In vivo CAR T-cell generation in non-human primates using lentiviral vectors displaying a multi-domain fusion ligand.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high cost and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVecTM platform, a lentiviral vector capable of generating CAR T-cells in vivo. Here we describe the incorporation of T cell activation and costimulatory signals onto the surface of VivoVecTM particles (VVPs) in the form of a multi-domain fusion protein and show enhanced in vivo transduction and improved CAR-T cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into non-human primates resulted in the robust generation of anti-CD20 CAR T-cells and the complete depletion of B cells for more than 10 weeks. These data validate the VivoVecTM platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies.

Temporal and spatial shifts in gun violence, before and after a historic police killing in Minneapolis.

OBJECTIVE: To determine the impact of the police murder of George Floyd in Minneapolis, MN on firearm violence, and examine the spatial and social heterogeneity of the effect. METHODS: We analyzed a uniquely constructed panel dataset of Minneapolis Zip Code Tabulation Areas from 2016-2020 (n = 5742), consisting of Minnesota Hospital Association, Minneapolis Police Department, Minneapolis Public Schools, Census Bureau, and Minnesota Department of Natural Resources data. Interrupted time-series and random effects panel models were used to model the spatiotemporal effects of police killing event on the rate of firearm assault injuries. RESULTS: Findings reveal a rising and falling temporal pattern post-killing and a spatial pattern in which disadvantaged, historically Black communities near earlier sites of protest against police violence experienced the brunt of the post-killing increase in firearm assault injury. These effects remain after adjusting for changes in police activity and pandemic-related restrictions, indicating that rising violence was not a simple byproduct of changes in police behavior or COVID-19 response. CONCLUSIONS: The results suggest that the increases in firearm violence as a result of police violence are disproportionately borne by underserved communities.

Evaluation of "Caserotek" a low cost and effective artificial blood-feeding device for mosquitoes.

Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system ("Caserotek") to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21-22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions.

Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformational outcomes in the treatment of B-cell malignancies, but their widespread use is hindered by technical and logistical challenges associated with ex vivo cell manufacturing. To overcome these challenges, we developed VivoVec, a lentiviral vector-based platform for in vivo engineering of T cells. UB-VV100, a VivoVec clinical candidate for the treatment of B-cell malignancies, displays an anti-CD3 single-chain variable fragment (scFv) on the surface and delivers a genetic payload that encodes a second-generation CD19-targeted CAR along with a rapamycin-activated cytokine receptor (RACR) system designed to overcome the need for lymphodepleting chemotherapy in supporting successful CAR T-cell expansion and persistence. In the presence of exogenous rapamycin, non-transduced immune cells are suppressed, while the RACR system in transduced cells converts rapamycin binding to an interleukin (IL)-2/IL-15 signal to promote proliferation. METHODS: UB-VV100 was administered to peripheral blood mononuclear cells (PBMCs) from healthy donors and from patients with B-cell malignancy without additional stimulation. Cultures were assessed for CAR T-cell transduction and function. Biodistribution was evaluated in CD34-humanized mice and in canines. In vivo efficacy was evaluated against normal B cells in CD34-humanized mice and against systemic tumor xenografts in PBMC-humanized mice. RESULTS: In vitro, administration of UB-VV100 resulted in dose-dependent and anti-CD3 scFv-dependent T-cell activation and CAR T-cell transduction. The resulting CAR T cells exhibited selective expansion in rapamycin and antigen-dependent activity against malignant B-cell targets. In humanized mouse and canine studies, UB-VV100 demonstrated a favorable biodistribution profile, with transduction events limited to the immune compartment after intranodal or intraperitoneal administration. Administration of UB-VV100 to humanized mice engrafted with B-cell tumors resulted in CAR T-cell transduction, expansion, and elimination of systemic malignancy. CONCLUSIONS: These findings demonstrate that UB-VV100 generates functional CAR T cells in vivo, which could expand patient access to CAR T technology in both hematological and solid tumors without the need for ex vivo cell manufacturing.

