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1.
Biol Lett ; 17(8): 20210207, 2021 08.
Article in English | MEDLINE | ID: mdl-34428958

ABSTRACT

Chytridiomycosis, an infectious disease of amphibians caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), poses an imminent conservation threat. The global spread of Bd has led to mass mortality events in many amphibian species, resulting in at least 90 species' extinctions to date. Exposure to Bd metabolites (i.e. non-infectious antigenic chemicals released by Bd) partially protects frogs during subsequent challenges with live Bd, suggesting its use as a prophylactic treatment and potential vaccine. However, we do not know whether Bd metabolite exposure protects against strains beyond the one used for treatment. To address this knowledge gap, we conducted a 3 × 2 experiment where we exposed adult Cuban treefrogs, Osteopilus septentrionalis, to one of three treatments (Bd metabolites from California-isolated strain JEL-270, Panamá-isolated strain JEL-419, or an artificial spring water control) and then challenged individuals with live Bd from either strain. We found that exposure to Bd metabolites from the California-isolated strain significantly reduced Bd loads of frogs challenged with the live Panamá-isolated strain, but no other treatments were found to confer protective effects. These findings demonstrate asymmetric cross-protection of a Bd metabolite prophylaxis and suggest that work investigating multiple, diverse strains is urgently needed.


Subject(s)
Chytridiomycota , Mycoses , Amphibians , Animals , Anura , Humans
2.
Epidemiol Psychiatr Sci ; 30: e18, 2021 Feb 26.
Article in English | MEDLINE | ID: mdl-33632368

ABSTRACT

AIMS: Refugees and asylum-seekers are typically exposed to multiple potentially traumatic events (PTEs) in the context of war, persecution and displacement, which confer elevated risk for psychopathology. There are significant limitations, however, in extant approaches to measuring these experiences in refugees. The current study aimed to identify profiles of PTE exposure, and the associations between these profiles and key demographics, contextual factors (including ongoing stressors, method of travel to Australia and separation from family), mental health and social outcomes, in a large sample of refugees resettled in Australia. METHODS: Participants were 1085 from Arabic, Farsi, Tamil and English-speaking refugee backgrounds who completed an online or pen-and-paper survey in their own language. Constructs measured included PTE exposure, demographics, pre-displacement factors, ongoing stressors, post-traumatic stress disorder symptoms, depression symptoms, anger reactions, plans of suicide and social engagement. RESULTS: Latent class analysis identified four profiles of PTE exposure, including the torture and pervasive trauma class, the violence exposure class, the deprivation exposure class and the low exposure class. Compared to the low exposure class, participants in the trauma-exposed classes were more likely to be male, highly educated, from Farsi and Tamil-speaking backgrounds, have travelled to Australia by boat, experience more ongoing stressors and report both greater psychological symptoms and social engagement. CONCLUSIONS: This study found evidence for four distinct profiles of PTE exposure in a large sample of resettled refugees, and that these were associated with different demographic, psychological and social characteristics. These findings suggest that person-centred approaches represent an important potential avenue for investigation of PTE exposure in refugees, particularly with respect to identifying subgroups of refugees who may benefit from different types or levels of intervention according to their pre-migration PTE experiences.


Subject(s)
Depression/psychology , Exposure to Violence , Refugees/psychology , Stress Disorders, Post-Traumatic/psychology , Adolescent , Adult , Anger , Australia , Female , Humans , Latent Class Analysis , Mental Health
3.
J Fish Biol ; 90(3): 980-1000, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27896814

