Prevalence and clinical significance of anti-C1q antibodies in cutaneous and systemic lupus erythematosus

Autoantibodies against C1q are strongly linked to immune-complex disorders like systemic lupus erythematosus (SLE). Although anti-C1q antibodies have received much interest in the recent years, their biological functions remain unclear. Anti-C1q antibodies are strongly associated with lupus nephritis. The aim of this study was to determine the prevalence of anti-C1q antibodies in Egyptian lupus patients as well as to evaluate the associations between anti C1q antibodies and clinical and serologic parameters of patients with cutaneous and systemic lupus erythematosus. Fifty-eight patients of lupus erythematosus were recruited in the study, and they were divided into 3 groups according to their clinical presentations and laboratory investigations; group (1) consists of 20 patients with musculoskeletal manifestations, mainly arthritis (34.5%), group (2) consists of 12 patients with lupus nephritis (20%), and group (3) consists of 26 patients with cutaneous lupus (44.8%). Fourteen age and sex matched healthy subjects served as controls. Complete blood picture, kidney function tests, liver function tests and anti-double stranded DNA were done for all the studied patients. Anti-C1q antibodies were determined by immunometric enzyme immunoassay for all the studied subjects. Anti-C1q antibodies were positive in (63.8%) of lupus erythematosus (LE) patients and (0%) of controls. Moreover, the serum anti-C1q antibodies titers were significantly higher (P < 0.001) in all lupus erythematosus patients (both systemic and cutaneous) when compared to healthy controls. Surprisingly, serum anti-C1q antibodies were significantly higher in patients with cutaneous lupus than those with lupus nephritis (P <0.001). Anti-C1q titers were significantly correlated with levels of anti–double stranded DNA (P <0.001), as well as with proteinuria (<0.05) in lupus nephritis patients. It was concluded that anti C1q antibodies might play a pathogenic role in the pathogenesis of cutaneous lupus and could positively be associated with evolution to SLE. Moreover, it could predict patients who subsequently develop nephritis, thus early use of immune modulators in cutaneous lupus could improve patients’ prognosis by decreasing the possibility of evolution to systemic lupus complications, mainly nephritis.Keywords: Anti-C1q; Systemic lupus erythematosus; Cutaneous lupus erythematosus; Lupus nephritis; Complement; Proteinuri

Carotid axillary bypass in a patient with blocked subclavian stents: a case report

<p>Abstract</p> <p>Introduction</p> <p>Surgical treatment of symptomatic occlusive lesions of the proximal subclavian artery is infrequently necessary. Carotid subclavian bypass has gained popularity and is now considered standard treatment when stenting is not possible. Exposure of the subclavian artery and bypass grafting onto it is difficult, as the vessel is delicate, thin-walled and located deep in the supraclavicular fossa. The thoracic duct and brachial plexus are in close proximity to the left subclavian artery and are therefore susceptible to damage. Distal grafting to the axillary artery instead of the subclavian artery has the potential of avoiding some of these risks. Infraclavicular exposure of the axillary artery is more straightforward. The vessel wall is thicker and is easier to handle. In this case report, we describe a patient with a left proximal subclavian occlusion which was stented twice and blocked on both occasions. The patient underwent a carotid axillary bypass, as grafting onto the subclavian artery was impossible because of the two occluded metal stents.</p> <p>Case presentation</p> <p>A 56-year-old Caucasian woman, a heavy smoker, presented acutely with left arm numbness and pain and blood pressure discrepancies in both arms. A diagnosis of subclavian stenosis was confirmed on the basis of a computed tomographic scan and a magnetic resonance angiogram. The patient had undergone subclavian artery stenting twice, and unfortunately the stents blocked on both occasions. The patient underwent carotid axillary bypass surgery. She had an uneventful recovery and was able to return to a full, normal life.</p> <p>Conclusion</p> <p>Carotid axillary bypass appears to be a good alternative to carotid subclavian bypass in the treatment of symptomatic proximal stenosis or occlusion of the subclavian artery.</p

Role of oesophageal cooling in the prevention of oesophageal injury in atrial fibrillation catheter ablation: a systematic review and meta-analysis of randomized controlled trials.

AIMS: To evaluate the efficacy of oesophageal cooling in the prevention of oesophageal injury in patients undergoing atrial fibrillation (AF) catheter ablation. METHODS AND RESULTS: Comprehensive search of MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) evaluating the role of oesophageal cooling compared with control in the prevention of oesophageal injury during AF catheter ablation. The study primary outcome was the incidence of any oesophageal injury. The meta-analysis included 4 RCTs with a total of 294 patients. There was no difference in the incidence of any oesophageal injury between oesophageal cooling and control [15% vs. 19%; relative risk (RR) 0.86; 95% confidence interval (CI) 0.31-2.41]. Compared with control, oesophageal cooling showed lower risk of severe oesophageal injury (1.5% vs. 9%; RR 0.21; 95% CI 0.05-0.80). There were no significant differences among the two groups in mild to moderate oesophageal injury (13.6% vs. 12.1%; RR 1.09; 95% CI 0.28-4.23), procedure duration [standardized mean difference (SMD) -0.03; 95% CI -0.36-0.30], posterior wall radiofrequency (RF) time (SMD 0.27; 95% CI -0.04-0.58), total RF time (SMD -0.50; 95% CI -1.15-0.16), acute reconnection incidence (RR 0.93; 95% CI 0.02-36.34), and ablation index (SMD 0.16; 95% CI -0.33-0.66). CONCLUSION: Among patients undergoing AF catheter ablation, oesophageal cooling did not reduce the overall risk of any oesophageal injury compared with control. Oesophageal cooling might shift the severity of oesophageal injuries to less severe injuries. Further studies should evaluate the long-term effects after oesophageal cooling during AF catheter ablation

