One Health Surveillance: perceived benefits and workforce motivations.

One Health Surveillance (OHS) implements the One Health approach to improving health by collecting data and producing information to support integrated action across the animal health, human health and environment sectors. The purpose of this study was to survey the biosurveillance community to assess its OHS practices and capabilities, its attitudes towards OHS (perceived value), and the factors that motivate its members to implement OHS practices. The authors used a convenience sample of 185 professionals from multiple domains and 44 nations. They examined the extent to which these professionals implemented OHS, gathered their opinions on the value of OHS, assessed their perceptions of the capacity to perform specific OHS tasks and identified their priorities for change. Over 85% of all respondents said that they considered OHS to be beneficial, with no significant differences between work domains or country income groups; over 50% indicated that they already applied OHS. Obtaining access to data collected by other domains was both the most frequent challenge and the most difficult to improve. The highest priority for improvement was having the ability to send and receive electronic data. Respondents from low-income or middle-income countries were more motivated to make improvements than stakeholders from high-income countries. These findings provide a snapshot of current opinions and practices and, together with suggestions for improvements from professionals in the field, can help to target priority needs for OHS information, training and resources.

La surveillance Une seule santé opérationnalise la méthode Une seule santé pour une meilleure santé à travers la collecte de données et la production d'informations visant à soutenir la mobilisation transversale des secteurs de la santé animale, de la santé publique et de la santé environnementale en vue d'une action intégrée. Les auteurs présentent les résultats d'une enquête menée auprès des professionnels en charge de la biosurveillance afin d'évaluer leurs pratiques et capacités en matière de surveillance Une seule santé, leurs attitudes à l'égard de cette surveillance (c'est-à-dire leur perception de l'intérêt de la démarche) et les facteurs susceptibles de les motiver à la mettre en oeuvre. Les auteurs ont procédé à un échantillonnage de commodité de 185 intervenants issus de plusieurs secteurs dans 44 pays. Ils ont ensuite analysé le niveau de mise en oeuvre de la surveillance Une seule santé chez ces intervenants, recueilli leurs opinions concernant l'intérêt de la démarche, évalué la perception qu'ils avaient de leur capacité à mener à bien certaine tâches spécifiques dans ce domaine et identifié leurs priorités en vue du changement. Plus de 85 % des répondants ont déclaré considérer la surveillance Une seule santé comme étant bénéfique, résultat ne présentant pas de corrélation significative avec le secteur professionnel des personnes interrogées ni avec le niveau de revenu de leur pays ; plus de 50 % des répondants ont par ailleurs indiqué qu'ils appliquaient déjà les principes d'une surveillance Une seule santé. La difficulté la plus fréquente et qui paraissait la plus difficile à résoudre était celle de pouvoir accéder aux données enregistrées par d'autres secteurs. La première des priorités identifiées en vue d'une amélioration concernait la capacité d'envoyer et de recevoir des données électroniques. La motivation à introduire des améliorations était plus forte chez les répondants des pays à revenu faible ou intermédiaire que chez les parties prenantes des pays à revenus élevés. Ces résultats, qui offrent un instantané des opinions et des pratiques actuelles assorti de propositions concrètes d'amélioration formulées par les professionnels de terrain devraient pouvoir contribuer à cibler les besoins prioritaires en matière d'information, de formation et de ressources dédiées à la surveillance Une seule santé.

Practicar la vigilancia en clave de Una sola salud significa traducir esta idea en la práctica con el fin de mejorar la salud reuniendo datos y generando información a partir de la cual actuar de forma integrada en los sectores de la sanidad animal, la salud humana y el medio ambiente. Los autores describen un estudio de los círculos dedicados a la vigilancia biológica que tenía por objetivo evaluar sus procedimientos y capacidades de vigilancia en clave de Una sola salud, sus actitudes al respecto (valor atribuido) y los factores que los motivan a instaurar procedimientos concebidos desde la lógica de Una sola salud. Para ello los autores utilizaron una muestra de conveniencia de 185 profesionales de múltiples disciplinas y 44 países. Tras determinar en qué medida esos profesionales practicaban la vigilancia en clave de Una sola salud, les pidieron su opinión sobre la utilidad de este tipo de vigilancia, evaluaron la capacidad que subjetivamente se atribuían de efectuar labores específicas de vigilancia en clave de Una sola salud y determinaron aquellos cambios que esas personas juzgaban prioritarios. Más de un 85% de los encuestados dijo considerar beneficiosa la vigilancia en clave de Una sola salud, sin que se observaran diferencias significativas por ámbito de trabajo o por países según el grupo de ingresos. Más de un 50% afirmó que ya aplicaba este tipo de vigilancia. El problema señalado con más frecuencia y juzgado a la vez más difícil de resolver era el del acceso a datos obtenidos desde otros ámbitos de trabajo. El aspecto que más urgía mejorar era el de la capacidad de enviar y recibir datos electrónicos. Los encuestados de países de nivel bajo o medio de ingresos mostraban mayor motivación a la hora de introducir mejoras que sus homólogos de países de ingresos altos. Estas conclusiones, que ofrecen una «instantánea¼ de las opiniones y prácticas imperantes, pueden ayudar, junto con las propuestas de mejora procedentes de esos profesionales que trabajan sobre el terreno, a seleccionar las necesidades prioritarias de información, formación y recursos para la práctica de la vigilancia en clave de Una sola salud.