ABSTRACT

The swimming performance of longnose dace Rhinichthys cataractae, the most widely distributed minnow (Cyprinidae) in North America, was assessed in relation to potential passage barriers. The study estimated passage success, maximum ascent distances and maximum sprint speed in an open-channel flume over a range of water velocities and temperatures (10·7, 15·3 and 19·3° C). Rhinichthys cataractae had high passage success (95%) in a 9·2 m flume section at mean test velocities of 39 and 64 cm s-1 , but success rate dropped to 66% at 78 cm s-1 . Only 20% of fish were able to ascend a 2·7 m section with a mean velocity of 122 cm s-1 . Rhinichthys cataractae actively selected low-velocity pathways located along the bottom and corners of the flume at all test velocities and adopted position-holding behaviour at higher water velocities. Mean volitional sprint speed was 174 cm s-1 when fish volitionally sprinted in areas of high water velocities. Swimming performance generally increased with water temperature and fish length. Based on these results, fishways with mean velocities <64 cm s-1 should allow passage of most R. cataractae. Water velocities >100 cm s-1 within structures should be limited to short distance (<1 m) and structures with velocities ≥158 cm s-1 would probably represent movement barriers. Study results highlighted the advantages of evaluating a multitude of swimming performance metrics in an open-channel flume, which can simulate the hydraulic features of fishways and allow for behavioural observations that can facilitate the design of effective passage structures.


Subject(s)
Cyprinidae/physiology , Swimming/physiology , Water Movements , Animals , Body Size , Cyprinidae/anatomy & histology , Temperature
4.
Br J Pharmacol ; 172(17): 4430-41, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26103136

ABSTRACT

BACKGROUND AND PURPOSE: Nicotinic (ACh) receptor recovery from desensitization is modulated by PKC, but the PKC isozymes and the phosphorylation sites involved have not been identified. We investigated whether PKCε phosphorylation of α4ß2 nAChRs regulates receptor recovery from desensitization. EXPERIMENTAL APPROACH: Receptor recovery from desensitization was investigated by electrophysiological characterization of human α4ß2 nAChRs. Phosphorylation of the α4 nAChR subunit was assessed by immunoblotting of mouse synaptosomes. Hypothermia induced by sazetidine-A and nicotine was measured in Prkce(-/-) and wild-type mice. KEY RESULTS: Inhibiting PKCε impaired the magnitude of α4ß2 nAChR recovery from desensitization. We identified five putative PKCε phosphorylation sites in the large intracellular loop of the α4 subunit, and mutating four sites to alanines also impaired recovery from desensitization. α4 nAChR subunit phosphorylation was reduced in synaptosomes from Prkce(-/-) mice. Sazetidine-A-induced hypothermia, which is mediated by α4ß2 nAChR desensitization, was more severe and prolonged in Prkce(-/-) than in wild-type mice. CONCLUSIONS AND IMPLICATIONS: PKCε phosphorylates the α4 nAChR subunit and regulates recovery from receptor desensitization. This study illustrates the importance of phosphorylation in regulating α4ß2 receptor function, and suggests that reducing phosphorylation prolongs receptor desensitization and decreases the number of receptors available for activation.


Subject(s)
Protein Kinase C-epsilon/metabolism , Receptors, Nicotinic/metabolism , Recovery of Function/physiology , Animals , Humans , Hypothermia/chemically induced , Hypothermia/physiopathology , Male , Mice , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Nicotine/pharmacology , Phosphorylation/physiology , Recovery of Function/drug effects
5.
Phys Chem Chem Phys ; 17(6): 4237-49, 2015 Feb 14.
Article in English | MEDLINE | ID: mdl-25573245

