the past decades in medicine to evaluate sepsis, each one better than the previous and having its own pros and cons. In this study, we assess the role of presepsin, which is a CD-14 polypeptide, and procalcitonin which has for some time been the inflammatory marker of choice in sepsis. This is the first study of presepsin as a sepsis biomarker in Indian adults. A prospective observational study was conducted in 48 patients who were diagnosed to have sepsis either on admission to the hospital or during their stay in hospital according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) guidelines during the period from October 2015 to January 2017, after fulfilling all inclusion and exclusion criteria. Efficacy of both inflammatory markers was studied from blood drawn from the patient at the same time, with the same prick. A total of 48 patients were included in this study. The superiority of presepsin over procalcitonin was evident with presepsin having a sensitivity of 46.2 and specificity of 100 and procalcitonin having a sensitivity of 46.2 and specificity of 31.8. The P value of the presepsin results was significant at <0.001. Along with it, presepsin also proved to be a very reliable marker for 28-day mortality with all 12 patients in the presepsin positive group expiring (P value: <0.001). Receiver operating characteristic (ROC) curve was plotted to try and define an optimal normal value for presepsin in an Indian population and the value calculated was 93.71 with a sensitivity of 65.4 and a specificity of 68.2. This study shows the superiority of presepsin over procalcitonin as it has much better specificity and a similar sensitivity than procalcitonin and is a better indicator of 28-day mortality. The new cut off that we have postulated here for presepsin improves the efficiency of the inflammatory marker by increasing its sensitivity at the cost of decreasing its specificity slightly.


An Analysis of Risk Factors for the Development of Acneiform Eruptions in Patients on Monoclonal Antibody Epidermal Growth Factor Receptor Inhibitors.
Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, P = .027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients.


Analysis of homothallic Saccharomyces cerevisiae strain mating during must fermentation.
Genetic instability and genome renewal may cause loss of heterozygosity (LOH) in homothallic wine yeasts (Saccharomyces cerevisiae), leading to the elimination of the recessive lethal or deleterious alleles that decrease yeast fitness. LOH was not detected in genetically stable wine yeasts during must fermentation. However, after sporulation, the heterozygosity of the new yeast population decreased during must fermentation. The frequency of mating between just-germinated haploid cells from different tetrads was very low, and the mating of haploid cells from the same ascus was favored because of the physical proximity. Also, mating restriction between haploid cells from the same ascus was found, leading to a very low frequency of self spore clone mating. This mating restriction slowed down the LOH process of the yeast population, maintaining the heterozygote frequency higher than would be expected assuming a fully random mating of the haploid yeasts or according to the Mortimer genome renewal proposal. The observed LOH occurs because of the linkage of the locus MAT to the chromosome III centromere, without the necessity for self spore clone mating or the high frequency of gene conversion and rapid asymmetric LOH observed in genetically unstable yeasts. This phenomenon is enough in itself to explain the high level of homozygosis found in natural populations of wine yeasts. The LOH process for centromere-linked markers would be slower than that for the nonlinked markers, because the linkage decreases the frequency of newly originated heterozygous yeasts after each round of sporulation and mating. This phenomenon is interesting in yeast evolution and may cause important sudden phenotype changes in genetically stable wine yeasts.


Developing Asthma-Friendly Childcare Centers with Online Training and Evaluation.
In 2011, the Florida Asthma Coalition (FAC) began offering its Asthma-Friendly Childcare Center (AFCC) training online. This course teaches childcare center employees the fundamentals of effective asthma management. It covers basic asthma physiology, ways to recognize asthma attacks, techniques to help children experiencing attacks, and strategies to create healthy environments for asthmatics. A team of health services researchers evaluated both years of the online training. Evaluators used a quasi-experimental design with pretest, posttest, and follow-up assessment. Questions measured knowledge gain and retention, user satisfaction, and implementation of management strategies. Over 650 people from nearly all 67 Florida counties took AFCC training online between 2011 and 2013. Test scores improved by a minimum of 11% points in all program years evaluated. Gains in both knowledge and confidence were substantial and highly significant across years. While individual trainees did forget some content on follow-up, they seemed to retain the specific messages most relevant for their own workplaces. Most trainees also planned to implement multiple management strategies recommended by the training. A large majority of participants rated the training as excellent on all quality metrics, including relevance of content and time efficiency of the online format. Nearly all respondents perceived the training as useful for both providing improved care and fulfilling licensure or certification requirements. Many participants also indicated that their centers would pursue formal certification as AFCCs via the program offered by FAC. The online AFCC course performed strongly in its first years, yielding both high participant satisfaction and substantial improvement in workplace asthma management activity. This training holds promise for introducing and improving multidimensional asthma management strategies at childcare facilities nationwide.


A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference.
Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities. The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight-independent effects of KBP-089 using a weight-matched group. Rats fed a high-fat diet were treated, s.c., with KBP-089 0.625, 1.25, 2.5 μg·kg-1 or vehicle. KB-089 induced in a dose-dependent and sustained weight loss (~17% by 2.5 μg·kg-1 ). Moreover, KBP-089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP-089 improved glucose homeostasis through improved insulin action. To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP-089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP-089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle. The novel DACRA, KBP-089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet-induced weight loss.


"Demonstration" vs. "designation" of measurement competence: the need to link accreditation to metrology.
Formal acceptance of the results of chemical laboratories is increasingly organized through a) accreditation of measuring laboratories nationally and b) mutual recognition of accreditation internationally (through formal Multilateral Recognition Agreements, MRAs). However, real comparability of results of measurements is realized by using common (internationally agreed) measurement scales which make these results traceable to this scale, i.e. "traceable" to the same (internationally agreed) value of the unit of that scale. In addition, the criterion against which the evaluation is done, should be "external" to the measurement laboratories which are being evaluated. This is realized in IRMM's International Measurement Evaluation Programme (IMEP) where evaluation is performed against values which are anchored using "metrology", the science of measurement with its own rules, which offers a sound foundation for measurement in all scientific disciplines. It is argued in this paper that the demonstration of measurement capability against values on such scales provides a result-oriented rather than a procedure-oriented evaluation. Thus, competence can be "demonstrated" rather than just "designated" and this can be shown to both customers and regulators. It inspires more confidence.


Transition of Renal Patients Using AlloSure Into Community Kidney Care (TRACK): Protocol for Long-Term Allograft Surveillance in Renal Transplant Recipients.
Patients with end-stage kidney disease require complex and expensive medical management. Kidney transplantation remains the treatment of choice for end-stage kidney disease and is considered superior to all other modalities of renal replacement therapy or dialysis. However, access to kidney transplant is limited by critical supply and demand, making it extremely important to ensure longevity of transplanted kidneys. This is prevented through lifelong immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury are undertaken through an armamentarium of screening modalities. Posttransplant surveillance for kidney function and injury remains key to follow-up care. While kidney function, quantified by estimated glomerular filtration rate and serum creatinine, and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection posttransplant, they have recently been demonstrated to be inferior in performance to that of AlloSure (CareDx Inc, Brisbane, CA) circulating donor-derived, cell-free DNA (dd-cfDNA). The outcomes and methods of monitoring renal transplant recipients posttransplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure dd-cfDNA in an actively managed protocol, assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology. The study protocol will acquire data from a phase IV observational trial to assess a cohort of renal transplant patients managed using AlloSure dd-cfDNA and patient care managers versus 1000 propensity-matched historic controls using United Network for Organ Sharing U.S. Scientific Registry of Transplant Recipients data. Data will be managed in a centralized electronic data server. The primary outcome will be superior allograft survival, as a composite of return to dialysis, retransplant, death due to allograft failure, and death with a functional graft (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in estimated glomerular filtration rate and immune activity through development of donor-specific antibodies. The total sample is anticipated to be 3500 (2500 patients managed with AlloSure dd-cfDNA and 1000 propensity-matched controls). Active enrollment began in November 2020. Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior. PRR1-10.2196/25941.


