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Significant progress has been made in the management of traumatic spinal cord injuries. However, deep disparities persist in developing countries. This work aims to describe the different challenges in the surgical management of traumatic spinal cord injuries at the Kinshasa University Teaching Hospital and some strategies implemented to overcome them. This is a cross-sectional study of 105 patients from January 2016 to June 2023. The variables of interest included: gender, age, cause, levels of lesion, hospital admission modalities, time to admission, time to surgery, AIS score at admission and on discharge, treatment, pre, peri- and post-operative complications and outcome. We admitted 105 patients. Only 16 % of them were taken to hospital in an ambulance. The average admission time was 49.9 ± 81.79 days. Seventy-two patients (68.6 %) were operated. The average time to surgery was 62.43 ± 85.20 days. No patient was stabilized at the trauma site. Osteosynthesis was performed with appropriate implants in 63.2 % and with improvised elements in 26.8 %. Four patients were operated without an image intensifier. Short-segmental fixation was performed in 8 patients. Twenty-one patients developed pressure ulcers. At discharge, 24 patients recovered their neurological function. Neurological status remained stationary in 43 patients. Five patients died. Seventeen patients went to rehabilitation center. There was no significant difference between the improvised strategies implemented and conventional procedures on functional recovery upon discharge from hospital or rehabilitation centre (p-value : 0.838 and 0.468 respectively). Our establishment faces many challenges in TSCI surgery: lack of pre-hospital emergency services and mutual health insurance, delay in admission, lack of surgical implants and image intensifier, the poverty of the population. Some strategies have been implemented to overcome some of them. [ABSTRACT FROM AUTHOR]

Volcanic CO 2 is widely acknowledged as an important geochemical precursor for volcanic activity; however, obtaining observations through remote sensing remains a challenge. It is well established that volcanic CO 2 diffusely degases during magma ascent, and the volatiles interact with the ecosystem on the surface through CO 2 fertilization, which can improve vegetation health. A normalized difference vegetation index (NDVI) is a remote sensing method that quantifies vegetation health. This study compared NDVI signals from Landsat 8, MODIS, Sentinel 2, and VIIRS to soil CO 2 flux signals from 5 ground-based EtnaGas stations on Mt. Etna from 2011 to 2018. Due to variances in sensor and spectral characteristics, the NDVI values were calibrated across all 4 sensors. The 2nd derivatives of NDVI and soil CO 2 flux highlight the timeframes of the increase/decrease cycles of CO 2 degassing, which in turn, correspond to the change in storage levels as magma rises from an intermediate chamber to a shallow one. Between 2017 and 2018, the 2nd derivative spikes showed 16 magma recharge events in both NDVI and soil CO 2 signals. A flank analysis of homogenous trees across Mt. Etna showed the same 2nd derivative spike pattern for NDVI when compared to individual EtnaGas stations, indicating that trees do not have to be located within 30 m of volcano-tectonic structures to be affected by diffusely escaping volcanic CO 2. This study highlights the potential of NDVI as a remote sensing method for monitoring volcanic CO 2 emissions, paving the way for innovative approaches to volcanic surveillance. • Characterized diffuse, volcanic CO 2 degassing using a tree health index. • Changes in the accelerations of tree health and soil CO 2 flux correspond in time. • 2nd derivative spikes indicate 16 magmatic recharge events on Mt. Etna. • Trees not near volcano-tectonic structures were similarly affected by volcanic CO 2. • Potential application of remote sensing method on other un-monitored volcanoes. [ABSTRACT FROM AUTHOR]

This review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.1 cases/100,000); however, there is notable regional and temporal variation. Outbreaks persist in at-risk subpopulations, such as people experiencing homelessness in the US and migrants in Mexico. The recent emergence of β-lactamase-positive and ciprofloxacin-resistant meningococci in the US is a major concern. While vaccination practices vary across North America, vaccine uptake remains relatively high. Monovalent and multivalent conjugate vaccines (which many countries in North America primarily use) can provide herd protection. However, there is no evidence that group B vaccines reduce meningococcal carriage. The coronavirus pandemic illustrates that following public health crises, enhanced surveillance of disease epidemiology and catch-up vaccine schedules is key. Whole genome sequencing is a key epidemiological tool for identifying IMD strain emergence and the evaluation of vaccine strain coverage. The Global Roadmap on Defeating Meningitis by 2030 remains a focus of the GMI. [ABSTRACT FROM AUTHOR]

This study examines the variations in the organization of secondary and post-secondary educational institutions in England and the United States and the effect it has on achievement. The authors find students in U.S. schools have a higher deflection rate than those participating in the British system, even though British schools have a greater stratified and standardized organization.

