Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial.

Background: Promising results from a trauma reactivation study on post-traumatic stress disorder suggest that propranolol is capable of attenuating symptoms of traumatically induced mental disorders by blocking memory reconsolidation. Methods: A randomized, parallel, placebo-controlled, quadruple-blind trial was designed to determine the effectiveness of perioperative propranolol during exposure to dental extractions in reducing dental anxiety in patients with dental anxiety or dental phobia. Between November 2014 and December 2018, 52 patients with high levels of fear in anticipation of dental extractions who were referred to a department of oral and maxillofacial surgery for at least two tooth and/or molar removals with 1 month in between were included. On the first visit participants received either 120 mg of perioperative oral propranolol (n = 19) or placebo (n = 17), and a core fear memory was reactivated 1 h preoperatively. The primary outcome was change in severity of dental anxiety from baseline to 1-month follow-up, as indexed by the short version of the dental anxiety inventory (S-DAI). Secondary outcome measures were change in intra-operative state anxiety and specific phobia diagnoses. Results: Linear mixed model (LMM) yielded no statistically significant difference in change of dental trait anxiety from baseline to 1-month follow-up between propranolol and placebo groups (Cohen's d = 0.23). S-DAI scores decreased in both study arms from baseline to follow-up (propranolol arm: from 32.1 [SD = 7.3] to 29.1 [SD = 8.8]; placebo arm: from 31.6 [SD = 7.5] to 27.1 [SD = 6.5]). Also, administering propranolol was not associated with a significant difference in change of intra-operative state anxiety or phobia diagnoses between groups over time. Conclusions: The results do not concur with earlier findings regarding post-traumatic stress disorder, and suggest that individuals with traumatically induced fears or phobias do not benefit from the application of perioperative propranolol.

High molecular weight hyper-branched PCL-based thermogelling vitreous endotamponades.

Vitreous endotamponades play essential roles in facilitating retina recovery following vitreoretinal surgery, yet existing clinically standards are suboptimal as they can cause elevated intra-ocular pressure, temporary loss of vision, and cataracts while also requiring prolonged face-down positioning and removal surgery. These drawbacks have spurred the development of next-generation vitreous endotamponades, of which supramolecular hydrogels capable of in-situ gelation have emerged as top contenders. Herein, we demonstrate thermogels formed from hyper-branched amphiphilic copolymers as effective transparent and biodegradable vitreous endotamponades for the first time. These hyper-branched copolymers are synthesised via polyaddition of polyethylene glycol, polypropylene glycol, poly(ε-caprolactone)-diol, and glycerol (branch inducing moiety) with hexamethylene diisocyanate. The hyper-branched thermogels are injected as sols and undergo spontaneous gelation when warmed to physiological temperatures in rabbit eyes. We found that polymers with an optimal degree of hyper-branching showed excellent biocompatibility and was able to maintain retinal function with minimal atrophy and inflammation, even at absolute molecular weights high enough to cause undesirable in-vivo effects for their linear counterparts. The hyper-branched thermogel is cleared naturally from the vitreous through surface hydrogel erosion and negates surgical removal. Our findings expand the scope of polymer architectures suitable for in-vivo intraocular therapeutic applications beyond linear constructs.

Coronary artery vasculitis: a review of current literature.

Cardiac vasculitis is recognized as a heterogeneous disease process with a wide spectrum of manifestations including pericarditis, myocarditis, valvular heart disease and less frequently, coronary artery vasculitis (CAV). CAV encompasses an emerging field of diseases which differ from conventional atherosclerotic disease and have a proclivity for the younger population groups. CAV portends multiple complications including the development of coronary artery aneurysms, coronary stenotic lesions, and thrombosis, all which may result in acute coronary syndromes. There are several aetiologies for CAV; with Kawasaki's disease, Takayasu's arteritis, Polyarteritis Nodosa, and Giant-Cell Arteritis more frequently described clinically, and in literature. There is a growing role for multi-modality imaging in assisting the diagnostic process; including transthoracic echocardiography, cardiac magnetic resonance imaging, computed tomography coronary angiography, fluorodeoxyglucose-positron emission tomography and conventional coronary angiogram with intravascular ultrasound. Whilst the treatment paradigms fundamentally vary between different aetiologies, there are overlaps with pharmacological regimes in immunosuppressive agents and anti-platelet therapies. Interventional and surgical management are is a consideration in select populations groups, within a multi-disciplinary context. Further large-scale studies are required to better appropriately outline management protocols in this niche population.