A Follow-Up to the Geographical Distribution of Anopheles Species in Malaria-Endemic and Non-Endemic Areas of Honduras.

Anopheles species are the vectors of malaria, one of the diseases with the greatest impact on the health of the inhabitants of the tropics. Due to their epidemiological relevance and biological complexity, monitoring of anopheline populations in current and former malaria-endemic areas is critical for malaria risk assessment. Recent efforts have described the anopheline species present in the main malaria foci in Honduras. This study updates and expands knowledge about Anopheles species composition, geographical distribution, and genetic diversity in the continental territory of Honduras as in the Bay Islands. Outdoor insect collections were carried out at 25 sites in eight municipalities in five departments of Honduras between 2018 and 2021. Specimens were identified using taxonomic keys. Partial COI gene sequences were used for molecular species identification and phylogenetic analyses. In addition, detection of Plasmodium DNA was carried out in 255 female mosquitoes. Overall, 288 Anopheles mosquitoes were collected from 8 municipalities. Eight species were morphologically identified. Anopheles albimanus was the most abundant and widely distributed species (79.5%). A subset of 175 partial COI gene sequences from 8 species was obtained. Taxonomic identifications were confirmed via sequence analysis. Anopheles albimanus and An. apicimacula showed the highest haplotype diversity and nucleotide variation, respectively. Phylogenetic clustering was found for An. argyritarsis and An. neomaculipalpus when compared with mosquitoes from other Neotropical countries. Plasmodium DNA was not detected in any of the mosquitoes tested. This report builds upon recent records of the distribution and diversity of Anopheles species in malaria-endemic and non-endemic areas of Honduras. New COI sequences are reported for three anopheline species. This is also the first report of COI sequences of An. albimanus collected on the island of Roatán with apparent gene flow relative to mainland populations.

Felon history and change in U.S. employment rates.

In recent decades, the share of U.S. adults with felony-level criminal records has risen and the growth in the employment rate has slowed. Sociological theories of labeling and stigmatization, as well as economic theories of statistical discrimination, suggest a possible causal connection between the two phenomena. Surveys of employers have shown increasing reliance on criminal background checks, for example, and audit studies reveal explicit discrimination against people with felony-level criminal records. This paper draws on novel, state-level annual measures of individuals with felony-level records to estimate pooled cross-sectional, panel models predicting changes in aggregate employment rates. Estimates from these models indicate that a 1 percentage point increase in the share of a state's adult population with a felony history is associated with 0.3 percentage point increase in non-employment (being unemployed or not in the labor force) among those aged 18 to 54. Subgroup analysis shows that effects are stronger for women and whites. These results suggest that the stigma of a felony record may play an important part in aggregate employment rates as well as in individual hiring practices.

Maize stalk stiffness and strength are primarily determined by morphological factors.

The maize (Zea mays) stem is a biological structure that must balance both biotic and structural load bearing duties. These competing requirements are particularly relevant in the design of new bioenergy crops. Although increased stem digestibility is typically associated with a lower structural strength and higher propensity for lodging, with the right balance between structural and biological activities it may be possible to design crops that are high-yielding and have digestible biomass. This study investigates the hypothesis that geometric factors are much more influential in determining structural strength than tissue properties. To study these influences, both physical and in silico experiments were used. First, maize stems were tested in three-point bending. Specimen-specific finite element models were created based on x-ray computed tomography scans. Models were validated by comparison with experimental data. Sensitivity analyses were used to assess the influence of structural parameters such as geometric and material properties. As hypothesized, geometry was found to have a much stronger influence on structural stability than material properties. This information reinforces the notion that deficiencies in tissue strength could be offset by manipulation of stalk morphology, thus allowing the creation of stalks which are both resilient and digestible.

High Prevalence of Borrelia mayonii (Spirochaetales: Spirochaetaceae) in Field-Caught Tamias striatus (Rodentia: Sciuridae) From Northern Wisconsin.