Wetting properties of porous high temperature polymer electrolyte fuel cells materials with phosphoric acid.
Wetting properties of phosphoric acid in porous materials of high temperature fuel cells (HT-PEFC), operating at around 160 °C, are important for cell performance and durability, but the underlying wetting parameters have been unknown so far. Therefore, the influence of phosphoric acid temperature and concentration on the wetting behavior of porous HT-PEFC materials is investigated. The acid filling of gas diffusion and catalyst layers as function of capillary pressure is monitored with X-ray tomographic microscopy under the well defined conditions of an ex situ set-up at temperatures up to 160 °C. For the wetting of gas diffusion layers, with pore sizes in the order of few 10 μm, two opposing trends are shown. With increasing phosphoric acid concentration, less capillary pressure is required, while with increasing temperatures, higher capillary pressures are needed for filling up to a given saturation. The same trends are also found for the contact angle of phosphoric acid on PTFE. A higher contact angle is observed with increasing temperature while increasing the phosphoric acid concentration decreases the contact angle. As both trends are of a similar order of magnitude, the wetting behavior of concentrated (113 wt%) phosphoric acid at 160 °C is astonishingly similar to the wetting behavior of water at room temperature. Another important property for HT-PEFC operation is the filling of cracks in the catalyst layer, which have widths up to 100 μm. For large cracks (>60 μm), a capillary pressure of only 15 mbar was deduced from the measurement, increasing to 30 mbar for cracks between 20 and 60 μm. This, for the first time, allows for assessing the membrane phosphoric acid pressure during fuel cell operation. This can guide the development of improved porous materials for HT-PEFC.


Yuanansuchus maopingchangensis sp. nov., the second capitosauroid temnospondyl from the Middle Triassic Badong Formation of Yuanan, Hubei, China.
A second species of Yuanansuchus, Y. maopingchangensis, is erected for new temnospondyl material from the Maopingchang site, Yuanan County, Hubei Province, China. These specimens are from the same horizon that produced Y. laticeps, the type species. Y. maopingchangensis shares the following features with Y. laticeps: postorbital portion of skull occupied more than 1/3 of skull length; tabular horn directed laterally; lateral line sulci continuous, well impressed; supraorbital sensory canal enters lacrimal; preorbital projection of jugal less than half length of snout; and vomerine plate short. However, Y. maopingchangensis differs from Y. laticeps in having an elongated skull, frontal extending posteriorly to the level of the posterior orbital margin, closed otic fenestra, cultriform process of parasphenoid extending to the level of the anterior margin of the interpterygoid vacuities, and absence of fodina vomeralis. Analysis of a new capitosaur phylogenetic data matrix, containing 56 characters and 29 species, confirms that the two species from Yuanan are sister taxa and that Capitosauroidea can be divided into two major clades: one including Parotosuchus, Eryosuchus, Calmasuchus and Cherninia, and another including Mastodonsaurus, Yuanansuchus, Stanocephalosaurus, Procyclotosaurus, Paracyclotosaurus, Antarctosuchus, Eocyclotosaurus, Quasicyclotosaurus, Tatrasuchus and Cyclotosaurus.


[Functional vision assessment in children with low vision from two to six years of age - a comparative study].
The Functional Vision Assessment (AVIF-2 to 6 years)'s capacity to differentiate visual ability levels in children with low vision was analyzed. The AVIF-2 to 6 years was created at the Infantile Low Vision Sector from São Geraldo Hospital, Brazil. After a debate among professionals from different areas regarding the appropriateness of the test items, AVIF-2 to 6 years was applied to 40 children aged from 2 to 6 years; twenty children with low vision (Group 1) and twenty without it (Group 2) were assessed. Group 1 was recruited from the Infantile Low Vision Sector from São Geraldo Hospital. Group 2 comprised children from two different public day care centers and children were matched by age, gender and social level with group 1. Seven domains were studied: visual fixation, visual following, visual field confrontation, eye-hand coordination and surrounding locomotion, contrast vision and color vision discrimination. Group 1 children were submitted to a complete ophthalmologic exam and group 2 to ophthalmologic screening. Children with low vision and neurologic disease were excluded. Comparative analyzes were performed for both groups and for distinct subgroups classified by age (24 to 35 months, 36 to 59 months and 60 to 78 months) and by visual acuity subgroups (<1.0 logMAR and ≥1.0 logMAR). The scores at total AVIF-2 to 6 years and its domains were statistically significant (p<0.05), except for the contrast vision and color vision discrimination domains. The total AVIF- 2 to 6 years median was lower for group 1 at the three interval ages. AVIF- 2 to 6 years can discriminate different levels of functional vision of low vision children, however the authors emphasize that although the results are encouraging, further studies shall be done until the test is ready for clinical use.


Ballistic Transport and Exchange Interaction in InAs Nanowire Quantum Point Contacts.
One-dimensional ballistic transport is demonstrated for a high-mobility InAs nanowire device. Unlike conventional quantum point contacts (QPCs) created in a two-dimensional electron gas, the nanowire QPCs represent one-dimensional constrictions formed inside a quasi-one-dimensional conductor. For each QPC, the local subband occupation can be controlled individually between zero and up to six degenerate modes. At large out-of-plane magnetic fields Landau quantization and Zeeman splitting emerge and comprehensive voltage bias spectroscopy is performed. Confinement-induced quenching of the orbital motion gives rise to significantly modified subband-dependent Landé g factors. A pronounced g factor enhancement related to Coulomb exchange interaction is reported. Many-body effects of that kind also manifest in the observation of the 0.7·2e(2)/h conductance anomaly, commonly found in planar devices.


Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery.
The primary objective of the study was to develop a pH and transit time controlled sigmoidal release polymeric matrix for colon-specific delivery of indomethacin. Tablet matrices were prepared using a combination of hydrophilic polymers (polycarbophil or carbopol) having pH sensitive swelling properties with hydrophobic polymer ethyl cellulose. The prepared matrices were characterized for physical properties and in vitro release kinetics. The presence of ethyl cellulose in a hydrophilic polymer matrix resulted in a sigmoidal in vitro drug release pattern with negligible to very low drug release in the initial phase (0-6 h) followed by controlled release for 14-16 h. The retardation in initial release can be attributed to the presence of ethyl cellulose that reduced swelling of hydrophilic polymer(s) while in the later portion, polymer relaxation at alkaline pH due to the ionization of acrylic acid units on carbopol and polycarbophil resulted in enhanced drug release. Thus, a sigmoidal release pattern was obtained that could be ideal for colonic delivery of indomethacin in the potential treatment of colon cancer.


Defining the determinants of endurance running performance in the heat.
In cool conditions, physiologic markers accurately predict endurance performance, but it is unclear whether thermal strain and perceived thermal strain modify the strength of these relationships. This study examined the relationships between traditional determinants of endurance performance and time to complete a 5-km time trial in the heat. Seventeen club runners completed graded exercise tests (GXT) in hot (GXTHOT; 32°C, 60% RH, 27.2°C WBGT) and cool conditions (GXTCOOL; 13°C, 50% RH, 9.3°C WBGT) to determine maximal oxygen uptake (V̇O2max), running economy (RE), velocity at V̇O2max (vV̇O2max), and running speeds corresponding to the lactate threshold (LT, 2 mmol.l-1) and lactate turnpoint (LTP, 4 mmol.l-1). Simultaneous multiple linear regression was used to predict 5 km time, using these determinants, indicating neither GXTHOT (R2 = 0.72) nor GXTCOOL (R2 = 0.86) predicted performance in the heat as strongly has previously been reported in cool conditions. vV̇O2max was the strongest individual predictor of performance, both when assessed in GXTHOT (r = -0.83) and GXTCOOL (r = -0.90). The GXTs revealed the following correlations for individual predictors in GXTHOT; V̇O2maxr = -0.7, RE r = 0.36, LT r = -0.77, LTP r = -0.78 and in GXTCOOL; V̇O2maxr = -0.67, RE r = 0.62, LT r = -0.79, LTP r = -0.8. These data indicate (i) GXTHOT does not predict 5 km running performance in the heat as strongly as a GXTCOOL, (ii) as in cool conditions, vV̇O2max may best predict running performance in the heat.