Rapid diagnostic tests (RDTs) are increasingly recognized as valuable, transformative tools for the diagnosis of infectious diseases. Although there are a variety of meningitis RDTs currently available, certain product features restrict their use to specific levels of care and settings. For this reason, the development of meningitis RDTs for use at all levels of care, including those in low-resource settings, was included in the "Defeating Meningitis by 2030" roadmap. Here we address the limitations of available meningitis RDTs and present test options and specifications to consider when developing the next generation of meningitis RDTs. [ABSTRACT FROM AUTHOR]

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data. [ABSTRACT FROM AUTHOR]

Eight papers were presented at a session on 'Current Work in Historical Geography' at the 1994 conference of the Institute of British Geographers in Nottingham. Presenters were Colin Pooley, Martin Purvis, Cheryl McEwan, Klaus Dodds, Craig Young, John Stobart, James Higgins, and Keith Dawson.

Highlights • Spine surgeons may not have detailed knowledge about costs. • Detailed instrumentation cost information will reduce costs in the operating room. • Detailed cost information has no impact on overall costs of admission to hospital. • There are considerable variations in cost for inpatient care depending on the treating surgeon. Abstract Surgeons may not have a thorough knowledge about the costs of devices or surgical equipment. The main reason for this in many systems is price insensitivity. The purpose of this study was to determine whether spine surgical procedural expenses change once physicians are aware of the costs for surgical implants and the total associated costs with the procedure. A thorough bottom up case costing methodology was used to capture the costs of admission for three comparable spine surgical procedures at a large tertiary care center. Costs were collected for an initial 5-month period where surgeons were not aware of costs, followed by another 5-month period with detailed cost information. Instrumental costs, procedural costs and costs of admission were captured as well as health related quality of life (HRQOL) measures at 3 months. Statistical analysis was undertaken with STATA software. Costs decreased by $478 for instrumentation once actual prices were known (p = 0.069). Only ACDF procedures demonstrated statistically significant instrumental cost savings of $754 (p = 0.009). Total procedural costs were also less ($297, p = 0.194) but the total overall costs of admission increased ($401, p = 0.228). There were no differences in VAS, EQ-5D, or SF-12 scores. Although costs decrease for implants in surgery when prices are known, this appears to have little or no effect on overall costs of care. Length of stay and operating room time have greater effects on global costs. Future efforts to encourage efficient cost savings should focus on practice patterns/pathways for similar conditions rather than limiting the use of certain implants. [ABSTRACT FROM AUTHOR]

Forestry practices affect various habitat characteristics that influence wildlife populations. Understanding the relative importance of the broad effects of forestry practices versus specific habitat variables for wildlife may help managers balance multiple forest management objectives and potentially adjust forestry practices to better conserve biodiversity. We compared the relative importance of experimental timber harvest treatments (clearcutting, thinning to remove undesirable tree species) to habitat variables (coarse down wood, herbaceous vegetation, leaf litter) for captures of reptiles in central Missouri, USA for two years post-harvest. We also used drift fences along the edges between uncut control forest and clearcut to detect changes in movements between treatments after timber harvest, which is one potential mechanism for differences in captures among timber harvest treatments. We found that habitat variables best predicted captures of small snakes, while both habitat and timber harvest treatment predicted lizard captures. Two lizard taxa ( Plestiodon spp., Sceloporus undulatus ) had higher captures in clearcuts than in the no harvest control, which is consistent with studies across the southeastern United States. Plestiodon spp. showed significantly more movements into clearcuts from control forest than in the opposite direction, demonstrating that higher captures in clearcuts were at least in part due to immigration from adjacent forested areas. Small snakes and Sceloporus undulatus captures were higher in areas with more coarse down wood and higher herbaceous vegetation cover, which were associated with the clearcut plots. These results for small snakes are consistent with another study in Missouri, but in contrast to two from South Carolina, indicating that there may be regional differences in the response of small snakes to forestry practices. Further work on the effects of forestry management on reptiles should examine regional differences and seek to understand underlying mechanisms. [ABSTRACT FROM AUTHOR]

