Plant Growth and Photosynthetic Characteristics of Mesembryanthemum crystallinum Grown Aeroponically under Different Blue- and Red-LEDs.
Mesembryanthemum crystallinum is a succulent, facultative crassulacean acid metabolism (CAM) plant. Plant growth and photosynthetic characteristics were studied when M. crystallinum plants were grown indoor under light emitting diodes (LED)-lighting with adequate water supply. Plants were cultured aeroponically for a 16-h photoperiod at an equal photosynthetic photon flux density of 350 μmol m-2 s-1 under different red:blue LED ratios: (1) 100:0 (0B); (2) 90:10 (10B); (3) 80:20 (20B); (4) 70:30 (30B); (5) 50:50 (50B); and (6)100:0 (100B). M. crystallinum grown under 10B condition had the highest shoot and root biomass and shoot/root ratio while those grown under 0B condition exhibited the lowest values. Compared to plants grown under 0B condition, all other plants had similar but higher total chlorophyll (Chl) and carotenoids (Car) contents and higher Chl a/b ratios. However, there were no significant differences in Chl/Car ratio among all plants grown under different red- and blue-LEDs. Photosynthetic light use efficiency measured by photochemical quenching, non-photochemical quenching, and electron transport rate, demonstrated that plants grown under high blue-LED utilized more light energy and had more effective heat dissipation mechanism compared to plants grown under 0B or lower blue-LED. Statistically, there were no differences in photosynthetic O2 evolution rate, light-saturated CO2 assimilation rate (Asat), and light-saturated stomatal conductance (gssat) among plants grown under different combined red- and blue-LEDs but they were significantly higher than those of 0B plants. No statistically differences in total reduced nitrogen content were found among all plants. For the total soluble protein, all plants grown under different combined red- and blue-LEDs had similar values but they were significantly higher than that of plants grown under 0B condition. However, plants grown under higher blue-LEDs had significant higher ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) protein than those plants grown under lower blue-LED. High Asat and gssat but very low CAM acidity of all M. crystallinum plants during light period, imply that this facultative CAM plant performed C3 photosynthesis when supplied with adequate water. Results of this study suggest that compared to red- or blue-LED alone, appropriate combination of red- and blue-LED lighting enhanced plant growth and photosynthetic capacities of M. crystallinum.


Clinical Applications of the T-Scan Quantitative Digital Occlusal Analysis Technology ASystematic Review.
Occlusion is associated with all disciplines of dentistry and plays a major role in the longevity of both implant and tooth borne restorations. Achieving occlusal harmony ensures balance is established between the dental and myofascial structures, which can be measurably established to high numerical tolerances with the T-Scan digital occlusal analysis system. To describe and evaluate the known and proven applications of T-Scan digital occlusal analysis in various dental practice disciplines, with a systematic review of the literature. An electronic English language Medline/PubMed and Cochrane central library database search using key words "T-Scan", "TMD", "Occlusion", "Implant Protected Occlusion", "Orthodontics", was conducted without any date restrictions. The related journal findings were hand searched to determine studies that met a systematic review's inclusion. The PubMed/MEDLINE identified 423 articles. After removing duplicates the titles and abstracts of the 421 studies were screened. 274 ineligible articles were excluded leaving 147 articles. Of those, 33 articles were not in English, 27 full text articles were not available, 4 were comments and Letter to the Editors, and 2 articles described techniques. 86 articles total met the eligibility criteria for inclusion. Much scientific evidence supports the use of T-Scan, as it measures relative occlusal contact forces and occlusal contacts time-sequence durations objectively, accurately, and repeatedly for improved treatment outcomes. It's hardware, sensor, and software evolution from T-Scan I up to today's T-Scan10 Novus system, has overcome early sensor and system drawbacks to improve T-Scan's clinical performance in many disciplines of Dental Medicine.


Diagnosis and management of neurocardiogenic syncope.
The medical term syncope is derived from the Greek word "synkoptein," the original meaning of which was "to cut short". Because it is both a symptom and a sign, the physician may often find the evaluation of syncope a difficult and frustrating endeavor. Over the course of the past decade it has become apparent that transient alterations in autonomic nervous system activity, resulting in hypotension and bradycardia, are common causes of syncope. At the same time it has become apparent that these are a heterogenous group of disorders which, while sharing some characteristics, are nonetheless distinct maladies. This article attempts to briefly review our current understanding of these disorders and suggests guidelines on their diagnosis and management.


The Risk of Cardiovascular Disease Among Immigrants in Canada.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. The global surge in migration to high-income countries, especially Canada, highlights the importance of studies evaluating the risk factors and the disparities in the rate of incidence of CVD among immigrants. Canada is home to a diverse group of immigrants, each presenting with a risk profile that is unique to their ethnicity and country of birth. A variety of cardiac risk factors, such as dietary habits, physical activity, smoking, cultural traditions as well as preponderance to certain diseases like type II diabetes mellitus, hypertension, and high lipid levels act in concert and impact CVD risk and overall incidence. This narrative review focuses on CVD risks and how it is related to the immigration status among various ethnic groups in Canada.


Zmym4 is required for early cranial gene expression and craniofacial cartilage formation.
Introduction: The Six1 transcription factor plays important roles in the development of cranial sensory organs, and point mutations underlie craniofacial birth defects. Because Six1's transcriptional activity can be modulated by interacting proteins, we previously screened for candidate interactors and identified zinc-finger MYM-containing protein 4 (Zmym4) by its inclusion of a few domains with a bona fide cofactor, Sine oculis binding protein (Sobp). Although Zmym4 has been implicated in regulating early brain development and certain cancers, its role in craniofacial development has not previously been described. Methods: We used co-immunoprecipitation and luciferase-reporter assays in cultured cells to test interactions between Zmym4 and Six1. We used knock-down and overexpression of Zmym4 in embryos to test for its effects on early ectodermal gene expression, neural crest migration and craniofacial cartilage formation. Results: We found no evidence that Zmym4 physically or transcriptionally interacts with Six1 in cultured cells. Nonetheless, knockdown of endogenous Zmym4 in embryos resulted in altered early cranial gene expression, including those expressed in the neural border, neural plate, neural crest and preplacodal ectoderm. Experimentally increasing Zmym4 levels had minor effects on neural border or neural plate genes, but altered the expression of neural crest and preplacodal genes. At larval stages, genes expressed in the otic vesicle and branchial arches showed reduced expression in Zmym4 morphants. Although we did not detect defects in neural crest migration into the branchial arches, loss of Zmym4 resulted in aberrant morphology of several craniofacial cartilages. Discussion: Although Zmym4 does not appear to function as a Six1 transcriptional cofactor, it plays an important role in regulating the expression of embryonic cranial genes in tissues critical for normal craniofacial development.


Analysis of Risk and Burden of Dysentery Associated with Floods from 2004 to 2010 in Nanning, China.
This study aimed to examine the association between floods and the morbidity of dysentery and to quantify the burden of dysentery due to floods in Nanning, China. A generalized additive mixed model was conducted to assess the relationship between monthly morbidity of dysentery and floods from 2004 to 2010. The years lived with disability (YLDs) of dysentery attributable to floods were then estimated based on the WHO framework of the burden of disease study for calculating the potential impact fraction. The relative risk (RR) of floods on the morbidity of dysentery was 1.44 (95% confidence interval [CI] = 1.18-1.75). The models suggest that a potential 1-day rise in flood duration may lead to 8% (RR = 1.08, 95% CI = 1.04-1.12) increase in the morbidity of dysentery. The average attributable YLD per 1,000 of dysentery caused by floods were 0.013 in males, 0.005 in females, and 0.009 in persons. Our study confirms that floods have significantly increased the risk and the burden of dysentery in the study area. Public health action should be taken to prevent and control the potential risk of dysentery after floods. Vulnerable groups such as males and children should be paid more attention.


Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods.
Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application. Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed.


[Effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080].
To investigate the effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080. The proliferation inhibitory rate of HT1080 cells treated by LY294002 at doses of 5, 10, 25, 50, 100 micromol/L for 12 and 24 h, respectively, was evaluated using SunBio Am-Blue method. HT1080 cells were divided into two groups, that is, A and B. The A group was control group without treatment. The B group received LY294002 (100 micromol/L) for 24 h. The changes of cell morphology and quantity were observed by phase contrast microscope. The apoptosis rate of HT1080 cells was detected by flow cytometry. And the protein expression of p-Akt and p-mTOR in HT1080 cells were detected by Western Blotting. The proliferation of HT1080 cells was inhibited in time- and dose- dependent manner by LY294002. After the treatment of 100 micromol/L LY294002 for 24 h, the growth of HT1080 cell line was remarkably inhibited by LY294002. The rate of apoptosis increased. And the protein expression of p-Akt (0.23 +/- 0.01) and p-mTOR (0.32 +/- 0.06) in LY294002 group was lower than p-Akt (0.63 +/- 0.02) and p-mTOR (0.71 +/- 0.02) in control group (P<0. 01). LY294002 can inhibit the growth of HT1080 cells through PI3K-mTOR pathway. PI3K-mTOR pathway presents an appealing therapeutic target on fibrosarcoma.


Selective acalculia with sparing of the subtraction process in a patient with left parietotemporal hemorrhage.
We describe a patient with left parietotemporal hemorrhage with selective acalculia for addition, multiplication, and division, but with an intact ability to subtract. There was no impairment in the ability to distinguish mathematical signs. This case suggests that different processing systems are responsible for each of the basic arithmetic operations.


