"Re-educating" tumor-associated macrophages by targeting NF-kappaB

The nuclear factor kappaB (NF-kappaB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-kappaB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive "alternative" phenotype that requires IkappaB kinase beta-mediated NF-kappaB activation. When NF-kappaB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a "classically" activated phenotype; IL-12(high), major histocompatibility complex II(high), but IL-10(low) and arginase-1(low). Targeting NF-kappaB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12-dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to "re-educate" the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies

Salt- and sodium-affected soils

This publication is designed to help identify salt- and sodium-affected soils, the salt or sodium sources, how to take soil and water samples, how to reduce the harmful effects of salts and sodium and where to get advice in making reclamation and management decisions for each situation. Salt- and sodium-affected soils, and waters used for irrigation, present a complex combination of problems and possible solutions. It is not the intent here to cover all technical aspects or possible treatment approaches available, but rather to give a simplified overview of what should be considered in diagnosing and managing salt- and sodium-affected soils and irrigation waters. Since summarizing the effects of salt and sodium on soils and plants is difficult without using the appropriate terminology, a glossary is included

Mobility impairment is associated with reduced microstructural integrity of the inferior and superior cerebellar peduncles in elderly with no clinical signs of cerebellar dysfunction☆

While the cerebellum plays a critical role in motor coordination and control no studies have investigated its involvement in idiopathic mobility impairment in community-dwelling elderly. In this study we tested the hypothesis that structural changes in the cerebellar peduncles not detected by conventional magnetic resonance imaging are associated with reduced mobility performance. The analysis involved eighty-five subjects (age range: 75–90 years) who had no clinical signs of cerebellar dysfunction. Based on the short physical performance battery (SPPB) score, we defined mobility status of the subjects in the study as normal (score 11–12, n = 26), intermediate (score 9–10, n = 27) or impaired (score < 9, n = 32). We acquired diffusion tensor imaging data to obtain indices of white matter integrity: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Using a parcellation atlas, regional indices within the superior, middle, and inferior cerebellar peduncles (ICP, MCP, SCP) were calculated and their associations with mobility performance were analyzed. Subjects with impaired mobility showed reduced FA and AD values in the ICP and SCP but not in the MCP. The ICP-FA, ICP-AD and SCP-FA indices showed a significant association with the SPPB score. We also observed significant correlation between ICP-FA and walk time (r = − 0.311, p = 0.004), as well as between SCP-AD and self-paced maximum walking velocity (r = 0.385, p = 0.003) and usual walking velocity (r = 0.400, p = 0.002). In logistic regression analysis ICP-FA and ICP-AD together explained 51% of the variability in the mobility status of a sample comprising the normal and impaired subgroups, and correctly classified more than three-quarters of those subjects. Our findings suggest that presence of microstructural damage, likely axonal, in afferent and efferent connections of the cerebellum contributes to the deterioration of motor performance in older people

Effect of in-hospital delays on surgical mortality for emergency general surgery conditions at a tertiary hospital in Malawi

Background: In sub-Saharan Africa, surgical access is limited by an inadequate surgical workforce, lack of infrastructure and decreased care-seeking by patients. Delays in treatment can result from delayed presentation (pre-hospital), delays in transfer (intrafacility) or after arrival at the treating centre (in-hospital delay; IHD). This study evaluated the effect of IHD on mortality among patients undergoing emergency general surgery and identified factors associated with IHD. Methods: Utilizing Malawi's Kamuzu Central Hospital Emergency General Surgery database, data were collected prospectively from September 2013 to November 2017. Included patients had a diagnosis considered to warrant urgent or emergency intervention for surgery. Bivariable analysis and Poisson regression modelling was done to determine the effect of IHD (more than 24 h) on mortality, and identify factors associated with IHD. Results: Of 764 included patients, 281 (36·8 per cent) had IHDs. After adjustment, IHD (relative risk (RR) 1·68, 95 per cent c.i. 1·01 to 2·78; P = 0·045), generalized peritonitis (RR 4·49, 1·69 to 11·95; P = 0·005) and gastrointestinal perforation (RR 3·73, 1·25 to 11·08; P = 0·018) were associated with a higher risk of mortality. Female sex (RR 1·33, 1·08 to 1·64; P = 0·007), obtaining any laboratory results (RR 1·58, 1·29 to 1·94; P < 0·001) and night-time admission (RR 1·59, 1·32 to 1·90; P < 0·001) were associated with an increased risk of IHD after adjustment. Conclusion: IHDs were associated with increased mortality. Increased staffing levels and operating room availability at tertiary hospitals, especially at night, are needed

The Impact of Lesion In-Painting and Registration Methods on Voxel-Based Morphometry in Detecting Regional Cerebral Gray Matter Atrophy in Multiple Sclerosis