Borrelia mayonii is a recently discovered bacterial spirochete that causes Lyme disease and is transmitted by the blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae). To date, B. mayonii has been isolated from two vertebrate host species in Minnesota: field-caught white-footed mice (Peromyscus leucopus Rafinesque; Rodentia: Cricetidae) and American red squirrel (Tamiasciurus hudsonicus Erxleben). Here, we describe the first detection of B. mayonii in field-caught eastern chipmunks (Tamias striatus L. (Rodentia: Cricetidae)) from northern Wisconsin. During our study, we captured 530 unique small mammals and found an infection prevalence of 23.50% in field-caught eastern chipmunks (4/17) and 1.19% in Peromyscus spp. (5/420). Mean larval and nymphal burdens were determined for captured Blarina brevicauda (0, 0), Glaucomys volans (0.29, 0.14), Myodes gapperi (0.27, 0), Napaeozapus insignis (0, 0.25), Peromyscus spp. (1.88, 0.11), T. striatus (1.06, 0.65), and Sorex cinereus (0.09, 0). The high B. mayonii infection prevalence in eastern chipmunks suggests that the species may be an important reservoir for B. mayonii in the Upper Midwest.

Criminal punishment and violent injury in Minnesota.

BACKGROUND: Violence is one of the leading causes of injury and death in the United States. One-way society attempts to eliminate violence is through criminal punishment. Yet, in many contexts, punishment fails to reduce violence and may cause other harms. Current research on violence often suffers from same-source bias which can produce spurious associations. This study assesses the associations of different forms of criminal punishment (monetary sanctions, incarceration, and probation) with violent injuries in two unique datasets. METHODS: This study examines a unique combination of hospital discharge data and court administrative data, two Minnesota county-level data sources. First, we assess the spatial distribution of the three criminal punishment variables and two violent injury variables, violent injury overall and violent injury in children by county from 2010 to 2014, using Moran's I statistic and Local Indicators of Spatial Autocorrelation. Then we assess the association of criminal punishment on violent injury and child abuse injury using a two-way fixed effects panel models. RESULTS: Child abuse injuries are relatively rare in our data but are significantly concentrated geographically, unlike violent injuries which are more dispersed throughout Minnesota. Incarceration and probation are significantly geographically concentrated in similar regions while monetary sanctions are not geographically concentrated. We find a link between probation loads and violent injury, specifically, with a 1 day increase in per capita probation supervision associated with a 0.044 increase in violent injury incidence per 1000 people. In contrast, monetary sanctions and incarceration loads have little association with either violent injury or child abuse injury incidence. CONCLUSIONS: Criminal punishment is intended to reduce harm in society, but many argue that it may bring unintended consequences such as violence. This study finds that county-level probation has a modest positive association with county-level violent injury rates, but monetary sanctions and incarceration are less associated with violence injury rates. No measure of criminal punishment was associated with a reduction in violence. This study addresses a gap in previous literature by examining the association of punishment and violence in two unrelated datasets. High rates of criminal punishment and violent injury are both urgent public health emergencies. Further individual-level investigation is needed to assess potential links.

Immature Ixodes scapularis (Acari: Ixodidae) Collected From Peromyscus leucopus (Rodentia: Cricetidae) and Peromyscus maniculatus (Rodentia: Cricetidae) Nests in Northern Wisconsin.

The blacklegged tick, Ixodes scapularis Say, is the primary Lyme disease vector in the eastern United States. Both immature stages of I. scapularis take blood meals from mice belonging to the genus Peromyscus. Mice are active during the night and spend the majority of diel periods in nests. Thus, immature I. scapularis have a greater opportunity to drop from Peromyscus hosts while in nests compared with the forest floor. Here, we collected 11 Peromyscus nests during a 3-mo period during which the immature I. scapularis are known to be active. We then examined nesting materials for the presence of I. scapularis. Immature I. scapularis were detected in 64% of Peromyscus nests examined. Additionally, 55% of the nests contained at least one Dermacentor variabilis Say larva. Eighty-seven percent of all larval ticks found within nests were blood-fed. Because Peromyscus spp. are highly competent reservoirs of numerous tick-borne pathogens, the ticks that detach in their nests may be important for the maintenance of tick-borne diseases. However, further studies are needed to determine the fate of the I. scapularis that detach in Peromyscus nests.