A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma.
HCC is the leading cause of cancer in chronic liver disease. A growing body of experimental mouse models supports the notion that gut-resident and liver-resident microbes control hepatic immune responses and, thereby, crucially contribute to liver tumorigenesis. However, a comprehensive characterization of the intestinal microbiome in fueling the transition from chronic liver disease to HCC in humans is currently missing. Here, we profiled the fecal, blood, and liver tissue microbiome of patients with HCC by 16S rRNA sequencing and compared profiles to nonmalignant cirrhotic and noncirrhotic NAFLD patients. We report a distinct bacterial profile, defined from 16S rRNA gene sequences, with reduced α-and β-diversity in the feces of patients with HCC and cirrhosis compared to NAFLD. Patients with HCC and cirrhosis exhibited an increased proportion of fecal bacterial gene signatures in the blood and liver compared to NAFLD. Differential analysis of the relative abundance of bacterial genera identified an increased abundance of Ruminococcaceae and Bacteroidaceae in blood and liver tissue from both HCC and cirrhosis patients compared to NAFLD. Fecal samples from cirrhosis and HCC patients both showed a reduced abundance for several taxa, including short-chain fatty acid-producing genera, such as Blautia and Agathobacter. Using paired 16S rRNA and transcriptome sequencing, we identified a direct association between gut bacterial genus abundance and host transcriptome response within the liver tissue. Our study indicates perturbations of the intestinal and liver-resident microbiome as a critical determinant of patients with cirrhosis and HCC.


Cloning and restriction mapping of human HBV genome serotype adr.
A Bam HI cleaved 3.2 Kb fragment from the HBV adr genome was cloned in E. coli using pBR322 as vector. Sixteen restriction sites from the action of Bam HI, Hind III, Bgl I, Bgl II, Ava I, Hinc II, Sph I, Xba I, Xho I and Sst II were determined and mapped. No cleavage sites were found for Eco RI, Pst I, Sma I, Hpa I, Kpn I, Pvu II and Sst I. The restriction map for HBV adr is significantly different from those reported for the subtypes adw, ayw and adyw.


BPEI-Induced Delocalization of PBP4 Potentiates β-Lactams against MRSA.
With its high morbidity rate and increasing resistance to treatment, methicillin-resistant Staphylococcus aureus (MRSA) is a grave concern in the medical field. In methicillin-susceptible strains, β-lactam antibiotics disable the penicillin binding proteins (PBPs) that cross-link the bacterial cell wall. However, methicillin-resistant strains have PBP2a and PBP4, which continue enzymatic activity in the presence of β-lactam antibiotics. The activity of PBP2a and PBP4 is linked to the presence of wall teichoic acid (WTA); thus, WTA has emerged as a target for antibiotic drug discovery. In this work, we disable WTA in situ using its anionic phosphodiester backbone to attract cationic branched polyethylenimine (BPEI). Data show that BPEI removes β-lactam resistance in common MRSA strains and clinical isolates. Fluorescence microscopy was used to investigate this mechanism of action. The results indicate that BPEI prevents the localization of PBP4 to the cell division septum, thereby changing the cellular morphology and inhibiting cell division. Although PBP4 is not required for septum formation, proper cell division and morphology require WTA; BPEI prevents this essential function. The combination of BPEI and β-lactams is bactericidal and synergistic. Because BPEI allows us to study the role of WTA in the cell wall without genetic mutation or altered translocation of biomolecules and/or their precursors, this approach can help revise existing paradigms regarding the role of WTA in prokaryotic biochemistry at every growth stage.


Transient surfactant protein B deficiency in a term infant with severe respiratory failure.
A 38-day-old male infant with persistent pulmonary hypertension and respiratory failure since birth was found to have a complete absence of surfactant protein B (SP-B) along with an aberrant form of SP-C in his tracheal aspirate fluid, findings consistent with the diagnosis of hereditary SP-B deficiency. Surprisingly, SP-B and SP-B messenger ribonucleic acid were present in lung biopsy tissue. However, DNA sequence analysis demonstrated a point mutation in exon 5 of one of the SP-B gene alleles. The infant's mother was found to be a carrier of this mutation. The infant's other SP-B allele did not differ from the published DNA sequence for the SP-B gene. We conclude that this patient had a transient deficiency of SP-B, in contrast to that of previously described infants with irreversible respiratory failure caused by hereditary SP-B deficiency. We recommend that infants with suspected SP-B deficiency have serial analysis of tracheal fluid samples for both SP-B and SP-C before lung biopsy, along with genetic analysis for the known SP-B mutations. We speculate that the new mutation found in one of this patient's SP-B genes was in part responsible for the transient deficiency of SP-B.


Radiation-induced redox alteration in the mouse brain.
Time courses of the redox status in the brains of mice after X-ray or carbon-ion beam irradiation were observed by magnetic resonance redox imaging (MRRI). The relationship between radiation-induced oxidative stress on the cerebral nervous system and the redox status in the brain was discussed. The mice were irradiated by 8-Gy X-ray or carbon-ion beam (C-beam) on their head under anesthesia. C-beam irradiation was performed at HIMAC (Heavy-Ion Medical Accelerator in Chiba, NIRS/QST, Chiba, Japan). MRRI measurements using a blood-brain-barrier-permeable nitroxyl contrast agent, MCP or TEMPOL, were performed using 7-T scanner at several different times, i.e., 5-10 h, 1, 2, 4, and 8 day(s) after irradiation. Decay rates of the nitroxyl-enhanced T1-weighted MR signals in the brains were estimated from MRRI data sets, and variation in the decay rates after irradiation was assessed. The variation in decay rates of MCP and TEMPOL after X-ray or C-beam irradiation was similar, but different variation patterns were observed between X-ray and C-beam. The apparent decay rate of both MCP and TEMPOL decreased due to the temporal reduction of blood flow in the brain several hours after X-ray and/or C-beam irradiation. After decreasing, the apparent decay rates of nitroxyl radicals in the brain gradually increased during the following days after X-ray irradiation or rapidly increased 1 day after C-beam irradiation. The sequential increase in nitroxyl decay rates may have been due to the oxidative atmosphere in the tissue due to ROS generation. X-ray and C-beam irradiation resulted in different redox responses, which may have been due to time-varying oxidative stress/injury, in the mouse brain. The C-beam irradiation effects were more acute and larger than those of X-ray irradiation.


Diet-quality scores and the risk of type 2 diabetes in men.
To 1) compare associations of diet-quality scores, which were inversely associated with cardiovascular disease, with incident type 2 diabetes and 2) test for differences in absolute-risk reduction across various strata. Men from the Health Professionals Follow-Up Study, who were initially free of type 2 diabetes, cardiovascular disease, or cancer (n = 41,615), were followed for ≤ 20 years. The Healthy Eating Index (HEI) 2005, the alternative HEI (aHEI) the Recommended Food Score, the alternative Mediterranean Diet (aMED) Score, and the Dietary Approaches to Stop Hypertension (DASH) Score were calculated from food-frequency questionnaires. Cox proportional hazard models with time-varying covariates were used to assess risk by quintiles and continuous intervals. There were 2,795 incident cases of type 2 diabetes. After multivariate adjustment, the aHEI, aMED, and DASH scores were significantly associated with reduced risk. A 1-SD increase was associated with 9-13% reduced risk (P < 0.01), and the DASH score was associated with lower risk independent of other scores. These scores were associated with lower absolute risk among those who were overweight or obese compared with normal weight (P for interaction < 0.01). Several diet-quality scores were associated with a lower risk of type 2 diabetes and reflect a common dietary pattern characterized by high intakes of plant-based foods such as whole grains; moderate alcohol; and low intakes of red and processed meat, sodium, sugar-sweetened beverages, and trans fat. High-quality diets may yield the greatest reduction in diabetes cases when followed by those with a high BMI.


Mechanisms of nitrogen retention in forest ecosystems: a field experiment.
Intensive forest management led to elevated losses of nitrogen from a recently harvested loblolly pine plantation in North Carolina. Measurements of nitrogen-15 retention in the field demonstrated that microbial uptake of nitrogen during the decomposition of residual organic material was the most important process retaining nitrogen. Management practices that remove this material cause increased losses of nitrogen to aquatic ecosystems and the atmosphere.