A feasibility study for the establishment of a national wildlife health centre in Sri Lanka.

Sri Lanka is a tropical nation within a zoogeographic zone that is at high risk for infectious disease emergence. In 2010, a study was conducted on the feasibility of enhancing capacity in Sri Lanka to manage wildlife diseases through the establishment of a national wildlife health centre. The Canadian Cooperative Wildlife Health Centre was assessed as a potential model for adaptation in Sri Lanka. Interviews and group meetings were conducted with potential key participants from the Sri Lankan Departments of Wildlife Conservation and Animal Production and Health, and the Faculty of Veterinary Medicine and Animal Science of the University of Peradeniya. In addition, site visits were made to potentially participating facilities and the literature on best practices in building scientific capacity was consulted. With strategic enhancements in education and training, additional personnel, improvements in transportation and diagnostic facilities, and central coordination, Sri Lanka appears very well positioned to establish a sustainable wildlife health centre and programme.

Myocardial infarction and remodeling in mice: effect of reperfusion.

Anatomic and functional changes after either a permanent left anterior descending coronary artery occlusion (PO) or 2 h of occlusion followed by reperfusion (OR) in C57BL/6 mice were examined and compared with those in sham-operated mice. Both interventions generated infarcts comprising 30% of the left ventricle (LV) measured at 24 h and equivalent suppression of LV ejection velocity and filling velocity measured by Doppler ultrasound at 1 wk. Serial follow-up revealed that the ventricular ejection velocity and filling velocity returned to the levels of the sham-operated controls in the OR group at 2 wk and remained there; in contrast, PO animals continued to display suppression of both systolic and diastolic function. In contrast, ejection fractions of PO and OR animals were depressed equivalently (50% from sham-operated controls). Anatomic reconstruction of serial cross sections revealed that the percentage of the LV endocardial area overlying the ventricular scar (expansion ratio) was significantly larger in the PO group vs. the OR group (18 +/- 1.7% vs. 12 +/- 0.9%, P < 0.05). The septum that was never involved in the infarction had a significantly (P < 0.002) increased mass in PO animals (22.5 +/- 1.08 mg) vs. OR (17.8 +/- 1.10 mg) or sham control (14.8 +/- 0.99 mg) animals. Regression analysis demonstrated that the extent of septal hypertrophy correlated with LV expansion ratio. Thus late reperfusion appears to reduce the degree of infarct expansion even under circumstances in which it no longer can alter infarct size. We suggest that reperfusion promoted more effective ventricular repair, less infarct expansion, and significant recovery or preservation of ventricular function.

Acetogenic bacteria: what are the in situ consequences of their diverse metabolic versatilities?