Measurement accuracy and uncertainty in plant biomechanics.

All scientific measurements are affected to some degree by both systematic and random errors. The quantification of these errors supports correct interpretation of data, thus supporting scientific progress. Absence of information regarding reliability and accuracy can slow scientific progress, and can lead to a reproducibility crisis. Here we consider both measurement theory and plant biomechanics literature. Drawing from measurement theory literature, we review techniques for assessing both the accuracy and uncertainty of a measurement process. In our survey of plant biomechanics literature, we found that direct assessment of measurement accuracy and uncertainty is not yet common. The advantages and disadvantages of efforts to quantify measurement accuracy and uncertainty are discussed. We conclude with recommended best practices for improving the scientific rigor in plant biomechanics through attention to the issues of measurement accuracy and uncertainty.

A Quarter Century of Participation in School-Based Extracurricular Activities: Inequalities by Race, Class, Gender and Age?

Extracurricular activity participation is linked to positive development, but it is also a setting for inequality. Using a quarter century of data from Monitoring the Future (N = 593,979; 51% female; 65% non-Hispanic white; 13% non-Hispanic black; 12% Hispanic; 4% non-Hispanic Asian/Pacific Islander; 7% other race), this article documents patterns and trends in school-based extracurricular participation by race, social class, gender, and age, and their links to academic and substance use outcomes. Findings reveal differences by race and confirm a division by social class that has worsened over time. Further, girls are gaining on boys and surpass them in some types of school-based activities. Participation is linked to better academic outcomes and less substance use, affirming the importance of redressing the inequalities revealed.

Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. The ability of each T cell population to control Mtb in the lungs of mice was restricted for opposite reasons: Ag85B-specific T cells were limited by reduced antigen expression during persistent infection, whereas ESAT-6-specific T cells became functionally exhausted due to chronic antigenic stimulation. Our findings suggest that different vaccination strategies will be required to optimize protection mediated by T cells recognizing antigens expressed at distinct stages of Mtb infection.

MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis.

The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.

Primary spontaneous pneumothorax presenting to a chiropractic clinic as undifferentiated thoracic spine pain: a case report.

OBJECTIVE: To present a case of primary spontaneous pneumothorax presenting to a chiropractic clinic as undifferentiated thoracic spine pain. CLINICAL FEATURES: A tall thin 25-year-old male anxiously presented to a chiropractic clinic with six days of sudden unexplained left thorax pain. His breathing was laboured and his dry cough aggravating. After assessment a high clinical suspicion of primary spontaneous pneumothorax prevailed. INTERVENTION AND OUTCOME: The patient was referred to hospital for further investigation and primary spontaneous pneumothorax was confirmed on chest radiograph. He underwent immediate tube thoracostomy to drain the air from his pleural space and to re-inflate his lung. After three days the tube was removed. By two weeks the lung had returned to full size. No recurrences have occurred to date. CONCLUSIONS: Primary spontaneous pneumothorax is a medical emergency in the presence of shortness of breath. The focus of treatment is to drain air from the pleural linings and to prevent recurrences. In less severe cases, patients may believe they have thoracic spine pain and seek manual therapy care. This case highlights the important role chiropractors have as primary contact health care providers.