ABSTRACT

The rate constants for H-D exchange reactions of sodiated polyglycines (GnNa(+), n = 2-8) and polyalanines (AnNa(+), n = 2, 3 and 5) with ND3 have been measured in the cell of an FT-ICR mass spectrometer. All peptides except G2Na(+) are found to undergo three exchange reactions, all of which are consecutive with no sign of multiple exchanges within a single collision event. This information has been used to construct full mechanistic scenarios with the help of detailed quantum chemical calculations of the possible reaction paths for H-D exchange. The first exchange is always located at the C terminus however with different mechanisms depending upon whether the peptide termini can (larger peptides) or cannot (smaller peptides) interact directly without strong energy penalty. The most favourable mechanisms for the second and third exchanges of the N terminus protons, are found to be different from those for the first for all peptide sizes. The peptide distortions that are necessary in order for some of these reactions to occur are made possible by the energy reservoir provided by the favorable interaction of the peptide ion with ND3. Their occurrence and variety preclude any general relationship between H-D exchange kinetics and the most stable ion structures. There is however a break at G7Na(+) in the kinetics trend, with a first exchange rate which is much smaller than for all other peptide sizes. This break can be directly related to a different structural type in which the C terminus is neither free nor close to the N terminus.

6.
J Am Mosq Control Assoc ; 28(4): 292-300, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23393751

ABSTRACT

In this study, we explore the potential of a commercially available mechanical mosquito control device, the Liberty Plus Mosquito Magnet (hereafter referred to as Mosquito Magnet), to reduce the abundance of adult nuisance mosquito populations in public recreational areas. Mosquitoes were trapped on 2 replicate sites close to a campground at Brae Island Regional Park near Fort Langley, British Columbia, Canada. Each site comprised a treatment (Mosquito Magnets used) and control subsection (Mosquito Magnets not used). Mosquito numbers were assessed before and after the treatment period in both subsections at each site with Centers for Disease Control and Prevention (CDC) black light traps. Although nearly 200,000 mosquitoes from 14 different species were collected over 366 trap-nights from May 31 to July 31, 2008, the majority of those identified were Aedes sticticus (68%) and Ae. vexans (22%)-2 of the most notorious nuisance mosquito species in British Columbia. The number of mosquitoes captured by CDC black light traps increased overall during the study period due to natural seasonal variation. Nevertheless, a significant treatment effect (P = 0.0389) was associated with an average decrease of about 32% in the average number of adult mosquitoes collected per day. These results strongly suggest that Mosquito Magnets can reduce the abundance of nuisance mosquitoes, potentially reducing the biting pressure on the public, and providing another tool in mosquito control operations.


Subject(s)
Culicidae/physiology , Mosquito Control/instrumentation , Mosquito Control/methods , Animals , British Columbia , Population Density
7.
Gynecol Oncol ; 123(1): 105-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21723596

ABSTRACT

OBJECTIVE: The aim of the study was to determine the response rate and response duration of cervical cancer previously treated by cisplatin (with or without radiation) to a combination of docetaxel and gemcitabine. Secondary endpoints were assessment of toxicity and quality of life (QoL) of patients receiving the treatment. METHODS: This was a multicentre phase II trial of 3 weekly docetaxel 75 mg/m(2) day 1 (reduced to 60 mg/m(2) after 32 cycles had been administered) and gemcitabine 1000 mg/m(2) (days 1 and 8). A two stage Gehan design was used initially. Twenty-nine patients recruited had disease outside the irradiated pelvis (Group 1), and 21 had disease confined to the irradiated pelvis (Group 2). The target response for the Gehan 2 design was 25% (Group 1) and 10% (Group 2). RESULTS: The overall response rate for Group 1 was 21.4% (95% CI 8.3-41.0%). Amongst those who had at least 3 cycles of chemotherapy the response rate was 27.3% (95% CI 10.7-50.2%). The median survival was 7.3 months (95% CI 5.4 to 9.2 months) with 39.3% (95% CI 21.7-56.5%) alive at 1 year. In Group 2 the overall response rate was 9.5% (95% CI 1.2%-30.4%). The response rate for those who had at least 3 cycles of chemotherapy was 12.5% (95% CI 1.6-38.4%). The median survival was 7.9 months (95% CI 2.2-13.6 months). Toxicity was mainly haematological with 51% developing grade 3 or 4 neutropenia after at least 1 cycle of chemotherapy. QoL showed a significant deterioration from baseline for physical and role function but there was an improvement in emotional function during treatment. CONCLUSION: Response rates and survival duration were similar to those reported following treatment with platinum based doublets. In view of the relatively poor response rates (no more than 36%) to conventional chemotherapy future developments should be a combination of chemotherapy and biological agents such as VEGFR inhibitors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Docetaxel , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Quality of Life , Taxoids/administration & dosage , Taxoids/adverse effects , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Gemcitabine
8.
Genes Brain Behav ; 8(5): 493-9, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19243450