It is controversial whether the surgical restoration of sagittal balance and spinopelvic angulation in a single level lumbar degenerative spondylolisthesis results in clinical improvements. The purpose of this study to systematically review the available literature to determine whether the surgical correction of malalignment in lumbar degenerative spondylolisthesis correlates with improvements in patient-reported clinical outcomes. Literature searches were performed via Ovid Medline, Embase, CENTRAL and Web of Science using search terms “lumbar,” “degenerative/spondylolisthesis” and “surgery/surgical/surgeries/fusion”. This resulted in 844 articles and after reviewing the abstracts and full-texts, 13 articles were included for summary and final analysis. There were two Level II articles, four Level III articles and five Level IV articles. Most commonly used patient-reported outcome measures (PROMs) were Oswestery disability index (ODI) and visual analogue scale (VAS). Four articles were included for the final statistical analysis. There was no statistically significant difference between the patient groups who achieved successful surgical correction of malalignment and those who did not for either ODI (mean difference −0.94, CI −8.89–7.00) or VAS (mean difference 1.57, CI −3.16–6.30). Two studies assessed the efficacy of manual reduction of lumbar degenerative spondylolisthesis and their clinical outcomes after the operation, and there was no statistically significant improvement. Overall, the restoration of focal lumbar lordosis and restoration of sagittal balance for single-level lumbar degenerative spondylolisthesis does not seem to yield clinical improvements but well-powered studies on this specific topic is lacking in the current literature. Future well-powered studies are needed for a more definitive conclusion. [ABSTRACT FROM AUTHOR]

Background: There are various possible methods of skin closure in total hip arthroplasty (THA) through a lateral skin incision. The cost and time required for each can vary between techniques. The objective of this study was to determine whether there is a difference in patient and surgeon rating of scar outcome using a combination of subcuticular suture and skin adhesive (subcuticular MONOCRYL and DERMABOND [SMD]) vs staples for skin closure after THA.Methods: Patients undergoing THA were recruited from a university hospital. Patients were randomized to staples or SMD. Patient and Observer Scar Assessment Scale data were collected postoperatively. In addition, visual analog scale pain scores, wound drainage, length of stay, time to closure, and total cost were collected.Results: One hundred twenty-nine patients were available for final analysis. There was no significant difference in Patient and Observer Scar Assessment Scale scores at 6 weeks or 3 months (P = .71). There was no difference in visual analog scale pain scores (P = .64, P = .49). The staple group had a higher rate of discharge on postoperative days 1 and 3 (P < .001, P < .001) but had a 1.6-minute shorter time of closure (P < .001). There was no significant difference in length of stay or total cost (P = .5).Conclusion: Although there are some small initial advantages to each method of skin closure, there is little difference in scar outcome when comparing SMD and staples. [ABSTRACT FROM AUTHOR]

The Global Meningococcal Initiative (GMI) has recently considered current issues in Middle Eastern and African countries, and produced two recommendations: (i) that vaccination of attendees should be considered for some types of mass-gathering events, as some countries mandate for the Hajj, and (ii) vaccination of people with human immunodeficiency virus should be used routinely, because of increased meningococcal disease (MD) risk. Differences exist between Middle Eastern and African countries regarding case and syndrome definitions, surveillance, and epidemiologic data gaps. Sentinel surveillance provides an overview of trends and prevalence of different capsular groups supporting vaccine selection and planning, whereas cost-effectiveness decisions require comprehensive disease burden data, ideally counting every case. Surveillance data showed importance of serogroup B MD in North Africa and serogroup W expansion in Turkey and South Africa. Success of MenAfriVac® in the African "meningitis belt" was reviewed; the GMI believes similar benefits may follow development of a low-cost meningococcal pentavalent vaccine, currently in phase 1 clinical trial, by 2022. The importance of carriage and herd protection for controlling invasive MD and the importance of advocacy and awareness campaigns were also highlighted. [ABSTRACT FROM AUTHOR]

