Functional outcomes and quality of life at 1-year follow-up after an open tibia fracture in Malawi: a multicentre, prospective cohort study

Background: Injuries are a major cause of disability globally and injury incidence is rapidly increasing, largely due to road traffic injuries in low-income and middle-income countries. Current estimates of the scale and consequences of disability from injury are largely based on modelling studies, with a scarcity of empirical evidence from severe injuries in low-income countries. We aimed to better understand the outcomes for individuals with open tibia fractures in Malawi. Methods: In this multicentre, prospective cohort study, adults (aged ≥18 years) with open tibia fractures were systematically recruited at six hospitals in Malawi (two tertiary hospitals and four district hospitals). Follow-up lasted at least 1 year, during which in-person follow-up reviews were done at 6 weeks, 3 months, 6 months, and 1 year post-injury. The primary outcome was function at 1 year post-injury, measured by the Short Musculoskeletal Functional Assessment (SMFA) score. Secondary outcomes included quality-adjusted life-years (QALYs; as determined via the European Quality of Life 5-Dimensions 3-Levels [EQ-5D-3L] survey) and fracture-related infection at 1 year post-injury. Multilevel regression models investigated associations between SMFA score, EQ-5D-3L, baseline factors, and orthopaedic management. Findings: Between Feb 12, 2021, and March 14, 2022, 287 participants were enrolled (median age 34 years [IQR 25–44]; 84% male). The most common mode of injury was road traffic injuries (194 [68%] of 287). Overall, 268 (93%) participants had debridement; of the 63 participants who were debrided in district hospitals, 47 (75%) had the procedure under local or no anaesthesia. Following substantial declines by 6 weeks after injury, function and quality of life had not recovered by 1 year post-injury for participants with Gustilo grade I–II fractures (posterior mean SMFA at 1 year: 10·5, 95% highest density interval [HDI]: 9·5–11·6; QALYs: 0·73, 95% HDI: 0·66–0·80) nor Gustilo grade III fractures (posterior mean SMFA at 1 year: 14·9, 95% HDI: 13·4–16·6; QALYs: 0·67, 95% HDI: 0·59–0·75). For all fracture grades, intramedullary nailing substantially improved function and quality of life at 1 year post-injury. Delayed definitive fixation after 5 days had 5-times greater odds of infection compared with early management within 2 days (adjusted odds ratio: 5·1, 95% CI 1·8–16·1; p=0·02). Interpretation: Adults with open tibia fractures in Malawi have poor function and quality of life in the 1 year following injury. Centralised orthopaedic surgical management, including early definitive fixation and intramedullary nailing for more severe injuries, might improve outcomes. Funding: Wellcome Trust

Mast Cells and Gastrointestinal Dysmotility in the Cystic Fibrosis Mouse

BACKGROUND: Cystic fibrosis (CF) has many effects on the gastrointestinal tract and a common problem in this disease is poor nutrition. In the CF mouse there is an innate immune response with a large influx of mast cells into the muscularis externa of the small intestine and gastrointestinal dysmotility. The aim of this study was to evaluate the potential role of mast cells in gastrointestinal dysmotility using the CF mouse (Cftr(tm1UNC), Cftr knockout). METHODOLOGY: Wild type (WT) and CF mice were treated for 3 weeks with mast cell stabilizing drugs (ketotifen, cromolyn, doxantrazole) or were treated acutely with a mast cell activator (compound 48/80). Gastrointestinal transit was measured using gavage of a fluorescent tracer. RESULTS: In CF mice gastric emptying at 20 min post-gavage did not differ from WT, but was significantly less than in WT at 90 min post-gavage. Gastric emptying was significantly increased in WT mice by doxantrazole, but none of the mast cell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptying in WT mice but not in CF mice. Small intestinal transit was significantly less in CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole significantly affected small intestinal transit in WT mice and none had any effect in CF mice. Mast cell activation resulted in a small but significant increase in small intestinal transit in CF mice but not WT mice. CONCLUSIONS: The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulate small intestinal transit in cystic fibrosis

Ultrastructural Characterization of Pandemic (H1N1) 2009 Virus

We evaluated pandemic influenza A (H1N1) 2009 virus isolates and respiratory tissues collected at autopsy by electron microscopy. Many morphologic characteristics were similar to those previously described for influenza virus. One of the distinctive features was dense tubular structures in the nuclei of infected cells

Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

<div><p>Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the <i>Bunyaviridae</i> family. Basic research on CCHFV has been severely hampered by biosafety requirements and lack of available strains and molecular tools. We report the development of a CCHF transcription- and entry-competent virus-like particle (tecVLP) system that can be used to study cell entry and viral transcription/replication over a broad dynamic range (~4 orders of magnitude). The tecVLPs are morphologically similar to authentic CCHFV. Incubation of immortalized and primary human cells with tecVLPs results in a strong reporter signal that is sensitive to treatment with neutralizing monoclonal antibodies and by small molecule inhibitors of CCHFV. We used glycoproteins and minigenomes from divergent CCHFV strains to generate tecVLPs, and in doing so, we identified a monoclonal antibody that can prevent cell entry of tecVLPs containing glycoproteins from 3 pathogenic CCHFV strains. In addition, our data suggest that different glycoprotein moieties confer different cellular entry efficiencies, and that glycoproteins from the commonly used strain IbAr10200 have up to 100-fold lower ability to enter primary human cells compared to glycoproteins from pathogenic CCHFV strains.</p></div

Isolation of Rickettsia parkeri and Identification of a Novel Spotted Fever Group Rickettsia sp. from Gulf Coast Ticks (Amblyomma maculatum) in the United States▿

Until recently, Amblyomma maculatum (the Gulf Coast tick) had garnered little attention compared to other species of human-biting ticks in the United States. A. maculatum is now recognized as the principal vector of Rickettsia parkeri, a pathogenic spotted fever group rickettsia (SFGR) that causes an eschar-associated illness in humans that resembles Rocky Mountain spotted fever. A novel SFGR, distinct from other recognized Rickettsia spp., has also been detected recently in A. maculatum specimens collected in several regions of the southeastern United States. In this study, 198 questing adult Gulf Coast ticks were collected at 4 locations in Florida and Mississippi; 28% of these ticks were infected with R. parkeri, and 2% of these were infected with a novel SFGR. Seventeen isolates of R. parkeri from individual specimens of A. maculatum were cultivated in Vero E6 cells; however, all attempts to isolate the novel SFGR were unsuccessful. Partial genetic characterization of the novel SFGR revealed identity with several recently described, incompletely characterized, and noncultivated SFGR, including “Candidatus Rickettsia andeanae” and Rickettsia sp. Argentina detected in several species of Neotropical ticks from Argentina and Peru. These findings suggest that each of these “novel” rickettsiae represent the same species. This study considerably expanded the number of low-passage, A. maculatum-derived isolates of R. parkeri and characterized a second, sympatric Rickettsia sp. found in Gulf Coast ticks

Exchanging surface glycoproteins has a greater impact on tecVLP titer and NanoLuc signal than exchanging minigenomes.

<p>(A) TCID₅₀ titers/mL and NanoLuc signals in relative light units (RLU) measured in SW-13 cells treated with tecVLPs with Afg09 GPC and with L segment NCR minigenomes from indicated CCHFV strains. NanoLuc data are presented as standard error of the mean (average of 3 experiments), and results of 3 TCID₅₀ experiments are shown. (B) TCID₅₀ titers/mL and NanoLuc signals measured in SW-13 cells treated with tecVLPs with Oman GPC and L segment NCR minigenomes from indicated CCHFV strains. NanoLuc signal data in tecVLP-treated cells are presented as absolute RLU values which are calculated as signal in SW-13 cells treated with entry-competent VLPs (i.e., containing NP, L, and GPC) minus signal in SW-13 cells treated with VLPs containing only NP, L and the corresponding minigenome. NanoLuc data are reported as standard error of the mean (average of 3 experiments), and results of 3 TCID₅₀ experiments are shown.</p

CCHFV strain IbAr10200 replication machinery does not significantly discriminate against minigenomes from other CCHFV strains.

<p>(A) Absolute NanoLuc signal in relative light units (RLU) in BSR-T7 cells transfected with IbAr10200 NP, L, and GPC plasmids, and with minigenomes encoding L NCR of other CCHFV strains, as indicated. Data are reported as standard error of the mean (n = 8 from 2 experiments). (B) TCID₅₀ determination in SW-13 cells treated with supernatants from cells in (A). Results from 2 experiments are shown. (C) NanoLuc signal in SW-13 cells treated as in (B) (n = 8 from 2 experiments). NanoLuc signal data in VLP-treated cells are presented as absolute RLU values which are calculated as signal in SW-13 cells treated with entry-competent VLPs (i.e., containing NP, L, and GPC) minus signal in SW-13 cells treated with VLPs containing only NP, L and the corresponding minigenome. All data are reported as standard error of the mean.</p