The immediate effects of cervical spine manipulation on pain and biochemical markers in females with acute non-specific mechanical neck pain: a randomized clinical trial.

Study Design: Randomized clinical trial with pre-test, post-test control group design. Objectives: To examine the immediate effects of cervical spinal manipulation (CSM) on serum concentration of biochemical markers (oxytocin, neurotensin, orexin A, and cortisol). Background: Several studies have found an association between spinal manipulation (SM) and pain perception. However, the mechanism by which SM modulates pain remains undefined. Methods: Twenty-eight female subjects with non-specific mechanical neck pain were randomly assigned to one of two interventions (CSM versus sham CSM). Blood samples were drawn before and immediately after the respective interventions. Oxytocin, neurotensin, orexin A, and cortisol were measured from the blood and serum using the Milliplex Map Magnetic Bead Panel Immunoassay on the Luminex 200 Platform. Results: In the CSM group, there were significant increases in pre- versus post-manipulation mean oxytocin (154.5 ± 60.1 vs. 185.1 ± 75.6, p = .012); neurotensin (116.0 ± 26.5 vs.136.4 ± 34.1, p < . 001); orexin A (52.2 ± 31.1 vs. 73.8 ± 38.8, p < .01) serum concentration; but no significant differences in mean cortisol (p = .052) serum concentration. In the sham group, there were no significant differences in any of the biomarkers (p > .05). Conclusion: The results of the current study suggest that the mechanical stimuli provided through a CSM may modify neuropeptide expression by immediately increasing the serum concentration of nociception-related biomarkers (oxytocin, neurotensin, orexin A, but not cortisol) in the blood of female subjects with non-specific mechanical neck pain.

Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication.

Certain amino acid substitutions in the reverse transcriptase (RT), including D67N, K70R, T215Y, and K219Q, cause high-level resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (3'-azidothymidine; AZT) and appear to approximate the template strand of the enzyme-template-primer complex in structural models. We studied whether this set of mutations altered RT-template-primer interaction as well as their effect on virus replication in the absence of inhibitor. When in vitro polymerization was limited to a single association of an RT with an oligodeoxynucleotide-primed heteropolymeric RNA template (a single processive cycle), recombinant-expressed mutant 67/70/215/219 RT synthesized 5- to 10-fold more high-molecular-weight DNA products (>200 nucleotides in length) than wild-type RT. This advantage was maintained as deoxynucleoside triphosphate (dNTP) concentrations were decreased to limiting levels. In contrast, no difference was seen between wild-type and mutant RTs under conditions allowing repeated associations of enzyme with template-primer. Because intracellular dNTP concentrations are low prior to mitogenic stimulation, we compared replication of mutant 67/70/215/219 virus and wild-type virus in peripheral blood mononuclear cells (PBMC) stimulated before and after infection. In the absence of inhibitor, mutant 67/70/215/219 virus had a replication advantage in PBMC stimulated with phytohemagglutinin and interleukin-2 after infection, but virus replication was similar in PBMC stimulated before infection in vitro. The results confirm that RT mutations D67N, K70R, T215Y, and K219Q affect an enzyme-template-primer interaction in vitro and suggest that such substitutions may affect HIV-1 pathogenesis during therapy by increasing viral replication capacity in cells stimulated after infection.

Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase.