ABSTRACT

Alcoholism is a progressive disorder that involves the amygdala. Mice lacking protein kinase C epsilon (PKCepsilon) show reduced ethanol consumption, sensitivity and reward. We therefore investigated whether PKCepsilon signaling in the amygdala is involved in ethanol consumption. Local knockdown of PKCepsilon in the amygdala reduced ethanol consumption and preference in a limited-access paradigm. Further, mice that are heterozygous for the PKCepsilon allele consume less ethanol compared with wild-type mice in this paradigm. These mice have a >50% reduction in the abundance of PKCepsilon in the amygdala compared with wild-type mice. We conclude that amygdala PKCepsilon is important for ethanol consumption in mice.


Subject(s)
Alcohol-Induced Disorders, Nervous System/enzymology , Alcoholism/enzymology , Amygdala/enzymology , Genetic Predisposition to Disease , Protein Kinase C-epsilon/genetics , Alcohol-Induced Disorders, Nervous System/genetics , Alcohol-Induced Disorders, Nervous System/physiopathology , Alcoholism/genetics , Alcoholism/physiopathology , Amygdala/drug effects , Amygdala/physiopathology , Animals , Brain Chemistry/genetics , Central Nervous System Depressants/pharmacology , Conditioning, Psychological/drug effects , Conditioning, Psychological/physiology , Disease Models, Animal , Ethanol/pharmacology , Gene Frequency/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Reward
9.
J Vector Ecol ; 33(1): 198-204, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18697324

ABSTRACT

In 2003, a survey at waste management grounds and tire dealerships was conducted to determine the species composition of mosquitoes in tires in southern Manitoba, Canada. Over 25% of the 1,142 tires sampled contained a total of 32,474 mosquito larvae and pupae. Culex restuans made up at least 95% of the larvae collected for each month of the summer. Culiseta inornata and Culex tarsalis reached their greatest numbers in July and August, respectively, though they were never abundant. Ochlerotatus triseriatus was also found but never reached more than 1% of the total larvae collected in any given month. Mosquito prevalence was more than three times greater in August (36.1%) than in June (11.7%). Orientation affected prevalence of mosquitoes in tires: 31.4% of vertical tires (tires standing on their treads) contained mosquitoes, whereas mosquitoes were found in only 18.9% of horizontal tires (tires parallel to the ground). Tires in the eastern region of Manitoba contained mosquitoes more often (61.7%), irrespective of date, than Winnipeg (25.9%), the central region (29.1%), or the western region (19.8%). Mosquito prevalence was similar across three size categories of tires, car tires (18.8%), truck tires (19.8%), and semi-trailer tires (26.7%), though tractor tires (47.8%) contained significantly more mosquitoes than tires in the other categories.


Subject(s)
Culicidae/growth & development , Ecosystem , Refuse Disposal , Animals , Culex/growth & development , Environmental Monitoring , Larva/growth & development , Manitoba , Motor Vehicles , Rubber , Seasons
10.
Br J Ophthalmol ; 92(8): 1108-11, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18653604

ABSTRACT

BACKGROUND/AIMS: To determine if disease severity is associated with a family history of keratoconus. METHODS: Markers of disease severity in the CLEK Study cohort were assessed to determine if they could discriminate individuals with and without family history. Logistic regression was used to examine association between corneal scarring, average corneal power, flat and steep keratometry readings, and higher-order root mean square (RMS) wavefront error with family history. RESULTS: In univariate analyses, none of the severity indices had any significant associations with family history; however, contact lens use, gender, and Caucasian race were found to be significant predictors. After controlling for these confounders, there were no significant associations between any severity indices and family history. CONCLUSIONS: Presence or absence of family history is not associated with more severe clinical disease, at least when each marker for severity is considered independently. The results of this analysis are important for genetic studies of keratoconus in that it will allow recruitment of keratoconus patients across all stages of disease severity because it does not influence familial aggregation.