Characterization of the cellulolytic activity of a Bacillus isolate.
A group I Bacillus strain, DLG, was isolated and characterized as being most closely related to Bacillus subtilis. When grown on any of a variety of sugars, the culture supernatant of this isolate was found to possess cellulolytic activity, as demonstrated by degradation of trinitrophenyl-carboxymethyl cellulose. Growth in medium containing cellobiose or glucose resulted in the greatest production of cellulolytic activity. The cellulolytic activity was not produced until the stationary phase of growth, and the addition of glucose or cellobiose to a culture in this phase had no apparent effect on enzyme production. Fractionation of the culture supernatant showed that the molecular weight of the enzymatic activity was less than 100,000. Maximum cellulolytic activity in assays was observed at pH 4.8 and at 58C, although maximum thermal stability of the activity. Kinetic experiments suggested that more than one enzyme was acting upon trinitrophenyl-carboxymethyl cellulose. Exocellular protein produced by this Bacillus isolate showed roughly one-fifth the cellulolytic activity displayed by Trichoderma reesei C30 on noncrystalline, cellulosic substrates. In contrast to T. reesei cellulase, the Bacillus enzymatic activity showed no ability to degrade crystalline forms of cellulose, nor was cellobiase activity detectable.


Src Family Kinases Regulate Interferon Regulatory Factor 1 K63 Ubiquitination following Activation by TLR7/8 Vaccine Adjuvant in Human Monocytes and B Cells.
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors. A role for Src family kinases (SFKs) in this signaling pathway has also been established. Our work and that of others have shown that this type of kinases is activated following engagement of several TLRs, and that this event is essential for the initiation of specific downstream cellular response. In particular, we have previously demonstrated that activation of SFKs is required for balanced production of pro-inflammatory cytokines by monocyte-derived dendritic cells after stimulation with R848, an agonist of human TLRs 7/8. We also showed that TLR7/8 triggering leads to an increase in interferon regulatory factor 1 (IRF-1) protein levels and that this effect is abolished by inhibition of SFKs, suggesting a critical role of these kinases in IRF-1 regulation. In this study, we first confirmed the key role of SFKs in TLR7/8 signaling for cytokine production and accumulation of IRF-1 protein in monocytes and in B lymphocytes, two other type of antigen-presenting cells. Then, we demonstrate that TLR7 triggering leads to an increase of K63-linked ubiquitination of IRF-1, which is prevented by SFKs inhibition, suggesting a key role of these kinases in posttranslational regulation of IRF-1 in the immune cells. In order to understand the mechanism that links SFKs activation to IRF-1 K63-linked ubiquitination, we examined SFKs and IRF-1 possible interactors and proved that activation of SFKs is necessary for their interaction with TNFR-associated factor 6 (TRAF6) and promotes the recruitment of both cIAP2 and IRF-1 by TRAF6. Collectively, our data demonstrate that TLR7/8 engagement leads to the formation of a complex that allows the interaction of cIAP2 and IRF-1 resulting in IRF-1 K63-linked ubiquitination, and that active SFKs are required for this process.


Causes and Characteristics of Children Unintentional Injuries in Emergency Department and Its Implications for Prevention.
Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China. Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged <18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t-test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital. Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93-4.63, P < 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93-433.14, P < 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07-1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48-4.49, P < 0.001) had a significantly higher risk of admission. Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission.


Associations between physical behaviour patterns and levels of depressive symptoms, anxiety and well-being in middle-aged adults: a cross-sectional study using isotemporal substitution models.
To examine the compositional effects of physical behaviour on mental health. Cross-sectional study. A population-representative random sample (Mitchelstown cohort) was recruited from a large primary care centre in Mitchelstown, County Cork, Ireland. In total 3807 potential participants were selected from the practice list. Following exclusion of duplicates, deaths and ineligibles, 3043 were invited to participate and of these, 2047 (49.2% men) completed the questionnaire and physical examination components of the baseline assessment during the study period (April 2010 and May 2011). Accelerometers were introduced into the study in January 2011. Of the 745 participants seen between January and May of 2011, 475 (44.6% men) subjects (response rate 64%) agreed to participate and of these 397 (46.1% men) had valid accelerometer data. Participants wore the wrist GENEActiv accelerometer for 7 consecutive days. Data were summarised into 60 s epochs and activity categorised as sedentary behaviour, light or moderate-to-vigorous physical activity (MVPA). Levels of depressive and anxiety symptoms were assessed using the Centre for Epidemiologic Studies Depression scale and the Hospital Anxiety and Depression Scale. Well-being was assessed using the WHO-5 well-being scale. In adjusted isotemporal models, a 30 min increase in light activity per day was associated with a significant decrease in levels of anxiety symptoms (B=-0.34; 95% CI -0.64 to -0.04) and a significant increase in levels of well-being (B=0.58; 95% CI 0.05 to 1.11). No statistically significant associations were observed between any physical behaviour and depressive symptoms or when sedentary behaviour was substituted with MVPA (P>0.05). Although based on a cross-sectional study, the findings suggest that substituting light activity for sedentary behaviour may have positive associations with symptoms of anxiety and reported well-being among middle-aged adults.


Experimental Evolution of Escherichia coli Persister Levels Using Cyclic Antibiotic Treatments.
Persister cells are difficult to study owing to their transient nature and their usually small number in bacterial populations. In the past, numerous attempts have been made to elucidate persistence mechanisms. However, because of the challenges involved in studying persisters and the clear redundancy in mechanisms underlying their generation, our knowledge of molecular pathways to persistence remains incomplete. Here, we describe how to use experimental evolution with cyclic antibiotic treatments to generate mutants with an increased persister level in stationary phase, ranging from the initial ancestral level up to 100 %. This method will help to unravel molecular pathways to persistence, and opens up a myriad of new possibilities in persister research, such as the convenient study of nearly pure persister cultures and the possibility to investigate the role of time and environmental aspects in the evolution of persistence.


Determination of ochratoxin A in licorice extract based on modified immunoaffinity column clean-up and HPLC analysis.
Contamination of ochratoxin A (OTA) is a common concern for the quality and safety of licorice and its derivatives, while their complex sample matrices always restrict the monitoring and regulation of OTA. Taking the much more concentrated and complicated licorice extract as the representative, a modified analysis method was established for OTA by HPLC. Parameters were comprehensively investigated based on liquid-liquid extraction and immunoaffinity column clean-up. In comparison to other methods, the developed method achieved effective clean-up efficiency and selectivity without tedious procedures and specialized instrumentation. Good linearity (R2 ≥0.9995), low LOD/LOQ (0.10 μg/kg/0.33 μg/kg), and satisfactory recovery (90.0%-96.4%, RSDs <7.0%) indicated the satisfactory sensitivity and reliability of the method. In addition, the applicability and robustness of the method was demonstrated by the analysis of large numbers of licorice extract samples. It is noteworthy that 66.5% of 176 samples were contaminated with OTA, while the concentrations of 9.1% of samples exceeded the maximum limit (ML, 80 μg/kg) defined by the EU. On account of the high contamination frequency and broad concentration range of OTA, the daily intake limit of licorice extract was preliminarily determined to be 123.18-123.93 g/day (chronic exposure) and 24.24 g/day (acute exposure), indicating a potential of acute risk through daily exposure. This calls for improved supervision and regulation for OTA contamination in licorice samples. This study suggests a prospective option for the efficient determination and routine monitoring of OTA in licorice and its derivatives, simultaneously providing a valuable data base for its health risk assessment.


[Results of therapy of severe metabolic alkalosis using hydrochloric acid infusions].
Severe metabolic alkalosis is often treated by infusion of arginine-HCl. Since we know that this substance leads to a supplemental increase of intracellular pH and fails to reduce intracellular bicarbonate concentration we use HCl for correction of this disturbance of acid-base equilibrium. 18 intensive-care patients with severe metabolic alkalosis were treated with an infusion of 0.2 m HCl. While base excess and sodium decreased significantly, chloride increased slightly. Arterial plasma pH, potassium, Hb, Hk, pCO2, pO2, and SO2 remained unchanged. Instructions for preparing different HCl solutions and advice on dosage are given.


Applying the International Classification of Functioning-Children and Youth Version to Pediatric Neuro-oncology.
Given the increased survival rates in patients with pediatric central nervous system tumors, late effects such as treatment- and/or illness-related neurologic sequelae as well as neuropsychological deficits and social difficulties have moved into focus in follow-up care. In order to provide personalized treatment recommendations for pediatric brain tumor survivors, it is crucial not only to assess cognitive impairments but also to measure a patient's functional deficiencies, for example, restricted participation in everyday social activities. Thus, this article introduces the International Classification of Functioning-Children and Youth version (ICF-CY) as a conceptual framework for quantifying functional limitations and informing long-term care in pediatric neuro-oncology. A standardized self-report and proxy-report questionnaire for measuring participation is briefly discussed and specific recommendations based on so-called core sets for clinical practice in pediatric neuro-oncology are provided.


The metal/tissue interface effect in irradiation of the oral cavity.
Metal dental prostheses or overlays may lead to increased mucosal reactions of adjacent tissue surfaces during intensive irradiation of the oral cavity. The dosimetry of this phenomenon was investigated by irradiating dental phantoms with 4-and 6-MeV photons. Gold and amalgam interfaces may produce local mucosal doses as high as 150-170% depending on the beam geometry, but doses of 111-126% for gold crowns and about 109-118% for amalgam fillings were found for opposed-beam configurations. 2-4 mm of tissue-equivalent absorber is sufficient to re-establish a homogeneous dose distribution and should be employed throughout therapy whenever dental extraction is unwarranted. The radiobiological exaggeration of the interface effect in treatment with opposed beams using one field per day is discussed.