OBJECTIF: Présenter un cas de pneumothorax spontané primaire présenté à une clinique chiropratique comme douleur de la colonne thoracique indifférenciée. CARACTÉRISTIQUES CLINIQUES: Un homme grand et mince de 25 ans s'est présenté anxieusement à une clinique de chiropratique en se plaignant d'une douleur soudaine inexpliquée dans le thorax gauche pendant six jours. Sa respiration était laborieuse et sa toux sèche s'aggravait. Après l'examen, une forte suspicion clinique de pneumothorax spontané primaire s'est imposée. INTERVENTION ET RÉSULTATS: Le patient a été orienté à l'hôpital pour des examens supplémentaires, et le pneumothorax spontané primaire a été confirmé à la suite de la radiographie thoracique. Il a immédiatement subi une insertion du drain thoracique afin de drainer l'air à partir de sa cavité pleurale et de regonfler son poumon. Au bout de trois jours, le drain a été retiré. En deux semaines, le poumon a retrouvé sa taille normale. Pas de récidive à ce jour. CONCLUSIONS: Le pneumothorax spontané primaire est une urgence médicale en cas d'essoufflement. L'objectif du traitement est de vider l'air des doublures pleurales et de prévenir les récidives. Dans les cas moins graves, les patients peuvent croire qu'ils ont une douleur à la colonne thoracique et chercher des soins de thérapie manuelle. Ce cas met en évidence le rôle important des chiropraticiens en tant que fournisseurs de soins de santé primaires.

Presentation of Coronary Artery Disease in a Chiropractic Clinic: A Report of 2 Cases.

OBJECTIVE: The purpose of this report is to describe 2 patients with coronary artery disease presenting with musculoskeletal symptoms to a chiropractic clinic. CLINICAL FEATURES: A 48-year-old male new patient had thoracic spine pain aggravated by physical exertion. A 61-year-old man under routine care for low back pain experienced a secondary complaint of acute chest pain during a reevaluation. INTERVENTION AND OUTCOME: In both cases, the patients were strongly encouraged to consult their medical physician and were subsequently diagnosed with coronary artery disease. Following their diagnoses, each patient underwent surgical angioplasty procedures with stenting. CONCLUSION: Patients may present for chiropractic care with what appears to be musculoskeletal chest pain when the pain may be generating from coronary artery disease necessitating medical and possibly emergency care.

Comparison of BG-Sentinel® Trap and Oviposition Cups for Aedes aegypti and Aedes albopictus Surveillance in Jacksonville, Florida, USA.

The BG-Sentinel® (BGS) trap and oviposition cups (OCs) have both proven effective in the surveillance of Aedes species. This study aimed to determine which of the 2 traps could best characterize the relative population sizes of Aedes albopictus and Aedes aegypti in an urban section of Jacksonville, FL. Until 1986, Ae. aegypti was considered the dominant container-breeding species in urban northeastern Florida. Since the introduction of Ae. albopictus, Ae. aegypti has become almost completely extirpated. In 2011, a resurgence of Ae. aegypti was detected in the urban areas of Jacksonville; thus this study initially set out to determine the extent of Ae. aegypti reintroduction to the area. We determined that the BGS captured a greater number of adult Ae. aegypti than Ae. albopictus, while OCs did not monitor significantly different numbers of either species, even in areas where the BGS traps suggested a predominance of one species over the other. Both traps were effective at detecting Aedes spp.; however, the BGS proved more diverse by detecting over 20 other species as well. Our results show that in order to accurately determine vectorborne disease threats and the impact of control operations on these 2 species, multiple trapping techniques should be utilized when studying Ae. aegypti and Ae. albopictus population dynamics.

ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis.

Immune control of persistent infection with Mycobacterium tuberculosis (Mtb) requires a sustained pathogen-specific CD4 T cell response; however, the molecular pathways governing the generation and maintenance of Mtb protective CD4 T cells are poorly understood. Using MHCII tetramers, we show that Mtb-specific CD4 T cells are subject to ongoing antigenic stimulation. Despite this chronic stimulation, a subset of PD-1(+) cells is maintained within the lung parenchyma during tuberculosis (TB). When transferred into uninfected animals, these cells persist, mount a robust recall response, and provide superior protection to Mtb rechallenge when compared to terminally differentiated Th1 cells that reside preferentially in the lung-associated vasculature. The PD-1(+) cells share features with memory CD4 T cells in that their generation and maintenance requires intrinsic Bcl6 and intrinsic ICOS expression. Thus, the molecular pathways required to maintain Mtb-specific CD4 T cells during ongoing infection are similar to those that maintain memory CD4 T cells in scenarios of antigen deprivation. These results suggest that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new avenues to prevent TB.

