Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysis

Background The performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection methods to improve tuberculosis diagnosis are poorly characterised. We therefore aimed to investigate the effects of sputum collection methods on tuberculosis diagnosis. Methods We did a systematic review and meta-analysis to investigate whether non-invasive sputum collection methods in people aged at least 12 years improve the diagnostic performance of laboratory testing for pulmonary tuberculosis. We searched PubMed, Google Scholar, ProQuest, Web of Science, CINAHL, and Embase up to April 14, 2017, to identify relevant experimental, case-control, or cohort studies. We analysed data by pairwise meta-analyses with a random-effects model and by network meta-analysis. All diagnostic performance data were calculated at the sputum-sample level, except where authors only reported data at the individual patient-level. Heterogeneity was assessed, with potential causes identified by logistic meta-regression. Findings We identified 23 eligible studies published between 1959 and 2017, involving 8967 participants who provided 19 252 sputum samples. Brief, on-demand spot sputum collection was the main reference standard. Pooled sputum collection increased tuberculosis diagnosis by microscopy (odds ratio [OR] 1·6, 95% CI 1·3–1·9, p<0·0001) or culture (1·7, 1·2–2·4, p=0·01). Providing instructions to the patient before sputum collection, during observed collection, or together with physiotherapy assistance increased diagnostic performance by microscopy (OR 1·6, 95% CI 1·3–2·0, p<0·0001). Collecting early morning sputum did not significantly increase diagnostic performance of microscopy (OR 1·5, 95% CI 0·9–2·6, p=0·2) or culture (1·4, 0·9–2·4, p=0·2). Network meta-analysis confirmed these findings, and revealed that both pooled and instructed spot sputum collections were similarly effective techniques for increasing the diagnostic performance of microscopy. Interpretation Tuberculosis diagnoses were substantially increased by either pooled collection or by providing instruction on how to produce a sputum sample taken at any time of the day. Both interventions had a similar effect to that reported for the introduction of new, expensive laboratory tests, and therefore warrant further exploration in the drive to end the global tuberculosis epidemic

Scopolamine Administration Modulates Muscarinic, Nicotinic and NMDA Receptor Systems

Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration

Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysis

Background: The performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection methods to improve tuberculosis diagnosis are poorly characterised. We therefore aimed to investigate the effects of sputum collection methods on tuberculosis diagnosis. Methods: We did a systematic review and meta-analysis to investigate whether non-invasive sputum collection methods in people aged at least 12 years improve the diagnostic performance of laboratory testing for pulmonary tuberculosis. We searched PubMed, Google Scholar, ProQuest, Web of Science, CINAHL, and Embase up to April 14, 2017, to identify relevant experimental, case-control, or cohort studies. We analysed data by pairwise meta-analyses with a random-effects model and by network meta-analysis. All diagnostic performance data were calculated at the sputum-sample level, except where authors only reported data at the individual patient-level. Heterogeneity was assessed, with potential causes identified by logistic meta-regression. Findings: We identified 23 eligible studies published between 1959 and 2017, involving 8967 participants who provided 19 252 sputum samples. Brief, on-demand spot sputum collection was the main reference standard. Pooled sputum collection increased tuberculosis diagnosis by microscopy (odds ratio [OR] 1·6, 95% CI 1·3–1·9, p<0·0001) or culture (1·7, 1·2–2·4, p=0·01). Providing instructions to the patient before sputum collection, during observed collection, or together with physiotherapy assistance increased diagnostic performance by microscopy (OR 1·6, 95% CI 1·3–2·0, p<0·0001). Collecting early morning sputum did not significantly increase diagnostic performance of microscopy (OR 1·5, 95% CI 0·9–2·6, p=0·2) or culture (1·4, 0·9–2·4, p=0·2). Network meta-analysis confirmed these findings, and revealed that both pooled and instructed spot sputum collections were similarly effective techniques for increasing the diagnostic performance of microscopy. Interpretation: Tuberculosis diagnoses were substantially increased by either pooled collection or by providing instruction on how to produce a sputum sample taken at any time of the day. Both interventions had a similar effect to that reported for the introduction of new, expensive laboratory tests, and therefore warrant further exploration in the drive to end the global tuberculosis epidemic. Funding: Wellcome Trust, Joint Global Health Trials consortium, Innovation For Health and Development, and Bill & Melinda Gates Foundation

Vaccination of Rhesus Macaques with the Anthrax Vaccine Adsorbed Vaccine Produces a Serum Antibody Response That Effectively Neutralizes Receptor-Bound Protective Antigen In Vitro ▿