Shock waves generated by toroidal bubble collapse are imperative for kidney stone dusting during Holmium:YAG laser lithotripsy.
Holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy (LL) has been the treatment of choice for kidney stone disease for more than two decades, yet the mechanisms of action are not completely clear. Besides photothermal ablation, recent evidence suggests that cavitation bubble collapse is pivotal in kidney stone dusting when the Ho:YAG laser operates at low pulse energy (Ep) and high frequency (F). In this work, we perform a comprehensive series of experiments and model-based simulations to dissect the complex physical processes in LL. Under clinically relevant dusting settings (Ep = 0.2 J, F = 20 Hz), our results suggest that majority of the irradiated laser energy (>90 %) is dissipated by heat generation in the fluid surrounding the fiber tip and the irradiated stone surface, while only about 1 % may be consumed for photothermal ablation, and less than 0.7 % is converted into the potential energy at the maximum bubble expansion. We reveal that photothermal ablation is confined locally to the laser irradiation spot, whereas cavitation erosion is most pronounced at a fiber tip-stone surface distance about 0.5 mm where multi foci ring-like damage outside the thermal ablation zone is observed. The cavitation erosion is caused by the progressively intensified collapse of jet-induced toroidal bubble near the stone surface (<100 μm), as a result of Raleigh-Taylor and Richtmyer-Meshkov instabilities. The ensuing shock wave-stone interaction and resultant leaky Rayleigh waves on the stone surface may lead to dynamic fatigue and superficial material removal under repeated bombardments of toroidal bubble collapses during dusting procedures in LL.


The association between conventional antidepressants and the metabolic syndrome: a review of the evidence and clinical implications.
Major depressive disorder is a prevalent recurrent medical syndrome associated with inter-episodic dysfunction. The metabolic syndrome is comprised of several established risk factors for cardiovascular disease (i.e. abdominal obesity, dyslipidaemia, dysglycaemia and hypertension). The criterion items of the metabolic syndrome collectively represent a multi-dimensional risk factor for cardiovascular disease and type 2 diabetes mellitus. Extant evidence indicates that both major depressive disorder and the metabolic syndrome, albeit distinct, often co-occur and are possibly subserved by overlapping pathophysiology and causative mechanisms. Conventional antidepressants exert variable effects on constituent elements of the metabolic syndrome, inviting the need for careful consideration prior to treatment selection and sequencing. Initiating and maintaining antidepressant therapy should include routine surveillance for clinical and/or biochemical evidence suggestive of the metabolic syndrome.


ClusterMap: compare multiple single cell RNA-Seq datasets across different experimental conditions.
Single cell RNA-Seq (scRNA-Seq) facilitates the characterization of cell type heterogeneity and developmental processes. Further study of single cell profiles across different conditions enables the understanding of biological processes and underlying mechanisms at the sub-population level. However, developing proper methodology to compare multiple scRNA-Seq datasets remains challenging. We have developed ClusterMap, a systematic method and workflow to facilitate the comparison of scRNA-seq profiles across distinct biological contexts. Using hierarchical clustering of the marker genes of each sub-group, ClusterMap matches the sub-types of cells across different samples and provides 'similarity' as a metric to quantify the quality of the match. We introduce a purity tree cut method designed specifically for this matching problem. We use Circos plot and regrouping method to visualize the results concisely. Furthermore, we propose a new metric 'separability' to summarize sub-population changes among all sample pairs. In the case studies, we demonstrate that ClusterMap has the ability to provide us further insight into the different molecular mechanisms of cellular sub-populations across different conditions. ClusterMap is implemented in R and available at https://github.com/xgaoo/ClusterMap. Supplementary data are available at Bioinformatics online.


Development of a coarse-grained water forcefield via multistate iterative Boltzmann inversion.
A coarse-grained water model is developed using multistate iterative Boltzmann inversion. Following previous work, the k-means algorithm is used to dynamically map multiple water molecules to a single coarse-grained bead, allowing the use of structure-based coarse-graining methods. The model is derived to match the bulk and interfacial properties of liquid water and improves upon previous work that used single state iterative Boltzmann inversion. The model accurately reproduces the density and structural correlations of water at 305 K and 1.0 atm, stability of a liquid droplet at 305 K, and shows little tendency to crystallize at physiological conditions. This work also illustrates several advantages of using multistate iterative Boltzmann inversion for deriving generally applicable coarse-grained forcefields.


Brevundimonas fluminis sp. nov., isolated from a river.
A Gram-stain-negative, rod-shaped, motile, facultatively aerobic and ivory-pigmented bacterium (designated strain LA-55T) was isolated from a river in the Republic of Korea. On the basis of 16S rRNA gene sequencing, strain LA-55T clustered with species of the genus Brevundimonas and was closely related to B revundimonas kwangchunensis KSL-102T (97.3 %), B revundimonas aurantiaca DSM 4731T (97.1 %), B revundimonas albigilva NHI-13T (97.0 %), B revundimonas balnearis FDRGB2bT (97.0 %) and Brevundimonas aveniformis DSM 17977T (97.0 %). The average nucleotide identity value between strain LA-55T and its closest-related strain was 74.1 %, indicating that strain LA-55T represents a novel species of the genus Brevundimonas. Growth occurred at 15-40 °C on Reasoner's 2A medium in the presence of 0-2 % NaCl (w/v) and at pH 6.0-8.0. The genomic DNA G+C content was 70.5 mol% and ubiquinone 10 (Q-10) was the major respiratory quinone. The major cellular fatty acids (>5 %) were C1 8 :1 ω6c and/or C1 8 :1 ω7c (summed feature 8), C16 : 0, C1 6 :1 ω6c and/or C1 6 :1 ω7c (summed feature 3) and C18 : 1 ω7c 11-methyl. The polar lipids consisted of phosphatidylglycerol, 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-α-d-glucopyranuronosyl]glycerol, 1,2-di-O-acyl-3-O-α-d-glucopyranuronosyl glycerol, unidentified aminolipid, unidentified phosphoglycolipid and unidentified lipids. Physiological and biochemical characteristics indicated that strain LA-55T represents a novel species of the genus Brevundimonas, for which the name Brevundimonas fluminis sp. nov. is proposed. The type strain is LA-55T (=KACC 19639T=LMG 30850T).


Characterization of the spatiotemporal evolution of ultrashort optical pulses using FROG holography.
We propose holographically recorded frequency-resolved-optical-gating (FROG) measurement for probing the evolution of ultrashort optical pulses at multiple locations. As a proof-of-concept demonstration of our method, we record holographic FROG traces at five axial locations as we traverse through the focus of an objective lens along its axis using BaTiO(3) micro-cluster as the nonlinear medium and retrieve the amplitude and phase of the ultrashort pulse at each location. Moreover, the group delay of the pulse retrieved numerically using FROG holography is used to compute the separation between the five locations which agree well with the experimentally measured distances. This study suggests that FROG holography can be used to remove the ambiguity regarding arbitrary constant phase and arbitrary temporal shift in the retrieved pulse at each location (upto to an overall constant phase).


beta-Adrenoceptor agonists-induced desensitization in rat trachea.
The development and the characteristics of beta-adrenoceptor agonists-induced desensitization in rat trachea were studied. Tracheal strips were contracted with carbachol and cumulative concentration-response curves for various beta-adrenoceptor agonists were constructed before and after 30-min incubation either with the same beta-adrenoceptor agonist or with another beta-adrenoceptor agonist. Some problems of the in vitro desensitization in rat trachea were also considered.


[Abdominal non-Hodgkin's lymphoma in children].
Study of the clinical manifestations and the results of treatment of abdominal lymphomas in 58 children showed that the poor results of therapy were due first of all to the high proportion (67.2%) of generalized forms by the time of their detection. Among the patients who were under observation, the 3-5-year survival was 41.3%. Late recognition of the disease was linked with the absence of proper oncological alertness among the physicians. Profound preventive examinations with the wide use of modern diagnostic techniques will be conducive to an early diagnosis of this pathological condition and improvement of the results of treatment.


Carotid proliferative plaque formation in a canine model of chronic hypertension.
There are few reports describing arterial plaque formation induced by hypertension alone. The aim of this study was to establish a canine model of chronic hypertension and investigate carotid plaque development. Ten beagles were studied; 5 underwent bilateral renal artery constriction via a novel vascular clip, and 5 sham-operated animals served as controls. Systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid values, the intima-media thickness, and the carotid artery plaque score were investigated during 1 year after placement of the clips. The mean SBP and DBP over time were significantly greater in the constriction group (P < 0.001 for SBP, P < 0.01 for DBP). There were no significant differences in blood lipid levels or other biochemical parameters. Carotid plaques were demonstrated at 4 months postoperation in the constriction group; and in the constriction group, intima-media thickness became significantly greater at 4 months (P < 0.05), and plaque scores became significantly higher at 8 months (P = 0.034) after clip placement. Carotid stenosis was proved by digital subtraction angiography 1 year after clip placement, and histological examination revealed that the plaques were mainly comprised of smooth muscle cells, proteoglycans, and collagen fibers, but few macrophages and little lipid. Carotid proliferative plaques were developed in a canine model of chronic hypertension induced by a novel vascular clip. The plaques were mainly comprised of smooth muscle cells, proteoglycans, and collagen fibers.