Subject(s)
Eye Diseases, Hereditary/genetics , Keratoconus/genetics , Cicatrix/complications , Contact Lenses/adverse effects , Cornea/physiopathology , Corneal Topography/methods , Eye Diseases, Hereditary/etiology , Eye Diseases, Hereditary/physiopathology , Female , Follow-Up Studies , Humans , Keratoconus/etiology , Keratoconus/physiopathology , Male , Risk Factors , Severity of Illness Index , Sex Factors
11.
Genes Brain Behav ; 7(3): 323-33, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17908177

ABSTRACT

Corticotropin-releasing factor (CRF), its receptors, and signaling pathways that regulate CRF expression and responses are areas of intense investigation for new drugs to treat affective disorders. Here, we report that protein kinase C epsilon (PKCepsilon) null mutant mice, which show reduced anxiety-like behavior, have reduced levels of CRF messenger RNA and peptide in the amygdala. In primary amygdala neurons, a selective PKCepsilon activator, psiepsilonRACK, increased levels of pro-CRF, whereas reducing PKCepsilon levels through RNA interference blocked phorbol ester-stimulated increases in CRF. Local knockdown of amygdala PKCepsilon by RNA interference reduced anxiety-like behavior in wild-type mice. Furthermore, local infusion of CRF into the amygdala of PKCepsilon(-/-) mice increased their anxiety-like behavior. These results are consistent with a novel mechanism of PKCepsilon control over anxiety-like behavior through regulation of CRF in the amygdala.


Subject(s)
Amygdala/enzymology , Anxiety/psychology , Corticotropin-Releasing Hormone/physiology , Protein Kinase C-epsilon/metabolism , Amygdala/drug effects , Animals , Anxiety/genetics , Corticotropin-Releasing Hormone/administration & dosage , Corticotropin-Releasing Hormone/pharmacology , Mice , Mice, Knockout , Neurons/enzymology , Neurons/physiology , Protein Kinase C-epsilon/deficiency , Protein Kinase C-epsilon/genetics , RNA Interference , RNA, Messenger/genetics
12.
Br J Cancer ; 97(6): 705-11, 2007 Sep 17.
Article in English | MEDLINE | ID: mdl-17848908

ABSTRACT

Recruitment to cancer clinical trials needs to be improved, as does patient knowledge and understanding about clinical trials, in order for patients to make an informed choice about whether or not to take part. Audiovisual patient information (AVPI) has been shown to improve knowledge and understanding in various areas of practice, but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to consent rates. In this study, 173 patients were randomised to receive either the AVPI, in addition to the standard trial-specific written information, or the written information alone. There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% CI 0.55-2.58, P=0.661). Knowledge scores increased more in the AVPI group compared to the standard group (P=0.0072). The change in anxiety score between the arms was also statistically significant (P=0.011) with anxiety improving in the intervention arm more than in the no intervention arm. Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety, but further work is necessary in relation to its effect on clinical trial recruitment rates.