The four decades of the now classic studies by Harland G. Wood and Lars G. Ljungdahl lead to the resolution of the autotrophic acetyl-CoA 'Wood/Ljungdahl' pathway of acetogenesis. This pathway is the hallmark of acetogens, but is also used by other bacteria, including methanogens and sulfate-reducing bacteria, for both catabolic and anabolic purposes. Thus, the pathway is wide spread in nature and plays an important role in the global turnover of carbon. Because most historical studies with acetogens focused on the biochemistry of the acetyl-CoA pathway, the metabolic diversity and ecology of acetogens remained largely unexplored for many years. Although acetogens were initially conceived to be a somewhat obscure bacteriological group with limited metabolic capabilities, it is now clear that acctogens are arguably the most metabolically diverse group of obligate anaerobes characterized to date. Their anaerobic metabolic arsenal includes the capacity to oxidize diverse substrates, including aromatic, C1, C2, and halogenated compounds, and engage a large number of alternative energy-conserving, terminal electron-accepting processes, including classic fermentations and the dissimilation of inorganic nitrogen. In this regard, one might consider acetogens on a collective basis as the pseudomonads of obligate anaerobes. By virtue of their diverse metabolic talents, acetogens can be found in essentially all habitats. This review evaluates the metabolic versatilities of acetogens relative to both the engagement (regulation) of the acetyl-CoA pathway and the ecological roles likely played by this bacteriogical group.

Bidirectional transformation of aromatic aldehydes by Desulfovibrio desulfuricans under nitrate-dissimilating conditions.

Desulfovibrio desulfuricans ATCC 27774 was screened for reactivity against aromatic compounds during lactate-dependent, nitrate-dissimilating growth. Only aromatic aldehydes (benzaldehyde, 2-hydroxybenzaldehyde, 3-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, vanillin, iso-vanillin and o-vanillin) were reactive and, with the exception of 2-hydroxybenzaldehyde, were stimulatory to lactate-dependent growth. Aromatic aldehydes were transformed to their corresponding benzoate and benzyl alcohol derivatives, with the ratio of benzoate-to-benzyl alcohol derivatives being dependent upon lactate availability. In presence of lactate, aromatic aldehydes were primarily reduced to their corresponding benzyl alcohol derivatives; in the absence of lactate, aromatic aldehydes were mainly oxidized to their corresponding benzoate derivatives. In the absence of nitrate, 3-hydroxybenzaldehyde was neither reduced nor oxidized. These results indicate that D. desulfuricans is competent in the bidirectional transformation of aromatic aldehydes under nitrate-dissimilating conditions and that the direction of transformation (i.e. reduction or oxidation) is regulated by reductant availability.

Hermeneutical clinical ethics: a commentary.

Essays by Thomasma and ten Have recommend hermeneutical clinical ethics. The use Thomasma makes of hermeneutics is not radical enough because it leaves out basic interpretation of clinical practice and focuses narrowly on ethical principles and rules. Ten Have, while failing to notice that the hyperreality of clinical ethics is a feature of all language, rightly distinguishes four characteristic parameters of a thoroughgoing interpretive clinical ethics: experience, attitudes and emotions, community, and ambiguity. Suggestions are made for implementing hermeneutical ethics in clinical teaching.

Nitrate as a preferred electron sink for the acetogen Clostridium thermoaceticum.

Nitrate enhanced the vanillin- and vanillate-dependent growth of Clostridium thermoaceticum. Under nitrate-enriched conditions, these aromatic substrates were subject to O demethylation. However, acetate, the normal product obtained from O demethylation, was not detected. Acetate was also not detected when methanol and CO cultures were supplemented with nitrate; glucose cultures likewise produced approximately one-third less acetate when enriched with nitrate. Reductant derived from the oxidation of these substrates was recovered in nitrite and ammonia. With an ammonia-limited medium employed to evaluate N turnover, the following stoichiometry was observed concomitantly with the consumption of 2.0 mM O-methyl groups (the recovery of nitrate-derived N approximated 89%): 3.9 mM NO3(-)-->2.8 mM NO2- +0.7 mM NH3. The results demonstrated that (i) nitrate was preferentially used as an electron sink under conditions that were otherwise acetogenic, (ii) nitrate dissimilation was energy conserving and growth supportive, and (iii) nitrate-coupled utilization of O-methyl groups conserved more energy than acetogenic O demethylation.

Oxalate- and Glyoxylate-Dependent Growth and Acetogenesis by Clostridium thermoaceticum.