[New Developments in CKD-MBD. New aspects in phosphate binders].
In patients with end-stage renal disease (ESRD) , hyperphosphatemia contributes to secondary hyperparathyroidism and can lead to skeletal complications including fracture, and vascular calcification. Currently employed phosphate binders include calcium carbonate, sevelamer hydrochloride, and lanthanum carbonate. While these agents are effective at binding orally ingested phosphates, they vary in safety, potency, and off-target effects, some of which may be salutary (e.g., low-density lipoprotein and uric acid lowering with sevelamer) and others adverse (low turnover bone disease and progressive vascular calcification with calcium) . There remains a large unmet need for safe and effective phosphate binders with favorable off-target effects.


The role of macrophages in Wallerian degeneration.
The present review focuses on macrophage properties in Wallerian degeneration. The identification of hematogenous phagocytes, the involvement of cell surface receptors and soluble factors, the state of activation during myelin removal and the signals and factors leading to macrophage recruitment into degenerating peripheral nerves after nerve transection are reviewed. The main effector cells in Wallerian degeneration are hematogenous phagocytes. Resident macrophages and Schwann cells play a minor role in myelin removal. The macrophage complement receptor type 3 is the main surface receptor involved in myelin recognition and uptake. The signals leading to macrophage recruitment are heterogenous and not yet defined in detail. Degenerating myelin and axons are suggested to participate. The relevance of these findings for immune-mediated demyelination are discussed since the definition of the role of macrophages might lead to a better understanding of the pathogenesis of demyelination.


Relationship between in vivo age and in vitro aging: assessment of 669 cell cultures derived from members of the Baltimore Longitudinal Study of Aging.
We examined the in vitro proliferative potential of 669 cell cultures established from skin biopsies of members of the Baltimore Longitudinal Study of Aging. The colony size distribution was used to estimate the proliferative life span of the cultures. A significant decline in proliferative potential with donor age was observed for female but not male donors. For both male and female donors, the proliferative potential was significantly greater for donors under the age of 30 years compared with all donors over the age of 30 years. In an attempt to reduce genetic heterogeneity, we examined the proliferative potential of cultures derived at different ages from the same donor. These studies revealed a trend (approaching statistical significance) toward low proliferative potential as donors aged. Interestingly, samples obtained from donors who had a history of skin cancer at the time of biopsy had a significantly lower doubling potential than those from donors who did not. The implications of these results for the use of cells derived from donors of different ages for aging research are discussed.


Reliability of traditional and fractal dimension measures of quiet stance center of pressure in young, healthy people.
To assess reliability of traditional and fractal dimension measures of quiet stance center of pressure (COP). Cross-sectional study. University laboratory. Thirty young healthy men (n=20) and women (n=10) (mean age, 23 y). Not applicable. COP was recorded for 3 trials across 4 conditions: eyes open and eyes closed standing on firm and foam surfaces. Traditional COP variables--peak sway velocity and range of sway, both in the anteroposterior (AP) and mediolateral (ML) directions, and total excursion area, and fractal dimension of the COP in the AP and ML directions--were calculated. Reliability statistics were calculated. Range of sway (AP) was the most reliable traditional variable (intraclass correlation coefficient model 2,1 [ICC(2,1)] range -.28 to .72.). Peak sway velocity (AP) had poorest reliability (ICC(2,1) range, .05-.29). Only 1 of the traditional variables had excellent reliability; total excursion area (firm, eyes closed) (ICC(2,1)=.95). All bar 1 fractal dimension measures had excellent ICCs. Relative technical error of measurement ranged from 4% to 7% for the fractal dimension measures. Coefficients of variation were also very good, ranging from 1.8% to 6.7%. Fractal dimension measures were more reliable than traditional measures of COP. Although traditional measures are used extensively to assess COP, their reliability is questionable. Fractal dimension measures show promise to reliably quantify COP and warrant further investigation.


Knee height as a predictor of recumbent length for individuals with mobility-impaired cerebral palsy.
Because accurate measures of recumbent length are essential to assess growth and energy requirements of mobility-impaired individuals with cerebral palsy (CP), a reliable and simple method of estimating recumbent length is required. Prediction of recumbent length from knee height in this population has not yet been investigated. i) To correlate direct measures of recumbent length in mobility-impaired individuals having lower leg extremity cerebral palsy (LECP) involvement with indirect measures of recumbent length calculated using knee-height prediction equations and ii) to determine if knee height is a reliable predictor of recumbent length in this population. Subjects (n = 34; 15F, 19M), aged 6 to 30 years, were participants in a six-month nutrition rehabilitation program. All subjects had varying degrees of LECP involvement. Recumbent length to the nearest 0.5 cm was measured by standardised techniques. Knee height was measured to the nearest 0.5 centimetre using sliding callipers. Equations based on normal, healthy individuals with application to mobility-impaired or handicapped individuals were used to predict recumbent length from knee height. Direct measures of recumbent length of subjects significantly correlated with indirect measures calculated using knee height prediction equations (R = 0.88, p< or =0.0001). In addition, knee height of these subjects was a reliable predictor of recumbent length (R2 = 0.78, p<0.0001). Results suggest that knee height may be a reliable predictor for recumbent length in this population.


Thyroid hormone regulation of alpha-lactalbumin: differential glycosylation and messenger ribonucleic acid synthesis in mouse mammary glands.
Mouse mammary tissue, when cultured in the presence of insulin, corticoids, PRL, and physiological levels of T3, shows increased synthesis and secretion of alpha-lactalbumin. Tissue cultured in the presence of insulin, hydrocortisone, PRL, and T3 synthesizes two distinct forms of alpha-lactalbumin, but secretes only one form. Tissue cultured in the absence of T3 synthesizes and secretes only one form. To address the question of whether these two electrophoretically distinct forms arose by differential glycosylation of the same polypeptide or by synthesis of two different polypeptide precursor chains, mammary tissue was cultured in the presence of insulin, corticoids, and PRL with or without T3, and the mRNA and alpha-lactalbumins were isolated. Northern blot analyses indicated that mammary gland tissue cultured in the presence of T3 contained 2.46 times more alpha-lactalbumin mRNA than tissue cultured only in the presence of insulin, hydrocortisone, and PRL. This enhanced mRNA level was confirmed by in vitro translation experiments where tissue cultured in the presence of insulin, hydrocortisone, PRL, and T3 produced mRNA that resulted in 2.1 times as much radiolabeled alpha-lactalbumin as tissue cultured in the absence of T3. Sodium dodecyl sulfate-polyacrylamide gel analysis of the in vitro translation products revealed only one band, suggesting the presence of only one message. Endoglycosidase digestion of the two forms of alpha-lactalbumin produced in the presence of T3 resolved them into a single band on sodium dodecyl sulfate-polyacrylamide gels. Thus, the electrophoretic differences between the two forms synthesized in the presence of T3 appear to be due to differential N-linked glycosylation of the same polypeptide chain and not to synthesis of two different polypeptide precursor chains.


Shallow knee flexion angle during femoral tunnel creation using modified transtibial technique can reduce femoral graft bending angle in ACL reconstruction.
The purpose of this study was to compare femoral graft bending angle between patients with femoral tunnel reamed at less than 80° of knee flexion and those with 80° and above in anatomical anterior cruciate ligament (ACL) reconstruction using modified transtibial technique. Forty-eight patients who underwent ACL reconstruction using bone-patellar-tendon-bone autograft in modified transtibial technique and CT scan at 1 week postoperatively were included in this study. A femoral guidewire insertion into aimed femoral position at the medial wall of the femoral lateral condyle was started at about 75° of knee flexion. When the tip of the guidewire was blown out into femoral posterior wall, the guidewire was inserted again after increasing knee flexion angle. Distance from femoral tunnel exit on the femoral lateral cortex-femoral posterior cortex (Distance-E) was measured on postoperative lateral radiograph. Femoral and tibial tunnel position was measured on 3-D CT images. In addition, femoral graft bending angle was measured on reconstructed 2-D CT images. Patients were divided into two groups depending on whether femoral tunnel was created at less than 80° of knee flexion (group A) or 80° or more (group B). There were 32 patients in group A and 16 patients in group B, respectively. Average knee flexion angle was 77.2° [standard deviation (SD) 1.6] in group A and 83.6° (SD 2.4) in group B, respectively (p < 0.05). Average Distance-E was 5.1 mm (SD 2.6) in group A and 6.6 mm (SD 3.8) in group B, respectively. There was no significant difference in the femoral and tibial tunnel position between group A and B. Femoral graft bending angle was significantly smaller in group A [average angle: 50.9° (SD 6.6)] than in group B [average angle: 55.0° (SD 6.6)] (p < 0.05). Anatomical femoral tunnel was able to be created at less than 80° of knee flexion in two-thirds of patients. Shallower flexion angle (less than 80°) provided gentler femoral graft bending angle compared to 80° or more of knee flexion. Therefore, femoral tunnel creation in modified transtibial technique should be started at between 75° and 80° of knee flexion to reduce femoral graft bending angle. Shallow knee flexion angle during femoral tunnel creation using modified transtibial technique can reduce femoral graft bending angle and may lead to better clinical outcomes in ACL reconstruction. Retrospective comparative study, Level III.


[Nutritional Status of Japanese Women of Childbearing Age and the Ideal Weight Range for Pregnancy].
According to the recent 2015 Nutrition Survey, the prevalence of being underweight (Body Mass Index, BMI <18.5 kg/m2) among women in their 20s is 22.3%. Women of childbearing age tend to have a lower intake of protein and their total energy intake is lower than the requirements established by the 2015 Dietary Reference Intakes for Japanese. There is a growing body of evidence showing that underweight women tend to bear small babies and that these babies have an increased risk of diabetes or cancer in their adulthood. In order to prevent Japanese women from bearing small babies, the literature has suggested that women of childbearing age should be encouraged to remain at a normal weight before pregnancy. For optimal weight gain during pregnancy, existing guidelines recommend different ranges of weight gain based on prepregnancy BMI. Owing to the absence of official GWG recommendations in Asian countries, including China and Taiwan, the US Institute of Medicine (IOM) guidelines are generally followed. However, Asian women are smaller and experience lower weight gains; therefore, excessive weight gain may lead to harmful events including macrosomia, preterm birth, preeclampsia, gestational diabetes, pregnancy-induced hypertension, and short- and long-term postpartum weight retention. Thus, an accurate GWG range should be determined for Asian women. We introduce one epidemiological study in which the optimal weight gain range was investigated by analyzing receiver-operating characteristic curves together with potential research ideas in this field with the aim of encouraging young researchers to solve this public health problem affecting mothers and children.