Excess Folic Acid Supplementation Before and During Pregnancy and Lactation Activates Fos Gene Expression and Alters Behaviors in Male Mouse Offspring.
Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects and other birth defects. After 20 years mandate food fortification with FA, serum concentration of folate and unmetabolized FA increased significantly in the North American population. But whether excess FA intake impairs neurodevelopment and behavior is still controversial. Here, we treated mice with approximately 2.5-fold (moderate dose of FA, MFA) or 10-fold (high dose of FA, HFA) the dietary requirement of FA 1 week before mating and throughout pregnancy and lactation, and examined behaviors in adult male offspring using open field test, three-chamber sociability and social novelty test, elevated plus maze, rotarod and Morris water maze. We found that early life MFA supplementation increased long-term body weight gain in adults, elevated anxiety-like behavior, and impaired social preference, motor learning and spatial learning ability without modifying motor ability and spatial memory. In contrast, HFA supplementation only induced mild behavioral abnormality. RNA sequencing revealed that FA supplementation altered the expression of brain genes at weaning, among which Fos and related genes were significantly up-regulated in MFA mice compared with control and HFA mice. Quantitative real time-PCR (qRT-PCR) and western blots confirmed the increase of these genes. Our results suggested that FA supplementation during early life stage affected gene expression in weaning mice, and exhibited long-term impairments in adult behaviors in a dose-sensitive manner.


The use of saralasin to evaluate the function of the brain renin-angiotensin system.
The demonstration that the components required for the generation of angiotensin II are present in the brain has led to the proposal that there is a brain renin-angiotensin system. To test this hypothesis, experiments were performed to determine if biologically active amounts of angiotensin II are formed when renin is injected into the cerebral ventricles. The effects of central administration of agents known to block the peripheral renin-angiotensin system were also investigated. It was shown that intraventricular renin increased water intake, blood pressure and ADH secretion and that these effects were blocked by saralasin. These findings indicated an interaction between injected renin, brain angiotensinogen and converting enzyme, resulting in the formation of angiotensin II in physiologically active concentrations. However, these experiments did not demonstrate a role for endogenous brain renin activity. Central administration of saralasin in normal animals did not decrease water intake, blood pressure or ADH secretion. These studies thus failed to demonstrate a physiological role for the proposed brain renin-angiotensin system in controlling water balance and blood pressure.


Video-assisted radiofrequency ablation for pleural disseminated non-small cell lung cancer.
Clinically, some patients would have false-negative results in the diagnosis of non-small cell lung cancer (NSCLC) with pleural dissemination, losing their chances of prolonged survival from surgery. Hence, this study aimed to clarify the benefit of radiofrequency ablation (RFA) for NSCLC with malignant pleural dissemination that is detected during thoracoscopic lobectomy. From July 2006, we started the application of RFA in combination with talc pleurodesis (R-TP) for pleural disseminated NSCLCs diagnosed by thoracoscopy. Patients who underwent TP alone (from December 30, 2005 to June 30, 2006) were retrospectively evaluated in compared with R-TP (from July 1, 2006 to June 30, 2008). Clinical features were collected and compared to identify the difference in clinical outcomes between R-TP and TP alone. After discharge (three months after surgery), tumor response to treatment was assessed, and follow-up results were recorded to determine the perioperative and mid-time survival difference between the two groups. In our study, the two groups were comparable in age, sex, performance status (PS) score, tumor location, and histological diagnosis. The incidence rate of intraoperative pleural dissemination was 5.98%, as diagnosed by video-assisted thoracoscopy. All the surgeries were completed without conversion to open thoracotomy. Except for the longer operation duration in the R-TP group (p < 0.001), there was no significant difference between the two groups in terms of surgical features. Postoperatively, no mortality occurred in either group during hospital stay; however, two patients from the R-TP group developed complications (9.52%). The complete and partial remission rates in the R-TP group were 80% and 10%, respectively, and the stabilization rate was 10%. After the three-year follow-up, the overall survival (OS) rates of the R-TP and TP groups were 14.29% and 0%, respectively. The median survival and median tumor progression-free survival (PFS) periods were longer in the R-TP group than in the TP group (OS: 19 months versus 12.5 months, p = 0.045; PFS: 9.5 months versus 5.5 months, p = 0.028). The introduction of RFA to TP offered survival benefits to pleural disseminated NSCLC patients, making it a potential alternative palliative treatment for local tumor. However, multicenter randomized controlled trials are required to confirm these findings.


Polybrominated diphenyl ethers (PBDEs) in U.S. mothers' milk.
No previous reports exist on polybrominated diphenyl ether (PBDE) congeners in human milk from individual U.S. mothers. This article on PBDEs is an extension of our previous studies on concentrations of dioxins, dibenzofurans, polychlorinated biphenyls, and other chlorinated organic compounds in human milk in a number of countries. PBDE commercial products are used as flame retardants in flexible polyurethane foam (penta-BDE), in acrylonitrile-butadiene-styrene resins (octa-BDE), and in high-impact polystyrene resins (deca-BDE). Their use is permitted in the United States but is banned in some European countries because of presumed toxicity, demonstrated persistence, and bioaccumulation. Different commercial products can be found in various consumer products such as television sets, computers, computer monitors and printers, carpets, and upholstery. Analyses of human levels of these compounds suggest low but rising levels in European human milk, which may have peaked, at least in Sweden, in the late 1990s. Very few data exist on levels of PBDEs in humans in the United States, and none from milk from individual nursing mothers. To address this issue, we analyzed 47 individual milk samples from nursing mothers, 20-41 years of age, from a milk bank in Austin, Texas, and a community women's health clinic in Dallas, Texas. Up to 13 PBDE congeners were measured. The concentrations of the sum of PBDE congeners varied from 6.2 to 419 ng/g (or parts per billion) lipid, with a median of 34 ng/g and a mean of 73.9 ng/g lipid. The PBDE levels in breast milk from Texas were similar to levels found in U.S. blood and adipose tissue lipid from California and Indiana and are 10-100 times greater than human tissue levels in Europe. Their detection in breast milk raises concern for potential toxicity to nursing infants, given the persistence and bioaccumulative nature of some of the PBDE congeners. These results indicate a need for more detailed investigation of the levels of PBDE in people and food, as well as determining if animal fat in food is the major route of exposure of the general U.S. population. Other routes of intake may also be significant.


Wii-based movement therapy to promote improved upper extremity function post-stroke: a pilot study.
Virtual-reality is increasingly used to improve rehabilitation outcomes. The Nintendo Wii offers an in-expensive alternative to more complex systems. To investigate the efficacy of Wii-based therapy for post-stroke rehabilitation. Seven patients (5 men, 2 women, aged 42-83 years; 1-38 months post-stroke, mean 15.3 months) and 5 healthy controls (3 men, 2 women, aged 41-71 years) undertook 1 h of therapy on 10 consecutive weekdays. Patients progressively increased home practice to 3 h per day. Functional ability improved for every patient. The mean performance time significantly decreased per Wolf Motor Function Test task, from 3.2 to 2.8 s, and Fugl-Meyer Assessment scores increased from 42.3 to 47.3. Upper extremity range-of-motion increased by 20.1º and 14.33º for passive and active movements, respectively. Mean Motor Activity Log (Quality of Movement scale) scores increased from 63.2 to 87.5, reflecting a transfer of functional recovery to everyday activities. Balance and dexterity did not improve significantly. No significant change was seen in any of these measures for healthy controls, despite improved skill levels for Wii games. An intensive 2-week protocol resulted in significant and clinically relevant improvements in functional motor ability post-stroke. These gains translated to improvement in activities of daily living.