The acetogenic bacterium Clostridium thermoaceticum ATCC 39073 grew at the expense of the two-carbon substrates oxalate and glyoxylate. Other two-carbon substrates (acetaldehyde, acetate, ethanol, ethylene glycol, glycolaldehyde, glycolate, and glyoxal) were not growth supportive. Growth increased linearly with increasing substrate concentrations up to 45 mM oxalate and glyoxylate, and supplemental CO(2) was not required for growth. Oxalate and glyoxylate yielded 4.9 and 9.4 g, respectively, of cell biomass (dry weight) per mol of substrate utilized. Acetate was the major reduced end product recovered from oxalate and glyoxylate cultures. C labeling studies showed that oxalate was subject to decarboxylation, and product analysis indicated that oxalate was utilized by the following reaction: 4OOC-COO + 5H(2)O --> CH(3)COO + 6HCO(3) + OH. Oxalate- and glyoxylate-dependent growth produced lower acetate concentrations per unit of cell biomass synthesized than did H(2)-, CO-, methanol-, formate-, O-methyl-, or glucose-dependent growth. Protein profiles of oxalate-grown cells were dissimilar from protein profiles of glyoxylate-, CO-, or formate-grown cells, suggesting induction of new proteins for the utilization of oxalate. C. thermoaceticum DSM 2955 and Clostridium thermoautotrophicum JW 701/3 also grew at the expense of oxalate and glyoxylate. However, oxalate and glyoxylate did not support the growth of C. thermoaceticum OMD (a nonautotrophic strain) or six other species of acetogenic bacteria tested.

Isolation and functional studies on feline bone marrow derived macrophages.

In this report, we describe an in vitro culture method for feline bone marrow cells, which yields large numbers of quiescent macrophages after 14 days of culture. The bulk of the cultured cell population consists of macrophages as assessed by morphology, macrophage specific cytochemistry, and phagocytosis. The remaining cells were lymphocytes, bone marrow stromal cells, fibroblasts and occasional polymorphonuclear leukocytes. While resting cells produced no detectable interleukin 1, stimulation with lipopolysaccharide (LPS) induced the production of biologically active interleukin 1. After 6 h LPS stimulation, mRNA for tumor necrosis factor alpha and interleukin 1 beta was detectable. The absence of mRNA in unstimulated cells indicates cultured macrophages were not activated until stimulated by LPS or plastic adherence. This approach provides a useful means to measure potential modulatory effects by virus infections or other agents upon feline macrophage gene expression.

Comparative evaluation of the metabolic potentials of different strains of Peptostreptococcus productus: utilization and transformation of aromatic compounds.

Three strains of Peptostreptococcus productus were tested for growth at the expense of methoxylated aromatic compounds. Strain M8A-18 (human fecal isolate) was unable to utilize methoxylated aromatic compounds. While the type strain ATCC 27340 (human septicemia isolate) was capable of minimal growth with methoxylated aromatic compounds, ATCC 35244 (sewage sludge isolate) displayed significant growth on methoxylated aromatic compounds. Methoxylated phenols, benzoates, benzyl alcohol and phenylacrylates supported the growth of ATCC 35244 and were O-demethylated to their respective hydroxylated derivatives. During O-methyl- or CO-dependent growth, the double bond of the acrylate side chain of certain methoxylated and non-methoxylated phenylacrylates was reduced. Although other aromatic substituent groups (-COOH and -CH3) were transformed during CO-dependent growth, in short-term growth studies, the aromatic ring was not subject to reduction or degradation. Of the three strains tested, only strain M8A-18 failed to grow at the expense of carbon monoxide (CO).

In vitro comparison of equine granulocytes labeled with 99mTc-hexamethylpropyleneamine oxime or 111In-oxine.