Fooled by the fragments: vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura.
Background: Thrombotic thrombocytopenic purpura (TTP) is a hematological emergency requiring prompt plasmapheresis. Conversely, vitamin B12 deficiency is a relatively benign diagnosis that can mimic microangiopathic hemolytic anemia, characterized by the presence of anemia, thrombocytopenia, indirect hyperbilirubinemia, markers of hemolysis, and schistocytes. This case series highlights the association of vitamin B12 deficiency and its TTP-like presentations. Cases: The first case describes a 72-year-old man with shortness of breath and weakness. Diagnostics were notable for pancytopenia, schistocytes, and a low reticulocyte index. Intriguingly, total bilirubin was only mildly elevated however LDH and Haptoglobin were elevated and low, respectively. Additional diagnostic workup demonstrated an undetectable B12, elevated methylmalonic acid and elevated homocysteine. Initiation of B12 supplementation resolved his pancytopenia. The second case describes a 57-year-old man with chest tightness, dyspnea on exertion, and night sweats. Diagnostic evaluation demonstrated pancytopenia, schistocytes, a low reticulocyte index, and a remarkably low B12. He had associated high methylmalonic acid and homocysteine levels, confirming the diagnosis. B12 supplementation resolved his pancytopenia. Conclusion: The polysymptomatic presentation of vitamin B12 deficiency-induced pseudothrombotic microangiopathy highlights the vitamin's role in essential physiological cellular functions. Rapid recognition of the underlying etiology of microangiopathic hemolytic anemia is necessary as treatment approaches diverge greatly.


Preventing and Treating Trauma, Building Resiliency: The Movement Toward Compassionate Schools in Watauga County, North Carolina.
Trauma affects the brain in many ways, including impairing one's ability to learn, creating psychological and emotional issues, and contributing to poorer health outcomes. This is not only true for children but for adults as well, contributing to social issues such as erratic job performance, increase in homelessness rates, addiction rates, and higher rates of domestic violence and child abuse. We must be more effective at preventing and treating trauma and promoting resiliency in order to make the members of our societies as safe and productive as they can be. In Watauga County, North Carolina, an initiative is taking on that very challenge.


Curcuminoids modulates oxidative damage and mitochondrial dysfunction in diabetic rat brain.
Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage and mitochondrial dysfunction. The aim of the present study is to investigate the effects of curcuminoids, polyphenols of Curcuma longa (L.) on oxidative stress and mitochondrial impairment in the brain of streptozotocin (STZ)-induced diabetic rats. A marked increase in lipid peroxidation and nitrite levels with simultaneous decrease in endogenous antioxidant marker enzymes was observed in the diabetic rat brain, which was restored to normal levels on curcuminoids treatment. Down-regulation of mitochondrial complex I and IV activity caused by STZ induction was also up-regulated on oral administration of curcuminoids. Moreover, curcuminoids administration profoundly elevated the ATP level, which was earlier reduced in the diabetic brain. These results suggest that curcuminoids exhibit a protective effect by accelerating antioxidant defense mechanisms and attenuating mitochondrial dysfunction in the brain of diabetic rats. Curcuminoids thus may be used as a promising therapeutic agent in preventing and/or delaying the progression of diabetic complications in the brain.


Mesorhizobium helmanticense sp. nov., isolated from Lotus corniculatus nodules.
In this study, three strains belonging to the genus Mesorhizobium, CSLC115NT, CSLC19N and CSLC37N, isolated from Lotus corniculatus nodules in Spain, were characterized. Their 16S rRNA gene sequences were closely related to those of Mesorhizobium metallidurans STM 2683T, Mesorhizobium tianshanense A-1BST, Mesorhizobium tarimense CCBAU 83306T, Mesorhizobium gobiense CCBAU 83330T and Mesorhizobium caraganae CCBAU 11299T with similarity values higher than 99.7 %. The analysis of concatenated recA and glnII genes showed that the most closely related type strains were M. metallidurans STM 2683T, M. tianshanense A-1BST and M. tarimense CCBAU 83306T with 96, 95 and 94 % similarity values in the recA gene and 95, 94 and 94 % in the glnII gene, respectively. M. metallidurans LMG 24485T, M. tianshanense USDA 3592T and M. tarimense LMG 24338T showed means of 44, 41 and 42 % DNA-DNA relatedness, respectively, with respect to strain CSLC115NT. The major fatty acids were those from summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), C16 : 0 and C18 : 1ω7c 11-methyl. The results of phenotypic characterization support that the L. corniculatus nodulating strains analysed in this work belong to a novel species of the genus Mesorhizobium for which the name Mesorhizobium helmanticense sp. nov. is proposed, and the type strain is CSLC115NT (= LMG 29734T=CECT 9168T).


Use of cone beam computed tomography in identifying postmenopausal women with osteoporosis.
The aim of this study is to correlate radiometric indices from cone beam computed tomography (CBCT) images and bone mineral density (BMD) in postmenopausal women. Quantitative CBCT indices can be used to screen for women with low BMD. Osteoporosis is a disease characterized by the deterioration of bone tissue and the consequent decrease in BMD and increase in bone fragility. Several studies have been performed to assess radiometric indices in panoramic images as low-BMD predictors. The aim of this study is to correlate radiometric indices from CBCT images and BMD in postmenopausal women. Sixty postmenopausal women with indications for dental implants and CBCT evaluation were selected. Dual-energy X-ray absorptiometry (DXA) was performed, and the patients were divided into normal, osteopenia, and osteoporosis groups, according to the World Health Organization (WHO) criteria. Cross-sectional images were used to evaluate the computed tomography mandibular index (CTMI), the computed tomography index (inferior) (CTI (I)) and computed tomography index (superior) (CTI (S)). Student's t test was used to compare the differences between the indices of the groups' intraclass correlation coefficient (ICC). Statistical analysis showed a high degree of interobserver and intraobserver agreement for all measurements (ICC > 0.80). The mean values of CTMI, CTI (S), and CTI (I) were lower in the osteoporosis group than in osteopenia and normal patients (p < 0.05). In comparing normal patients and women with osteopenia, there was no statistically significant difference in the mean value of CTI (I) (p = 0.075). Quantitative CBCT indices may help dentists to screen for women with low spinal and femoral bone mineral density so that they can refer postmenopausal women for bone densitometry.


High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF.
Pancreatic cancer still has one of the worst prognoses in gastrointestinal cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. In this study, we investigated the prognostic values of HIF1a, bFGF, VEGF, and PDGFA gene expressions as well as their interrelationships. Formalin-fixed paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma (age, 65; range, 34-85 years). After laser capture microdissection, direct quantitative real-time reverse transcription-polymerase chain reaction assays were performed in triplicates to determine HIF1a, PDGFA, VEGF, and bFGF gene expression levels. Multivariate Cox proportional hazards regression analysis was used to assess the impact of HIF1a gene expression on prognosis. HIF1a was significantly correlated to every gene we tested: bFGF (P = .04), VEGF (P = .02), and PDGFA (P = .03). Tumor size, P = .04, and high HIF1a mRNA expression (cutoff, 75th percentile) had a significant impact on survival, P = .009 (overall model fit, P = .02). High HIF1a expression had a sensitivity of 87.1% and a specificity of 55.6% for the diagnosis short (<6 months) versus long (6-60 months) survival. Measuring PDGFA, bFGF, and HIF1a expression may contribute to a better understanding of the prognosis of patients with pancreatic cancer and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Larger studies including patients treated with actual chemotherapeutics seem to be warranted.


Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman.
Pipobroman (PB) is a neutral amide of piperazine with a chemical structure close to that of alkylating agents, although the exact mechanism of action of PB has not been demonstrated. PB has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). Recent long-term follow-up studies on PV and ET patients receiving PB have facilitated the definition of the risk of late transformation into myelofibrosis with myeloid metaplasia (MMM) or acute leukemia (AL). This report gives an overview of the treatment with PB in patients with PV and ET focusing on clinical activity, administration dose and schedule, toxicity, impact on short- and long-term complications. From our experience and from the data reported in the literature the high clinical activity of PB in both PVand ET becomes evident. This drug allows, within 3 months, to attain a response in more than 90% of patients, without clinically relevant toxicities. The 10-years risk of thrombosis of patients treated with PB is about 15%, similar to that registered with hydroxyurea, the most widely used agent in PVand ET. The antiproliferative activity of PB on bone marrow megakaryocytes seems of particular value in lowering the occurrence of post-PV and post-ET MMM, whose risk (< 4% at 10 years) is the lowest registered with available treatments. The 10-year risk of acute leukemia with PB is 5% in PVand 3% in ET, which is only slightly higher than that expected as a natural evolution of the disease. In conclusion, the use of PB is a definite alternative to hydroxyurea in patients with PV and ET at high risk of thrombosis.