Varied clinical presentation of os odontoideum: a case report.

OBJECTIVE: To present a case of an os odontoideum and to provide insight into the varied clinical presentations. CLINICAL FEATURES: A 54 year old man presented with chronic neck pain without headache. A clinical examination was performed and the chiropractor viewed his AP and lateral radiographs. Previous flexion/ extension radiographs and MRI imaging from 2009 were requested for review. The patient was diagnosed with grade II mechanical neck pain. Treatment was rendered that day which included spinal manipulation/ mobilization. Several days later the requested imaging reports were received and described the presence of an os odontoideum. CONCLUSION: In the presence of os odontoideum, familiarity with the signs and symptoms of potential cervical instability is imperative. Health care providers must remain diligent in their patient histories, physical exams, and imaging. This case highlights the importance of following up on imaging studies to rule out diagnoses that would involve treatment contraindications thus ensuring safe and effective treatment.

OBJECTIF: Présenter un cas d'os odontoïde, et donner un aperçu des différents tableaux cliniques. CARACTÉRISTIQUES CLINIQUES: Un homme de 54 ans qui souffre de douleurs cervicales chroniques, sans maux de tête. Un examen clinique a eu lieu et le chiropraticien a vérifié sa pression artérielle et ses radiographies latérales. Des radiographies et images IRM antérieures de la flexion et l'extension, datant de 2009, ont aussi été requises pour examen. On avait diagnostiqué sur ce patient une cervicalgie mécanique de stade II. Un traitement avait été administré ce même jour, dont une manipulation / mobilisation vertébrale. Quelques jours plus tard, les rapports demandés d'imagerie sont reçus, qui font état d'un os odontoïde. CONCLUSION: Il est impératif de reconnaître les signes et les symptômes d'une instabilité cervicale potentielle, en la présence d'un os odontoïde. Les fournisseurs de soins de santé doivent faire preuve de vigilance à l'égard des antécédents de leurs patients, des examens physiques, et de l'imagerie médicale. Ce cas souligne l'importance de faire le suivi des examens d'imagerie pour écarter tout mauvais diagnostic qui engendrerait un traitement contre-indiqué, pour assurer une prise en charge sûre et efficace du patient.

Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.

The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis infects macrophages, which transport it to deeper tissues. How mycobacteria survive in these broadly microbicidal cells is an important question. Here we show in mice and zebrafish that M. tuberculosis, and its close pathogenic relative Mycobacterium marinum, preferentially recruit and infect permissive macrophages while evading microbicidal ones. This immune evasion is accomplished by using cell-surface-associated phthiocerol dimycoceroserate (PDIM) lipids to mask underlying pathogen-associated molecular patterns (PAMPs). In the absence of PDIM, these PAMPs signal a Toll-like receptor (TLR)-dependent recruitment of macrophages that produce microbicidal reactive nitrogen species. Concordantly, the related phenolic glycolipids (PGLs) promote the recruitment of permissive macrophages through a host chemokine receptor 2 (CCR2)-mediated pathway. Thus, we have identified coordinated roles for PDIM, known to be essential for mycobacterial virulence, and PGL, which (along with CCR2) is known to be associated with human tuberculosis. Our findings also suggest an explanation for the longstanding observation that M. tuberculosis initiates infection in the relatively sterile environment of the lower respiratory tract, rather than in the upper respiratory tract, where resident microflora and inhaled environmental microbes may continually recruit microbicidal macrophages through TLR-dependent signalling.