Isolated equine granulocytes (WBC), radiolabeled with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) or 111In-oxine, were evaluated in vitro for their labeling characteristics, viability, and phagocytic function over a 6-hour postlabeling period. Mean +/- SD labeling efficiency for 111In-oxine-WBC was 62.2 +/- 15.3%, which was significantly (P less than 0.001) higher than that for 99mTc-HMPAO-WBC (32.0 +/- 17.0%). In vitro elution of radiolabel from cells was significantly (P less than 0.02) greater for 99mTc-HMPAO-WBC at 0.5, 2, and 4 hours, but was not significantly different from elution of radiolabel for 111In-oxine-WBC at 6 hours. Viability, assessed by trypan blue dye exclusion, for 99mTc-HMPAO-WBC, 111In-oxine-WBC, and nonlabeled control WBC ranged from 97 to 100%, and was not significantly different among groups. Cell function was assessed by use of a phagocytosis assay and was reported as phagocytic index. The phagocytic index ranged from 0.86 to 0.96 for 99mTc-HMPAO-WBC, and from 0.76 to 0.97 for 111In-oxine-WBC. The phagocytic index was not significantly different at 0.5, 2, or 4 hours, but was significantly (P = 0.038) greater at 6 hours for 99mTc-HMPAO-WBC. Because of the superior imaging characteristics of 99mTc-HMPAO-WBC and equal or better labeling characteristics than those for 111In-oxine at 6 hours, 99mTc-HMPAO-WBC appear to be a good alternative to 111In-oxine-WBC.

Utilization of methoxylated aromatic compounds by the acetogen Clostridium thermoaceticum: expression and specificity of the co-dependent O-demethylating activity.

The aromatic CO-dependent O-demethylating activity of Clostridium thermoaceticum was evaluated. Secondary aromatic substituent groups (-OH, -CO2H, -CH2OH, and -OCH3) were critical to O demethylation. O-demethylating activities and specificities were similar from cells grown at the expense of different methoxylated aromatic compounds; all O-methyl-grown cells catalyzed the same sequential O demethylation of multi-methoxylated compounds, suggesting that a broad specificity O demethylase was involved in O demethylation. In cell-fractionation studies, CO-dependent O demethylation was catalyzed by membrane-associated components.

Characterization of the H2- and CO-dependent chemolithotrophic potentials of the acetogens Clostridium thermoaceticum and Acetogenium kivui.

Strains of Clostridium thermoaceticum were tested for H2- and CO-dependent growth in a defined medium containing metals, minerals, vitamins, cysteine-sulfide, CO2-bicarbonate, and H2 or CO. Ten of the thirteen strains tested grew at the expense of H2 and CO, and C. thermoaceticum ATCC 39073 was chosen for further study. The doubling times for H2- and CO-dependent growth under chemolithotrophic conditions (the defined medium with nicotinic acid as sole essential vitamin and sulfide as sole reducer) were 25 and 10 h, respectively. Product stiochiometries for chemolithotrophic cultures approximated: 4.1H2 + 2.4CO2----CH3COOH + 0.1 cell C + 0.3 unrecovered C and 6.8CO----CH3COOH + 3.5CO2 + 0.4 cell C + 0.9 unrecovered C. H2-dependent growth produced significantly higher acetate concentrations per unit of biomass synthesized than did CO- or glucose-dependent growth. In contrast, the doubling time for H2-dependent growth under chemolithotrophic conditions (the defined medium without vitamins and sulfide as sole reducer) by Acetogenium kivui ATCC 33488 was 2.7 h; as a sole energy source, CO was not growth supportive for A. kivui. The YH2 values for A. kivui and C. thermoaceticum were 0.91 and 0.46 g of cell dry weight per mol of H2 consumed, respectively; the YCO value for C. thermoaceticum was 1.28 g of cell dry weight per mol of CO consumed. The specific activities of hydrogenase and CO dehydrogenase in both acetogens were influenced by the energy source utilized for growth and were significantly lower in C. thermoaceticum than in A. kivui. With extracts of H2-cultivated cells and benzyl viologen as electron acceptor, the Vmax values for hydrogenase from C. thermoaceticum and A. kivui were 155.7 and 1,670 micromoles of H2 oxidized per min mg of protein, respectively; the Vmax values for CO dehydrogenase from C. thermoaceticum and A. kivui were 90.6 and 2,973 micromoles of CO oxidized per min per mg of protein, respectively.