Synthetic Osteogenic Growth Peptide Stimulates Osteoblast Osteogenic Activity and Enhances Fracture Healing in Rabbits.
sOGP was synthesized by standard solid phase method, with the purity of 99.2% shown by HPLC and CE. Its amino acid sequence and MS were consistent with theoretical values. In New Zealand white rabbits, sOGP could promote the for mation of new bone and up-regulate the serum level of ALP and BGP as observed by means of biochemical analysis, X-ray, bone mineral density, callus tissue histological analysis and biomechanical tests, demonstrating that sOGP might play a significant role in the tibia fracture healing. Particularly the bone density at 4 weeks and the amounts of trabecular bone in the callus at 2 and 4 weeks of the sOGP-treated group were significantly different from those of control group (P<0.05). Effects of sOGP in different medium in vitro has been studied. sOGP could accelerate osteogenic cell proliferation in 1%BSA-10%NCS-MEM in a dose dependent manner, with a peak at 10(-11) mol/L. But interestingly, this prolife ration activity was not observed in 10%NCS-MEM or 4%BSA-serum free MEM. It suggests that sOGP's osteogenic cell proliferation effects may depend on the involvement of BSA and some regulatory molecules in serum.


Effect of D-Ala-Ended Peptidoglycan Precursors on the Immune Regulation of Lactobacillus plantarum Strains.
The resistance of Lactobacillus plantarum to vancomycin depends on its peptidoglycan composition. Vancomycin has poor binding affinity with peptidoglycan precursors ending in D-alanyl-D-lactate (D-Ala-D-Lac) but binds strongly to peptidoglycan precursors ending in D-alanyl-D-alanine (D-Ala-D-Ala), resulting in resistance and sensitivity, respectively. The ligase Ddl, which generates D-Ala-D-Lac or D-Ala-D-Ala incorporated into the peptidoglycan precursor chain, is responsible for this specificity. To study the effect of peptidoglycan precursors on immunity, we constructed several strains of L. plantarum expressing the ddl gene of Lactococcus lactis to change their peptidoglycan precursors. The change in the termini of the peptidoglycan precursors was determined by the sensitivity of the strains to vancomycin. The overexpression of ddl increased the susceptibility of the strains to vancomycin. We further explored the regulation of the macrophage inflammatory response pathway by the wild-type and constructed strains, and found that these strains induced the MyD88-dependent TRAF6/MAPK pathway, and the increase in D-Ala L. plantarum peptidoglycan precursors increased the secretion of the inflammatory factors IL-6, IL-1β and TNF-α. These results indicate that D-Ala-ended peptidoglycan precursors play a central role in the variable immunomodulatory ability of L. plantarum.


Human nasal turbinates as a viable source of respiratory epithelial cells using co-culture system versus dispase-dissociation technique.
To compare a co-culture system with a conventional dispase-dissociation method for obtaining functional human respiratory epithelial cells from the nasal turbinates for tissue engineering application. Human respiratory epithelial cells were serially passaged using a co-culture system and a conventional dispase-dissociation technique. The growth kinetics and gene expression levels of the cultured respiratory epithelial cells were compared. Four genes were investigated, namely cytokeratin-18, a marker for ciliated and secretory epithelial cells; cytokeratin-14, a marker for basal epithelial cells; MKI67, a proliferation marker; and MUC5B, a marker for mucin secretion. Immunocytochemical analysis was performed using monoclonal antibodies against the high molecular-weight cytokeratin 34 beta E12, cytokeratin 18, and MUC5A to investigate the protein expression from cultured respiratory epithelial cells. Respiratory epithelial cells cultured using both methods maintained polygonal morphology throughout the passages. At passage 1, co-cultured respiratory epithelial showed a 2.6-times higher growth rate compared to conventional dispase dissociation technique, and 7.8 times higher at passage 2. Better basal gene expression was observed by co-cultured respiratory epithelial cells compared to dispase dissociated cells. Immunocytochemical analyses were positive for the respiratory epithelial cells cultured using both techniques. Co-culture system produced superior quality of cultured human respiratory epithelial cells from the nasal turbinates as compared to dispase dissociation technique.


Kinetic Modeling of the Nickel-Catalyzed Esterification of Amides.
Nickel-catalyzed coupling reactions provide exciting tools in chemical synthesis. However, most methodologies in this area require high catalyst loadings, which commonly range from 10-20 mol % nickel. Through an academic-industrial collaboration, we demonstrate that kinetic modeling can be used strategically to overcome this problem, specifically within the context of the Ni-catalyzed conversion of amides to esters. The successful application of this methodology to a multigram-scale coupling, using only 0.4 mol % Ni, highlights the impact of this endeavor.


Esophageal gel-shifting technique facilitating eradicative boost or reirradiation to upper mediastinal targets of recurrent nerve lymph node without damaging esophagus.
We developed a new technique using hyaluronic gel injection as a spacer to safely move the esophagus away from the high-dose area during interstitial brachytherapy of a mediastinal target close to the esophagus. We percutaneously injected a high-molecular-weight hyaluronic gel mixed with contrast medium to create a space between the esophagus and the target during interstitial brachytherapy. We applied this technique to two cases of relapsed recurrent nerve lymph node metastasis from esophageal cancer: one refractory tumor after 50 Gy of radiotherapy, and one recurrence after mediastinal radiotherapy of total 64 Gy. We prescribed 20 Gy and 18 Gy in one fraction to each target, with calculated esophageal D2cc (the minimum dose to the most irradiated volume of 2 cc) of 4.0 Gy and 6.8 Gy, respectively. Calculated enhancement factor by gel shifting in equivalent dose was 2.69 and 2.34, respectively. In each patient, accumulated esophageal D1cc (minimum dose to the most irradiated volume of p cc. minimum dose to the most irradiated volume of 1 cc) was 74.4 Gy and 85.6 Gy without shifting, and 59.1 Gy and 37.6 Gy with shifting, respectively. There were no procedure-related complications. Four months after the brachytherapy, each tumor was remarkably diminished. No evidence of recurrences or late complications were observed 8 months and 9 months after the procedure, respectively. The esophageal gel-shifting technique may facilitate eradicative brachytherapy to upper mediastinal targets without damaging the esophagus, and can be used in conjunction with boost irradiation or reirradiation to overcome the problem of salvage failure.


miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway.
Silica exposure triggers inflammatory response and pulmonary fibrosis that is a severe occupational or environmental lung disease with no effective therapies. The complicated biological and molecular mechanisms underlying silica-induced lung damages have not yet been fully understood. miR-135a inhibits inflammation, apoptosis, and cancer cell proliferation. But the roles of miRNA135a involved in the silica-induced lung damages remain largely unexplored. We investigated the roles and mechanisms of miR-135a underlying silica-induced pulmonary fibrosis. The present study showed silica exposure caused the decrease in miR-135a level but the increase in inflammatory mediators. Transduction of lentivirus expressing miR-135a reduced the level of inflammatory mediators in lung tissues from silica-treated mice and improved pulmonary fibrosis which was consistent with the downregulated α-SMA but enhanced E-cadherin. Moreover, miR-135a overexpression inhibited p-p65 level in lung tissues. Overexpression of miR-135a inhibitor strengthened TLR4 protein level and NF-κB activation in BEAS-2B cells. Injection of PDTC, an inhibitor of NF-κB, further reinforced miR-135a-mediated amelioration of inflammation and pulmonary fibrosis induced by silica. The collective data indicate miR-135a restrains NF-κB activation probably through targeting TLR4 to alleviate silica-induced inflammatory response and pulmonary fibrosis.


Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostate Cancer and Glioblastoma Cells.
Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA4 giant amphiphiles to access DTX carriers with tunable properties.


Risk factors associated with weak and asymmetric handgrip strength in older Chinese adults.
This study sought to investigate the potential risk factors associated with weak and asymmetric handgrip strength (HGS) in older Chinese adults. A total of 2702 participants aged ≥65 years from the two waves of data (2011 and 2013) from the China Health and Retirement Longitudinal Study were analyzed. The highest recorded HGS values (Method A) or the average HGS values (Method B) for the dominant hand were used to compute the HGS asymmetry (nondominant HGS/dominant HGS out of 0.9-1.1) and HGS weakness (male <28 kg, female <18 kg). Risk factors associated with the weak and asymmetric HGS were identified by logistic regression analysis. Risk factors associated with weak and asymmetric HGS of varying severity differed between the two methods. Both methods identified age and illiteracy as risk factors for weak HGS with 10%-20% asymmetry. Method A also identified speech impediment, stroke, and sleep duration as additional risk factors. Similarly, both methods identified age, illiteracy, primary school education and below, diabetes, and stroke as risk factors for weak HGS and asymmetry over 30.1%. Method B additionally identified a history of falls as a risk factor. However, apart from age, the risk factors for weak HGS with 20.1%-30% asymmetry differed between the two methods-Method A identified kidney disease, while Method B identified illiteracy and asthma. The results revealed that risk factors associated with the abnormal HGS in older adults varied based on the methods used to define these conditions.


W323S variant of Xiap-Bir3 binds to SMAC but not caspase-9.
The ability of the wild-type XIAP BIR3 domain as well as its Trp323Ser variant in inhibition of human caspase-9, binding to AVPFVASLPN (SMAC-peptide), SMAC protein, and mature caspase-9 was investigated. In order to investigate the role of W323 on these interactions, this residue was mutated to Serine. Circular dichroism as well as thermal denaturation studies showed that W323S mutation did not hamper proper folding of the protein. The dissociation constants for the interaction of the wild type BIR3 as well as its mutant to Smac-type peptide were found to be 1.8 and 27 muM, respectively. The inhibition of and binding to caspase-9 by wild-type BIR3 and its mutant were also compared. While the wild-type protein potently inhibited the enzyme, the mutant failed to do so. The lack of caspase-9 inhibition was due to absence of interaction of the mutant BIR3 with mature caspase-9. These results indicate that Trp323 of BIR3 plays a pivotal role both in maintaining necessary conformation for caspase-9 interaction and to a lesser extent, recognition of Smac-type peptide. Moreover, decreased stability of the mutant compared with the wild type indicates that W323 is essential for maintaining the stability BIR3-Smac-peptide complex.