Characterization of Volatile Flavor Compounds in Chinese Rice Wine Fermented from Enzymatic Extruded Rice.
Enzymatic extrusion, instead of traditional steam cooking, to treat rice is an efficient and alternative pretreatment for Chinese rice wine fermentation. In order to determine the formation of volatiles in enzymatic extrusion-processed rice wine (EE), and to confirm its characteristic flavor compounds, headspace solid-phase micro-extraction followed by GC-MS was used. A total of 66 volatile compounds were identified in EE. During fermentation, most volatiles generated from enzymatic extruded rice had the similar trends with those from steam-cooked rice, but the differences in the concentration of volatiles indicated a changed balance of flavors release caused by enzymatic extrusion. Besides, the concentrations and sorts of volatiles in EEs fermented from different rice particle sizes, were not dramatically different. By principal component analysis, EE could be distinctly separated from other traditional Chinese rice wines according to its characteristic volatiles, namely, 2-heptanol, 1-octen-3-ol, ethyl 4-hydroxybenzoate, methylpentyl 2-propenoate, γ-hexalactone, and 4-vinylguaiacol. Enzymatic extrusion liquefaction has been a popular thermal treatment for cereals, and gradually being applied in fermentation and liquor-making industry all over the world. The characterization of volatile flavor compounds in Chinese rice wine processed by enzymatic extrusion liquefaction pretreatment, might be made use not only for a better understanding of this new-type rice wine, but for the further utilization of enzymatic extrusion in other wine or alcohol production as well.


Family members' experiences of being cared for by nurses and physicians in Norwegian intensive care units: a phenomenological hermeneutical study.
When patients are admitted to intensive care units, families are affected. This study aimed to illuminate the meaning of being taken care of by nurses and physicians for relatives in Norwegian intensive care units. Thirteen relatives of critically ill patients treated in intensive care units in southern Norway were interviewed in autumn 2013. Interview data were analysed using a phenomenological hermeneutical method inspired by the philosopher Paul Ricoeur. Two main themes emerged: being in a receiving role and being in a participating role. The receiving role implies experiences of informational and supportive care from nurses and physicians. The participating role implies relatives' experiences of feeling included and being able to participate in caring activities and decision-making processes. The meaning of being a relative in ICU is experienced as being in a receiving role, and at the same time as being in a participating role. Quality in relations is described as crucial when relatives share their experiences of care by nurses and physicians in the ICU. Those who experienced informational and supportive care, and who had the ability to participate, expressed feelings of gratitude and confidence in the healthcare system. In contrast, those who did not experience such care, especially in terms of informational care expressed feelings of frustration, confusion and loss of confidence. However, patient treatment and care outweighed relatives' own feelings.


Application of the 2013 American Urological Association early detection of prostate cancer guideline: who will we miss?
The American Urological Association (AUA) published new prostate cancer (CaP) screening guidelines in 2013. We apply the guidelines to a retrospective cohort to compare tumor characteristics of those no longer recommended for screening with those who remain screening candidates. We identified cases of screening detected CaP (stage cT1c) in the Surveillance Epidemiology and End Results database from October 2005 to December 2010. The 2013 AUA Guidelines were retrospectively applied to the cohort. Men were categorized into three groups for comparison based on whether or not they would now be recommended for CaP screening (Unscreened, Young Unscreened, and Screened). We compared clinical and pathological characteristics of CaP across study groups. A total of 142,382 men were identified. Screening would no longer be recommended for 40,160. Those no longer recommended for screening had higher median PSA (6.4 vs. 5.8 ng/mL, p < 0.01), more Gleason 7 and ≥8 CaP on prostate biopsy (36.4 vs. 34.8 %, p < 0.001; 12.4 vs. 9.2 %, p < 0.001, respectively) and slightly more Gleason ≥8 CaP (9.0 vs. 7.5 %, p = 0.03), and T3 tumors (17.3 vs. 16.5 %, p = 0.01) at prostatectomy. Nodal and distant metastasis rates were clinically equivalent among men screened and unscreened. Subgroup analysis of young patients (40-54 years old) no longer recommended for screening identified intermediate or high-risk Gleason scores at prostatectomy 57.6 % of the time. Features of CaP in men no longer recommended for routine screening are largely equivalent to if not worse than those in screened men.


Antioxidant Potential of Sulfated Polysaccharides from Padina boryana; Protective Effect against Oxidative Stress in In Vitro and In Vivo Zebrafish Model.
Elevated levels of reactive oxygen species (ROS) damage the internal cell components. Padina boryana, a brown alga from the Maldives, was subjected to polysaccharide extraction. The Celluclast enzyme assisted extract (PBE) and ethanol precipitation (PBP) of P. boryana were assessed against hydrogen peroxide (H2O2) induced cell damage and zebra fish models. PBP which contains the majority of sulfated polysaccharides based on fucoidan, showed outstanding extracellular ROS scavenging potential against H2O2. PBP significantly declined the intracellular ROS levels, and exhibited protection against apoptosis. The study revealed PBPs' ability to activate the Nrf2/Keap1 signaling pathway, consequently initiating downstream elements such that catalase (CAT) and superoxide dismutase (SOD). Further, ROS levels, lipid peroxidation values in zebrafish studies were declined with the pre-treatment of PBP. Collectively, the results obtained in the study suggest the polysaccharides from P. boryana might be a potent source of water soluble natural antioxidants that could be sustainably utilized in the industrial applications.


Population genetic relationships between Casearia sylvestris (Salicaceae) varieties occurring sympatrically and allopatrically in different ecosystems in south-east Brazil.
Species delimitation can be problematic, and recently diverged taxa are sometimes viewed as the extremes of a species' continuum in response to environmental conditions. Using population genetic approaches, this study assessed the relationship between two Casearia sylvestris (Salicaceae) varieties, which occur sympatrically and allopatrically in the landscape of south-east Brazil, where intermediate types are also found. In total, 376 individuals from nine populations in four different ecosystems were sampled, and nine microsatellite markers were used to assess the relative effects of the ecosystems and varieties on the distribution of genetic diversity among populations of this species. As a by-product of this study, several PCR products with more than two alleles were observed. The possibility that extra bands represent non-specific amplification or PCR artefacts was discarded by sequencing a sample of these bands. We suggest that (partial) genome duplication in C. sylvestris most probably explains this phenomenon, which may be a key factor in the differentiation of the two taxa, as it was markedly more frequent in one of the varieties. AMOVA indicated that approx. 22 % of the total genetic diversity was found between the two varieties. Bayesian analysis identified varieties and ecosystems as evolutionary units, rather than the individual populations sampled. The results are in agreement with field observations and support the recognition of two varieties, as well as documenting the occurrence of hybridization between them.


Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.
Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.


Comparison of voiding cystourethrography and urosonography with second-generation contrast agents in simultaneous prospective study.
The invasiveness and exposure to radiation in voiding cystourethrography led to the introduction of alternative methods of diagnosis of vesicoureteral reflux, including contrast enhanced voiding urosonography. While there is a limited number of studies comparing these methods using new generation ultrasound contrast agents, none of them compared both methods simultaneously. This study is aimed at assessing agreement between contrast enhanced voiding urosonography with second-generation ultrasound contrast agents and voiding cystourethrography. From April 2013 to May 2014, 83 children (37 female and 46 male), mean age 3.5 years, age range from 1 month to 17.5 years, underwent prospective simultaneous assessment by contrast enhanced voiding urosonography and voiding cystourethrography, with a total of 166 uretero-renal units evaluated. The sensitivity of voiding cystourethrography and contrast enhanced voiding urosonography were comparable, amounting to 88%, however, neither reached 100% for the entire studied population. The negative predictive value of voiding urosonography and voiding cystourethrography was 97%, and there was no difference between both methods. Voiding cystourethrography and contrast enhanced voiding urosonography are comparable methods in diagnosis of vesicoureteral reflux, and can be performed alternatively. However, some limitations of contrast enhanced voiding urosonography must be remembered.


Reactivity characteristics of nanoscale zerovalent iron--silica composites for trichloroethylene remediation.
Spherical silica particles containing nanoscale zerovalent iron were synthesized through an aerosol-assisted process. These particles are effective for groundwater remediation, with the environmentally benign silica particles serving as effective carriers for nanoiron transport. Incorporation of iron into porous sub-micrometer silica particles protects ferromagnetic iron nanoparticles from aggregation and may increase their subsurface mobility. Additionally, the presence of surface silanol groups on silica particles allows control of surface properties via silanol modification using organic functional groups. Aerosolized silica particles with functional alkyl moieties, such as ethyl groups on the surface, clearly adsorb solubilized trichloroethylene (TCE) in water. These materials may therefore act as adsorbents which have coupled reactivity characteristics. The nanoscale iron/silica composite particles with controlled surface properties have the potential to be efficiently applied for in situ source depletion and in the design of permeable reactive barriers.