Subject(s)
Audiovisual Aids , Informed Consent , Patient Education as Topic/methods , Patient Selection , Aged , Anxiety/prevention & control , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Odds Ratio , Research Design , Videotape Recording
13.
J Phys Chem A ; 111(36): 8792-802, 2007 Sep 13.
Article in English | MEDLINE | ID: mdl-17705353

ABSTRACT

The gas-phase ion-molecule reactions of 1,1,3,3-tetrafluorodimethyl ether and water have been examined using Fourier transform ion cyclotron resonance mass spectrometry, infrared multiphoton dissociation (IRMPD) spectroscopy, and ab initio molecular orbital calculations. This reaction sequence leads to the efficient bimolecular production of the proton-bound dimer of water (H5O2+). Evidence for the dominant mechanistic pathway involving the reaction of CF2H-O=CHF+, an ion of m/z 99, with water is presented. The primary channel occurs via nucleophilic attack of water on the ion of m/z 99 (CF2H-O=CHF+), to lose formyl fluoride and yield-protonated difluoromethanol (m/z 69). Association of a second water molecule with protonated difluoromethanol generates a reactive intermediate that decomposes via a 1,4-elimination to release hydrogen fluoride and yield the proton-bound dimer of water and formyl fluoride (m/z 67). Last, the elimination of formyl fluoride occurs by the association of a third water molecule to produce H5O2+ (m/z 37). The most probable isomeric forms of the ions with m/z 99 and 69 were found using IRMPD spectroscopy and electronic structure theory calculations. Thermochemical information for reactant, transition state, and product species was obtained using MP2(full)/6-311+G**//6-31G* level of theory.

14.
J Phys Chem A ; 110(4): 1350-63, 2006 Feb 02.
Article in English | MEDLINE | ID: mdl-16435795

ABSTRACT

Density functional theory computations and pulsed-ionization high-pressure mass spectrometry experiments have been used to explore the potential energy surfaces for gas-phase S(N)2 reactions between halide ions and trifluoromethyl halides, X(-) + CF(3)Y --> Y(-) + CF(3)X. Structures of neutrals, ion-molecule complexes, and transition states show the possibility of two mechanisms: back- and front-side attack. From pulsed-ionization high-pressure mass spectrometry, enthalpy and entropy changes for the equilibrium clustering reactions for the formation of Cl(-)(BrCF(3)) (-16.5 +/- 0.2 kcal mol(-1) and -24.5 +/- 1 cal mol(-1) K(-1)), Cl(-)(ICF(3)) (-23.6 +/- 0.2 kcal mol(-1)), and Br(-)(BrCF(3)) (-13.9 +/- 0.2 kcal mol(-1) and -22.2 +/- 1 cal mol(-1) K(-1)) have been determined. These are in good to excellent agreement with computations at the B3LYP/6-311+G(3df)//B3LYP/6-311+G(d) level of theory. It is shown that complex formation takes place by a front-side attack complex, while the lowest energy S(N)2 reaction proceeds through a back-side attack transition state. This latter mechanism involves a potential energy profile which closely resembles a condensed phase S(N)2 reaction energy profile. It is also shown that the Cl(-) + CF(3)Br --> Br(-) + CF(3)Cl S(N)2 reaction can be interpreted using Marcus theory, in which case the reaction is described as being initiated by electron transfer. A potential energy surface at the B3LYP/6-311+G(d) level of theory confirms that the F(-) + CF(3)Br --> Br(-) + CF(4) S(N)2 reaction proceeds through a Walden inversion transition state.

15.
J Mass Spectrom ; 40(8): 1076-87, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15971295

ABSTRACT

Mass spectrometry-based methods have been employed in order to study the reactions of non- (h(6)/h(6)), half (d(6)/h(6)), and fully (d(6)/d(6)) deuterium labeled protonated dimers of acetone in the gas phase. Neither kinetic nor thermodynamic isotope effects were found. From MIKES experiments (both spontaneous and collision-induced dissociations), it was found that the relative ion yield (m/z 65 vs m/z 59) from the dissociation reaction of half deuterium labeled (d(6)/h(6)) protonated dimer of acetone is dependent on the internal energy. A relative ion yield (m/z 65 vs m/z 59) close to unity is observed for cold, nonactivated, metastable ions, whereas the ion yield is observed to increase (favoring m/z 65) when the pressure of the collision gas is increased. This is in striking contrast to what would be expected if a kinetic isotope effect were present. A combined study of the kinetics and the thermodynamics of the association reaction between acetone and protonated acetone implicates the presence of at least two isomeric adducts. We have employed G3(MP2) theory to map the potential energy surface leading from the reactants, acetone and protonated acetone, to the various isomeric adducts. The proton-bound dimer of acetone was found to be the lowest-energy isomer, and protonated diacetone alcohol the next lowest-energy isomer. Protonated diacetone alcohol, even though it is an isomer hidden behind many barriers, can possibly account for the observed relative ion yield and its dependence on the mode of activation.