Purification and gene cloning of an enantioselective thioesterification enzyme from Brevibacterium ketoglutamicum KU1073, a deracemization bacterium of 2-(4-chlorophenoxy)propanoic acid.
We succeeded in the purification and gene cloning of a new enzyme, α-methyl carboxylic acid deracemizing enzyme 1 (MCAD1) from Brevibacterium ketoglutamicum KU1073, which catalyzes the (S)-enantioselective thioesterification reaction of 2-(4-chlorophenoxy)propanoic acid (CPPA). The cloned gene of MCAD1 contained an ORF of 1,623 bp, encoding a polypeptide of 540 amino acids. In combination with cofactors ATP, coenzyme A (CoASH), and Mg(2+), MCAD1 demonstrated perfect enantioselectivity toward CPPA. The optimal pH and temperature for reaction were found to be 7.25 and 30 °C. Under these conditions, the K(m) and k(cat) values for (S)-CPPA were 0.92 ± 0.17 mM and 0.28 ± 0.026 s(-1) respectively. The results for substrate specificity revealed that MCAD1 had highest activity toward fatty acid tails with a medium chain-length (C(8)). This result indicates that MCAD1 should be classified into a family of medium-chain acyl-CoA synthetase. This novel activity has never been reported for this family.


Identifying behavior change techniques for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia.
Nursing home residents with dementia are commonly prescribed antipsychotics despite the associated increased risk of harms. Interventions to optimize prescribing practice have been found to be effective in the short term, but there is a lack of evidence to support sustainability of effects, along with a lack of theory, public involvement, and transparency in the intervention development process. Using theory has been advocated as a means of improving intervention sustainability. The aim of this study was, therefore, to identify behavior change techniques (BCTs) for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia. A comprehensive approach to identifying a long list of all potential BCTs from three different sources was undertaken. The most appropriate BCTs were then selected through a two-round Delphi consensus survey with a broad range of experts (n = 18 panelists). Advisory groups of people with dementia, family carers, and professional stakeholders provided feedback on the final BCTs included. After two Delphi survey rounds, agreement was reached on 22 BCTs. Further refinement of the selected BCTs based on advisory group and panelists' feedback, along with use of the APEASE criteria (Affordability, Practicability, Effectiveness, Acceptability, Side effects/safety, and Equity) resulted in a final list of 16 BCTs. The next step in intervention development will be to identify the most appropriate mode of delivery of the 16 BCTs identified for inclusion. The study provides a case example of a systematic approach to incorporating evidence with stakeholder views in the identification of appropriate BCTs.


Multicentre study, in patients with imported malaria, on the sensitivity and specificity of a dipstick test (ICT Malaria P.f./P.v.) compared with expert microscopy.
A prospective, multicentre study was carried out in Italy to assess the sensitivity and specificity of a rapid dipstick test (ICT Malaria P.f./P.v.) in the diagnosis of imported malaria caused by Plasmodium falciparum and other Plasmodium spp. The test is based on the detection of histidine-rich protein-2 (HRP-2) from P. falciparum and 'panmalarial' antigen in peripheral blood. The 241 subjects were international travellers or immigrants from areas where malaria is endemic. When compared with the microscopical examination of bloodsmears (used as the 'gold standard'), the dipsticks were found to be 94.4% sensitive and 94.5% specific for pure infections with P. falciparum. The performance of the tests when used on patients infected with species other than P. falciparum or more than one Plasmodium spp. showed a high degree of variability. Although the dipsticks represent a very simple, rapid, and valuable diagnostic aid, they should not be considered a complete substitute for direct microscopical diagnosis using stained bloodsmears.


Unusual Case of Long Head of Biceps Tendon Synovial Chondromatosis.
Synovial chondromatosis is a rare benign tumor involving the major joints. This condition results from metaplasia of synovium into chondrocytes leading to formation of multiple loose bodies. Extra articular glenohumeral joint synovial chondromatosis involving long head of biceps is very rare. A 38-year-old male presented with history of insidious onset, dull aching pain in right shoulder for 6 months. Clinicoradiological examination revealed calcific mass around the long head of biceps tendon. The calcific mass and loose bodies were removed en bloc. Histopathological examination concurred to be synovial chondromatosis. We hereby report a rare case of long head biceps tendon synovial chondromatosis of shoulder which was successfully treated by combined arthroscopic and open method. The results of surgical excision are excellent.


The strength and fracture toughness of calcium hydroxide preparations.
The strength of a brittle material depends upon the toughness of the material itself and the degree of perfection with which it can be placed. This study shows that both the compressive and tensile strength of calcium hydroxide lining materials is dependent on the fracture toughness at unstable crack propagation, KIC, and the size, number and distribution of pores (which are the defects that nucleate fracture). Of the products tested here, Dycal possesses the greatest actual strength due to a higher than average KIC value and relatively few isolated small pores. However, the greatest potential for strength exists in Reocap which has a KIC value a factor of 2.4 greater than its nearest rival (Dycal). Unfortunately its strength, as determinedhere, is less than Dycal due to the large number of pores in close proximity to each other.


[SUPPRESSION OF A NON-TRAUMA-RELATED THREATENING THOUGHT AS AN AVOIDANCE STRATEGY IN POST-TRAUMATIC STRESS DISORDER PATIENTS].
Our goal was to examine how suppression of nontrauma- related thoughts differs between PTSD patients and patients with non-PTSD anxiety disorder compared to a group of matched controls. Intrusive recollections of aspects of the traumatic event and its sequelae are at the core of the post-traumatic stress disorder (PTSD). People who have suffered a traumatic event may implement some form of avoidance coping strategies in order to deal with the unwanted memories that accompany them. Thought suppression refers to the conscious effort that is made in order NOT to think about a particular thought and is used to regulate affect. The effects of thought suppression on trauma survivors indicates that suppression of trauma related thoughts produces a rebound effect, increasing frequency of negative autobiographical memory recall and may result in the maintenance of PTSD symptoms. The results show that PTSD patients differed in their performance of purposeful suppression of non-traumarelated thoughts, and spent significantly longer time thinking about the target thought during suppression as compared to the control groups. The duration to disengage attention from any thought content was significantly longer in PTSD patients as compared to the anxiety group and controls. We suggest that PTSD patients demonstrated a mental control deficient in self-regulatory mechanisms involved in coping with threat. While PTSD patients used external objects in the room, the control groups used mental contents as distractors. When given suppression instructions, such as distraction thought, all groups demonstrated shorter duration to disengage attention, but the PTSD patients exhibited the significant advantage.


Biological significance of perineural invasion (PNI) in prostate cancer.
In order to better understand the biological significance of perineural invasion (PNI) in prostate cancer, we aimed to analyze in situ the expression of molecules involved in tumor growth or nerve trophicity. Tissues from 66 radical prostatectomies performed for prostate cancer (40 with PNI and 26 without PNI) were selected and included in a tissue microarray (TMA): PNI areas (when available), cancer far from nerves, and nerves far from cancer. The expression of the following molecules was analyzed using immunohistochemistry on TMA slides: macrophage migration inhibitory factor (MIF) and its receptor CD74, EGF receptor (EGFR), heregulin (HRG) and its receptor ErbB3, and the proliferation marker Ki67. Cancer cells in the PNI areas showed increased proliferation, EGFR and CD74 expression, when compared to cells far from nerves (P = 0.009, 0.0005, and 0.02, respectively). Moreover, cell proliferation and CD74 staining were increased in cancers with PNI features compared to cancers without PNI (P = 0.001), even when adjusting for Gleason score, tumor size, and pathological stage. These results suggest that cancer cells in the PNI areas could acquired a growth advantage that could be triggered by the growth factor receptors EGFR and CD74.


[Clinical and pharmacological approaches to the choice of a drug for a tension-type headache relief].
The article goes to describe clinical and pharmacological approaches to choosing a drug with an optimal efficacy/safety profile, providing the necessary analgesic effect in tension-type headache. TRPV1 brain receptors are considered the main action point of the mediator. The purpose of this study is a comparative analysis of the pharmacodynamic and pharmacokinetic parameters of ibuprofen and paracetamol as a part of fixed dose combination and as monotherapy in tension type headaches. Comparative dissolution kinetics test; Comparative analysis of pharmacokinetic parameters using the PubMed/MEDLINE database. The median Tmax of ibuprofen as a part of a fixed-dose combination and as a monotherapy is 75 minutes. The median Tmax of paracetamol is 30 min when taken in a fixed dose combination and 40 min as a monotherapy. In patients who received the fixed dose combination, the concentration of ibuprofen in the blood plasma after 10 minutes 6.64 g/ml-1; after 20 minutes 16.81 g/ml-1, while when taken in the same dose in as a monotherapy, respectively, 0.58 and 9.00 g/ml-1. The mean plasma concentrations of paracetamol after 10 and 20 minutes in patients receiving the fixed combination were 5.43 and 14.54 g/ml-1, respectively, compared with 0.33 and 9.19 g/ml-1 for paracetamol as monotherapy. dissolution kinetics test of the Paracytolgin: after 5 minutes, 20% of paracetamol passed into the solution in a system with a pH of 1.2; in a system with a pH of 4.5 36.4%; in a system with a pH of 6.8 33.5%; after 10 minutes, respectively 68.5, 98.0 and 89.6%. After 15 minutes, almost complete dissolution was noted in all systems: 98.5, 98.8 and 100.5%, respectively. The combination of ibuprofen and paracetamol makes it possible to enhance the analgesic effect as a result of additive action by the help of central mechanisms. The fixed dose combination of ibuprofen and paracetamol significantly increases the rate of absorption of paracetamol, which has potential therapeutic benefits in terms of a faster analgesias onset. The fixed dose combination of ibuprofen and paracetamol provides faster and long-term anaesthesia with a comparatively lower dosage of each analgesic.