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. [ABSTRACT FROM AUTHOR]

Degenerative lumbar spondylolisthesis (DLS) is a debilitating condition associated with poor preoperative functional status. Surgical intervention has been shown to improve functional outcomes in this population though the optimal surgical procedure remains controversial. The importance of maintaining and/or improving sagittal and pelvic spinal balance parameters has received increasing interest in the recent DLS literature. However, little is known about the radiographic parameters most associated with improved functional outcomes among patients undergoing surgery for DLS. To identify the effect of postoperative sagittal spinal alignment on functional outcome after DLS surgery. Retrospective cohort study. Two-hundred forty-three patients in the Canadian Spine Outcomes and Research Network (CSORN) prospective DLS study database. Baseline and 1-year postoperative leg and back pain on the 10-point Numeric Rating Scale and baseline and 1-year postoperative disability on the Oswestry Disability Index (ODI). All enrolled study patients had a DLS diagnosis and underwent decompression in isolation or with posterolateral or interbody fusion. Global and regional radiographic alignment parameters were measured at baseline and 1-year postoperatively including sagittal vertical axis (SVA), pelvic incidence and lumbar lordosis (LL). Both univariate and multiple linear regression was used to assess for the association between radiographic parameters and patient-reported functional outcomes with adjustment for possible confounding baseline patient factors. Two-hundred forty-three patients were available for analysis. Among participants, the mean age was 66 with 63% (153/243) female with the primary surgical indication of neurogenic claudication in 197/243 (81%) of patients. Worse pelvic incidence-LL mismatch was correlated with more severe disability [ODI, 0.134, p<.05), worse leg pain (0.143, p<.05) and worse back pain (0.189, p<.001) 1-year postoperatively. These associations were maintained after adjusting for age, BMI, gender, and preoperative presence of depression (ODI, R2 0.179, β, 0.25, 95% CI 0.08, 0.42, p=.004; back pain R2 0.152 (β, 0.05, 95% CI 0.022, 0.07, p<.001; leg pain score R2 0.059, β, 0.04, 95% CI 0.008, 0.07, p=.014). Likewise, reduction of LL was associated with worse disability (ODI, R2 0.168, β, 0.04, 95% CI -0.39, -0.02, p=.027) and worse back pain (R2 0.135, β, -0.04, 95% CI -0.06, -0.01, p=.007). Worsened SVA correlated with worse patient reported functional outcomes (ODI, R2 0.236, β, 0.12, 95% CI 0.05, 0.20, p=.001). Similarly, an increase (worsening) in SVA resulted in a worse NRS back pain (R2 0.136, β, 0.01, 95% CI.001, 0.02, p=.029) and worse NRS leg pain (R2 0.065, β, 0.02, 95% CI 0.002, 0.02, p=.018) scores regardless of surgery type. Preoperative emphasis on regional and global spinal alignment parameters should be considered in order to optimize functional outcome in lumbar degenerative spondylolisthesis treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to systematically search, critically appraise and summarize published randomized control trials (RCT) and non-RCT examining the effect of drains and dressings on wound healing rates and complications in posterior spine surgery. The use of post-operative drains and the type of post-operative dressing is at the discretion of the treating surgeon with no available clinical guidelines. Drains will theoretically decrease incidence of post-operative hematoma and therefore, potentially decrease the risk of neurologic compromise when the neural elements have been exposed. Occlusive dressings have more recently been advocated, potentially maintaining a sterile barrier for longer time periods post-operatively. A systematic review of databases from 1969–2013 was undertaken. All papers examining drains in spine surgery and dressings in primary healing of surgical wounds were included. Revman (version 5.2; The Nordic Cochrane Centre, The Cochrane Collaboration, Oxford, UK) was used to test for overall treatment effect, clinical heterogeneity and risk of bias. Of the papers identified, 1348 examined post-operative drains in spine surgery and 979 wound dressings for primary wound healing of all surgical wounds. Seven studies were included for analysis for post-operative drains and 10 studies were analyzed for primary wound healing. The use of a post-operative drain did not influence healing rates and had no effect secondarily on infection (odds ratio [OR] 1.33; 95% confidence interval [CI] 0.76–2.30). We were not able to establish whether surgical drains prevent hematomas causing neurologic compromise. There was a slight advantage to using occlusive dressings versus non-occlusive dressings in wound healing (OR 2.09; 95% CI 1.44–3.02). Incisional vacuum dressings as both an occlusive barrier and superficial drainage system have shown promise for wounds at risk of dehiscence. There is a relatively high risk of bias in the methodology of many of the studies reviewed. We recommend favoring of occlusive dressings based on heterogeneous and potentially biased evidence. Drain use does not affect wound healing based on similar evidence. Incisional vacuum dressings have shown promise in managing potentially vulnerable wounds. [ABSTRACT FROM AUTHOR]