16.
AIDS Care ; 14(2): 285-94, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11940285

ABSTRACT

This study analyzed the qualitative and quantitative responses of 60 minority teens affected by HIV. Relationships between adolescents' reports of: (1) feeling different, (2) having secrets, (3) worrying, and (4) caretaking were revealed. Six themes emerged from the content analysis of qualitative data that reflect how these adolescents have been affected by HIV: (1) core assumptions about life, (2) fearful anticipation of the death, (3) stigma and isolation, (4) current and future losses, (5) family role reassignment, and (6) lack of resources. Group treatment is presented as an effective method of intervention for adolescents living with an HIV-positive mother.


Subject(s)
Child of Impaired Parents/psychology , HIV Seropositivity/psychology , Mother-Child Relations , Psychology, Adolescent , Adolescent , Attitude to Death , Caregivers/psychology , Child , Family Health , Fear , Female , Humans , Male , Stereotyping , Truth Disclosure
17.
Optom Vis Sci ; 78(8): 599-604, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11525551

ABSTRACT

PURPOSE: To determine the test-retest reliability of three popular and commercially available Placido-ring videokeratography instruments in subjects with keratoconus. METHODS: Nine subjects (16 eyes) with keratoconus of varying degrees of severity had up to four images per eye generated, in random order, from the EyeSys Model II, Dicon CT 200 and the Keratron Corneal Analyzer. Test-retest analyses for the images were sampled at four locations: 1.5 mm nasal, inferior, temporal, and superior from center. The average standard deviation of all points was used to determine the short-term variability of the measurements. RESULTS: The short-term variability (in diopters) of the Dicon, EyeSys, and Keratron was 0.61 to 3.31 D, 0.94 to 1.51 D, and 0.58 to 2.85 D, respectively, for axial distance maps and 1.07 to 6.82 D, 0.79 to 1.77 D, and 1.23 to 3.03 D for tangential curvature maps. CONCLUSION: Results support the notion of a loss in repeatability for all three instruments when corneal irregularity is present, which reduces test-retest reliability.


Subject(s)
Cornea/pathology , Corneal Topography/standards , Keratoconus/diagnosis , Corneal Topography/instrumentation , Humans , Reproducibility of Results
18.
J Neurosci ; 21(17): 6933-9, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11517280

ABSTRACT

Inflammatory pain, characterized by a decrease in mechanical nociceptive threshold (hyperalgesia), arises through actions of inflammatory mediators, many of which sensitize primary afferent nociceptors via G-protein-coupled receptors. Two signaling pathways, one involving protein kinase A (PKA) and one involving the epsilon isozyme of protein kinase C (PKCepsilon), have been implicated in primary afferent nociceptor sensitization. Here we describe a third, independent pathway that involves activation of extracellular signal-regulated kinases (ERKs) 1 and 2. Epinephrine, which induces hyperalgesia by direct action at beta(2)-adrenergic receptors on primary afferent nociceptors, stimulated phosphorylation of ERK1/2 in cultured rat dorsal root ganglion cells. This was inhibited by a beta(2)-adrenergic receptor blocker and by an inhibitor of mitogen and extracellular signal-regulated kinase kinase (MEK), which phosphorylates and activates ERK1/2. Inhibitors of G(i/o)-proteins, Ras farnesyltransferases, and MEK decreased epinephrine-induced hyper-algesia. In a similar manner, phosphorylation of ERK1/2 was also decreased by these inhibitors. Local injection of dominant active MEK produced hyperalgesia that was unaffected by PKA or PKCepsilon inhibitors. Conversely, hyperalgesia produced by agents that activate PKA or PKCepsilon was unaffected by MEK inhibitors. We conclude that a Ras-MEK-ERK1/2 cascade acts independent of PKA or PKCepsilon as a novel signaling pathway for the production of inflammatory pain. This pathway may present a target for a new class of analgesic agents.