Recognition of polarization and phase states of light based on the interaction of non-uniformly polarized laser beams with singular phase structures.
We propose to analyze the polarization and phase states of laser beams using a fixed set of non-polarizing phase elements. The experimental implementation of the proposed method is based on the use of multi-order phase-diffractive optical elements (DOEs). The presence or absence of intensity maxima (information bits) corresponding to the numbers of diffraction orders allows an identification code (a codeword) to be obtained. The resulting codeword makes it possible to uniquely determine the order of the vortex singularity and the order of the cylindrical polarization of the laser beam in various combinations based on simple relations.


[Experimental techniques for developing new drugs acting on dementia (1)--Senescence-accelerated mouse: neurochemical approaches and the findings].
The senescence-accelerated mouse (SAM) was established by Takeda et al (1991) as a model of accelerated aging. A P/8 strain of SAM spontaneously shows learning and memory disturbances with increasing age. Several neurochemical markers were examined in the brain of mice of P/8 strain and were compared with those in the R/1 strain as a control. Here, the author describes neurochemical methods and our findings obtained by the methods regarding measurement of: 1) the glutamate content, 2) release of glutamate and acetylcholine (ACh) from brain slices, 3) ligand bindings to neurotransmitter receptors (NMDA, muscarinic ACh), protein kinase C and glial cells and 4) mRNA expression and metabolism of amyloid precursor protein (APP).


Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions.
Oxidative stress is damaging to cells and contributes to aging and neurodegenerative disease. This state is mediated by production of imbalanced molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The glyoxalase pathway is an antioxidant defense system utilized to detoxify methylglyoxal and neutralize free radicals. Pathway dysfunction leads to overproduction and accumulation of toxic, prooxidant compounds. We hypothesize flavonoid treatment as a means to enhance the glyoxalase pathway's ability to detoxify in neurons. This study found that flavonoid treatment in methylglyoxal treated cerebellar neurons increased the functioning of glyoxalase pathway by enhancing expression of glyoxalase-1 and glyoxalase-2 proteins, decreased cell death and increased cellular viability. Flavonoids also significantly contributed in the retention of synaptic functions (VGLUT1 and GAD65) in cerebellar neurons. In addition, flavonoids were found to be involved in pAkt - NF-κB signaling pathway through a reduction in phosphorylation of Akt. The data here show flavonoid compounds have the potential to protect the brain from aging and neurodegenerative disease.


Intra-operative parathyroid identification using methylene blue in parathyroid surgery.
The objective of this study was to determine the value of intra-operative methylene blue (MB) during parathyroid surgery. We did a retrospective study of 473 patients after initial exploration for previously untreated symptomatic primary hyperparathyroidism. Procedural and post procedural data were collected on four groups of patients: minimally invasive parathyroidectomy with MB (n = 147), and without MB (n = 205), bilateral parathyroid exploration with intra-operative parathormone assay with MB (n = 56), and without MB (n = 65). Length of surgery was shorter for patients explored with MB (P = 0.026). For the minimally invasive parathyroidectomy group, the difference between the MB and non-MB groups was seven minutes. Twelve minutes was the difference between the MB and non-MB intra-operative parathormone assay groups. Length of stay, local complications, and correction of hypercalcemia after parathyroidectomy were not significantly affected by the use of MB. Systemic complications were lower in the MB groups. Aside from a statistically significant, but quantitatively minimal decrease in the length of surgery, no consistent benefit was identified with the use of MB for intra-operative parathyroid identification.


Diagnosis of corticosteroid insufficiency in Thai patients with septic shock.
The reported incidence of critical illness-related corticosteroid insufficiency (CIRCI) varies widely, depending on the patient population studied and the diagnostic criteria used. Surviving Sepsis Campaign guidelines suggest that corticosteroid therapy should be considered for adult septic shock when hypotension responds poorly to adequate fluid resuscitation and vasopressors, regardless of any results of diagnostic tests. However, steroid treatment may be associated with an increase risk of infection. This study aims to identify the best diagnostic tool for predicting responsiveness to corticosteroid therapy in Thai septic shock patients with poorly responsive to fluid resuscitation and vasopressors. Twenty-nine septic shock patients who were poorly responsive to fluid therapy and vasopressors were studied. A baseline serum total cortisol was measured in all patients and then 250 mcg corticotropin was injected to patients. Cortisol level was obtained 30 and 60 minutes after injection. All patients were given hydrocortisone (100 mg i.v., then 200 mg i.v. in 24 hrs for at least 5 days). Patients were considered steroid responsive if vasopressor agent could be discontinued within 48 hrs after the first dose of hydrocortisone. Hospital mortality was 62% in which 45% of the patients were steroid responsive. Baseline serum cortisol was 27.6 +/- 11.4 microg/dl in the steroid-responsive patients compared with 40 +/- 16.9 microg/dl in the steroid-nonresponsive patients (p = 0.03). The area under the ROC curves for predicting steroid responsiveness was 0.72 for baseline cortisol level. Serum cortisol level of 35 microg/dl or less was the most accurate diagnostic threshold to determine hemodynamic response to hydrocortisone treatment (p = 0.04). Using baseline cortisol level of < or = 35 microg/dl to diagnose adrenal insufficiency, the sensitivity was 85%, the specificity was 62% and the accuracy was 72%. A use of (delta cortisol) showed sensitivity of 50%, specificity of 30% and accuracy of 41%. Baseline cortisol level < or = 35 microg/dl is a useful diagnostic threshold for diagnosis of steroid responsiveness in Thai patients with septic shock and ACTH stimulation test should not be used.


p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease.
p38γ MAPK (also called ERK6 or SAPK3) is a family member of stress-activated MAPKs and has common and specific roles as compared to other p38 proteins in signal transduction. Recent studies showed that, in addition to inflammation, p38γ metabolic signaling is involved in physiological exercise and in pathogenesis of cancer, diabetes, and Alzheimer's disease, indicating its potential as a therapeutic target. p38γphosphorylates at least 19 substrates through which p38γ activity is further modified to regulate life-important cellular processes such as proliferation, differentiation, cell death, and transformation, thereby impacting biological outcomes of p38γ-driven pathogenesis. P38γ signaling is characterized by its unique reciprocal regulation with its specific phosphatase PTPH1 and by its direct binding to promoter DNAs, leading to transcriptional activation of targets including cancer-like stem cell drivers. This paper will review recent findings about p38γ inflammation and metabolic signaling in physiology and diseases. Moreover, we will discuss the progress in the development of p38γ-specific pharmacological inhibitors for therapeutic intervention in disease prevention and treatment by targeting the p38γ signaling network.


Patients´ satisfaction concerning direct anterior dental restoration.
The objective of this study was to observe patients' satisfaction with their in-service direct anterior dental restorations and to compare it with clinical evaluation using FDI (Federation Dental International) criteria. Patients scored their own anterior dental restorations regarding satisfaction (satisfactory /dissatisfactory). If dissatisfaction was mentioned, then, they would be interviewed about the complaint. In the same session, the dental restorations were clinically evaluated by two dentists using FDI criteria (1-5 score) concerning esthetic, functional, and biological domains. Descriptive statistics were used for frequencies of scores attributed by patients and clinicians. In order to compare patients' to clinicians' frequencies, the Chi-square test was applied (p ≤ 0.05). A total of 106 restorations were evaluated by patients and clinicians. Patients reported 52.8% of restorations satisfactory and 47.8% dissatisfactory. Overall, clinicians reported the same restorations as 82,3% satisfactory and 17,6% dissatisfactory. Patients' most frequent complaints referred to color, followed by anatomical form, fracture of material and retention, and approximal anatomical form. Comparing patients' satisfaction and dissatisfaction rates to clinicians' evaluation per criteria, there was no difference regarding esthetics. The frequency of dissatisfactory restorations by clinicians was significantly lower when functional and biological properties were compared with patients' opinions. Direct anterior dental restorations were more frequently reported as satisfactory by patients and clinicians, being the main complaints related to esthetic issues. When clinicians and patients' evaluations were compared, it was observed that the frequencies of satisfactory restoration by patients and clinicians were similar regarding esthetic properties, and significantly different regarding functional and biological properties.


Complete Genome Sequence of Citrobacter freundii Myophage Mordin.
Citrobacter freundii is a Gram-negative opportunistic pathogen that is associated with urinary tract infections. Bacteriophages infecting C. freundii can be used as an effective treatment to fight these infections. Here, we announce the complete genome sequence of the C. freundii Felix O1-like myophage Mordin and describe its features.


General practitioners' use of a mobile coronary care unit in a non-urban setting.
The use that general practitioners made of the mobile coronary care unit operating from a district general hospital was monitored. Over half of the patients referred by their general practitioners to hospital with suspected acute myocardial infarction were removed by the mobile unit rather than by an ordinary ambulance. However, general practitioner selection of the more compromised patient for admission via the mobile unit indicated that the chance of this category of patient being admitted by the proven best means could be improved. Of the definite cases of infarcts removed to hospital by whatever means, the high proportion which were uncomplicated raises the question whether the general practitioner is attempting to select such patients for home rather than hospital care. The figures for the use of the mobile coronary care unit also indicate that education of the public remains an important task.


Molecular size/shape effects in the separation of the monosubstituted alkyl pyridines using capillary electrophoresis.
A series of monosubstituted alkyl pyridines have been used to investigate the presence of molecular size/shape effects in capillary electrophoresis and the applicability of various descriptors in discriminating not only between derivatives of differing chain length but also between positional isomers. Although van de Waals' radii and Offord's parameters are extremely good descriptors in predicting the relative mobilities of the derivatives, a further descriptor involving length and/or diameter of the molecule is necessary for discrimination between the positional isomers.