Anthrax toxin (ATx) is composed of the binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor and lethal factor) but have the same binding protein, protective antigen (PA). PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx-neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to the target cell surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell). To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (noncomplexed [NC] and receptor-bound [RB] TNA assays). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated rhesus macaques (Macaca mulatta) that survived an aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was prebound to cells. Neutralization titers in surviving versus nonsurviving animals and between prechallenge and postchallenge activities were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support the idea that the full-length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines

Early dispersal of domestic horses into the Great Plains and northern Rockies

The horse is central to many Indigenous cultures across the American Southwest and the Great Plains. However, when and how horses were first integrated into Indigenous lifeways remain contentious, with extant models derived largely from colonial records. We conducted an interdisciplinary study of an assemblage of historic archaeological horse remains, integrating genomic, isotopic, radiocarbon, and paleopathological evidence. Archaeological and modern North American horses show strong Iberian genetic affinities, with later influx from British sources, but no Viking proximity. Horses rapidly spread from the south into the northern Rockies and central plains by the first half of the 17th century CE, likely through Indigenous exchange networks. They were deeply integrated into Indigenous societies before the arrival of 18th-century European observers, as reflected in herd management, ceremonial practices, and culture.Fil: Taylor, William Timothy Treal. University of Colorado; Estados UnidosFil: Librado, Pablo. Université Paul Sabatier; FranciaFil: Hunska Tašunke Icu, Mila. Pine Ridge Reservation; Estados UnidosFil: Shield Chief Gover, Carlton. University of Colorado; Estados Unidos. Pawnee Nation of Oklahoma; Estados UnidosFil: Arterberry, Jimmy. Galindo Environmental Consulting LLC; Estados UnidosFil: Luta Wiƞ, Anpetu. Pine Ridge Reservation; Estados UnidosFil: Nujipi, Akil. Pine Ridge Reservation; Estados UnidosFil: Omniya, Tanka. Pine Ridge Reservation; Estados UnidosFil: Gonzalez, Mario. Pine Ridge Reservation; Estados UnidosFil: Means, Bill. Pine Ridge Reservation; Estados Unidos. International Indian Treaty Council; Estados UnidosFil: High Crane, Sam. Rosebud Indian Reservation; Estados UnidosFil: Dull Knife, Barbara. Pine Ridge Reservation; Estados Unidos. Rosebud Indian Reservation; Estados UnidosFil: Wiƞ, Wakiƞyala. Pine Ridge Reservation; Estados UnidosFil: Tecumseh Collin, Cruz. Pine Ridge Reservation; Estados UnidosFil: Ward, Chance. Cheyenne River Sioux Tribe; Estados Unidos. University of Colorado; Estados UnidosFil: Pasqual, Theresa A.. No especifíca;Fil: Chauvey, Lorelei. Université Paul Sabatier; FranciaFil: Tonasso Calviere, Laure. Université Paul Sabatier; FranciaFil: Schiavinato, Stéphanie. Université Paul Sabatier; FranciaFil: Seguin Orlando, Andaine. Université Paul Sabatier; FranciaFil: Fages, Antoine. Université Paul Sabatier; Francia. University of Basel; SuizaFil: Khan, Naveed. Université Paul Sabatier; Francia. Abdul Wali Khan University; PakistánFil: Der Sarkissian, Clio. Université Paul Sabatier; FranciaFil: Eché, Camille. Institut National de la Recherche Agronomique; FranciaFil: Belardi, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Tecnológica Nacional. Facultad Regional Santa Cruz. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Nacional de la Patagonia Austral. Centro de Investigaciones y Transferencia de Santa Cruz; ArgentinaFil: Wincker, Patrick. Centre National de la Recherche Scientifique; Francia. Universite Paris-Saclay ;Fil: Bethke, Brandi. Oklahoma State University; Estados UnidosFil: Roberts, Patrick. Max Planck Institute for Geoanthropology; AlemaniaFil: Jones, Emily Lena. University of New Mexico; Estados UnidosFil: Running Horse Collin, Yvette. Université Paul Sabatier; Francia. Pine Ridge Reservation; Estados UnidosFil: Orlando, Ludovic. Université Paul Sabatier; Franci

Early dispersal of domestic horses into the Great Plains and northern Rockies

International audienceThe horse is central to many Indigenous cultures across the American Southwest and the Great Plains. However, when and how horses were first integrated into Indigenous lifeways remain contentious, with extant models derived largely from colonial records. We conducted an interdisciplinary study of an assemblage of historic archaeological horse remains, integrating genomic, isotopic, radiocarbon, and paleopathological evidence. Archaeological and modern North American horses show strong Iberian genetic affinities, with later influx from British sources, but no Viking proximity. Horses rapidly spread from the south into the northern Rockies and central plains by the first half of the 17th century CE, likely through Indigenous exchange networks. They were deeply integrated into Indigenous societies before the arrival of 18th-century European observers, as reflected in herd management, ceremonial practices, and culture