Regulated Nuclear Trafficking of rpL10A Mediated by NIK1 Represents a Defense Strategy of Plant Cells against Virus

The NSP-interacting kinase (NIK) receptor-mediated defense pathway has been identified recently as a virulence target of the geminivirus nuclear shuttle protein (NSP). However, the NIK1–NSP interaction does not fit into the elicitor–receptor model of resistance, and hence the molecular mechanism that links this antiviral response to receptor activation remains obscure. Here, we identified a ribosomal protein, rpL10A, as a specific partner and substrate of NIK1 that functions as an immediate downstream effector of NIK1-mediated response. Phosphorylation of cytosolic rpL10A by NIK1 redirects the protein to the nucleus where it may act to modulate viral infection. While ectopic expression of normal NIK1 or a hyperactive NIK1 mutant promotes the accumulation of phosphorylated rpL10A within the nuclei, an inactive NIK1 mutant fails to redirect the protein to the nuclei of co-transfected cells. Likewise, a mutant rpL10A defective for NIK1 phosphorylation is not redirected to the nucleus. Furthermore, loss of rpL10A function enhances susceptibility to geminivirus infection, resembling the phenotype of nik1 null alleles. We also provide evidence that geminivirus infection directly interferes with NIK1-mediated nuclear relocalization of rpL10A as a counterdefensive measure. However, the NIK1-mediated defense signaling neither activates RNA silencing nor promotes a hypersensitive response but inhibits plant growth and development. Although the virulence function of the particular geminivirus NSP studied here overcomes this layer of defense in Arabidopsis, the NIK1-mediated signaling response may be involved in restricting the host range of other viruses

Utility of Repeated Praziquantel Dosing in the Treatment of Schistosomiasis in High-Risk Communities in Africa: A Systematic Review

Infection by Schistosoma worms causes serious disease among people who live in areas of Africa, South America, and Asia where these parasites are regularly transmitted. Although yearly treatment with the drug praziquantel is fairly effective in reducing or eliminating active infection, it does not cure everyone, and reinfection remains a continuing problem in high-risk communities. Studies have suggested that a repeat dose of praziquantel, given 2 to 8 weeks after the first dose, can improve cure rates and reduce remaining intensity of infections in population-based programs. Our systematic review of published research found that, on average, in Africa, such repeated dosing appears to offer particular advantages in the treatment of S. mansoni, the cause of intestinal schistosomiasis, but there was less consistent improvement after double-dosing for S. haematobium, the cause of urogenital schistosomiasis. Based on this evidence, we used a calibrated life-path model to predict the costs and benefits of a single-dose vs. a double-dose strategy in a typical high-risk community. Our projections suggest cost-effective incremental benefits from double dosing in terms of i) limiting a person's total years spent infected and ii) limiting the number of years they spend with heavy infection, with consequent improvements in quality of life

Impact of early psychosocial factors (childhood socioeconomic factors and adversities) on future risk of type 2 diabetes, metabolic disturbances and obesity: a systematic review

<p>Abstract</p> <p>Background</p> <p>Psychological factors and socioeconomic status (SES) have a notable impact on health disparities, including type 2 diabetes risk. However, the link between childhood psychosocial factors, such as childhood adversities or parental SES, and metabolic disturbances is less well established. In addition, the lifetime perspective including adult socioeconomic factors remains of further interest.</p> <p>We carried out a systematic review with the main question if there is evidence in population- or community-based studies that childhood adversities (like neglect, traumata and deprivation) have considerable impact on type 2 diabetes incidence and other metabolic disturbances. Also, parental SES was included in the search as risk factor for both, diabetes and adverse childhood experiences. Finally, we assumed that obesity might be a mediator for the association of childhood adversities with diabetes incidence. Therefore, we carried out a second review on obesity, applying a similar search strategy.</p> <p>Methods</p> <p>Two systematic reviews were carried out. Longitudinal, population- or community-based studies were included if they contained data on psychosocial factors in childhood and either diabetes incidence or obesity risk.</p> <p>Results</p> <p>We included ten studies comprising a total of 200,381 individuals. Eight out of ten studies indicated that low parental status was associated with type 2 diabetes incidence or the development of metabolic abnormalities. Adjustment for adult SES and obesity tended to attenuate the childhood SES-attributable risk but the association remained. For obesity, eleven studies were included with a total sample size of 70,420 participants. Four out of eleven studies observed an independent association of low childhood SES on the risk for overweight and obesity later in life.</p> <p>Conclusions</p> <p>Taken together, there is evidence that childhood SES is associated with type 2 diabetes and obesity in later life. The database on the role of psychological factors such as traumata and childhood adversities for the future risk of type 2 diabetes or obesity is too small to draw conclusions. Thus, more population-based longitudinal studies and international standards to assess psychosocial factors are needed to clarify the mechanisms leading to the observed health disparities.</p

Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A Research Agenda for Helminth Diseases of Humans: Diagnostics for Control and Elimination Programmes

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112