This study reviews the outcomes and revision rates of degenerative lumbar fusion surgery using cortical trajectory pedicle screws in lieu of traditional pedicle screw instrumentation. Pedicle screw fixation can be a challenge in patients with low bone mineral density. Wide posterior approaches to the lumbar spine exposing lateral to the facet joints and onto transverse processes causes an additional degree of muscular damage and blood loss not present with a simple laminectomy. A cortical bone trajectory pedicle screw has been proposed as an alternative to prevent screw pullout and decrease the morbidity associated with the wide posterior approach to the spine. We present a series of eight consecutive patients using a cortical bone trajectory instead of traditional pedicle screw fixation for degenerative conditions of the lumbar spine. A retrospective review of our institutional registry data identified eight patients who had cortical screws placed with the assistance of O-arm Stealth navigation (Medtronic Sofamor Danek, Memphis, TN, USA) from 2010–2013. We analyzed the need for revision, the maintenance of reduction and the incidence of screw pullout or breakage. Our review demonstrated that two of eight patients were revised at an average of 12 months. The reasons for these revisions were pseudarthrosis and caudal adjacent segment failure. All patients who were revised had frank screw loosening. We present early clinical results of a new technique that has been shown to have a better fixation profile in laboratory testing. Our less than favorable early clinical results should be interpreted with caution and highlight important technical issues which should be considered. [ABSTRACT FROM AUTHOR]

Background context Adverse events (AEs) in thoracic and lumbar spine fractures are common, but little is known about the type of AEs that are specific to this population. Furthermore, very little is known about the incidence and clinical impact of these AEs on patients in the presence of traumatic spinal cord injury and whether they are treated operatively or nonoperatively. Purpose The purpose of this study was to determine primarily the incidence of AEs in patients with thoracic or lumbar spine fractures treated both operatively and nonoperatively and their impact on length of stay (LOS) and secondarily the difference in the incidence of AEs in both neurologically intact and compromised patients. Study design/setting This is an ambispective cohort study at a quaternary referral center. Patient sample Patients admitted at our institution with thoracic or lumbar fractures from January 2009 to December 2013 were identified. Patients with full Spine Adverse Events Severity System (SAVES) data were included. Outcome measures Number and type of AEs collected from SAVES were assessed. Impact of AE on acute LOS was also determined. Methods Data on intraoperative, preoperative, and postoperative AEs were prospectively collected using the SAVES data collection. Logistic regression was used to model the likelihood of experiencing at least one AE based on the patient characteristics. The impact of the total number of AEs experienced by a patient and that of each of the most common AEs on LOS was determined using Poisson regression. Results Three hundred and ninety patients were included in the final analysis. Two hundred and seventy-six patients (70.8%) were treated operatively. One hundred and forty patients (36%) experienced neurologic deficit as a result of their initial injury. Adverse events occurred 56% of the time in the operatively treated patients and only 13% of the time in the nonoperative group. The presence of neurologic deficit increased the risk of AEs especially in high thoracic (T1–T6) trauma increasing the odds of having an AE by 12.1 (p<.0001). The most common AEs were urinary tract infections (19.7%), neuropathic pain (12.3%), pneumonias (11.8%), delirium (10.5%), and ileus (6.2%). Length of hospital stay increased significantly with pneumonia (p<.0001) and delirium (p=.0001). Conclusions The presence of neurologic injury and the need for operative fixation of thoracic or lumbar injuries lead to a greater risk of AEs. Only pneumonia and delirium consistently increase LOS. [ABSTRACT FROM AUTHOR]