Molecular profiles of mRNA levels in laser capture microdissected murine hippocampal regions differentially responsive to TMT-induced cell death.
Using a chemical-induced model of dentate granule (DG) cell death, cDNA microarray analysis was used to identify gene profiles from the laser-captured microdissected (LCM) hippocampal DG cell region versus the CA pyramidal cell layer (CA) from 21-day-old male CD1 mice injected with trimethyltin hydroxide (TMT; 3.0 mg/kg, i.p.). At 6 h post-TMT, lectin + microglia displaying a reactive morphology were in contact with active caspase 3+ neurons. By 18 h, amoeboid microglia and signs of phagocytosis, and a mild astrocytic response were present in the DG. There was no evidence of IgG extravasation in the hippocampus, or cell death and glial reactivity in the CA. Atlas 1.2K Clontech array detected 115 genes changed in the hippocampus with TMT and included genes associated with immediate-early responses, calcium homeostasis, cellular signaling, cell cycle, immunomodulation and DNA repair. Early responses localized to LCM DG samples consisted of elevations in inflammatory factors such as tumor necrosis factor-alpha and receptors, as well as MIP1alpha, CD14, CD18, and a decrease in factors associated with calcium buffering. By 18 h, in the DG, changes occurred in transcripts associated with apoptosis, cell adhesion, DNA repair, cell proliferation and growth. In the CA, a differential level of elevation was seen in CD86 antigen, zinc finger protein 38 and DNA damage inducible transcript 3. A significant number of genes was decreased at these early time points in both hippocampal regions.


Pipeline for High-Throughput Modeling of Marijuana and Hemp Extracts.
Authentication of Cannabis products is important for assuring the quality of manufacturing, with the increasing consumption and regulation. In this report, a two-stage pipeline was developed for high-throughput screening and chemotyping the spectra from two sets of botanical extracts from the Cannabis genus. The first set contains different marijuana samples with higher concentrations of tetrahydrocannabinol (THC). The other set includes samples from hemp, a variety of Cannabis sativa with the THC concentration below 0.3%. The first stage applies the technique of class modeling to determine whether spectra belong to marijuana or hemp and reject novel spectra that may be neither marijuana nor hemp. An automatic soft independent modeling of class analogy (aSIMCA) that self-optimizes the number of principal components and the decision threshold is utilized in the first pipeline process to achieve excellent efficiency and efficacy. Once these spectra are recognized by aSIMCA as marijuana or hemp, they are then routed to the appropriate classifiers in the second stage for chemotyping the spectra, i.e., identifying these spectra into different chemotypes so that the pharmacological properties and cultivars of the spectra can be recognized. Three multivariate classifiers, a fuzzy rule building expert system (FuRES), super partial least-squares-discriminant analysis (sPLS-DA), and support vector machine tree type entropy (SVMtreeH), are employed for chemotyping. The discriminant ability of the pipeline was evaluated with different spectral data sets of these two groups of botanical samples, including proton nuclear magnetic resonance, mass, and ultraviolet spectra. All evaluations gave good results with accuracies greater than 95%, which demonstrated promising application of the pipeline for automated high-throughput screening and chemotyping marijuana and hemp, as well as other botanical products.


Genomic signatures of local directional selection in a high gene flow marine organism; the Atlantic cod (Gadus morhua).
Marine fishes have been shown to display low levels of genetic structuring and associated high levels of gene flow, suggesting shallow evolutionary trajectories and, possibly, limited or lacking adaptive divergence among local populations. We investigated variation in 98 gene-associated single nucleotide polymorphisms (SNPs) for evidence of selection in local populations of Atlantic cod (Gadus morhua L.) across the species distribution. Our global genome scan analysis identified eight outlier gene loci with very high statistical support, likely to be subject to directional selection in local demes, or closely linked to loci under selection. Likewise, on a regional south/north transect of central and eastern Atlantic populations, seven loci displayed strongly elevated levels of genetic differentiation. Selection patterns among populations appeared to be relatively widespread and complex, i.e. outlier loci were generally not only associated with one of a few divergent local populations. Even on a limited geographical scale between the proximate North Sea and Baltic Sea populations four loci displayed evidence of adaptive evolution. Temporal genome scan analysis applied to DNA from archived otoliths from a Faeroese population demonstrated stability of the intra-population variation over 24 years. An exploratory landscape genetic analysis was used to elucidate potential effects of the most likely environmental factors responsible for the signatures of local adaptation. We found that genetic variation at several of the outlier loci was better correlated with temperature and/or salinity conditions at spawning grounds at spawning time than with geographic distance per se. These findings illustrate that adaptive population divergence may indeed be prevalent despite seemingly high levels of gene flow, as found in most marine fishes. Thus, results have important implications for our understanding of the interplay of evolutionary forces in general, and for the conservation of marine biodiversity under rapidly increasing evolutionary pressure from climate and fisheries induced changes in local environments.


Upper-Limb Rehabilitation of Patients with Neuromotor Deficits Using Impedance-Based Control of a 6-DOF Robot.
This paper presents a study on the use of impedance-based control of a 6-degree-of-freedom robot for upper-limb rehabilitation of patients with neuromotor deficits. The control strategy is based on impedance and does not require external force sensors at the end-effector for implementation. The experimental setup involved using the control algorithm to move the robot to a desired position, follow a desired trajectory while being moved out of the trajectory by the user, and reproduce three different rehabilitation exercises (passive, isometric, and ADL). The results suggest that the parameters of the control strategy can be adjusted to set the robot's compliance and support force according to the patient's needs. Ultimately, the study concluded that the proposed control strategy can serve as a foundation for rehabilitation robots, which could potentially improve access to continued upper-limb rehabilitation for stroke patients and reduce the number of healthcare professionals required per patient.Clinical Relevance- This paper proposes a human-robot interaction control scheme to be used in a robotic rehabilitation tool, with the goal of assisting both clinicians and patients during the rehabilitation exercises and ultimately reducing the load on healthcare system. This platform can be potentially used in telemedicine solutions for upper-limb rehabilitation of a wide range of patients with neuromotor deficits such as stroke.


Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques.
C-reactive protein (CRP) is a predictor of cardiovascular risk. It circulates as a pentamer (pentameric CRP) in plasma. The in vivo existence of monomeric (m)CRP has been postulated, but its function and source are not clear. We show that mCRP is deposited in human aortic and carotid atherosclerotic plaques but not in healthy vessels. pCRP is found neither in healthy nor in diseased vessels. As source of mCRP, we identify a mechanism of dissociation of pCRP to mCRP. We report that activated platelets, which play a central role in cardiovascular events, mediate this dissociation via lysophosphatidylcholine, which is present on activated but not resting platelets. Furthermore, the dissociation of pCRP to mCRP can also be mediated by apoptotic monocytic THP-1 and Jurkat T cells. The functional consequence is the unmasking of proinflammatory effects of CRP as demonstrated in experimental settings that are pathophysiologically relevant for atherogenesis: compared to pCRP, mCRP induces enhanced monocyte chemotaxis; monocyte activation, as determined by conformational change of integrin Mac-1; generation of reactive oxygen species; and monocyte adhesion under static and physiological flow conditions. In conclusion, we demonstrate mCRP generation via pCRP dissociation on activated platelets and H(2)O(2)-treated apoptotic THP-1 and Jurkat T cells, thereby identifying a mechanism of localized unmasking of the proinflammatory properties of CRP. This novel mechanism provides a potential link between the established cardiovascular risk marker, circulating pCRP, and localized platelet-mediated inflammatory and proatherogenic effects.


Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial.
Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions. The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling. This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention. ClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017.


Antinociceptive action and redox properties of citronellal, an essential oil present in lemongrass.
Citronellal (CT) is a monoterpenoid and the major constituent of the mixture of terpenoids that give the citronella oil its lemon scent. Citronella oil is widely used around the world for various purposes and is mainly obtained from plants of the Cymbopogon genus, which are known as "lemongrass." Considering these plants have been used worldwide for various medicinal purposes, the interest of researchers to understand the biological activities of monoterpenoids related to the Cymbopogon genus has been increasing. In the present work, we investigated the antinociceptive action and the redox properties of CT. Our results indicate that intraperitoneal injection of CT was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CT also evoked antinociceptive response in the capsaicin and glutamate tests. The total radical-trapping antioxidant parameter and total antioxidant reactivity assays indicate that CT at doses of 0.1 and 1 mg/mL exerts a significant antioxidant activity, which is probably related to its ability to scavenge superoxide and nitric oxide, but not H(2)O(2) or hydroxyl radicals, as evaluated separately by specific in vitro tests. These results show for the first time the antinociceptive potential of CT and indicate that the antioxidant properties of this compound may rely on its mechanism of biological actions because CT-containing natural products are used to treat various diseases related to oxidative stress and reactive species.