Modulation of canine lymphocyte blastogenesis via histamine.

The effect of histamine on in vitro T cell blastogenic responses of canine peripheral blood lymphocytes to phytohemagglutinin-P (PHA-P) was investigated. A dose dependent inhibition of blastogenesis was observed; an effect which could be blocked by cimetidine, a type II histamine receptor antagonist, but not by diphenhydramine, a type I receptor antagonist, suggesting that histamine's inhibitory effect is mediated through a type II histamine receptor. The inhibitory effect of histamine on blastogenesis was also reversible by indomethacin, a prostaglandin synthetase inhibitor, implicating prostaglandin involvement in histamine suppression. Histamine release at sites of inflammation may result in down regulation of local immune responses by activation of specific immunoregulatory cells. This could permit the escape of certain neoplasia from local immunosurveillance mechanisms. Cimetidine may block activation of histamine responsive regulatory cells bearing type II receptors, which may help explain the beneficial effect cimetidine therapy has on regression of certain human tumors (i.e., malignant melanomas).

Biotransformations of carboxylated aromatic compounds by the acetogen Clostridium thermoaceticum: generation of growth-supportive CO2 equivalents under CO2-limited conditions.

Clostridium thermoaceticum ATCC 39073 converted vanillate to catechol. Although carboxylated aromatic compounds which did not contain methoxyl groups were not by themselves growth supportive, protocatechuate and p-hydroxybenzoate (nonmethoxylated aromatic compounds) were converted to catechol and phenol, respectively, during carbon monoxide-dependent growth. Syringate is not subject to decarboxylation by C. thermoaceticum (Z. Wu, S. L. Daniel, and H. L. Drake, J. Bacteriol. 170:5705-5708, 1988), and sustained growth at the expense of syringate-derived methoxyl groups was dependent on supplemental CO2. In contrast, vanillate was growth supportive in the absence of supplemental CO2, and 14CO2 was the major 14C-labeled product during [carboxyl-14C]vanillate-dependent growth. Furthermore, the decarboxylation of protocatechuate and p-hydroxybenzoate supported methanol- and 1,2,3-trimethoxybenzene-dependent growth (CO2 is required for growth at the expense of these substrates) when supplemental CO2 was depleted from the growth medium, and the decarboxylation of protocatechuate was concomitant with improved cell yields of methanol cultures. These findings demonstrate that (i) C. thermoaceticum is competent in the decarboxylation of certain aromatic compounds and (ii) under certain conditions, decarboxylation may be integrated to the flow of carbon and energy during acetogenesis.

Nickel transport by the thermophilic acetogen Acetogenium kivui.

Exogenous 63Ni was incorporated into carbon monoxide dehydrogenase when Acetogenium kivui ATCC 33488 was cultivated in the presence of 63NiCl2. The capacity for nickel (63NiCl2) transport was greatest with cells harvested from the mid- to late exponential phases of growth. Nickel transport was linear during the transport assay period and displayed saturation kinetics. The apparent Km and Vmax for nickel transport by H2-cultivated cells approximated 2.3 microM Ni and 670 pmol of Ni transported per min per mg (dry weight) of cells, respectively. The nickel transport system was not appreciably affected by the other divalent cations that were tested, and transported nickel was not readily exchangeable with exogenous nickel. Nickel transport was stimulated by glucose or H2 and was decreased by various metabolic inhibitors; however, nickel uptake by glucose- and H2-cultivated cells displayed differential sensitivities to ATPase inhibitors.