Decomposition can be a highly variable process with stages that are difficult to quantify. Using high accuracy terrestrial laser scanning a repeated three-dimensional (3D) documentation of volumetric changes of a human body during early decomposition is recorded. To determine temporal volumetric variations as well as 3D distribution of the changed locations in the body over time, this paper introduces the use of multiple degenerated cylinder models to provide a reasonable approximation of body parts against which 3D change can be measured and visualized. An iterative closest point algorithm is used for 3D registration, and a method for determining volumetric change is presented. Comparison of the laser scanning estimates of volumetric change shows good agreement with repeated in-situ measurements of abdomen and limb circumference that were taken diurnally. The 3D visualizations of volumetric changes demonstrate that bloat is a process with a beginning, middle, and end rather than a state of presence or absence. Additionally, the 3D visualizations show conclusively that cadaver bloat is not isolated to the abdominal cavity, but also occurs in the limbs. Detailed quantification of the bloat stage of decay has the potential to alter h ow the beginning and end of bloat are determined by researchers and can provide further insight into the effects of the ecosystem on decomposition. [ABSTRACT FROM AUTHOR]

In many developing countries, populations are under considerable pressure from high bacterial exposure on mucosal surfaces. Immune dysregulation in this setting is multifactorial and is driven by a range of environmental factors, undernutrition and coinfections such as measles, malaria and HIV. Disruption or subversion of respiratory-tract and intestinal epithelial barriers leads to increased invasion by mucosal pathogens and a high frequency of life-threatening bacterial disease. It is our opinion that a process of epithelial barrier dysfunction and immune dysregulation at these mucosal surfaces leads to the much higher rates of pneumonia, meningitis and severe sepsis seen in resource-limited countries. [Copyright &y& Elsevier]

Abstract: CD20 is a cell-surface marker expressed on mature B cells and most malignant B cells, but not stem or plasma cells. It is an ideal target for monoclonal antibodies (mAb), such as rituximab and ofatumumab, as it is expressed at high levels on most B-cell malignancies, but does not become internalized or shed from the plasma membrane following mAb treatment. This allows mAb to persist on the cell surface for extended periods and deliver sustained immunological attack from complement and FcR-expressing innate effectors, particularly macrophages. CD20 can also generate transmembrane signals when engaged by certain mAb which, although unproven, might provide an important element of the therapeutic success of anti-CD20 mAb. These favourable characteristics have led to anti-CD20 mAb being developed and exploited for use in immunotherapy, where they have proven remarkably efficacious in both the treatment of malignant disease and autoimmune disorders by deleting malignant or normal B cells, respectively. In this review, we discuss how these mAb have driven research in the immunotherapy field over the last decade, detail their likely modes of action and their limitations in terms of effector exhaustion, and explore ways in which they might be enhanced and further exploited in the future. [Copyright &y& Elsevier]

Heat shock protein (HSP) 27 has long been known to be a component of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. p38 MAPK has important functions in the inflammatory response, but the role of HSP27 in inflammation has remained unknown. We have used small interfering RNAs to suppress HSP27 expression in HeLa cells and fibroblasts and found that it is required for pro-inflammatory cell signaling and the expression of pro-inflammatory genes. HSP27 is needed for the activation by interleukin (IL)-1 of TAK1 and downstream signaling by p38 MAPK, JNK, and their activators (MKK-3, -4, -6, -7) and IKKβ. IL-1-induced ERK activation appears to be independent of HSP27. HSP27 is required for both IL-1 and TNF-induced signaling pathways for which the most upstream common signaling protein is TAK1. HSP27 is also required for IL-1-induced expression of the pro-inflammatory mediators, cyclooxygenase-2, IL-6, and IL-8. HSP27 functions to drive cyclooxygenase-2 and IL-6 expression by augmenting the activation of the kinase downstream of p38 MAPK, MK2, resulting in stabilization of cyclooxygenase-2 and IL-6 mRNAs. The mechanism may not occur in cells of myeloid lineage because HSP27 protein was undetectable in human monocytes and murine macrophages. [ABSTRACT FROM AUTHOR]