The deafferented visual cortex and interhemispheric relationships: a physiological approach.
A condition of asymmetrical activation in the visual system, induced by unilateral optic tract section (OTX) was examined in nine adult cats, four of which had been reared after early onset of monocular deprivation (MD-OTX) during the critical developmental period. Their results were compared to those of monocularly deprived (MD) and normal control cats. Extracellular single-unit recordings from areas 17, 18 and their border were performed at various intervals after OTX to study the effects of this isolation of one hemisphere from direct geniculo-cortical input. Electrophysiological results from the isolated hemispheres of both OTX and MD-OTX cats revealed that contralateral input via the corpus callosum was virtually undetectable in the majority of cats. Only in the cats in which the deprivation was ipsilateral to the OTX, 3.5% of the cells exhibited visual activity in the isolated hemisphere. In the intact hemisphere of the OTX group, binocularity was unaffected overall in comparison to the normal control animals, except for a slight decrease within the 0-4 degrees region from the vertical meridian. In the MD-OTX group, the cats with onset of deprivation prior to natural eye opening possessed an increase in deprived eye responsiveness compared to the control MD cats. No such an increase was seen in later onset of deprivation (3-4 weeks following natural eye opening) in the MD-OTX cats. Overall, visual responsiveness was reduced in all of the OTX and MD-OTX cats, with a return towards normal control values seen only in one animal with extended recovery (6 months). Orientation and direction selectivity were dramatically decreased in the OTX and MD-OTX cats. As the majority of receptive fields mapped from the OTX cats were in the ipsilateral visual field to the section, the remaining small number of receptive fields in the contralateral "blind" visual fields adds further support for a nasotemporal overlap in the retina of the cat. The conclusion from these results is that an asymmetrical level of direct geniculo-cortical input in the visual system of the adult cat yields a physiological bidirectional inactivation of the callosal pathway for the transfer of visual information. Thus, activation of the callosal pathway connecting the cortical visual areas has been postulated to be dependent upon simultaneous, reciprocal interaction between the two hemispheres.


Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease.
To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo. The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations. Blood cells from 19 IBD patients on a thiopurine, 19 IBD patients not on a thiopurine, and 38 matched healthy control subjects were analyzed by multiple multi-color flow cytometry panels to quantify the immune cell subsets contained therein, both as a percent of cells, and as an absolute cell count. Similar analyses were performed on colon biopsies from 17 IBD patients on a thiopurine, 17 IBD patients not on a thiopurine, and 49 healthy screening colonoscopy recipients. Complete blood counts revealed lower lymphocyte, but not monocyte or granulocyte, counts in IBD patients who were taking thiopurines at the time of sampling. This reduction was restricted to CD3-negative lymphocytes, wherein both natural killer (NK) and B cells were significantly reduced among thiopurine recipients. Among CD19+ B cells, the transitional B cells were particularly depleted, being nearly absent in both blood and colon biopsies of thiopurine recipients. No differences were associated with thiopurine use in CD8+ T cells, mucosa-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, gamma/delta T cells, Th1, Th17, regulatory T cells (Tregs) or naïve CD4+ T cells. However, patients with IBD had significantly more circulating FOXP3+, Helios+ Tregs and fewer iNKT and MAIT cells than healthy controls. Thiopurine use is associated with reduced B and NK cell, but not T cell, subpopulations in the blood of IBD patients.


Fusion expression of bovine lactoferricin in Escherichia coli.
The drug resistance problem has been growing with the utilization of current antibiotics in feed and medical industries. LfcinB, a 25-amino acid antibacterial peptide derived from bovine lactoferrin, is one of potential alternatives of antibiotics. According to the bias of codon utilization of Escherichia coli, a fragment encoding LfcinB has been chemically synthesized, inserted into vector pGEX-4T-2 and expressed in E. coli. The antibacterial peptide was fused with GST with a protease cleavage site located between them. Two constructs with different cleavage sites were made. One construct, pGEX-Th-LfcinB, contains a thrombin cleavage site carried by the vector, and the other, pGEX-Th-Xa-LfcinB, contains a Factor Xa cleavage site which was introduced after the thrombin cleavage site. Fusion protein GST-Th-LfcinB protein was efficiently cleaved by thrombin, yielding recombinant LfcinB showing antibacterial activity. However, fusion protein GEX-Th-Xa-Lfcin B containing Factor Xa recognition site could not be cleaved by Factor Xa at the conditions tried in this study. Successful expression of LfcinB in E. coli provides a possible method to produce LfcinB in large amounts.


Simple transport medium for the isolation of Chlamydia psittaci from clinical material.
Infectious elementary bodies of Chlamydia psittaci in tissue samples from field cases of enzootic abortion were placed in five different transport media (A to E). In one medium, in the absence of refrigerative storage, the organism remained viable for 30 days and at 4 degrees C for 34 days. This was medium D; it consisted of sucrose (74.6 g/litre), K2HPO4 (1.237 g/litre), L-glutamic acid (0.721 g/litre), fetal calf serum (10 per cent v/v), vancomycin and streptomycin (100 micrograms/ml) and nystatin and gentamicin (50 micrograms/ml). Samples of this transport medium were supplied to veterinary investigation centres throughout the UK. Of 1862 samples submitted for diagnosis of enzootic abortion only 1.55 per cent were so contaminated that chlamydiae could not be detected. This transport medium permits the isolation of C psittaci from clinical material for up to about one month, even in the absence of conventional storage facilities.


[Surface of the floor of the anterior cranial fossa and orbital roof as well as angles and measurements of the orbits].
With the aid of diagraphic drawings the floor-space of the anterior cranial fossa and of that orbital roof area of adults which is adjacent to the floor of the anterior cranial fossa (separated by the paranasal sinuses) were investigated. On the right side there is a mean of 730 mm2 and on the left side 717 mm2. The paries medialis orbitae on the right side runs by about 1 degree more to the rostral and medial side as left. The angle on the right side between frontomolare orbitale , the lateral end of the fissura orbitalis superior and the mediansagittal plane is somewhat bigger (35 degrees) than on the left side (33.9 degrees). Different angles inside the orbita, the extension of the orbita behind the frontozygomatic suture, the depth of the orbita, right-left-differences of the apertura orbitae canalis optici and the greater retardation of the laterally border of the orbita on the right side were investigated. The medical importance for neurosurgeons and ophthalmologists is demonstrated.


Approaches for adolescents with an affected family member with schizophrenia.
Prospective studies of adolescents at risk for schizophrenia (high-risk studies) can shed light on the possible premorbid precursors of schizophrenia. Recent studies have provided evidence of neurobehavioral, brain structural, physiologic, and neurochemical deficits in adolescent nonpsychotic high-risk relatives that may date back to childhood or earlier. These results are collectively providing a critical window into the inter-relationships between genetic predisposition, neurodevelopment, and premorbid indicators of risk in schizophrenia. Convergent approaches are inherently powerful in mutually informing each other in enriching the knowledge of the risk factors that predict the eventual onset of schizophrenia. Defining such reliable predictors of the onset of schizophrenia may provide us with the tools to better understand the etiology and pathophysiology of the illness, and may pave the way for innovative methods of treatment and possibly prevention. The authors review the relevant literature in this promising field of inquiry and summarize recent findings from high-risk studies.


Effect of Icariin on Engineered 3D-Printed Porous Scaffolds for Cartilage Repair.
In recent times, cartilage defects have been the most common athletic injuries, often leading to dreadful consequences such as osteoarthritis, pain, joint deformities, and other symptoms. It is also evident that damage to articular cartilage is often difficult to recover or self-heal because of poor vascular, nervous, and lymphatic supplies. Moreover, cartilage cells have poor regeneration ability and high maturity. Inspired by these facts and the rapid advances in the field of tissue engineering (TE), we fabricated highly porous three-dimensional (3D) scaffold architectures based on cell-responsive polymeric inks, i.e., sodium alginate and gelatin (SA-Gel, 1:3 ratio), by a novel 3D printing method. Moreover, the effect of various processing parameters was systematically investigated. The printed scaffolds of polymer composites gels with excellent transparency, moderate viscosity, and excellent fluid properties showed good surface morphology, better thermal stability and swelling effect, and unique interconnected porous architectures at the optimized operating parameters. In vitro cell proliferation experiments of these cytocompatible scaffolds showed the excellent adhesion rate and growth behavior of chondrocytes. In addition, the porous architectures facilitated the efficient distribution of cells with only a few remaining on the surface, which was confirmed by confocal laser scanning microscopic (CLSM) observations. Icariin (ICA) addition at a concentration of 10 μg/mL further significantly enhanced the proliferation of chondrocytes. We envision that these cell-responsive polymeric inks in the presence of growth regulators like ICA may have potential in engineering complex tissue constructs toward diverse applications in TE.


Pitfalls and complications of fractures of the distal radius and ulna in childhood.
Fortunately, most bone forearm fractures in children heal with minimal functional disability. My approach to management of the most common injuries is presented. By following the guidelines outlined in this article, the generalist as well as the most sophisticated upper extremity surgeon should be able to avoid pitfalls and complications when managing forearm fractures in children.


Sex and acid phosphatase in childhood non-T lymphoblastic leukaemia.
A semiquantitative assessment of blast cell acid phosphatase activity, expressed as a score, was made in 41 unselected children with newly diagnosed and untreated non-T acute lymphoblastic leukaemia (ALL). Despite a wide range of enzyme activity in both sexes boys had significantly higher scores than girls, and, in view of the known association between males and T ALL on the one hand, and between acid phosphatase and T ALL on the other, these findings raise the possibility that boys may have a predisposition to a type of pre-T ALL which could contribute to the as yet unexplained difference in prognosis between the sexes.