A human immunodeficiency virus type 1 variant resistant to zalcitabine (2',3'-dideoxycytidine [ddC]) was selected by sequential passage in the presence of increasing concentrations of ddC in peripheral blood mononuclear cell cultures. A mutation causing a lysine-to-arginine substitution was noted in reverse transcriptase (RT) codon 65 of this ddC-selected virus. A cloned mutant virus with this codon 65 mutation was constructed by using a novel PCR approach for site-directed mutagenesis. Characterization of this virus confirmed that the RT Lys-65-->Arg substitution was necessary and sufficient for a fourfold increase in the ddC 50% inhibitory concentration, as well as for resistance to didanosine (2',3'-dideoxyinosine [ddI]). Lys-65-->Arg and virus resistance to ddC and ddI also developed during therapy in isolates from one ddC-treated patient and two ddI-treated patients. Recombinant-expressed codon 65 mutant RT enzyme was resistant to ddCTP and ddATP in cell-free polymerase assays. Results of mutant enzyme studies are consistent with Lys-65-->Arg leading to changes in binding of the triphosphate forms of these nucleoside analogs to the RT. These data have implications for future studies of ddC resistance, particularly those aimed at defining its clinical relevance.

pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo.

Specific mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene that cause zidovudine (3'-azido-2',3'-dideoxythymidine; AZT) and didanosine (2',3'-dideoxyinosine; ddI) resistance were studied. The 50% inhibitory concentrations (IC50s) of nucleosides for cloned viruses containing these mutations were compared with the IC50s of the corresponding triphosphate analogs for mutant recombinant-expressed reverse transcriptases (RTs). Changes in ddATP inhibition of RNA-dependent DNA polymerase activity fully accounted for the ddI resistance of the virus caused by a Leu-74-->Val substitution in RT, including an augmentation by the AZT-selected substitutions Thr-215-->Tyr and Lys-219-->Gln in RT. In contrast, the AZT-selected substitutions studied did not cause as great a change in the IC50 of AZT-triphosphate (AZT-TP) for polymerase as they did in the IC50 of AZT for mutant virus. In addition, the mutation at codon 74 suppressed AZT resistance in the virus caused by the mutations at codons 215 and 219 but did not suppress the AZT-TP resistance of enzyme containing these same mutations in RT. The mutation at codon 74 was found in clinical isolates whether or not the patient had received AZT prior to starting ddI therapy. AZT resistance coexisted with ddI resistance following acquisition of Leu-74-->Val in three clinical isolates, indicating that the suppressive effect of Val-74 on the AZT resistance of the virus does not occur in all genetic contexts. When this suppression of AZT resistance was seen in the virus, Val-74 did not appear to cause mutually exclusive changes in AZT-TP and ddATP binding to RT in vitro. The results of the in vitro experiments and characterization of clinical isolates suggest that there are differences in the functional effects of these AZT and ddI resistance mutations.

Characterization of testosterone 16 alpha-hydroxylase (I-P-450(16) alpha) induced by phenobarbital in mice.

Cytochrome P-450 (I-P-450(16) alpha), which is associated with phenobarbital-induced testosterone 16 alpha-hydroxylation activity, was purified from livers of phenobarbital-treated female 129/J mice on the basis of the specific hydroxylation activity in fractions eluted from columns of octylamino-Sepharose 4B, hydroxylapatite, DEAE-Bio-Gel A, and isobutyl-Sepharose 4B. The specific cytochrome P-450 content of the purified I-P-450(16) alpha fraction was 12.4 nmol/mg of protein, and it had an apparent molecular weight of 54K. The specific activity of reconstituted testosterone 16 alpha-hydroxylation activity with the purified I-P-450(16) alpha fraction was 6-8 nmol min-1 (nmol of cytochrome P-450)-1. Rabbit antibody raised against the purified I-P-450(16) alpha fraction inhibited nearly 100% of the 16 alpha-hydroxylation activity in liver microsomes of phenobarbital-treated female 129/J mice but did not affect hepatic microsomal 16 alpha-hydroxylation activity of untreated male and female 129/J mice at all. In hepatic microsomes of phenobarbital-treated male 129/J mice, 70% of the 16 alpha-hydroxylation activity, at most, was catalyzed by I-P-450(16) alpha, and the residual 30% of the activity was catalyzed by C-P-450(16) alpha. The increase of I-P-450(16) alpha by phenobarbital was due to de novo synthesis of I-P-450(16) alpha, and this induction was not sexually regulated in 129/J mice. Anti-C-P-450(16) alpha [Harada, N., & Negishi, M. (1984) J. Biol. Chem. 259, 12285-12290] did not inhibit the 16 alpha-hydroxylation catalyzed by I-P-450(16) alpha; thus, I-P-450(16) alpha and C-P-450(16) alpha are immunochemically distinct isozymes of testosterone 16 alpha-hydroxylase.