[Retropharyngeal phlegmon caused by a group B Streptococcus in a diabetic patient: report of one case].
We report a 47 year-old diabetic male, admitted due to metabolic decompensation, malaise, purulent pharyngeal discharge and a mass in the posterior cervical region. Blood glucose was 270 mg/dl, a nasopharyngoscopy showed a pharyngeal phlegmon and CT scan confirmed the presence of a phlegmon in the retropharyngeal region. He was treated with sodium penicillin, cloxacillin and ceftriazone and the phlegmon was drained surgically. The culture of the purulent discharge gave growth to a Group B Streptococcus. The evolution was favorable and the patient completed seven days with intravenous antimicrobials and additional seven days with oral ampicillin/sulbactam.


High resolution mapping of modafinil induced changes in glutamate level in rat brain.
Modafinil is marketed in the United States for the treatment of narcolepsy and daytime somnolence due to shift-work or sleep apnea. Investigations of this drug in the treatment of cocaine and nicotine dependence in addition to disorders of executive function are also underway. Modafinil has been known to increase glutamate levels in rat brain models. Proton magnetic resonance spectroscopy (1HMRS) has been commonly used to detect the glutamate (Glu) changes in vivo. In this study, we used a recently described glutamate chemical exchange saturation transfer (GluCEST) imaging technique to measure Modafinil induced regional Glu changes in rat brain and compared the results with Glu concentration measured by single voxel 1HMRS. No increases in either GluCEST maps or 1HMRS were observed after Modafinil injection over a period of 5 hours. However, a significant increase in GluCEST (19 ± 4.4%) was observed 24 hours post Modafinil administration, which is consistent with results from previous biochemical studies. This change was not consistently seen with 1HMRS. GluCEST mapping allows regional cerebral Glu changes to be measured and may provide a useful clinical biomarker of Modafinil effects for the management of patients with sleep disorders and addiction.


Nuclear receptor steroidogenic factor 1 directs embryonic stem cells toward the steroidogenic lineage.
The orphan nuclear receptor steroidogenic factor 1 (SF-1) is expressed in the adrenal gland and gonads and is an important regulator of the expression of cytochrome P-450 steroidogenic enzymes in cultured cells. Targeted disruption of the SF-1 gene in mice shows that it is a critical participant in the genetic program that promotes the development of urogenital mesoderm into the adrenal gland and gonads. To assess the ability of SF-1 to regulate this differentiation pathway, we ectopically expressed SF-1 in murine embryonic stem (ES) cells. We found that stable expression of SF-1 is sufficient to alter ES cell morphology, permit cyclic AMP (cAMP) and retinoic acid-induced expression of the endogenous side chain cleavage enzyme gene, and consequently, promote steroidogenesis. While steroid production is dependent upon SF-1, cAMP induction of steroidogenesis does not enhance the responsiveness of an SF-1-specific reporter. Furthermore, the activity of a P450SCC promoter/luciferase reporter construct, which is induced by cAMP in steroidogenic cells and ES cells converted by stable expression of SF-1, is not induced by cAMP in wild-type ES cells transiently transfected with SF-1, suggesting that the induction of downstream gene products is required before steroidogenesis can occur. We demonstrate that mutants which disrupt the DNA binding domain or the AF2 transcriptional activation domain of SF-1 do not confer the steroidogenic phenotype to ES cells. Interestingly, however, AF2 mutants fused to the VP16 activation domain do confer the steroidogenic phenotype to ES cells, but only in the presence of a portion of the ligand binding domain. These studies extend the role of SF-1 in steroidogenic tissues to that of a dominant regulator of the steroidogenic cell phenotype.


[Peritoneal dialysis impact on quality of life in elderly].
Nowadays elderly live longer but with more diseases and geriatric syndromes which can deteriorate their quality of life (QoL). Peritoneal dialysis (PD) is a renal replacement therapy which seeks to prolong an improve QoL; however, this is uncertain in elderly. Therefore, comparing QoL before and after starting dialysis in this population may let us know if there is a benefit at this level. Identify the QoL that patients have before and after PD. Longitudinal, comparative, prospective cohort, before and after study. Elderly with End Stage Renal Disease in whom hospitalization for PD was indicated. QoL was measured the instrument KDQOL SF 1.3. before and after 2 months of PD. Statistical Analysis: T paired test was performed with the basal value of QoL and after. Risks with 95% confidence intervals and X2 were obtained between the basal characteristics and the dependent variable of QoL. 21 patients. After 2 months the QoL had an increment in comparison to basal QoL, but with no statistical significance (63.47 [SD 16.63] Vs 56.83 [16.01], P= 0.22. In the 7th decade PD increased QoL by 13.01 points (P= 0.04). PD increases QoL in the 7th decade.


Overview of Next-generation Sequencing Platforms Used in Published Draft Plant Genomes in Light of Genotypization of Immortelle Plant (Helichrysium Arenarium).
Major advancements in DNA sequencing methods introduced in the first decade of the new millennium initiated a rapid expansion of sequencing studies, which yielded a tremendous amount of DNA sequence data, including whole sequenced genomes of various species, including plants. A set of novel sequencing platforms, often collectively named as "next-generation sequencing" (NGS) completely transformed the life sciences, by allowing extensive throughput, while greatly reducing the necessary time, labor and cost of any sequencing endeavor. of this paper is to present an overview NGS platforms used to produce the current compendium of published draft genomes of various plants, namely the Roche/454, ABI/SOLiD, and Solexa/Illumina, and to determine the most frequently used platform for the whole genome sequencing of plants in light of genotypization of immortelle plant. 45 papers were selected (with 47 presented plant genome draft sequences), and utilized sequencing techniques and NGS platforms (Roche/454, ABI/SOLiD and Illumina/Solexa) in selected papers were determined. Subsequently, frequency of usage of each platform or combination of platforms was calculated. Illumina/Solexa platforms are by used either as sole sequencing tool in 40.42% of published genomes, or in combination with other platforms - additional 48.94% of published genomes, followed by Roche/454 platforms, used in combination with traditional Sanger sequencing method (10.64%), and never as a sole tool. ABI/SOLiD was only used in combination with Illumina/Solexa and Roche/454 in 4.25% of publications. Illumina/Solexa platforms are by far most preferred by researchers, most probably due to most affordable sequencing costs. Taking into consideration the current economic situation in the Balkans region, Illumina Solexa is the best (if not the only) platform choice if the sequencing of immortelle plant (Helichrysium arenarium) is to be performed by the researchers in this region.


Unique chromatin remodeling and transcriptional regulation in spermatogenesis.
Most of our knowledge of transcriptional regulation comes from studies in somatic cells. However, increasing evidence reveals that gene regulation mechanisms are different in haploid germ cells. A number of highly specialized strategies operate during spermatogenesis. These include a unique chromatin reorganization program and the use of distinct promoter elements and specific transcription factors. Deciphering the rules governing transcriptional control during spermatogenesis will provide valuable insights of biomedical importance.


Hard palate hyperpigmentation secondary to chronic chloroquine therapy: report of five cases.
Antimalarials are commonly prescribed in medical practice for conditions such as rheumatoid arthritis, lupus erythematosus, as well as malaria. They are generally well-tolerated, but side effects, although infrequent, are well known. The antimalarial chloroquine diphosphate may be associated with a bluish-gray to black hyperpigmentation of the oral mucosa, mainly on the hard palate. In this report we described five additional cases of palate hyperpigmentation related to the chronic use of chloroquine diphosphate. Professionals must be aware of the adverse effects of antimalarials as chloroquine diphosphate in order to make the correct diagnosis and appropriate management of the patient. Early diagnosis of oral pigmentation by antimalarials may be of great relevance, because it might be an early sign of ocular involvement, and therefore it may be helpful to prevent further complications of antimalarial therapy for the patient.