Background and Purpose: VBM has been widely used to study GM atrophy in MS. MS lesions lead to segmentation and registration errors that may affect the reliability of VBM results. Improved segmentation and registration have been demonstrated by WM LI before segmentation. DARTEL appears to improve registration versus the USM. Our aim was to compare the performance of VBM-DARTEL versus VBM-USM and the effect of LI in the regional analysis of GM atrophy in MS. Materials and Methods: 3T T1 MR imaging scans were acquired from 26 patients with RRMS and 28 age-matched NC. LI replaced WM lesions with normal-appearing WM intensities before image segmentation. VBM analysis was performed in SPM8 by using DARTEL and USM with and without LI, allowing the comparison of 4 VBM methods (DARTEL + LI, DARTEL − LI, USM + LI, and USM − LI). Accuracy of VBM was assessed by using NMI, CC, and a simulation analysis. Results: Overall, DARTEL + LI yielded the most accurate GM maps among the 4 methods (highest NMI and CC, P < .001). DARTEL + LI showed significant GM loss in the bilateral thalami and caudate nuclei in patients with RRMS versus NC. The other 3 methods overestimated the number of regions of GM loss in RRMS versus NC. LI improved the accuracy of both VBM methods. Simulated data suggested the accuracy of the results provided from patient MR imaging analysis. Conclusions: We introduce a pipeline that shows promise in limiting segmentation and registration errors in VBM analysis in MS

Complications and 3-month outcomes of children with hydrocephalus treated with ventriculoperitoneal shunts in Malawi

OBJECTIVE Hydrocephalus is the most common pediatric neurosurgical condition, with a high prevalence in low- and middle-income countries. Untreated, hydrocephalus leads to neurological disability or death. The epidemiology and outcomes of hydrocephalus treated by ventriculoperitoneal (VP) shunts in Sub-Saharan Africa are not well defined and vary by region. The aim of the present study was to examine the mortality and morbidity rates and predictors of mortality in children treated by VP shunt placement for hydrocephalus at Kamuzu Central Hospital in Lilongwe, Malawi. METHODS This is a prospective study of 100 consecutive children presenting with hydrocephalus who were treated with VP shunt placement from January 2015 to August 2017. Demographics, nutritional status, maternal characteristics, developmental delay, shunt complications, readmissions, and in-hospital and 3-month mortality data were collected. Multivariate logistic regression was used to identify predictors of death within 3 months of surgery. RESULTS Overall, 46% of participants were female, with an average age of 5.4 ± 3.7 months at the time of surgery. The majority of patients were term deliveries (87.8%) and were not malnourished (72.9%). Only 10.8% of children were diagnosed with meningitis before admission. In-hospital and 3-month mortality rates were 5.5% and 32.1%, respectively. The only significant association with mortality was maternal age, with older maternal age demonstrating decreased odds of 3-month mortality (OR 0.9, 95% CI 0.8–1.0, p = 0.045). CONCLUSIONS Surgical management of hydrocephalus with VP shunts portends a high mortality rate in Malawi. The association of younger maternal age with mortality is likely a proxy for social determinants, which appear to contribute as much to mortality as patient factors. VP shunting is inadequate as a sole surgical management of hydrocephalus in resource-limited settings

Nurturing lifelong learning in communities through the National University of Lesotho: prospects and challenges

This paper analyses one aspect of a pan-African action research project called ITMUA (Implementing the Third Mission of Universities in Africa). This particular paper draws on the data from that project to explore the National University of Lesotho’s contribution to lifelong learning in its communities. It provides background information on the ITMUA initiative and analyses interview and focus group responses to two case studies in terms of their contribution to lifelong learning. It uses, as its analytical framework, a modified version of Mbigi’s African perspective on the four De Lors’ ‘pillars’, by adding a fifth pillar, courtesy of Torres. The paper argues that community engagement is a two-way process between universities and their wider constituencies with opportunities for mutual lifelong learning. But there are also challenges of understanding and process which must be addressed if the full range of these lifelong learning pillars is to be accommodated within African contexts. The paper provides an introduction to the history of community engagement in Africa as a university mission, followed by a brief discussion of lifelong learning within African perspectives. After describing the particular context of Lesotho, the concept of community service and community engagement in contemporary African contexts introduces the action research project and the case studies. The final part of the paper presents and discusses the research findings

Secondary Overtriage of Trauma Patients to a Central Hospital in Malawi

Introduction: Secondary overtriage (OT) is the unnecessary transfer of injured patients between facilities. In low- and middle-income countries (LMICs), which shoulder the greatest burden of trauma globally, the impact of wasted resources on an overburdened system is high. This study determined the rate and associated characteristics of OT at a Malawian central hospital. Methods: A retrospective analysis of prospectively collected data from January 2012 through July 2017 was performed at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. Patients were considered OT if they were discharged alive within 48 h without undergoing a procedure, and were not severely injured or in shock on arrival. Factors evaluated for association with OT included patient demographics, injury characteristics, and transferring facility information. Results: Of 80,915 KCH trauma patients, 15,422 (19.1%) transferred from another facility. Of these, 8703 (56.2%) were OT. OT patients were younger (median 15, IQR: 6–31 versus median 26, IQR: 11–38, p < 0.001). Patients with primary extremity injury (5308, 59.9%) were overtriaged more than those with head injury (1991, 51.8%) or torso trauma (1349, 50.8%), p < 0.001. The OT rate was lower at night (18.9% v 28.7%, p < 0.001) and similar on weekends (20.4% v 21.8%, p = 0.03). OT was highest for penetrating wounds, bites, and falls; burns were the lowest. In multivariable modeling, risk of OT was greatest for burns and soft tissue injuries. Conclusions: The majority of trauma patients who transfer to KCH are overtriaged. Implementation of transfer criteria, trauma protocols, and interhospital communication can mitigate the strain of OT in resource-limited settings