Subject(s)
Hyperalgesia/physiopathology , Mitogen-Activated Protein Kinases/metabolism , Nociceptors/physiopathology , Adrenergic beta-2 Receptor Antagonists , Animals , Cells, Cultured , Crosses, Genetic , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Ganglia, Spinal/physiopathology , Heterotrimeric GTP-Binding Proteins/antagonists & inhibitors , Heterotrimeric GTP-Binding Proteins/metabolism , Hyperalgesia/chemically induced , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Male , Mice , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Nociceptors/drug effects , Pain Measurement , Phosphorylation/drug effects , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , Protein Kinase C-epsilon , Rats , Receptors, Adrenergic, beta-2/metabolism , Signal Transduction/drug effects , ras Proteins/metabolism
19.
J Am Soc Mass Spectrom ; 12(8): 938-47, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11506226

ABSTRACT

In the gas phase, the CH2CHOH.+ enol radical cation 1 as well as its higher homologues CH3CHCHOH.+ 2 and (CH3)2CCHOH.+ 3, undergo exactly the same sequence of reactions with tert-butanol, leading to the losses of isobutene, water and water plus alkene. Fourier transform ion cyclotron resonance (FT-ICR) experiments using labeled reactants as well as ab initio calculations show that independent pathways can be proposed to explain the observed reactivity. For ion 1, taken as the simplest model, the first step of the reaction is formation of a proton bound complex which gives, by a simple exothermic proton transfer, the ter-body intermediate [CH2CHO., H2O, C(CH3)3+]. This complex, which was shown to possess a significant lifetime, is the key intermediate which undergoes three reactions. First, it can collapse to yield tert-butylvinyl ether with elimination of water. Second, by a regiospecific proton transfer, this complex can isomerize into three different ter-body complexes formed of water, isobutene and ionized enol. Within one of these complexes, which does not interconvert with the others, elimination of isobutene leads to the formation of a solvated enol ion. Within the others, a cycloaddition-cycloreversion process can proceed to yield the ionized enol 3 (loss of water and ethylene channel).

20.
J Am Chem Soc ; 123(17): 3980-5, 2001 May 02.
Article in English | MEDLINE | ID: mdl-11457148

ABSTRACT

Fourier transform ion cyclotron resonance mass spectrometry has been used to study the temperature and deuterium isotope effects on the methyl cation transfer reaction between protonated dimethyl ether and dimethyl ether to produce trimethyloxonium cation and methanol. From the temperature dependence of this bimolecular reaction it was possible to obtain thermodynamic information concerning the energy barrier for methyl cation transfer for the first time. From the slope of an Arrhenius plot, a value for DeltaH(++) of -1.1 +/- 1.2 kJ mol(-1) was obtained, while from the intercept a value for DeltaS(++) of -116 +/- 15 J K(-1) mol(-1) was derived. This yields a DeltaG(++)(298) value of 33.7 +/- 2.1 kJ mol(-1). All thermodynamic values were in good agreement with ab initio calculations. Rate constant ratios for the unimolecular dissociation forming trimethyloxonium cation and the dissociation re-forming reactants were extracted from the apparent bimolecular rate constant. Attempts at modeling the temperature dependence and isotope effects of the unimolecular dissociation forming trimethyloxonium cation were also made.

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